In this study, the changes in properties and structure of high amylose corn starch (70%) films with different concentrations of sodium hydroxide (NaOH), prepared by melting extrusion, were investigated. With increasing sodium hydroxide concentrations, the tensile strength of the high-amylose starch film decreased gradually, while the elongation at break increased. The tensile strength of the high amylose starch (HAS) film with 2% NaOH-treatment was 10.03 MPa and its elongation at break was 40%. A 2% NaOH-treatment promoted the orderly rearrangement of starch molecules and formed an E Petroleum-based plastics have caused serious environmental pollution , and thu−Na+). Therefore, alkali is an efficient catalyst for the chemical modification of starch [Alkali treatment is widely used in the process of many traditional foods. A certain level of edible alkali can enhance flour quality and improve the taste and appearance of the product ,10. Alkaf starch ,16. Prevf starch , reducesf starch , and inhf starch . Therefof starch ,20 and sf starch .Current research on alkali-treated starches focuses on the effect of alkali treatment on the structure and properties of starch and the reaction efficiency during the extraction or modification processes. However, the effect of alkali treatment on the properties of thermoplastic starch films prepared by melting extrusion has rarely been reported. In this paper, the properties and structural changes of thermoplastic high amylose corn starch films prepared by melting extrusion after applying different concentrations of sodium hydroxide were studied. The results of our study provide a theoretical basis for the subsequent study of starch extrusion modification and film formation with HAS.High amylose corn starch  was purchased from Ingredion China Limited . Dimethyl sulfoxide (DMSO), citric acid, and glycerol (AR) were purchased from Tianjin Kaitong Chemical Reagent Co., Ltd. . Deionized water was prepared using an AK Exceed-D lab pure-water system . The HAS was placed in a SHR-50A high-speed mixer  at pre-determined proportions  and slowThe melting extrusion of the HAS was completed by a SHJ-20B co-rotating twin-screw extruder Nanjing Giant Machinery Co., Ltd., Jiangsu, China) equipped with a single hole T-flat die, the length of the die was 40 mm and the diameter of the hole was 3.5 mm. The twin-screw was 20 mm in diameter with its L/D was 40. The extrusion temperature was set from the feeder to the die end: 85-100-115-135-120-115 °C. The extrusion screw speed was 100 rpm and the feeder rotation speed was 10 rpm. These parameters ensured the throughput was about 1 kg/h. An exhaust vent was equipped near the die to for exhausting steam. The extrudate was cooled to room temperature through an air-cooled conveyor belt which consisted of four fans, and cut into strips of 20 cm. Five strips were placed on a 20 cm × 20 cm stainless steel mold covered with tetrafluoroethylene to form a film by hot pressing. The process parameters of the hot pressing film formation were: 155 °C, 0 MPa preheated for 2 min, 10 MPa hot pressed for 10 min, 30 MPa hot pressed for 10 min, circulated water was used to cool the mold to room temperature and open the mold, and the HAS film was placed in an HWS constant-temperature and humidity chamber  at 23 °C and 53% RH for 72 h.The thicknesses of the HAS films were determined using 211-101F micrometers . All the films were tested randomly, and the thicknesses of the HAS films were calculated by averaging the results of six replicate measurements. The mechanical properties of the starch film including tensile strength  and elongation at break  were measured by a XLW (PC) Auto Tensile Tester  based on the standard of ASTM D882-12 . The tes−1. The number of accumulated scans, the scanning resolution and accumulated scans time were 32, 4 cm−1, and 47 s, respectively. The resulting spectra were normalized and difference processed using OMNIC software , and Peakfit software version 4.0  was used to fit the spectra, identify characteristic peaks, and calculate their intensity.Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was performed on the HAS films using a Nicolet iS 5 spectrometers with an attenuated total reflectance accessory  over a wavenumber range of 4000–400 cm13C solid-state nuclear magnetic resonance (13C SSNMR) was performed using a Bruker Avance III 400 MHz wide bore spectrometer  equipped with a 4-mm broadband double-resonance cross-polarized magic angle spinning probe. Each film sample (500 mg) was placed onto the rotor and introduced to the center of a magnetic field. The results were normalized and fitted by Peakfit software to calculate the peak areas of C1 and C4.The The surface morphology of HAS films was sprayed with gold and measured by a FEI QUANTA FEG25 electron microscope  with a magnification of 2000 times, at an accelerating voltage of 5 KV.One mg of the HAS film was dissolved in 1 mL of 50 mM LiCl-DMSO and stirred at 90 °C for 2 h in a water bath. The resulting solution was then magnetically stirred at room temperature for 8 h and injected into a sample vial through a 1.0 μm nylon-66 filter .w) and radius of gyration (Rg) of the HAS film.The average molecular weight of the starch film was measured using a BI-200SM laser light scattering system . The static light scattering (SLS) test had an observation angle of 30–120°, a step frequency of 5°, and the incident laser wavelength was λ = 633 nm. The refractive index of the sample solution was measured using a dn/dc meter to be 0.147. The test results were calculated by the Berry equation to obtain the average molecular weight (Mh) was obtained by mathematical derivation, and by calculating the Rg/Rh ratio, the morphology of the starch molecules in the solution was identified.The dynamic light scattering (DLS) test had an observation angle of 30–120°, a step frequency of 10°, test time of 3 min  and an incident laser wavelength of λ = 633 nm. The experimental results were calculated by the Contin equation, and the effective particle size of the starch molecules at various angles was identified. The hydrodynamic radius  using a D8 Advance X-ray diffractometer . The Cu target line was used, λ = 0.15406 nm, 2θ = 5–40°, and the step frequency was 0.02°/s.p < 0.05, after analysis of variance (ANOVA) with SPSS software 21 .Data are expressed as mean ± standard deviation, and differences were considered significant at As the concentration of NaOH increased, the melting extrusion process caused the color of the thermoplastic HAS to gradually darken from a translucent yellow to a dark brown . The surNaOH treatment increased the elongation at break, but decreased the tensile strength of HAS film as the NaOH concentration increased . The tenThe thickness of the control group was 0.193 mm. The thickness of HAS treated with 2%, 6%, and 10% NaOH was 0.229 mm, 0.249 mm, and 0.257 mm, respectively .The HAS films treated with different NaOH concentrations showed significantly different surface morphologies . The surH-type crystal structure  pattern of the control group showed a distinct Vtructure , which htructure ,28. Althcrystals ,29. Thiscrystals . The chatructure  led to atructure .−1 was the stretching vibration peak of -OH in the starch film, while the bending vibration peak of -OH at 1650 cm−1 was the characteristic absorption peak of water molecules. The double peaks located near 2925 cm−1 and 2881 cm−1 were symmetric and asymmetric stretching vibration peaks of -CH2 and -CH, and their bending vibration peaks were located at 1365 cm−1, 1235 cm−1, and 1200 cm−1. The vibrational peak of the glucose ring was located at 925 cm−1, and the stretching vibrational peak of the C-O-C group of the α-1,4-glycosidic bond was located near 1000 cm−1 [The Fourier transform infrared (FTIR) spectrum of the HAS film with different concentrations of NaOH  yielded 000 cm−1 .−1 increased. This was mainly due to the reaction of NaOH with the -OH group, which formed an -O−Na+ group, destroying the hydrogen bond structure that maintains the structural stability of the starch molecule and exposing more -OH groups [−1 decreased due to the reduced content of -OH after oxidization. The characteristic peaks at 2900–2850 cm−1 and 1500–1183 cm−1 showed similar trends. The presence of -O−Na+ enhanced the polarity of -CH and -CH2, resulting in enhanced absorption peaks at 2% NaOH-treatment; as the NaOH concentration further increased, the starch molecules oxidize, resulting in a decrease in the absorption peaks of -CH and -CH2.Compared to the control group, the absorption peak intensity of the 2% NaOH-treated HAS film at 3285 cmH groups . When th−1, indicating that the -OH group in anhydroglucose was oxidized [The oxidization of HAS during extrusion occurred in the HAS film with 6% NaOH, forming a new vibrational absorption peak of carbonyl (C=O) around 1591 cmoxidized . In the −Na+ groups. Under high temperatures and high shear stress conditions, NaOH reacted with the hydroxyl group of the starch molecule and formed a molecule containing a di-carbonyl group via molecular rearrangement [−1, which increased the band intensity at 800–500 cm−1. This indicates that during the melting extrusion process, NaOH initiated the degradation of starch molecules, broke the glycosidic bond, and produced a small molecule of carboxylic acid molecules or heterocyclic rings containing an unsaturated bond [The current explanation of the oxidation process of alkali-treated HAS in the extrusion process was based on the study of the degradation mechanism of cellulose by alkali solution  Figure . NaOH caangement . In addited bond . The HAS−1 band to move to lower wavenumbers [−1 and 1018 cm−1 (R1039/1018).Analysis of the short-range order of molecular chains in HAS films after treatment with varying concentrations of NaOH by FTIR further explored the molecular chain changes of starch during film formation . When HAenumbers . Therefo1039/1018 values of the HAS films treated with different concentrations of NaOH showed a tendency to first increase and then decrease, with a maximum value of about 0.707 at 6% NaOH  spectra of HAS films treated with different concentrations of NaOH (1 was located at 90–110 ppm, in which 99–101 ppm peak represented the double helix structure of HAS molecular chain and 102–103 ppm peak represented the single helix moiety in the starch granules. The characteristic peak of C4 was located at 78–88 ppm and its peak area ratio was related to the ratio of the amorphous zone in HAS film; the strong peak at 68–78 ppm was the characteristic peak produced by the interaction of C2, C3, and C5; and the characteristic peak of C6 was located at 58–68 ppm [The  of NaOH  showed t8–68 ppm .13C solid-state NMR spectra (The change in molecular chain conformation of the HAS films treated with different concentrations of NaOH was measured by fitting the  spectra . Compare5 g·mol−1, and its Rg/Rh value was 0.97, indicating that the starch molecules were hollow sphere structures with a dense shell and a relatively loose interior. This demonstrates that HAS maintained a tight outer shell after extrusion film formation, and the use of water/glycerol as a plasticizer is ineffective on HAS. The Rh of the HAS film treated with 2% and 6% NaOH increased gradually, the Rg decreased gradually, the Rg/Rh decreased, HAS particles retained a hard sphere state with a dense core remaining, while the outer shell became gradually looser, and the molecular gap increased. This demonstrates that the swelling of HAS particles caused by NaOH progresses from the outside to the inside. When the amount of NaOH reached 10%, the Rg/Rh of the HAS molecule increased to 1.20, indicating that the form of the HAS molecule in solution was a random coil [The molecular weight and molecular morphology of HAS films with different concentrations of NaOH changed significantly . The moldom coil  and thatThe molecular weight of HAS gradually increased as the NaOH concentration increased, and the molecular weight of 10% NaOH-treated HAS film was 1.84 times that of the control group. Starch molecules may not only undergo an oxidative decomposition reaction, but also undergo a cross-linking reaction during the HAS extrusion process with high concentration NaOH treatment . The subh-type crystal structures, increased the spacing in a single-helical structure, increased the mobility of starch molecules, and slowed the process of recrystallization. This would be beneficial for the further modification and film forming process of HAS.The study fills a research gap in the existing literature by demonstrating that treatment with alkali can affect the properties and performance of corn starch films. The data showed that as the dosage of NaOH increased, the tensile strength of HAS film decreased and the elongation at break increased gradually. A 2% NaOH-treatment HAS had a tensile strength at 10.03 MPa and its elongation at break was 40%. The 2% NaOH orderly rearranged the starch molecules, formed E5 g·mol−1 and caused random aggregation of the starch molecular chain, led to recrystallization of starch, and browned the starch film, which were not conducive to the further modification of starch and starch film performance improvement. These results provide a guiding framework for further investigation into HAS modification by extrusion and film formation.As the concentration increased, especially 10% NaOH, alkali oxidized the hydroxyl group of HAS significantly during extrusion and formed poly-carbonyl groups and small molecules. These might initiate various cross-linking of starch that increased the molecular weight to 4.97 × 10


