The underlying mechanism of the higher efficiency with ordered molecules was observed by analyzing the properties of the EML layer using AFM, SE, XRD, and an LCR meter. We confirmed that the electrical properties of the organic thin film can be improved by controlling the molecular ordering of the EML, which plays an important role in the electrical characteristics of the OLED.We investigated the effects of molecular ordering on the electro-optical characteristics of organic light-emitting diodes (OLEDs) with an emission layer (EML) of poly (MEH-PPV). The EML was fabricated by a solution process which can make molecules ordered. The performance of the OLED devices with the molecular ordering method was compared to that obtained through fabrication by a conventional spin coating method. The turn-on voltage and the luminance of the conventional OLEDs were 5 V and 34.75 cd/m The research on organic light-emitting diodes (OLEDs) has propelled the evolution of next-generation display technologies ,2,3. The3) and diamine  (MEH-PPV) in the OLED was fabricated by a conventional spin-coating method and a simple wire-bar-coating process proposed by Khim . We inveTo fabricate the OLED devices, patterned ITO substrates  were cleaned by an ultrasonic method with acetone, isopropyl alcohol, and distilled water for 30 min each, followed by UV treatment for 20 min. A HTL of PEDOT:PSS  was coated onto the cleaned ITO substrates by a spin coater with a speed of 5000 rpm for 1 min. And then baked at 150 °C for 15 min.2 atmosphere.Next, the MEH-PPV  dissolved in an organic solvent was coated onto the HTL by two kinds of coating methods to form the EML. MEH-PPV is one of the well-known materials for the solution process ,44,45,46The two different kinds of fabrication processes are shown schematically in −7 Torr using evaporation equipment . Finally, the device was encapsulated using encap glass in a glove box.An Al cathode layer was fabricated with a thickness of 100 nm under high vacuum conditions of 5.0 × 10We compared the performance of the OLEDs fabricated using these two coating methods. The molecular ordering of anisotropic molecules is influenced by the flow direction of the fluid as mentioned before ,48,49,50The two different solution processes were optimized to obtain the same thickness of the MEH-PPV layer. To confirm that the same thickness was obtained, we measured the thickness of the MEH-PPV layers fabricated by the spin coating and the molecular ordering coating methods using a gallium focused ion beam-scanning electron microscope . The MEH-PPV layers fabricated by two different methods, which are sandwiched between two Al layers, were observed by Ga-FIB. It was hypothesized that high electrical conductivity can be obtained with ordered molecules resulting from the molecular ordering coating method. To support this hypothesis, we analyzed the device characteristics by atomic force measurement , spectroscopic ellipsometry , X-ray diffraction , and an LCR meter . When we prepared the samples to analyze the characteristics of devices using various equipment, to maintain the same conditions, PEDOT:PSS was first coated onto each substrate. MEH-PPV was coated onto the PEDOT:PSS layer by two different methods. Then the characteristics of the devices were evaluated.z-axis are 26 nm and 33 nm for the spin coting and the molecular ordering coating, respectively. This is consistent with the Ga-FIB images, in which a uniform thickness of the emissive layer was obtained by the spin coating process. A periodic pattern was observed for the molecular ordering coating conditions, as shown in AFM images of the coated surfaces were compared to investigate the surface morphology and the texture fabricated by the different coating methods. To find the correlation between the periodic patterns and molecular ordering, the dielectric constants in the two orthogonal horizontal directions were measured using SE. The dielectric anisotropy was also compared from the measured dielectric constant values obtained by the different coating methods. we also compared the imaginary value of the dielectric constant ε^For the SE measurements, the MEH-PPV layers were coated onto PEDOT:PSS on the silicon wafers by two different coating processes. The measured data were analyzed by the Lorenz model. The measured dielectric anisotropy is shown in We set the order parameter value by the ordering direction of the molecular as the x-direction (extraordinary) and the perpendicular to the ordering direction of the molecular as the y-direction (ordinary). To analyze the degree of crystallization of the MEH-PPV film, X-ray diffraction measurements (XRD) were performed at 2° to 50° at a rate of 2°/min. Since Bragg diffraction depends on the periodic structure or on degree of alignment, it is useful to evaluate the arrangement of the MEH-PPV main chain. 