The first author maintains that the results in the article are correct, but he says the university has restricted the download of the thesis.The Scientific World Journal has retracted the article titled “Stimulatory Effects of Gamma Irradiation on Phytochemical Properties, Mitotic Behaviour, and Nutritional Composition of Sainfoin (Onobrychis viciifolia Scop.)” . As raisFigure 5(e)  in The Scientific World Journal is identical to Figure 5(f) (Laggard chromosomes) in Journal of Agricultural Science and Technology and Figure 4.36i  in the thesis. The same image of laggard/fragmented chromosomes is used for general cytology , gamma radiation , and UV-B (thesis).Table 1 (growth of seeds after gamma irradiation) in The Scientific World Journal is similar to Table 4.35 in the thesis. Growth statistics in The Scientific World Journal and the thesis differ for all but one measure, but many of the digits are the same even when the results differ, e.g. 17.89 ± 2.24 vs 38.89 ± 0.24.Figure 3 (Non-irradiated seeds) in The Scientific World Journal is the same as Figure 4.31a (UV-B exposed) in the thesis, meaning that the HPLC traces for a control in The Scientific World Journal and UVB exposed seeds in the thesis are identical. However, the areas reported are different: 7009 and 9421 vs 8523 and 8825.Table 4 (mitosis) in The Scientific World Journal is not the same as Table 4.38 (mitosis) in the thesis, but shares many digits. When data sets share mainly nonsignificant digits , this is unlikely to be due to chance.Details of the main concerns are as follows:(5) Figure 3(b) (non-irradiated seeds) in The Scientific World Journal is identical to Figure 2(b) (control seeds) in Journal of Animal & Plant Sciences. The control was reused across different experiments, on gamma radiation and humidity, respectively.μm in TSWJ vs 100 μm in Journal of Agricultural Science and Technology and the thesis)and the background above the chromosomes appears to be slightly different between the images .(6) As noted above, Figure 5(e)  in The Scientific World Journal is identical to Figure 5(f) (Laggard chromosomes) in Journal of Agricultural Science and Technology and Figure 4.36i  in the thesis. However, the scales are different (10 (7) Figure 5(f) (micronucleus) in The Scientific World Journal is identical to Figure 5(g) (micronucleus) in Journal of Agricultural Science and Technology. The same image is used for general cytology  and gamma radiation .(8) Figure 3  in The Scientific World Journal is the same as Figure 4.38a  in the thesis. However, the heights for sanguinarine differ, 6428 vs 7009, and the areas for berberine, 1078 vs 1087.(9) The control HPLC traces are very different between The Scientific World Journal  and the thesis .(10) Table 5 (mitosis) in The Scientific World Journal is not the same as Table 4.39 (mitosis) in the thesis. The cell and nuclear area results are very different in The Scientific World Journal and the thesis.Additional concerns are as follows:


The presence of errors in the preanalytical phase is a thoroughly studied problem. A strategy to increase their source detection might be the use of the Healthcare Failure Mode and Effects Analysis (HFMEA). The aim of this study is improving the capacity of identifying sources of error during the preanalytical period in samples provided by primary care clinics (PCC) with the use of the HFMEA as a tool in the laboratories of two tertiary hospitals.A HFMEA was carried out in each laboratory, by means of the creation of groups of experts with similar characteristics . The Risk Priority Number (RPN) was calculated.Items with elevated RPN were presented in both centers. The highest RPN were in LAB1: “two request notes for a patient” and “the segregation of oncology urgent samples” (both with 384), while in LAB2 was “the lack of information in patients with oral glucose overload test” (RPN 576). Considering the different steps in the preanalytical phase, LAB1 paid attention in sampling, samples reception and the programming in the Laboratory Information System, while LAB2 paid attention in the request form, the appointment system, sampling procedures, transport and reception.The laboratories prioritized the problems differently. However, both centers offer solutions to these possible sources of error. We proposed improvement actions that can be resolved easily, with a low cost for the system, mainly to schedule a specific formative programme and a deep revision of the existing protocols. The study was performed between April and October 2016.We included data obtained from two laboratories of the Andalusian public healthcare system: Virgen de la Victoria  and Juan Ramón Jiménez . Both centers receive samples from PCC to their areas, and both have a similar structure in preanalytical and samples reception areas.LAB1 processes approximately 890,000 blood and urine samples yearly provided by PCC, and LAB2 receives 580,000 (data from 2015). Both laboratories receive samples from PCC located at a similar distance, use similar transportation and refrigeration means, and also have the same sample reception areas structure. The difference between samples is due to the different population of the areas .The first step was, by means of the analysis of the process of study and a brainstorm by our research team, to develop a scheme based on the preanalytical phase in which the different steps of the process where errors could appear were described. This scheme included six key areas that might be considered potential error sources in the preanalytical phase: analytical request and request form, appointment system, patient preparation, sampling, transport, and reception - preparation of samples. Then, we summoned the participants in order to proceed as has been previously described.A group of professionals was set up, including two nurses (from PCC and laboratories), two laboratory technicians, two support staff and three doctors , who were informed in detail of the purpose of the study and the methodology to use. Each group was coordinated by a member of the research team .Every participant was invited to comment on relevant aspects about the possible error sources they identified, following the order of the previously designed scheme, and they were asked to give a score from 1 to 10 for the severity rate (SR) and the occurrence rate (OR), being in both cases 10 the indicator of maximum rate, and to score the detection rate (DR), that values the capacity of being detected, with an inverse scale . The RPN was calculated by multiplying the three data resulting (SR x OR x DR = RPN), then following a Pareto chart . The most commented effect was the delay in processing samples or non-performance of the tests requested.).In LAB2, 16 potential errors were detected, 12 of them out of the laboratory facilities. The most commented aspect was the need to request a new sample. The highest RPN was 576, and it was given to the lack of information in patients with oral glucose overload test  and the existence of duplicate requests, doubtlessly due to the novelty of the process and the communication errors detected in its implementation. In addition, LAB1 also considered factors such as the co-existence of general practitioner and specialist requests (both RPN 384) together with the lack of coincidence between the patients’ identification data and the labelled samples (RPN 210) and the existence of insufficient samples that prevent errors when aliquoting a sample (RPN 200). On its part, LAB2 highlighted the deficit of information given to the patient recipient of an oral overload of glucose (RPN 576), the delay in the transport of the samples to the laboratory (RPN 486), and the possible existence of the same code for two different patients (RPN 240). The rest of the data were very similar in both centers.It is necessary to point out findings such as different RPN compared with other studies previously published made in our work environment  analysis previously performed by our team (


Hernia repair with mesh graft is one of the most common procedures in general surgery. Mesh graft repair is the treatment of choice for umbilical and periumbilical hernias to minimize recurrence. One of the rare but serious complications is mesh graft migration to viscus. These complications can occur months to years after repair and their diagnosis can be challenging as they may present as vague abdominal pain only.A 74-year-old gentleman with multiple medical comorbidities was diagnosed with a para-umbilical hernia after which he underwent a laparoscopic hernia repair at our hospital using a mesh graft with no complications. On postoperative day 10, he presented to the emergency room (ER) complaining of colicky abdominal pain in the right iliac fossa for 1 day associated with diarrhea. A Computed Tomography (CT) scan of the abdomen and pelvis showed diffuse wall thickening of the cecum and terminal ileum with small free air worrisome for perforation. The decision was made in the ER to discharge him home on antibiotics. The patient then returned back multiple times to the ER for the same complaint along with bleeding per rectum for which he underwent further investigations. Months later, the patient presented again with the same symptoms. A CT scan revealed recurrence of a periumbilical hernia and thickening of the medial wall of the cecum with mesh graft material. The patient was then taken to surgery and intra-operative findings revealed migration of almost 50% of the mesh graft size to the cecum and part of the mesh graft was eroding the distal part of ileum just proximal to the ileocecal junction. Adhesolysis and limited right hemicolectomy with ileocolic anastomosis was done. The patient had an uneventful recovery after revisions surgery without any perioperative complications. He was discharged home on postoperative readmission day 5 and followed up at 2 weeks and 3 months without any delayed complications or subjective complaints.It is important to consider mesh graft migration to viscus as a cause of persistent abdominal pain and bleeding per rectum irrespective of the time of presentation post hernia repair. Mesh graft repair is the treatment of choice for umbilical and periumbilical hernias to minimize recurrence . Early cThese complications can occur months to years after the hernia repair . HoweverA 74-year-old male, known case of diabetes mellitus (DM), hypertension (HTN), bronchial asthma and hypothyroidism who was diagnosed with para-umbilical hernia. The defect size was 1 × 2 cm, after of which he underwent a laparoscopic hernia repair at our hospital using a 15 × 20 cm eTPES mesh Bard® Composix™ E/X Mesh  with no complications. The patient had uneventful admission period and was discharged home in good condition at day 2 post-op.Postoperatively day 10, he presented to the Emergency Room (ER) complaining of colicky abdominal pain in the right iliac fossa for 1 day associated with diarrhea (5 times/day). No other symptoms were reported by the patient. On physical examination, patient had normal vital signs and generalized mild abdominal tenderness. The maximum tenderness point was at the right iliac fossa. A Computed Tomography (CT) scan of the abdomen and pelvis was done which showed diffuse wall thickening of the cecum and terminal ileum with abnormal configuration of the cecum and ill definition of its anterior wall with small free air worrisome for perforation (Fig. Ten weeks post-operation, the patient presented again to his primary surgeon at our institute with the same complains where CT scan was ordered again and showed the same findings. Colonoscopy was ordered which showed small polyp that was removed and revealed benign adenoma, also showed a small solid structure in the cecum Fig. . Biopsy Three months after surgery, the patient returned back to his primary surgeon complaining of bleeding per rectum for which he underwent further investigations including second colonoscopy. The colonoscopy showed a polypoidal mass that was biopsied and showed granulating tissues Fig. . The patTen months post operation, the patient was seen in the outpatient clinic complaining of persistent vague abdominal pain and bleeding per rectum. CT scan of abdomen and pelvis was repeated which demonstrated opacity at the level of the cecum with dense opacity medial to it of low attenuation and contains some air bubbles Fig. . AnotherFollow up after more than 2 years of surgery indicated iron deficiency anemia and B12 deficiency. Thus, a colonoscopy was scheduled but the patient could not tolerate the bowel prep. A CT Colonography was ordered which showed a foreign object in the colon, possibly caused bleeding per rectum where the patient was referred back to the surgeon Fig. a. A CT sTen months later, we received the patient in our service for the first time when he was complaining of persistent abdominal pain and bleeding per rectum. After reviewing his previous investigations, we told the patient about the mesh graft migration and we discussed with him the mandatory of exploratory laparotomy and mesh graft removal with bowel resection and the possibility of stoma creation at any point of surgery. The patient was informed that he would have higher rate of hernia recurrence and a mesh graft will not be used in this procedure to avoid further complications like wound/mesh infection due to the risk of bowel contents spillage in the surgical field on top of his other comorbidities like DM and bronchial asthma.The patient then was taken to surgery by his primary surgeon, and intra-operative findings revealed migration of almost 50% of the mesh graft size to the cecum and part of the mesh graft was eroding the distal part of ileum just proximal to the ileocecal junction. Adhesolysis and limited right hemicolectomy with ileocolic anastomosis was done. Fascia closure was obtained primarily without mesh graft application. Skin closure completed with skin clips Figs. , 8 & 9. According to the literature, hernia repair with mesh graft is the gold standard technique for repairing umbilical and periumbilical hernias which helps in reducing the hernia recurrence rate . Due to Complications can be classified as major complications which are life threatening that require emergency surgery and those that are clinically alarming complications which are significant but do not require an emergency set-up. Major complications include bowel obstruction, perforation and bleeding. Clinically significant complications include enterocutaneous fistula, sinus tract formation, intra-abdominal abscess, seroma and non-healing wound. Complications can also be classified in relation to hernia repair with definite relation or possible relation. Bowel obstruction is one such complication which can be possibly related to hernia repair if it is correlated with the patient’s prior abdominal surgery rather than the mesh graft itself. This can be confirmed by ruling out the presence of adhesion to the mesh graft , 9.Similarly, most common long-term mesh graft related complications are bowel obstruction and sinus tract formation, keeping in mind that mesh graft size, which is determined by the size of the hernia, is a risk factor for the development of complications. Likewise, inflammation related to the mesh graft secures its repair due to fibrosis, compared to loose mesh without fibrosis leading to recurrence of the hernia. Therefore, Multiple measures to reduce the rate of inevitable mesh graft repair complications are considered during the repair , 10.The risk factors and exact pathophysiology of mesh graft migration is still unknown. However, various factors such as inadequate fixation of the mesh graft to the fascia or sliding due to external forces and entry of the mesh graft into the abdomen from points of least resistance, or presence of adhesions and inflammations from previous surgeries can increase the risk of mesh graft migration. It is also hypothesized that the sharp edges of the mesh graft can induce an inflammatory reaction which can erode the parietal peritoneum and penetrate into the colon . Mesh grOn the other hand, in our experience explained above, one of the causing factors for such complication is using large mesh graft 20 × 15 cm for a small defect especially if it was not applied properly which allowed a gap between the mesh graft and the abdominal wall which caused entrapment of the bowel. Also, frequent visit of our patient to the emergency with worrisome CT finding make the diagnostic laparoscopy mandatory and that would save the patient from undergoing a major surgery like laparotomy and hemicolectomy.Patients with mesh graft erosion and migration can present with acute intestinal obstruction, mass formation, bowel perforation and chronic abdominal pain between 1 and 20 years after repair . The golIt is recommended for physicians to be mindful of the fact that imaging could be misleading towards the diagnosis of mesh graft migration making the diagnosis of mesh graft migration left unnoticed or overlooked. It is important to consider mesh graft migration as a cause of abdominal pain and bleeding per rectum irrespective of the time of presentation post hernia repair. Our case didn’t demonstrate a typical presentation like those reported in the literature with fistulas. This case is a reminder that mesh graft migration cases are not always associated with fistulas.


In the past, aesthetics had a secondary role in implant rehabilitation. Nowadays, the search for a perfect and harmonious aesthetic has stimulated the development of new materials and techniques. Due to this aesthetic requirement, the hybrid abutment (titanium link + zirconia) emerged as an alternative to metallic pillars. The hybrid abutment made a more favorable aesthetic possible, provided reliable mechanical properties, and increased biocompatibility to the surrounding tissues. Additionally, the individual zirconia abutment improves the emergency profile and the final white aesthetics. The objective of this paper is to report a clinical case with a manufactured individualized hybrid abutment for a metal-free indirect restoration, showing the applicability, mechanical properties, and biocompatibility of the hybrid abutment. Aesthetic demands led us to new concepts and prosthetic resources in dentistry. We now use new materials with optical, mechanical, and biological properties . ZirconiZirconia abutments not only allow light transmission in the same manner as natural teeth , 4, 5 buThe aesthetic success of implant-supported prostheses is strongly related to the surrounding soft tissue appearance. Unlike metal abutments, which cause an unpleasant appearance in a fine gingival biotype , the useAs observed in several studies, zirconia has shown satisfactory results in aesthetic of prosthetic crowns as well as in adjacent gingival tissues , 7–11. DThe CAD/CAM system consists of a planning and production computerized system for crowns, facets, inlays, onlays, crown copings, implant abutments, and even zirconia structures for fixed and removable partial prostheses. Through this system, pieces are fabricated with quality, high accuracy, minimal human intervention, error reduction during production, and lowered manufacturing costs , 14.The objective of this paper was to show the importance of aesthetic customized prosthetic abutment and its indications and advantages and disadvantages, along with a clinical case presentation.A 46-year-old male patient with absence of element 24 presents with a need for aesthetic rehabilitation. The patient had tooth extraction indicated due to root fracture. After Anthogyr PX 4.0 × 8 mm implant installation, a provisional restauration for gingival tissue maintenance was made, in respect of the ideal critical and subcritical contour, providing a more predictable and stable gingival emergence profile.During the osseointegration period (120 days), the temporary customized crown did not have any occlusal contact. After this period, the acrylic temporary crown, previously prepared, was adjusted. For a better gingival tissue conditioning, we proceeded with temporary crown reassembly. Figures For the preparation of the working cast, customized transfer was used Figures  and moldEven though the working cast reproduces the clinical situation faithfully , we procThe zirconia project enables angular corrections in the trajectory position, in order to avoid or minimize differences between implant and crown position Figures .Once the crown is designed, the outer part of the abutment is adjusted to create support and to provide retention which is achieved by planning an ideal proportion between the hybrid abutment and restorative crown, interocclusal space, and cementation line appropriated to the final restoration Figures  and 9.An E-max  pure crown final restoration was manufactured Figures  and 11.To cement the zirconia abutment in the link abutment, the flex base, the bonding surfaces of the titanium, and the zirconia ceramic were air-abraded with 50 mm aluminum oxide particles at 2.0 bars of pressure (0.25 MPa) for 20 seconds at a distance of 10 mm, after which they were cleaned in alcohol and then cemented using a resin luting  . Excess The hybrid abutment was placed  with 25 The clinical results Figures  and 14, Dental implant treatment for dental element replacement considering the maintenance of gingival architecture and restoration has occurred for some years. However, by pursuing better aesthetics, hybrid abutments have surpassed metal abutments and provide a more natural appearance to the ceramic restorations.CAD/CAM systems enabled the fabrication of the customized zirconia for link abutments that are individualized for both the anterior region and posterior teeth. Nowadays, through the CAD/CAM technology, hybrid abutment can be designed and manufactured ensuring mechanical characteristics of the materials , 19, 20.CAD/CAM systems present several advantages, such as fast production, biocompatibility, aesthetics, and mechanical resistance with low fracture rate  , 22. FurThere are several studies comparing metal and hybrid abutment characteristics . Taking Studies have shown that the zirconia oxide presents mechanical resistance similar to titanium. This property combined with new automated techniques (CAD/CAM) made the use of hybrid abutment possible in rehabilitation both in the anterior region and in regions with higher masticatory load , 24–28.Material biocompatibility is very important for the longevity of implant-supported restorations. A great deal of studies observed that zirconia has presented low bacterial adherence, and hybrid abutments accumulate bacteria with lower pathogenic potential in relation to titanium abutments , 7.Single hybrid abutments have aesthetics, mechanical resistance, and biocompatibility which enable metal components to be replaced in implanted supported prostheses. However, each case should be evaluated carefully as these components were recently introduced to the market and there are no long-term studies on their clinical use.