5 S/m for the molecular ordering coating method and 3 × 105 S/m for the spin coating process. The molecular crystal obtained by the molecular ordering coating method has higher conductivity than the amorphous polymer obtained by the spin coating method. The AFM, SE, and XRD results show a strong correlation between the molecular ordering and conductivity. From the disorder-controlled transport mechanism, the charge mobility is coupled with the positional disorder and the width of the density of state distribution which is also related with polymer alignment [Because the molecular arrangement is strongly related to the conductivity of the organic layer, the LCR measurements were used to make comparison between the electrical conductivity caused by the molecular ordering and amorphous polymer. The electrical characteristics of the devices were analyzed by comparing the conductivity with respect to the frequency. We compared the conductivity of the MEH-PPV layer fabricated by the two types of methods as shown in lignment ,56,57,58lignment ,60.2. On the other hand, in the case of the OLED with the molecular crystal layer, the turn-on voltage was 4.5 V, and the maximum luminance was about 120.3 cd/m2. The measured electro-optical characteristics of OLED device fabricated by amorphous polymer and molecular crystal were listed on Finally, for OLEDs with the molecular crystal and amorphous polymer, the electro-optical characteristics such as the current density, luminance, luminous efficiency, power efficiency, quantum efficiency and EL spectrum were compared by the I-V-L system . We measured the voltage-current curves of the OLEDs fabricated by the two methods. The electric conductivity (g) can be obtained from the voltage-current curves and is related to the electric charge injection and transfer in the device ,62. AfteAt When charge is injected from the electrode into the organic polymer, the injected charges are transferred by a hopping mechanism. In the case of the organic polymer, the density of state (DOS) has a Gaussian distribution . The widIn the amorphous polymer, the charge injection is easier than in the molecular crystal. However, as the voltage increases, the current densities converge to a similar level. In addition, excellent luminescence properties of the molecular crystal were obtained. These results show that the Gaussian DOS with the amorphous polymer is more widely distributed, and the energy states are also extensively dispersed, so the mobility of the amorphous polymer is lower than that of the molecular crystal. Thus, with the Gaussian DOS in the ordered organic material, the charges can be easily transferred and form excitons, even if less charge is injected into the organic molecules. Therefore, the electro-optical properties of the OLED device are improved by allowing it to emit more light.We have investigated the effects of molecular ordering of MEH-PPV film as EML on the electro-optical characteristics of OLEDs. To clearly verify the effects of molecular alignment on the electrical and optical characteristics of the OLED device, it was fabricated with a simple structure. The EML was fabricated by the conventional spin coating method and the molecular ordering coating method of solution processes. The performance values of the OLEDs were compared. To understand the mechanism of the improved performance of our molecular ordering coating method, we analyzed the properties of the morphologically, dielectric anisotropy, degree of crystallization and conductivity by using AFM, SE, XRD, and LCR meter, respectively. We have confirmed that the electrical properties of the organic thin film can be improved by controlling the molecular ordering in the EML.2, while those obtained by the molecular crystal were 4.5 V and 120.3 cd/m2, respectively. Luminous efficiency, power efficiency, quantum efficiency of the molecular crystal are five times higher than those of the amorphous polymer. The molecular ordering plays an important role in the electrical characteristics of the OLEDs. The maximum luminance and efficiency can be improved further by applying a multi-layer structure with functional layers. If molecules of organic layer can be aligned, not only the electrical properties of the device can be improved, but also optical properties can be controlled, which enhance the out-coupling efficiency and emit polarized light.The turn-on voltage and the luminescence of the OLED fabricated with the amorphous polymer were 5 V and 34.75 cd/m