The journal was formally announced in 2015 and the first issue was published in 2016. This issue marks the completion of the fourth year of our publication. BioTM was launched to feature exciting fundamental and translational research at the interface of Chemical Engineering and Medicine/Biological Sciences. The journal has had a particular focus on the translational aspects of bioengineering research.I am delighted to report on the exciting progress made by Translation has undoubtedly become a key facet of scientific research in recent years. Engineering research has led to numerous scientific discoveries that have the potential to transform clinical medicine. However, converting these discoveries into actual useful clinical technologies is a major challenge. Several factors determine the likelihood of success of such translation including safety, manufacturability, regulatory hurdles, cost, and patient acceptance. These issues are not typically considered in fundamental academic research, yet they are increasingly becoming a key part of the DNA of academic research. Clinical translation also often requires concurrent commercial translation, which brings its own challenges and constraints.I want to take this opportunity to thank our supporters during the launch phase. We are grateful for the strong support and participation of our editorial board members. Our stellar advisory board represents 32 memberships of National Academies of Engineering, Medicine and Science. Our board members have provided the guidance and the vision to the journal, and have published their own research in BioTM. To celebrate our stellar advisory board, we started a feature to introduce them in each issue. To date, we have written features about Profs. Nicholas Peppas, David Tirrell, Matthew Tirrell, Mark Davis, Paula Hammond, Frank Doyle, R.A. Mashelkar and Kristi Anseth. These editorial profiles can be found on our website. We look forward to showcasing the biographies of additional board members in coming issues.https://aiche.onlinelibrary.wiley.com/toc/23806761/2018/3/2 and https://aiche.onlinelibrary.wiley.com/toc/23806761/2018/3/3) (edited by Prof. Kannan Rangaramajunam).I want to especially thank the AIChE and SBE community for the strong support to the journal, especially during the launch of a new conference in Bioengineering and Translational Medicine that accompanies BioTM journal. The first conference was chaired by Profs. Mark Prausnitz and Ravi Kane in San Francisco. The following conferences were chaired by Prof. Ali Khademhosseini and Efrosini Kokkoli , Profs. Rebecca Carrier and Stelios Andreadis , and Profs. Ashutosh Chilkoti and Joel Collier . Two special issues were also published from the 2017 edition of this conference. . The journal is now scheduled to receive its initial impact factor in 2020, which is an important milestone. I also look forward to the growth phase of the journal including expansion of covered topics, broader participation of industry researchers in the journal and a more critical discussion/analysis of translational challenges in the field. I thank you all for your strong support to the journal to date and look forward to your continued support in coming years.


Borage is an herb crop that is an important source of gamma‐linolenic acid.https://www.novozymes.com/en/advance-your-business/agriculture/crop-productionNovozymes is a global leader in industrial‐scale enzymes. This commercial page describes their interests in microbial processes for promoting plant growth and productivity, including seed treatments.http://cardycropsolutions.com/uploads/planting_soybeanbiologicalmicrobialseedtreatments.pdfThis commercial article provides a good overview of the overall process of, and developments in, microbial seed coatings. The experimental part focuses on soybean.https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205200Neonicotinoid pesticides are increasingly being used to treat seeds to prevent damage from pests such as aphids. This study examined the effect of neonicotinoinds on microbes.https://www.corteva.us/products-and-solutions/seed-treatments.htmlThis website describes commercial products. In the process, it provides good insights into the types and manner of microbial seed protection.https://agriculture.basf.com/us/en/Crop-Protection/Poncho-VOTiVO-2-0.htmlThis site highlights an ongoing trend of combining an insecticide and a microbe on the same seed for enhanced survival and performance.https://www.nature.com/articles/s41598-019-42865-9Seeds are transmitters of microbes into a soil upon planting. The transmission can be for beneficial or detrimental bacteria. This study looked at pathogen transmittal and how the pathogens might be out‐competed by other microbes.https://www.agriculture.com/crops/the-science-behind-microbial-and-biological-productsThis popular science article gives a good overview of this field of research and highlights some of the researchers working in the field.http://www.acceleronsas.com/Solutions/BioEnhancers/Pages/Acceleron-BioAg.aspxThis is a commercial website, but information on the products highlights important features of microbial seed treatments.http://www.syngenta-us.com/crop-protection/seed-treatmentThis website highlights the seed treatment products of the agricultural products company Syngenta.https://patents.google.com/patent/WO2017087939A1/enThis patent describes methods for encapsulating microorganisms in a polymer gel on seeds and the utility of such processes.https://patentscope.wipo.int/search/en/detail.jsf?docId=US243315432This patent focuses on formulations, specifically the most effective microbial combinations for particular seed treatments.https://headsupst.com/crops/soybean-crops/This page highlights an approval of microbial seed treatment for pest control by a regulatory body, in this case the U.S. Environmental Protection Agency.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738727/Bacillus strain and it effects on cotton seedlings.This publication describes a specific type of seed treament, a particular https://link.springer.com/content/pdf/10.1007%2F978-94-011-4926-6_8.pdfThis extensive review article is somewhat dated but it provides a good, comprehensive description of many aspects of coating microbes onto seeds.https://www.frontiersin.org/articles/10.3389/fmicb.2017.00011/fullThis study details an approach of applying a benefical microbe to flowers with the effect of ultimately transmitting the microbe to harvested seeds.https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176930This paper described a method for using electrospinning to nanoimmobilize microbes for subsequent seed applications.


Hybrid individuals were genotyped for establishing self-incompatibility status and grafted on the plum rootstock ‘Marianna 2624’. Phenotyping of graft incompatibility was done at two time points, one month and one year after grafting. Anatomical  and cytomorphological  characteristics related to graft compatibility displayed continuous variation within the progeny, suggesting a polygenic inheritance. Using the Pearson correlation test, strong and significant correlations were detected between anatomical and cytomorphological traits that may reduce the number of characters for screening genotypes or progenies for graft compatibility in segregating crosses. Furthermore, no correlation existed between self- and graft incompatibility traits suggesting that they are independent inheritance traits. Hence, screening an extended hybrid population is required for pyramiding these traits in breeding programs.Floral self-incompatibility affecting yearly yield in a weather-dependent manner and graft incompatibility affecting longevity of mature trees are two important traits for apricot production. However, genetic control of graft compatibility and relationship between these traits are unknown. Here, we analyzed its inheritance in an F Grafting is largely used in the production of vegetable and fruit-bearing crops to increase uniformity, vigor and adaptation to biotic and abiotic stresses. Compatibility of rootstock and scion plays crucial role for establishing highly efficient root systems through grafting , 2. HoweP. cerasifera L. × P. munsoniana L.). Nevertheless, graft incompatibility between most popular Prunus rootstocks and apricot cultivars is one of the major problems for rootstock usage and improvement. Failure in producing long-leaving healthy grafts greatly affects the range of available Prunus rootstocks for apricot cultivation [Prunus rootstocks [Citrus, melon) [Apricot is the third most important species of the stone fruit crops with a worldwide production of approximately 3.88 million tons in 2016 . Apricottivation , 6, 9. Totstocks –13. A lootstocks . The genotstocks –17. Receotstocks , 18–20. , melon) , 20, 21., melon) . It is n, melon) , 24, sugRosaceae  exhibit typical gametophytic self-incompatibility (SI) controlled by multi-allelic S-locus [Rosaceae may involve several signaling factors, activation of MAPKs, calcium levels, ROS or cell death. ROS accumulation and activation of apoptosis signaling pathways occurring during pollen-pistil interactions in the Rosaceae could be similar to the same biological processes that take place during the scion/rootstock interaction. However, whether the two traits (self- and graft-incompatibility) are genetically dependent or not is still unknown.Floral self-incompatibility (SI) is another trait affecting yield in apricot. Many fruit species in the  S-locus , 26. SI  S-locus . In cont S-locus , 29. SelAlthough the genetic control mechanisms of some agronomic traits in fruit trees  are well understood , there i1 individuals and the parents were grafted onto the plum rootstock ‘Marianna 2624’ (P. cerasifera L. × P. munsoniana L.) (1−year−old plants with a diameter of 1 cm). Twenty grafts were performed by chip-budding for each individual seedling and characterized for graft compatibility twice, in one month (spring 2014) and one year after grafting (spring 2015).The plant material for this study included a population of 156 apricot progeny from a cross between the Spanish cultivar ‘Moniqui’  and the French cultivar ‘Paviot’  . PollinaGrafts were cut 5 cm above and below the union one year after grafting. The internal characterization of the graft union was carried out through a longitudinal cut at the graft area with a DW876 saw . Anatomy on the surface of the union was observed using a stereomicroscope  equipped with a digital imaging system through a DC300 camera . The evaluation was performed as followed: necrotic line, woody and bark discontinuity (scored between 0 = absence and 5 = maximum) .Grafts were cut 5 cm above and below the union one month after grafting, fixed in ethanol (95%)/acetic acid 3:1 (v/v) over 24 h, and then transferred to ethanol (70%) at 4°C for conservation . LongituSelf-incompatibility phenotypes were assigned to progeny using molecular markers linked to the trait following published protocol with few modifications . GenomicAll statistical analyses were performed using SPSS 21.0 statistical software . The distribution of the seedling population for each trait was represented in frequency histograms using mean values of the two years of the study for each individual. The normality of each trait distribution was evaluated by the Kolmogorov–Smirnov and the Shapiro-Wilks tests implemented in the SPSS package. Traits with normal distribution linked to graft incompatibility were analyzed by ANOVA considering individuals and years as independent factors. Bivariate correlations between and within the different traits and years were calculated using the Pearson correlation coefficients. Hierarchical cluster