Staphylococcus aureus. Therefore, the prepared nanofibers with the coaxial porous structures could serve as promising drug delivery systems.The phenomenon of drug burst release is the main problem in the field of drug delivery systems, as it means that a good therapeutic effect cannot be acheived. Nanofibers developed by electrospinning technology have large specific surface areas, high porosity, and easily controlled morphology. They are being considered as potential carriers for sustained drug release. In this paper, we obtained polycaprolactone (PCL)/polylactic acid (PLA) core-shell porous drug-carrying nanofibers by using coaxial electrospinning technology and the nonsolvent-induced phase separation method. Roxithromycin (ROX), a kind of antibacterial agent, was encapsulated in the core layer. The morphology, composition, and thermal properties of the resultant nanofibers were characterized by scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetry analysis (TGA). Besides this, the in vitro drug release profile was investigated; it showed that the release rate of the prepared coaxial porous nanofibers with two different pore sizes was 30.10 ± 3.51% and 35.04 ± 1.98% in the first 30 min, and became 92.66 ± 3.13% and 88.94 ± 1.58% after 14 days. Compared with the coaxial nonporous nanofibers and nanofibers prepared by uniaxial electrospinning with or without pores, the prepared coaxial porous nanofibers revealed that the burst release was mitigated and the dissolution rate of the hydrophobic drugs was increased. The further antimicrobial activity demonstrated that the inhibition zone diameter of the coaxial nanofibers with two different pore sizes was 1.70 ± 0.10 cm and 1.73 ± 0.23 cm, exhibiting a good antibacterial effect against  At present, the problem of burst release during drug action should not be ignored. Drug burst release requires a high dose and multiple administrations, produces toxic and side effects, and fails to have a good therapeutic effect . TherefoDue to its low cost and easy operation, electrospinning technology stands out among many nanofiber preparation technologies and can prepare different forms of nanofibers ,3,4. TheThe functional parameters of drug release systems can be controlled by adjusting the morphology and specific surface areas of nanofibers . The encCoaxial structure nanofibers have been used in the research of drug release materials. The coaxial electrospinning nanofibers can encapsulate the drugs in the core layers, and the shell layers act as barriers for the release of the drugs. He and Huang et al. prepared core-shell tetracycline hydrochloride (TCH)/polylactic acid (PLLA) nanofibers. The experiment’s results showed that the release rate of TCH (3 wt%)/PLLA (10 wt%) uniaxial blended nanofibers was 30% in the first 8 h, while the release rate of coaxial TCH (10 wt%)/PLLA (10 wt%) fibers was only 22.9% after 144 h. The core-shell nanofibers inhibited the initial release and promoted the continuous release of the drugs . CompareThe porosity of the nanofibrous scaffold and the porosity of a single nanofiber affect the drug release effects . High suStaphylococcus aureus. The matching of hydrophobic drugs with the hydrophobic materials used is more beneficial to the sustained release of drugs [The ideal drug carriers should be compatible, and drug release behavior based on biodegradable materials is favorable in controlling sustained drug release ,19. PCL of drugs .Staphylococcus aureus. The results indicate that the coaxial porous nanofibers obtained in this paper are promising drug release materials.In this study, we used the electrospinning technique and nonsolvent-induced phase separation method to prepare coaxial porous PCL/PLA drug-loaded nanofibers. ROX was encapsulated in the core layer. The physicochemical properties of the nanofibers were characterized by different methods. Compared with the coaxial nonporous nanofibers and nanofibers prepared by uniaxial electrospinning with or without pores, the obtained coaxial porous nanofibers not only slowed down the drug burst release but also increased the dissolution of hydrophobic drugs. Besides this, the prepared nanofibers had good in vitro antibacterial activity against Staphylococcus aureus (S. aureus) was obtained from the China General Microbiological Culture Collection Center . The chloroform (CF) was purchased from Zhiyuan Chemical Reagent Co. Ltd. . The dimethyl sulfoxide (DMSO) was purchased from Chemical Works . The phosphate buffer solution  was obtained from Solarbio Science & Technology Co., Ltd. . The technical agar powder (TAP) was purchased from Huankai Microbial Sci. & Tech, Co., Ltd. . The tryptone soy broth (TSB) was supplied by Aoboxing Biotechnology Co., Ltd. . All of the chemical reagents were of analytical grade and were utilized as received.The polycaprolactone  was purchased from Perstorp  Chemical Products Trading Co., Ltd. . The polylactic acid  was obtained from Hisun Biological Materials Co., Ltd. . The 2,2,2-trifluoroethanol (TFE) was purchased from Macklin Biochemical Co., Ltd. . w/v) were prepared by adding PCL into TFE and 90/10 (v/v) CF/DMSO under constant stirring until it dissolved completely, respectively. Then, the weighed ROX powder was added to the PCL solution. The solution was stirred until the ROX was dissolved completely. The concentration of the ROX was 15 mg/mL with respect to the PCL solution. Two kinds of shell solution with a concentration of 8% (w/v) were prepared by dissolving PLA into CF and 90/10 (v/v) CF/DMSO under constant stirring until it completely dissolved, respectively. All of the solutions were prepared at room temperature. As shown in For the preparation of PCL/PLA coaxial nanofibers, two kinds of PCL polymer solutions with a concentration of 10%  was used to investigate the thermal properties of the samples. The samples were equilibrated at 0 °C and then heated to 200 °C at a heating rate of 10 °C/min in a nitrogen atmosphere. The thermal stability of the samples was also analyzed by thermogravimetry  in a nitrogen atmosphere, and the sample was heated from 0 °C to 600 °C at a heating rate of 10 °C/min.The microstructure of the nanofibers was characterized by an S-4800 scanning electron microscope . The functional groups of the nanofibers were recorded by Fourier Transform Infrared  Spectroscopy in ATR mode, and the wavelength range was 4000–600 cmS. aureus were determined by the inhibition zone method. TSB and TAP were used as the culturing media. First, the nanofibers were cut into circles 0.5 cm in diameter. Then, 500 μL S. aureus suspension was spread onto an agar plate. Finally, samples of the rounded nanofibers were placed under an ultraviolet lamp for 30 min to be sterilized, pasted onto the agar plates, and incubated at 37 °C. The bacterial growth on the plate was visualized directly, and the diameter of the inhibition zone was measured. All of the experiments were performed in triplicate.The in vitro antimicrobial activities of the nanofibers against The calibration curve of ROX was prepared by using solutions in six different concentrations: 0.015 g/L, 0.03 g/L, 0.05 g/L, 0.075 g/L, 0.1 g/L and 0.15 g/L. For the drug release test, nanofibers with a certain weight were immersed into the appropriate amount of PBS and then incubated at 37 °C in a shaking incubator  with mild shaking. At predetermined time intervals, 3 mL of the soaking solution was withdrawn for ROX detection to determine the amount of drug released, and was replaced by another 3 mL of fresh PBS to maintain a constant volume. The released ROX drugs were assessed at a wavelength of 202 nm using a UV-visible spectrophotometer . The concentration of the released ROX was back-calculated from the predetermined calibration curve of the ROX. The percentage of the drug released was calculated based on the initial weight of the drug incorporated into the nanofibers. The experiments were repeated three times for each nanofiber. The data are expressed as mean ± standard deviation.0V is the volume of the medium in the tubes (mL), V is the volume of the withdrawn solution for ROX detection (mL), nC is the drug concentration determined at No. n (g/L), iC is the drug concentration determined at No. i (g/L), and 0Q is the total amount of ROX in the nanofibers (mg).The accumulative percentage of the drug released from the nanofibers was calculated using the following equation:In this paper, coaxial porous nanofibers were prepared by nonsolvent-induced phase separation. The presence of nonsolvents caused the thermodynamic instability of the polymer solution and initiated phase separation. Compared with other phase separation mechanisms, nonsolvent-induced phase separation can be controlled, and can provide repeatable results . As seenIn the coaxial porous structure shown in In addition to the above, as shown in −1, corresponding to the bending vibration of C-H, the stretching vibration of carboxyl (C = O), and the stretching vibration of C-H