analysis of the quantitative phenotypic data was carried out using the squared Euclidian distance combined with the average linkage clustering method. A dendrogram was constructed to evaluate the homogeneity of the clusters using the inter-linkage group method.Labor-intensive and time-consuming process of evaluating graft compatibility is a major drawback in phenotyping multiple progeny. We evaluated different anatomical parameters related to graft incompatibility  in an apricot progeny one year after grafting in 2014 and 2015. Based on the two years of evaluation, we observed variability and noticeable segregation in the progeny for traits associated with graft incompatibility . The disWe performed a progeny classification based on quantitative phenotypic data for necrotic line, wood and bark discontinuity. Individuals plants that have missing values for traits at least one year were excluded from analysis. Remaining individuals with complete phenotypic datasets were grouped into two main clusters according to degree of incompatibility. As expected, male parent ‘Paviot’ was grouped with compatible progeny in Cluster I while female parent ‘Moniqui’ was clustered with incompatible progeny in Cluster II . In totaPrevious studies indicated that the content and nature of the callus cells involved in the first step of graft formation might play an important role in triggering the response that leads to the formation of a strong and successful union , 41. CelCorrelations were found among most agronomic traits linked to graft incompatibility during the two years of the study (2014 and 2015). Significant positive Pearson correlations existed between the phenotypic parameters observed in the F1 progeny, necrotic layer and wood discontinuity (r = 0.474**) and necrotic line and bark discontinuity r = 0.565**) in 2014. The same trend was observed in the year 2015 . Hence, 5** in 201 apricot cross was similar to that for other agronomic traits such as fruit quality related characters  or reproductive phenology [On the other hand, necrotic line, wood and bark discontinuity showed good correlations with a reduced influence of year. All the phenotypic parameters showed a positive and significant correlation between years. The average values between years were r = 0,648 for necrotic line, 0.686 for wood discontinuity and 0.885 for bark discontinuity . Thus, ohenology –46.The establishment of correlations between anatomical traits may reduce the number of characters for screening genotypes or progenies for graft compatibility. It helps to optimize time and labor required for evaluation of a high number of grafts per individuals in segregating crosses. Based on results presented here, we recommend using our phenotyping approach for phenotyping graft compatibility in other fruit and forest trees. Thus, we propose an earlier anatomical test for evaluation of compatibility between variety industrial rootstocks and new cultivars released to market.1 cross ‘Moniqui × Paviot’, together with the ‘Moniqui’ and ‘Paviot’ progenitor cultivars, were genotyped for an S-allelic composition using an express PCR test [2 = 1.043 at p<0.01) in agreement with findings by previous researchers [Self-incompatibility is an important genetic mechanism that prevents inbreeding and promotes genetic polymorphism and heterosis in flowering plants. The inheritance of apricot self-incompatibility has been studied in progenies within different programs carried out worldwide to obtain new self-compatible cultivars with good agronomical and commercial quality , 35. HowPCR test . In pareearchers .Rosaceae suggested striking alterations in the mitochondrial structure, disruption of reactive oxygen species (ROS) and induction of DNA degradation in incompatible pollen tubes [We estimated correlation between two traits, graft incompatibility and self-incompatibility, using the Pearson’s metrics . The Peaen tubes , 48. Allen tubes , 23, 49.en tubes , 51. Simen tubes , 52, 53.Prunus genus that can be used for development molecular markers for accurate prediction of graft compatibility between scion and rootstock in other woody plants.In our study most of the traits linked to graft incompatibility displayed continuous variation within the progeny and reflected the genetic difference between phenotypically contract progenitors, graft compatible ‘Moniqui’ and graft incompatible ‘Paviot’. Hence, patterns of phenotypic variation across progeny most likely reflects a polygenic inheritance of the trait in this cross. Wherein, the necrotic line, discontinuities in the bark and wood, and cell/tissue organization are highly correlated parameters. These morphological characters may reflect important aspects of developing a graft union and establishing vascular connections. Reported histomorphological approach for phenotyping paves a way for genetic approach using linkage genetic mapping and identification quantitative trait loci (QTLs) for graft compatibility in segregating crosses. Development of molecular markers associated with trait for marker-assisted selection (MAS) would be convenient for increasing efficiency of apricot breeding. A scion-rootstock interaction in apricot is currently a well-characterized model system within the


This study was carried out from winter to late spring in two successive years with different climatic conditions: 2014/2015 was typical, but the winter of 2015/2016 was the warmest on record. Rising water temperature was the main driver of phytoplankton blooms. However, blooms were sometimes correlated with winds and sometimes correlated with salinity, suggesting nutrients were supplied by water transport via winds, saltier seawater intake, rain and water flow events. This finding indicates the joint role of these factors in determining the success of phytoplankton blooms. Furthermore, interannual variability showed that winter water temperature was higher in 2016 than in 2015, resulting in lower phytoplankton biomass accumulation in the following spring. Moreover, the phytoplankton abundances and diversity also changed: cyanobacteria (< 1 μm), picoeukaryotes (< 1 μm) and nanoeukaryotes (3–6 μm) increased to the detriment of larger phytoplankton such as diatoms. Water temperature is a key factor affecting phytoplankton bloom dynamics in shallow productive coastal waters and could become crucial with future global warming by modifying bloom phenology and changing phytoplankton community structure, in turn affecting the entire food web and ecosystem services.Phytoplankton blooms are an important, widespread phenomenon in open oceans, coastal waters and freshwaters, supporting food webs and essential ecosystem services. Blooms are even more important in exploited coastal waters for maintaining high resource production. However, the environmental factors driving blooms in shallow productive coastal waters are still unclear, making it difficult to assess how environmental fluctuations influence bloom phenology and productivity. To gain insights into bloom phenology, Chl  Ocean phytoplankton generate almost half of global primary production , making For more than half a century, several paradigms and theories have been developed to explain the general mechanism of bloom initiation; however from the earliest critical depth hypothesis of Sverdrup in 1953 –7, allowRecently, the disturbance recovery hypothesis of Behrenfeld et al. ,10 formaCoastal waters and lakes are highly dynamic and productive ecosystems where phytoplankton blooms are common ,17. CoasNevertheless, in open oceans, increasing water temperature due to global warming changes the start and end timing of the blooms, and reduces their amplitude, affecting the survival and hatching time of commercially important species ,25. Furta (Chl a) fluorescence as a proxy of phytoplankton biomass, high-frequency monitoring of environmental parameters in the air and water and weekly water sampling of the phytoplankton community and nutrients in the water. The study was undertaken during winter and spring of 2015 and 2016 in Thau Lagoon, a typical productive coastal site on the edge of the Mediterranean Sea.The objective of the present study was to investigate spring bloom dynamics and the associated phytoplankton diversity in a typical shallow coastal system to identify the environmental factors triggering the blooms. The study combined high-frequency monitoring of chlorophyll 2 and is connected to the Mediterranean Sea by three channels. Thau Lagoon is a mesotrophic lagoon with a turnover rate of 2% (50 days), mostly through the Sète channel [The study site, Thau Lagoon , was cho channel . Recent  channel . The wat channel  near the channel ; therefoFor the meteorological parameters , air tem2 concentration and saturation were recorded using an optical sensor . The turbidity and the in situ Chl a fluorescence were recorded with an ECO FLNTU fluorometer (Wetlabs). Water properties were recorded at the same frequency and over the same periods as the meteorological parameters, except for water temperature and conductivity in 2016, where the monitoring started ten days later . All sensors were calibrated before deployment. The temperature sensor was calibrated from 5 to 25°C in 5°C steps using a reference thermometer and thermostatic bath. The salinity sensor was calibrated at 25°C using seawater standards of 10, 30, 35 and 38 . The 0 standard was made with ultrapure water (MilliQ). The oxygen sensor was calibrated at 0% and 100% O2 saturation using the Winkler method [2 concentration. The Chl a fluorescence sensor was calibrated using several types of phytoplankton cultures at various concentrations, with the concentrations measured by spectrofluorometry. All sensors were cleaned weekly to prevent biofouling, and measurement drift was checked after each measurement campaign using the same methods as those used to calibrate each sensor.For the water properties at mid-depth , the watr method  for measa concentrations and phytoplankton abundances and diversity , nitrite (NO2), phosphate (PO4) and silicate (Si(OH)4) concentrations were measured using an automated colorimeter  following standard nutrient analysis methods [To determine the nutrient concentrations, 50 mL seawater subsamples were taken using acid-precleaned polycarbonate bottles and then filtered through Gelman 0.45 μm filters that had been prewashed three times. Then, 13 mL of the filtrate was stored at -20°C until analysis. Nitrate , and stored at -80°C until analysis. Pigment concentrations, including Chl a concentrations, were measured by high performance liquid chromatography  following the extraction protocol described in Vidussi et al. (2011) [To determine Chl . (2011)  and the . (2011) .