of PCL, respectively. Five new peaks exhibited in PPR1, PPR2, and PPR3 containing PLA were assigned to the stretching vibration peak of C-H at 2995 cm−1, the stretching vibration peak of carboxyl (C = O) at 1753 cm−1, the bending vibration peak of C-H at 1455 cm−1, and the asymmetric stretching vibration of C-O-C at 1086 cm−1 and 1182 cm−1, respectively. Besides this, we can see that the asymmetric stretching vibration of C-O-C at 1167 cm−1 that appeared at PR1 and PR2 was missing, and the change of the characteristic peaks was caused by the blocking effect of the C-O-C of PLA. Because of the small amount of ROX in the solution, there were no evident characteristic peaks of ROX in the spectra. What we need to know is that the uniaxial electrospinning used the same solution as the core layer of the coaxial electrospinning, so we compared nanofibers prepared by uniaxial electrospinning with and without drugs in order to determine whether ROX was loaded into the nanofibers  of P1 was 54.81 °C, which corresponds to the melting temperature of PCL. After the addition of ROX, the melting peak shifted slightly, to 52.41 °C, indicating weak interactions between ROX and PCL. The melting point of ROX is around 120 °C. It should be noted that PR1 didn’t reflect the melting peak of the drugs, and ROX has good solubility in the solvents used, indicating that the drugs existed in the nanofibers in their non-crystalline state [c) of PLA was 117.42 °C. PPR1 also showed double melting peaks at 144.88 and 152.36 °C that were related to the two different crystalline morphologies of PLA. There might be hydrogen bonding among ROX, PLA, and PCL, which reduced the thermal stability of the drug-loaded nanofibers [e) of 380.14 °C. ROX was sensitive to heat, and the Te occurred at 272.53 °C. The degradation of PR1 began at 252.12 °C and reached the maximum decomposition rate at 401.06 °C as the temperature increased. The PPR1 has the maximum decomposition rate, at 332.46 °C, which is mainly attributed to PLA degradation. The results showed that the addition of ROX reduced the thermal stability of the nanofibers.We investigated the thermal characteristics of porous coaxial nanofibers by DSC and TGA. PCL is a semi-crystalline polyester. In ne state . It was nofibers . In FiguStaphylococcus aureus, and ROX maintained good antibacterial activity. As the drugs diffused to a larger volume, the efficacy of the drugs decreased and the diameter of the bacteriostatic zones reduced [Bioactive drugs can be released and remain bioactive after release from nanofibers . The ROX reduced . In this2 ≥ 0.99.The standard curve of ROX is shown in The drug release behavior of drug-loaded nanofibers is affected by the morphology of the nanofibers . A promiAs shown in 2 of the five fitted equations were all greater than 0.95. The diffusion index n of the coaxial nanofibers in the Ritger–Peppas model were all less than 0.45, indicating that the drug release followed the Fick diffusion mechanism. The fitted curves of the nanofibers are shown in At present, the commonly used drug release kinetics models include the zero-order model, the first-order model, the Higuchi model, and the Ritger–Peppas model, which are used to explore the kinetics of drug release from nanofibers ,33,34,35S. aureus. Therefore, coaxial porous nanofibers might have potential applications in the sustained release of drugs.In summary, we fabricated coaxial porous PCL/PLA nanofibers using coaxial electrospinning and nonsolvent-induced phase separation successfully. The SEM images revealed that pores were distributed on the surface of nanofibers. FTIR showed that the antimicrobial agent ROX was loaded onto the PCL layer. Additionally, DSC and TGA indicated that the drugs that existed in the nanofibers reduced the thermal stability of the nanofibers. Compared with the coaxial nonporous nanofibers and nanofibers prepared by uniaxial electrospinning with or without pores, the prepared coaxial porous nanofibers slowed down the drug burst release phenomenon, promoted sustained release, and increased the solubility of hydrophobic drugs. Besides this, coaxial porous nanofibers encapsulated with ROX showed good antibacterial activity against


Urolithiasis is characterized by high rates of prevalence and recurrence. Hyperuricemia is related to various diseases. We hope to determine the association between serum uric acid (UA) level and kidney stone (KS).OR) for KS, and mean difference between the two groups were applied to determine the association of UA level with KS.In this population-based cross-sectional study, a total of 82,017 Chinese individuals who underwent a comprehensive examination in 2017 were included. The KS was diagnosed based on ultrasonography examination outcomes. Fully adjusted odds ratio  μmol/L]. In men, the OR for KS significantly increases from 330 μmol/L UA level. Every 50 μmol/L elevation of UA level increases the risk of KS formation by about 10.7% above the UA level of 330 μmol/L in men. The subgroup analysis for male is consistent with the overall result except for the participants presenting underweight , low cholesterol  or high estimated glomerular filtration rate (eGFR) . However, no significant association is observed in women between UA and KS either in all female participants or in female subgroups.Among the 82,017 participants included in this study (aged 18~99 years), 9,435 participants (11.5%) are diagnosed with KS. A proportion of 56.3% of individuals is male. The mean UA level of overall participants is 341.77 μmol/L. The participants with KS report higher UA level than the participants without KS [mean UA level 369.91 vs. 338.11 μmol/L; mean difference (MD), 31.96 (95% Among Chinese adults, UA level is associated with KS in a dose-response manner in men but not in women. However, the association becomes considerably weak in male participants with malnutrition status. Kidney stone (KS) is one of the most common disorders in the urinary system, with prevalence rates ranging from 1~5% in Asia, 5~9% in Europe, and 7~13% in North America. About 14% of patients will recur within 1 year, while the rate climbs to 25% within 5 years, and 52% within 10 years . It urgeUric acid (UA) is the end product of purine metabolism and excreted by urine. A high level of UA can lower urine pH, leading to inadequate buffer capacity for ammonium salts, eventually resulting in the crystal formation. UA can promote calcium oxide stone through increased urinary excretion of calcium, reduced excretion of citrate, and supersaturation of urine concerning monosodium urate . HyperurTo obtain a more comprehensive understanding of the role of UA in KS formation in China, we analyze the relationship between serum UA level and KS first in the Chinese population. The research focuses on sex disparities and applies restricted cubic splines to unravel the risk of UA level for KS presence in men and women, respectively. The sex-specific cutoff value of UA level is computed for precise prevention for KS.This study was from the project Influencing Factors for Common Chronic Diseases among Chinese Population (IFCCDCP), where individuals underwent a comprehensive test at the Health Management Center of Tongji Hospital from January 1, 2017 to December 31, 2017 . This stn = 351), or they had kidney deformity (n = 14), kidney transplantation (n = 23), solitary kidney (n = 205), or the ultrasonography outcome was absent . Since the data were missing in some participants in a pairwise pattern (missing not at random), we used the deletion method to process the missing data . Finally, a total of 82,017 participants were included in the formal analysis.The information and test results of total 99,859 individuals were collected. Participants were excluded if they were under 18 years old (The primary outcome was the presence of KS. KS was confirmed based on an ultrasonography (US) examination. Experienced radiologists without acknowledgment of the study performed a routine abdominal US examination on the participants. Structures that were reported as a strong echo in the renal sinus with posterior acoustic shadows or comet tail signs were regarded as KS.eGFR = 175 × SCr−1.234 × age−0.179 × 0.79(if women) , diabetes , and coronary heart disease (CHD) were collected based on the medical history. Physical characteristics, such as body mass index  and blood pressure were measured by trained nurses. Blood parameters, such as fasting glucose (Glu), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (Alb), globulin (Glo), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL), indirect bilirubin (IBIL), direct bilirubin (DBIL), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), serum creatinine (SCr), and UA, were tested from blood specimens collected from anterior elbow veins. Urine pH (UpH) was acquired from urinalysis, which can indicate the crystal type of KSs (f women) . The SCrOR) and 95% CI were calculated taking per 50 μmol/L UA as a unit. Models were sequentially adjusted by age and sex (model 1), plus obesity  (Logistic regression models were used to assess the association of UA level with KS. The odds ratio (8 kg/m2) , diabeteOR for KS in each