-1 for cyanobacteria and 0.22 pgC μm-3 for picoeukaryotes and nanoeukaryotes [Phytoplankton (< 6 μm) abundances were estimated by flow cytometry , and phytoplankton (6–200 μm) abundances and diversity, by optical microscopy (Olympus IX-70). For the phytoplankton (< 6 μm) abundances, duplicate 1.8 mL subsamples were taken, fixed with glutaraldehyde following the protocol described in Marie et al. (2001)  and thenkaryotes . For mickaryotes , and carkaryotes ,42.a fluorescence is commonly used as a proxy for phytoplankton biomass. Chl a fluorescence data from the fluorometer were corrected using the weekly measurements of Chl a concentrations by HPLC to provide coherent high-frequency Chl a fluorescence data [Chl nce data .a fluorescence data over 24 h were used to calculate the daily mean phytoplankton biomass (Ct). The daily net growth rate (rt) was the difference in phytoplankton biomass between two consecutive days. A negative value indicates a biomass loss, whereas a positive r value indicates a biomass gain.Bloom periods were identified by estimating the net phytoplankton growth rate  using thA bloom was identified as a period 1) that started with at least 2 consecutive days of positive growth rates and 2) where the sum of net growth rates over at least 5 consecutive days was positive. The end of the bloom was the day before 5 consecutive days with negative growth. A 1-day peak of net growth was considered a “sporadic event” and not a bloom. When close successions of 5-day blooms were identified, they were coalesced into “bloom periods” followed by “post-bloom periods” to identify key events. The means of the daily net growth rates were calculated for bloom periods to compare the mean growth rates among the different periods.2 saturation, 2016). Only the UVA data in 2016 had a higher rejection rate (61.96%), due to a technical problem. Consequently, UVA data were not included in the data analysis for 2016 but were included in the 2015 analysis. All the other missing high-frequency data were estimated using a moving average in a 480 data point window (5 days) [Some of the operations required to maintain the quality of the high-frequency sampling, such as sensor recalibration and cleaning or drift correction, occasionally induced single or multiple missing measurements or outliers, which were removed from the data set. In our study, the fraction of missing values for each variable was generally low, i.e., between 0.06%  and 23.48% (O(5 days) .a may exhibit a delayed response to environmental forcing factors, time-lag correlation tests were performed on the 11 different data sets. Time-lag correlations are based on simple Spearman’s rank correlation tests between two variables repeated with time-shifted data to identify the delayed influence of a variable on the Chl a dynamics.The daily mean of the high-frequency data except for PAR, UVA and UVB was calculated to remove daily variation patterns; for the three exceptions, the daily cumulative value was calculated. The whole data set  was kept as a separate set for each study period. The two resulting data sets were divided into separate data sets for each period as bloom periods , post-bloom periods (post-winter bloom and post-early spring bloom) and a winter latency period. The winter latency period was defined as a period where the daily net growth rate was low, with a mean daily net growth rate close to zero. A post-spring bloom in 2015 and a pre-winter bloom in 2016 were identified. However, these blooms were too short to perform a strong statistical test; therefore, we did not keep them in the analysis of identified periods. These separations between different periods therefore provided therefore 5 data sets for 2015 and 4 data sets for 2016. Then, autoregressive and moving average (ARMA) models were used for each time series in each data set to identify ARMA processes  before fnd week of the year, were paired. To identify correlations between weekly data and high-frequency environmental data, daily means of the environmental data for the sampling days were added to the weekly data sets before using ARMA models and first-differencing each time series. Spearman’s rank correlation tests were then performed pairwise on the 2015 and 2016 data sets.The weekly data (nutrient concentrations and phytoplankton abundances and diversity) were kept as a separate data set for each study period but were not divided into identified periods because the quantity of data would have been insufficient (19 data points for 2015 and 23 data points for 2016). For the high-frequency data, ARMA models were used for each time series in each data set when needed. Paired Wilcoxon signed-rank tests were used to compare the mean values of the phytoplankton abundances and diversity and the nutrient concentrations between the 2015 and 2016 data sets. Sample dates were paired by week number (ISO 8601). For example, the sampling dates of January 8, 2015, and January 12, 2016, both corresponding to the 2a concentrations reaching 3.64 μg L-1 in 2016 and 2.77 μg L-1 in 2015 . This early spring bloom was followed by a post-bloom period, with the Chl a concentration falling to 0.54 μg L-1. In 2016, however, instead of an early spring bloom, there was a winter latency period from January 6 to March 11. During this period, the daily net growth rates were low  d-1 lower than that (0.022 μg L-1) d-1 recorded in 2015.Three blooms were identified in 2015, while only two blooms were identified in 2016 . Blooms  in 2015  and maxi in 2015 . The meawere low , with a 2 s-1 on April 19, 2015, and 2865 μmol m2 s-1 on June 18, 2016.The PAR was lowest when the winter blooms occurred in both 2015 and 2016 . Then, t-1), the early spring bloom period (max = 17.4 m s-1) and the post-early spring bloom period (max = 16.5 m s-1). The wind speed was lower during the winter bloom, the onset of the early spring bloom and the spring bloom . In 2016 (-1); otherwise, the wind was erratic, with numerous short windy events exhibiting mean wind speed values higher than those observed during the winter bloom.Two dominant winds were identified. Dominance of wind was based on the frequency of occurrence of wind directions over the two studied periods . The fir In 2016 , the winDuring the 2015 study period, the mean air temperature dropped from 19.9°C in early January to 1.1°C in early February . It thenThe water temperature was less variable than the air temperature . In 2015The salinity was also different between 2015 and 2016 . In 2015The turbidity  was 1.69a, meteorological and hydrological data in 2015 and 2016 based on PCA are shown in p-value < 0.001; 2016: ρ = 0.48, p-value < 0.001). However, the turbidity was correlated with the wind conditions in 2015  but not in 2016. Another group, on the first PCA axis of both data sets, comprised the light parameters, i.e., PAR, UVA (only in 2015) and UVB, and oxygen concentration and saturation. Spearman’s rank correlations were significant between light conditions and oxygen . Chl a fluorescence was opposed to both these groups in both 2015 and 2016, with significant negative correlations with the wind conditions  and the light conditions . The PCA for both data sets also showed a positive correlation between water temperature and air temperature . The water temperature was positively correlated with Chl a fluorescence in 2015  but not in 2016.The general relationships between Chl a fluorescence may have exhibited a delayed response to environmental forcing factors, the time series were tested for time-lag correlations  as well as salinity  in both the 2015 and 2016 data sets. As found using PCA, Chl a fluorescence was negatively correlated with the light conditions , with a 0-day lags in both 2015 and 2016. However, there was a positive correlation between Chl a fluorescence and light conditions with a 1-day lag, but only in 2015. There were negative correlations between Chl a fluorescence and wind conditions (speed and direction) with a lag of 0 to 2 days in both 2015 and 2016 .As Chl elations . Chl a fa fluorescence was positively correlated with water temperature, with a lag of from 0 to 5 days during four of the five bloom periods . Chl a fluorescence was negatively correlated with the wind conditions (speed and/or direction), with a range of lags between 0 and 4 days for four blooms . Salinity was positively correlated with Chl a fluorescence during the early spring bloom in 2015  and negatively correlated with Chl a fluorescence during the winter bloom in 2016 . Chl a fluorescence was negatively correlated with light conditions for 3 blooms with 0-day lags , while for the spring bloom in 2015, they were positively correlated with a 1-day lag . There was little correlation during the post-bloom periods. Chl a fluorescence was negatively correlated with PAR and UVA during the post-winter bloom in 2015  as well as with the wind speed in for 2016  and was positively correlated with the wind direction  during the post-early spring bloom period in 2015.For the separate periods , Chl 4, NO2 and NO3 concentrations were on average 3 to 9 times lower in 2015   (4 concentration (-1) was, however, twice that in 2016 (3.86±0.57 μmol L-1) over the same period. In 2015, the Si(OH)4 concentrations then gradually decreased until the end of the early spring bloom, reaching a mean of 2.14±0.29 μmol L-1 in March.During the winter bloom and the post-winter bloom periods, the POctively)  than in ctively) . The Si and NO3 (6.01 μmol L-1) concentrations on March 12. In 2016, over the same period, the PO4, NO2 and NO3 concentrations fluctuated more than in 2015, but the mean values were similar . The mean Si(OH)4 concentration during the spring bloom in 2015 (1.62±1.00 μmol L-1) was approximately half that in 2016 (2.74±0.80 μmol L-1).In 2015, from the early spring bloom to the end of the spring bloom, the PO4 and NO3 concentrations were significantly higher in 2016 than in 2015 . The N:P ratios (Redfield ratios) were between 11 and 94 (mean: 45±25) in 2015 and between 6 and 124 (mean: 46±35) in 2016. Spearman’s rank correlations showed significant correlations between Chl a and nutrient concentrations in neither 2015 nor 2016.Wilcoxon signed-rank tests showed that the PO4 cells mL-1 in 2015 and 2.84±1.41 × 104 cells mL-1 in 2016. However, the mean abundance of picoeukaryotes and nanoeukaryotes during the spring bloom in 2016 (6.53±1.38 × 104 cells mL-1) was more than twice that in 2015 (2.84±1.73 × 104 cells mL-1). One of the main differences between 2015 and 2016 was that during winter and early spring, the cyanobacteria (< 1 μm) abundance in 2016 (2.19±2.19 × 103 cells mL-1) was almost 10 times higher than that in 2015 (3.02±2.55 × 102 cells mL-1). Then, during the spring bloom, cyanobacteria abundances increased to a maximum on May 06, 2015 (6.01 × 104 cells mL-1), and a lower maximum on May 10, 2016 (2.70 × 104 cells mL-1). The Wilcoxon signed-rank test showed that the mean abundances of cyanobacteria , picoeukaryotes (< 1 μm)  and nanoeukaryotes  were significantly higher in 2016 than in 2015, but there was no significant difference for picoeukaryotes (1–3 μm). Tests for correlations between the biological variables (picophytoplankton and nanophytoplankton abundances and Chl a fluorescence) and the environmental variables  showed a negative correlation of picoeukaryotes (1–3 μm) with PO4 concentrations in 2015  and with NO3 in 2016 . Picoeukaryotes (< 1 μm) were negatively correlated with wind conditions in 2015 .Three groups of picophytoplankton, namely, cyanobacteria (< 1 μm diameter), picoeukaryotes (< 1 μm diameter) and picoeukaryotes (1–3 μm diameter), and one group of nanoeukaryotes (3–6 μm diameter) were enumerated by flow cytometry . The abu-1) and 2016 (212±91 cells mL-1). During the spring bloom, however, the total phytoplankton (6–200 μm) abundances in 2015 were almost three times those in 2016 . This result was confirmed by the Wilcoxon signed-rank test showing that total phytoplankton abundances (6–200 μm) were significantly higher in 2015 than in 2016 . The maximum abundances of phytoplankton (6–200 μm) were reached on May 6, 2015, and June 8, 2016 . In 2015, during the winter and early spring blooms and their post-bloom periods, the phytoplankton community was dominated numerically by Plagioselmis prolonga, a cryptophyte with a diameter of 8–12 μm (41±13%), and chlorophytes (~6 μm) (38.0±8.5%). In addition, chrysophyceae (~6 μm) were also abundant during the early spring bloom (18±2%). In 2016, P. prolonga dominated the phytoplankton (6–200 μm) community during the winter latency period and the first 11 weeks of the spring bloom (48±11%), and chlorophytes (~6 μm) were also abundant but less abundant than in 2015 (29±9%). Pseudo-nitzschia sp. (25–50 μm) and Chaetoceros spp. (10–50 μm), which are large, colonial diatoms, successively dominated the phytoplankton (6–200 μm) community during the spring bloom in early April 2015 (72±13%) and the second part of the spring bloom from mid-May 2016 (65±23%) until the end of the study periods. Chaetoceros spp. abundances were significantly lower in 2015 than in 2016 , but Pseudo-nitzschia sp. abundances were not.The patterns of community composition and total abundances of phytoplankton (6–200 μm) were different between 2015 and 2016 . The totP. prolonga in the winter and early spring blooms and by Chaetoceros spp. in the spring bloom. Nanoeukaryotes contributed most of the carbon biomass throughout 2016.The phytoplankton community was dominated numerically by picoeukaryotes (< 1 μm), accounting for 51 to 95%, depending on the period . Howevera fluorescence and environmental variables were calculated separately for 2015 and 2016. In 2015, P. prolonga abundance  was negatively correlated with PO4 concentration, and Chaetoceros spp. abundance was positively correlated with Chl a fluorescence . In 2016, Pseudo-nitzschia sp. abundance was positively correlated with Chl a fluorescence , and Chaetoceros sp. abundance was positively correlated with NO3 concentration .Correlations between weekly measurements of phytoplankton abundances (6–200 μm), Chl a dynamics, especially the onset of blooms  but the number of occurrence and non-consistent sign of the correlations suggested that they were not the main drivers. The water temperature was positively correlated with Chl a fluorescence with 0 to 5 days of lag suggesting that the biomass accumulation represented by increasing Chl a fluorescence was driven by the increase in water temperature over the 5 previous days. Furthermore, every bloom onset corresponded to a period of increase in water temperature, while such correspondence was not detected for other parameters.Based on the time-lag correlations, water temperature played a significant role in determining Chl f blooms . This is10 temperature coefficient) [in situ temperatures such as those in this study (6–14°C), can be more favorable for phytoplankton than for their grazers, allowing phytoplankton biomass accumulation, which starts the bloom. Therefore, the initiation of phytoplankton biomass accumulation can result from phytoplankton growth temporarily exceeding grazing-induced losses as a result of increasing temperature.The effect of temperature on phytoplankton physiology and metabolic processes is well known. First, under light-saturated conditions, higher temperature increases specific phytoplankton productivity by acting on photosynthetic carbon assimilation ,48. In aficient) . Furtherficient) ,52. ThusIn previous studies, water temperature was identified as the main driver of blooms of particular species, especially cyanobacteria ,54. Howehttp://www.meteofrance.fr/climat-passe-et-futur/bilans-climatiques/bilan-2016/hiver), which led to exceptionally high winter water temperatures. In contrast in 2015, the winter cooling of the water was typical of this coastal site. As a result, the Chl a dynamics in 2016 were completely different from those in 2015 , providing food for the whole plankton food web, and can sometimes be the most important biomass accumulation event during the year [a fluorescence during the winter bloom of 2016. For 2015, however, the winter bloom had already been triggered when the monitoring started, and the link between water temperature and Chl a for this winter bloom could not be established as the time-lag correlations could not be determined. Additional observations will be necessary to establish whether an annual winter bloom has become a rule, which might indicate that an ecological shift has occurred in this system. The winter bloom may also have been the result of particular climatic/environmental conditions that occurred during the study period. In fact, even though the impact of the El Niño-Southern Oscillation (ENSO) on the Mediterranean climate is still a source of discussion [There were short (2–3 weeks) winter blooms in both 2015 and 2016. Winter blooms are known to occur in marine ecosystems, but they are less common than spring blooms. Winter blooms can be rare, exceptional events , but thethe year . Winter the year . In thisscussion , 2015 wascussion , which ca fluorescence in this study, suggesting that nutrients are not the sole driver of Chl a dynamics and that a more complex functioning drives blooms in this mesotrophic system  and negative one time (for the winter bloom in 2016), suggesting that there was an indirect effect on phytoplankton biomass through nutrient inputs rather than a direct physiological effect of salinity [https://www.historique-meteo.net). This rain event may have enriched the system with nutrients, facilitating phytoplankton growth. Additionally, saltier water inputs from the sea due to strong winds from the southeast may have led to upwelling of nutrient-rich waters or induced the transport and/or accumulation of phytoplankton in the lagoon by currents. These nutrient enrichments can benefit phytoplankton growth [a fluorescence during the early spring bloom in 2015. The beginning of this period was characterized by winds coming from the southeast that may have input saltier and more nutrient-rich water from the Mediterranean Sea, in turn contributing to the phytoplankton bloom. The southeasterly wind may also have prevented the dispersion of the accumulated phytoplankton.Chl be input ,74. In tsalinity . Rain ann growth ,77; howea dynamics  and Chl dynamics . This lamics . Plagioselmis is a widespread genus in Mediterranean coastal waters throughout the year and is sometimes considered the key primary producer in these systems [Plagioselmis and cryptophytes in general “high-quality food” [P. prolonga abundance was the same as that in 2015. Nanoeukaryotes (3–6 μm) and P. prolonga dominated in terms of biomass and were probably the main sources of available energy for grazers, at least from winter to early spring.The dominant phytoplankton species in terms of carbon biomass in the 2015 winter bloom and the early spring bloom was the cryptophyte  systems ,84. Plagty food” , ensurinChaetoceros spp. and Pseudo-nitzschia sp., dominated the large-phytoplankton community (6–200 μm). Diatoms, including Chaetoceros spp. and Pseudo-nitzschia sp., are among the most frequent bloom-forming taxa, generally being dominant during spring blooms in coastal zones [Chaetoceros spp. and NO3 concentrations in 2015. This rapid response to nitrogen makes these species more competitive than others during the spring, when conditions are favorable . These large cells with a high fatty acid content are known to be a preferential source food for metazooplankton  [Chaetoceros spp. dominated the biomass during the 2015 spring bloom, nanophytoplankton (3–6 μm) dominated the 2016 spring bloom. In addition, picophytoplankton (< 1 μm) and nanophytoplankton (3–6 μm) abundances were significantly higher in 2016 than in 2015, while Chaetoceros spp. abundances were significantly lower. We suggest that the meteorological conditions and in particular the warm winter of 2016 were probably the causes of these differences. Several experimental studies have also suggested that water warming induces a phytoplankton community shift to picoeukaryote and nanoeukaryote dominance in both fresh and marine waters [2 and O2) and maximal growth rate under warmer conditions of the former. This advantage can be explained by the temperature-size relationship, which suggests that smaller organisms are more favored than larger ones in warmer conditions due to faster metabolic processes [In both 2015 and 2016, the spring bloom was dominated in terms of abundance by chain-forming diatoms. al zones ,75. Thisal zones ,87. Thisal zones ), as conopepods) ,90, whice waters ,56,91. Trocesses . The secrocesses ,56,92. TSynechococcus). During the winter and the early spring before the bloom, cyanobacterial abundances in 2016 were 10 times higher than those in 2015. Cyanobacteria are known to be strongly controlled by water temperature (and irradiance) and are more abundant during warmer months [Synechococcus).According to the first hypothesis, the shift from large phytoplankton to picophytoplankton and nanophytoplankton induced by warming will promote microzooplankton (mostly ciliates), creating an intermediate trophic link between primary producers and copepods. This link will lead to a reduction of the energy transfer from primary production to copepods and in turn to planktivorous fish ,90. Warmr months ,93,94. Tr months ,96. Furtr months , and wilPicoeukaryotes (< 1 μm) dominated the phytoplankton community in terms of abundance throughout the study, followed by picoeukaryotes (1–3 μm), even though they never dominated in terms of biomass . HoweverThe disturbance recovery hypothesis ,10 suggeIn these shallow coastal waters, previous studies reported that nutrient inputs via wind (sediment resuspension or water transport) and river inputs mainly drove phytoplankton production ,75. Howea fluorescence during the post-bloom periods (except with wind speed for the post-winter bloom period in 2016). This lack of correlations suggested that the end of the blooms in these systems is regulated by biological processes, in particular zooplankton grazing activity [In contrast, there were no clear contemporaneous correlations between the environmental variables, including water temperature, and Chl activity . After fMoreover, low winter water temperatures are important for conditioning the phytoplankton bloom phenology and composition. If there is no significant winter water cooling, then the blooms are delayed and reduced in magnitude, and the dominant phytoplankton in communities shift to smaller ones (cyanobacteria (< 1 μm), picoeukaryotes (< 1 μm) and nanoeukaryotes (3–6 μm)). Such a shift can affect primary production and the whole food web by reducing the energy transfer to higher trophic levels, promoting small predators over larger ones . With ga fluctuations and blooms in coastal waters with higher tidal amplitude [However, in the present study, the monitoring was conducted at only one sampling station in Thau Lagoon. In addition, only the winter and spring of two consecutive years were monitored, and 2015 was a “normal” climatic year while 2016 was an exceptional one with a particularly mild winter. Moreover, it is possible that 2015–2016 was influenced by ENSO or North Atlantic Oscillation (NAO) factors. Finally, the influence of tidal phases (spring/neap) on blooms was not studied as in Thau Lagoon the tidal amplitude is very low and frequently masked by climatic factors such as wind conditions . Howevermplitude .The crucial challenge concerning coastal waters, one of the most productive marine systems, is how these systems will respond to long-term climatic fluctuations such as those expected with global change. The results and conclusion of the present study are the first evidence of rising water temperature as a main driver of phytoplankton blooms in coastal waters. However, for the reasons mentioned above, to confirm our finding as a general rule, other diverse coastal waters should be investigated with adequate monitoring systems for several consecutive years.S1 Dataa concentrations.Sheets one and two correspond to the high-frequency parameters for 2015 and 2016 respectively; three and four to the nutrients concentrations; five and six to the phytoplankton (< 6 μm) abundances; seven and eight to the phytoplankton (6–200 μm) abundances and diversity; nine and ten to the HPLC Chl (XLSX)Click here for additional data file.