stratified UA level was quantified by setting the group with the lowest risk as the reference. The trend in characteristics of participants with increasing UA levels was assessed through the logistic regression. The median values for continuous variables or proportions for categorical variables replace the original values for the participants in each category of UA level to compute the p for trend.Restricted cubic splines with 5 knots  were used to determine the dose-response relationship between UA level and KS presence. The relationship was evaluated in different sex and age  groups. The incidence rates of KS in the participants with stratified UA levels  were calculated. The 2), Glu , and UpH . Mean differences (MDs) were calculated for each subgroup applying the bootstrap method to derive 95% CIs based on 100 bootstrap samples. In addition, the tests for interaction across subgroups were performed using the Wald test. A sensitivity analysis was conducted when the participants with missing data were included by comparing the effect sizes. R software (version 4.0.3) was used for the statistical analyses. Three R packages were used: dplyr, rms, and scales. All the values of p were two-tailed and p <0.05 was considered statistically significant.Subgroup analyses were conducted for men and women, respectively, by the following variables: obesity , hypertension , diabetes , CHD , Alb , TP , TC , HDL , LDL , TG , eGFR    included in the final analysis, 9,435 participants (11.5%) are diagnosed as KS based on the ultrasound examination. The mean age is 41.93 ± 12.88 years. A proportion of 56.3% individuals is male. The mean UA level for overall participants is 341.77 ± 95.51 μmol/L. The participants with KS have a much higher UA level than the participants without KS , diabetes , high TP , high TC , low HDL , high TG , low eGFR , high Glu , and low UpH . However, the association between UA level and KS is not significant for the men presenting underweight , CHD , low TC , and high eGFR [adjusted OR, 1.044 (0.983~1.108); MD, 5.61 (−1.84~13.36), In subgroup analysis for men, it was implied that the association between UA levels and KS is significant for participants presenting hypertension [adjusted ORs of KS are 1.179, 1.094, 1.079, and 1.073, respectively, after unadjusted, model 1 adjusted, model 2 adjusted, and model 3 adjusted. In the population with missing data, the ORs of KS are 1.184, 1.098, 1.084, and 1.073, respectively. The mean difference of UA is 31.96  μmol/L and 32.71 (31.00~34.16) μmol/L for participants without and with missing data. Both populations indicate non-linear trends for the association between UA level and OR of KS. These results demonstrate the statistical stability after excluding participants with missing data.The sensitivity analysis is performed between the population with and without missing data . In the Among 82,017 Chinese participants from the chronic diseases cohort who had undergone physical examination in 2017, it was discovered that increased UA levels were associated with a higher risk of KS in a dose-response manner in men above the UA level of 330 μmol/L. However, no significant increased risk of KS parallel to UA level is observed in women. These results indicate that the risk of KS starts at a lower UA level than the normal upper limit. Besides, for the men presenting underweight, low level of TC, or high level of eGFR, the association between UA level and KS development is no longer significant.To the best of our knowledge, this was the first study to investigate the association between serum UA levels and KS development in the Chinese population. The prevalence of urolithiasis presented great variations in different geographic locations in Asia. In West Asia, Southeast Asia, and South Asia, the prevalence was reported to be 5–19.1%, however, it was only 1–8% in East Asia and North Asia . The prePrevious studies have demonstrated the association between hyperuricemia and urolithiasis using the data from the National Health and Nutrition Examination Survey 2007–2008 and the data from Kangbuk Samsung Health Study , 20. ConWe found that UA differentially promoted the KS formation in male and female. One possible explanation for the sex disparities in the association between serum UA levels and KS is sex steroid differences that result in distinct states of oxidative stress, inflammation, and immune response between men and women . Testostn = 50), and low TP level  which also reflect a malnutrition status, subgroup analyses are not conducted for these two factors. Dietary factors have