International Journal of Molecular Sciences have established the Best Paper Award to recognize the most outstanding articles published in the areas of molecular biology, molecular physics, and chemistry that have been published in the International Journal of Molecular Sciences. The prizes have been awarded annually since 2012 [The Editors of the nce 2012 ,4,5,6,7.International Journal of Molecular Science Best Paper Award” for 2019. Nominations, chosen from all papers published in 2018, were made by the Editorial Board. The awards are issued to reviews and research articles separately. Following a review process by the Editorial Board, three top-voted research articles and the three top-voted reviews as follows, in no particular order, have won “International Journal of Molecular Science Best Paper Award” for 2019:We are pleased to announce the “Vitamin D Receptor Is Necessary for Mitochondrial Function and Cell HealthChiara Ricca, Alessia Aillon, Loredana Bergandi, Daniela Alotto, Carlotta Castagnoli and Francesca SilvagnoInt. J. Mol. Sci.2018, 19(6), 1672; doi:10.3390/ijms19061672http://www.mdpi.com/1422-0067/19/6/1672Available online: In addition to the known genomic and non-genomic activity of vitamin D, in the last few years our group has described the mitochondrial effects of the hormone and its receptor VDR, and we highlighted the relevance of the mitochondrial control in proliferation, differentiation, and epithelial-mesenchymal transition.In this article we investigated the importance of VDR not only in mitochondrial activity and integrity but also in cell health. The silencing of the receptor in different healthy, nontransformed, and cancer cells initially decreased cell growth and modulated the cell cycle. We demonstrated that in silenced cells the increased respiratory activity was associated with the elevated ROS production. In the long run, the absence of the receptor caused the impairment of mitochondrial integrity, and finally, cell death. Our observations reveal that VDR plays a central role in protecting the cell from the excessive respiration and production of ROS that leads to cell damage. Our data were obtained in different human cell types, cancerous and healthy cells; therefore, the novel function discovered by our work can be considered a general feature of vitamin D/VDR role in tissues.An intriguing consideration about this study is based on the observation that many respiratory chain dysfunctions and deleterious ROS overproduction are recurrent themes in human pathologies, ranging from neurodegenerative diseases to cancer, and may be of paramount importance in aging. The results of this study raise the possibility that the loss of VDR function or a repressed expression of the receptor could be partly responsible or at least could be an adverse event in such diseases.Excessive Endoplasmic Reticulum Stress Correlates with Impaired Mitochondrial Dynamics, Mitophagy and Apoptosis, in Liver and Adipose Tissue, but Not in Muscles in EMS HorsesKrzysztof Marycz, Katarzyna Kornicka, Jolanta Szlapka-Kosarzewska and Christine WeissInt. J. Mol. Sci.2018, 19(1), 165; doi:10.3390/ijms19010165http://www.mdpi.com/1422-0067/19/1/165Available online: Equine metabolic syndrome (EMS) become a cluster of symptoms triggered by obesity, hyperinsulinemia, and hyperleptinemia, increased adiposity, as well as insulin resistance (IR). Although the phenotypic features of horses suffered from EMS are described, the molecular mechanism underlying disease development remains unclear. Thus, in the present study, we used RT-qPCR and western blot methods to compare the expression of genes and proteins involved in apoptosis, IR, and endoplasmic reticulum stress in insulin-sensitive tissues, such as muscles, liver, and adipose tissue. In addition, we estimated mitochondrial dynamics and mitophagy in those tissues, because mitochondrial dysfunction is associated with the development of EMS. Cell ultrastructure was visualized using electron transmission microscopy (TEM). We demonstrated for the first time that liver and adipose tissue isolated from EMS individuals are characterized by enhanced mitochondrial damage and mitophagy, followed by occurrence of apoptosis as mitophagy failure to restore cellular homeostasis. This may indicate that liver and adipose tissue are affected by progressive p53-related apoptosis in EMS and, along with ER stress, promote autophagy to protect the cells against glucolipotoxicity. Nevertheless, in muscles, p53-related apoptosis was decreased, suggesting the existence of a protective mechanism allowing the muscle tissue to maintain homeostasis. Further detailed research is strongly required to explore this issue, since obtained results may be a valuable source of information which may contribute to the development of future clinical therapy of EMS.CircSMARCA5 Inhibits Migration of Glioblastoma Multiforme Cells by Regulating a Molecular Axis Involving Splicing Factors SRSF1/SRSF3/PTBDavide Barbagallo, Angela Caponnetto, Matilde Cirnigliaro, Duilia Brex, Cristina Barbagallo, Floriana D’Angeli, Antonio Morrone, Rosario Caltabiano, Giuseppe Maria Barbagallo, Marco Ragusa, Cinzia Di Pietro, Thomas Birkballe Hansen and Michele PurrelloInt. J. Mol. Sci.2018, 19(2), 480; doi:10.3390/ijms19020480http://www.mdpi.com/1422-0067/19/2/480Available online: Serine and Arginine Rich Splicing Factor 1 (SRSF1), a splicing factor (SF) known to be involved in promoting tumorigenesis. Aberrant splicing of another SF , whose alternative splicing is known to be regulated by SRSFS1, in GBM cell lines transfected with circSMARCA5, added value to our hypothesis. Overall, the data presented in this paper allow to candidate circSMARCA5 as a tumor suppressor circRNA in GBM and propose it as a reliable druggable target due to its role in the regulation of a known tumorigenic SF. Circular RNAs (circRNAs) are a large and functionally heterogeneous group of RNAs recently rediscovered thanks to the combination of RNA sequencing and downstream focused bioinformatic data analysis. Initially thought to be simple byproducts of the splicing process of their host genes’ transcripts, circRNAs are now under the spotlight due the important biomolecular functions they perform within eukaryotic organisms and their cells. Accordingly, it will be crucial to continue to investigate on the molecular mechanisms through which they act to characterize them as: (i) RNAs functionally involved in a disease state; (ii) diagnostic and prognostic biomarkers; (iii) druggable targets. In this scenario, we focused on a circRNA  quite abundantly expressed in the brain in physiological condition. qPCR analysis of biopsies from patients with Glioblastoma multiforme (GBM) and unaffected control tissues revealed the downregulation of circSMARCA5. After cloning its sequence in an expression vector, we also demonstrated its functional involvement in the control of GBM cell migration, by using U87MG cell line as in vitro model. Mechanistically, based on in silico prediction of RNA-protein interactions and publicly available eCLIP (enhanced UV crosslinking and immunoprecipitation) data, we also proposed that circSMARCA5 may exert its function by tethering and sponging the protein The Roles of Autophagy in CancerChul Won Yun, Sang Hun LeeInt. J. Mol. Sci.2018, 19(11), 3466; doi:10.3390/ijms19113466http://www.mdpi.com/1422-0067/19/11/3466Available online: This paper describes the roles of autophagy in cancer. Our increasing understanding of autophagy has revealed the very complex and sophisticated contribution of autophagy to tumorigenesis. In normal conditions, autophagy is an intracellular degradative process that occurs under several stressful conditions, including organelle damage, presence of abnormal proteins, and nutrient deprivation. The mechanism of autophagy initiates the formation of autophagosomes that capture degraded components and then fuse with lysosomes to recycle these components. Therefore, the aim of this review paper was to reveal the mechanism of autophagy in biological conditions and describe the biological and pathological roles in cancer. We summarized the typical biological mechanism of autophagy, as well as the role of autophagy in cancer, such as in tumor suppression and promotion. We also described that autophagy regulates the properties of cancer stem cells by contributing to the maintenance of stemness, the induction of recurrence, and the development of resistance to anticancer reagents. Furthermore, we discussed the potential clinical applications of autophagy, especially as novel therapeutic targets in cancer treatment .Noncoding RNA:RNA Regulatory Networks in CancerJia Jia Chan, Yvonne TayInt. J. Mol. Sci.2018, 19(5), 1310; doi:10.3390/ijms19051310http://www.mdpi.com/1422-0067/19/5/1310Available online: Noncoding RNAs constitute a large proportion of the human transcriptome. Despite this, they were previously regarded as “junk” due to their lack of coding potential. Insights into their functions and physiological relevance only began to emerge in the last two decades. This review focuses on the regulatory networks in cancer involving various noncoding RNA species termed “competing endogenous RNA (ceRNA) networks”. This phenomenon describes the competition between coding and noncoding RNAs for binding to specific microRNAs for which they have binding sites. As conventional microRNA binding is known to repress target expression, this competitive binding leads to the bidirectional regulation of expression of these ceRNAs and their downstream functions. Here, we comprehensively summarized the roles of various long noncoding RNAs, pseudogenes and circular RNAs in both oncogenic and tumor suppressive ceRNA axes. We highlighted the importance of stoichiometric balance and dynamic cellular localization that allow the different components to come together as part of the same ceRNA network upon specific physiological and extracellular cues. More importantly, with the recent advances in high throughput sequencing and computational platforms, many research groups are adopting an integrative computational approach to identify ceRNA interactions with clinical relevance, specifically ceRNA axes that could function as robust biomarkers and predict drug responses in a cancer-specific manner. This approach, coupled with cutting edge experimental techniques, including the CRISPR-Cas system, could be harnessed to advance the field of noncoding RNAs and ceRNA regulation to provide more detailed insights into their mechanistic functions and clinical values, facilitating more efficient “bench to bedside” translational research. The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative DisordersAnuradha Tarafdar, Giordano Pula Int. J. Mol. Sci.2018, 19(12), 3824; doi:10.3390/ijms19123824http://www.mdpi.com/1422-0067/19/12/3824Available online: 2●−), although hydrogen peroxide (H2O2) can also be generated. Elevated ROS leads to OS, which has been associated with a myriad of inflammatory and degenerative pathologies. OS is also the commonality in the pathophysiology of neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).In this review, we discussed the recent developments in our understanding of the mechanisms linking nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) activity, oxidative stress (OS), and neurodegenerative diseases, with particular focus on the neurovascular component of these conditions. For a long time, NOX enzymes were considered to be a peculiarity of professional phagocytic cells. However, over the last decade, several homologs have been identified and based on current research the NOX family consists of NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1, and DUOX2 enzymes. These enzymes have unique distribution patterns and expression levels in different tissues. NOXs are membrane-bound proteins with the main function of transferring electrons across the plasma membrane to molecular oxygen-which results in the generation of the reactive oxygen species (ROS)-primarily superoxide anion (ODr Pula’s lab  is interInternational Journal of Molecular Science and the scientific research field. On behalf of the International Journal of Molecular Science Editorial Board, we would like to congratulate these teams for their excellent work. In recognition of their accomplishment, they will receive the privilege of publishing an additional research article or review paper free of charge in open access format in the International Journal of Molecular Science, after the usual peer-review procedure.We believe that these six exceptional papers are valuable contributions to the International Journal of Molecular Science, and thank the International Journal of Molecular Science Editorial Board for voting and helping with this “Best Paper Award”.We would like to take this opportunity to thank all the nominated research groups of the aforementioned exceptional papers for their contributions to the International Journal of Molecular Science is committed to meeting the needs of the molecular research community by providing useful and timely reviews of all manuscripts submitted, and providing an open access journal for your results. Please consider submitting your work to the International Journal of Molecular Science, and we look forward to announcing your paper as an International Journal of Molecular Science Best Paper in the future.The Editorial Board and Editorial Staff at the International Journal of Molecular Science Editorial Board.