the potential of influencing the microbiota composition associated with KS formation, nevertheless, the correlation between malnutrition and KS remains to be elaborated  for the publication of any potentially identifiable images or data included in this article.X-ML, WG, and CL had full access to all the data in the study, take responsibility for the integrity of the data, and the accuracy of the data analysis. J-ZX, J-LL, LH, X-ML, WG, and CL contributed to conceptualization. J-ZX, J-LL, and LH contributed to formal analysis, methodology, software, statistical analysis, and writing—original draft. YX, Z-CW, Q-DX, X-YQ, Y-YY, S-YH, S-GW, X-ML, WG, and CL contributed to validation and visualization. S-GW, X-ML, WG, and CL contributed to resources, supervision, and writing—review and editing. All authors contributed to data curation and project administration. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This Action Framework identifies priority actions to prevent antimicrobial-resistant (AMR) through expanding the use of licensed vaccines, developing new vaccines that contribute to the prevention and control of AMR, and expanding knowledge about the impact of vaccines on AMR. Antimicrobial resistance (AMR) threatens to undermine the effectiveness of antimicrobials and undo progress made against infectious diseases. Pathogens resistant to all classes of antimicrobials can be found throughout the world, and the incidence of infections with resistant pathogens is growing . The risThe discovery and use of new antibiotics constitute a complex economic and scientific challenge. Few antibiotic classes have been developed in the past half-century , and resSalmonella typhi led to an introduction of TCV in children to help control the spread of extensively drug-resistant typhoid [The most direct way in which vaccines contribute to prevention and control of AMR is by reducing the incidence of disease from resistant pathogens . A study typhoid .By reducing the incidence of diseases, vaccines also reduce antibiotic use. Because the clinical presentations of many infections do not appreciably differ whether caused by bacteria or viruses, and antibiotic use is often presumptive, vaccines that reduce the incidence of syndromic diseases may also reduce antibiotic use. With current vaccine coverage, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children in LMICs each year . InfluenEscherichia coli, Klebsiella pneumoniae, or Staphylococcus aureus [Vaccines that reduce the incidence of antibiotic use can contribute to reducing selection for AMR in the target pathogen  as well as in bystander bacterial species, often present in the normal flora, which can transmit and cause disease (s aureus ).Streptococcus would reduce the need for presumptive antibiotic treatment for pharyngitis. Vaccines effective against key pathogens causing a given clinical syndrome might ultimately result in synergistic effects on antimicrobial use and therefore less resistance.Some vaccines could potentially reduce antibiotic use to an extent that exceeds the causal fraction of the disease syndrome resulting from the vaccine target pathogen. A vaccine effective against group A The World Health Organization (WHO) created a list of antibiotic-resistant bacteria for which new antibiotics are urgently needed  and the This Action Framework intends to guide vaccine stakeholders to maximize the impact of vaccines in preventing AMR. It is a result of a collaboration between WHO, the Wellcome Trust, the Bill & Melinda Gates Foundation, and the Center for Disease Dynamics, Economics & Policy and was developed through a consensus-building consultative process involving experts from academic institutions, country representatives, nongovernmental organizations, and the pharmaceutical industry. A formally constituted Vaccines for AMR WHO working group of experts on AMR and immunization provided suggestions throughout the process, and the Framework was drafted following a consultation in February 2019. The document has been circulated for comment and public review. The objective of this document is to support an alignment of activities among vaccine and AMR partners, and structure and articulate key priority actions with a goal to expedite the understanding, development, and use of vaccines against AMR. The document complements the global immunization strategy, the Immunization Agenda 2030: A Global Strategy to Leave No One Behind .This Action Framework supports a strategic vision for vaccines to contribute fully, sustainably, and equitably to the prevention and control of antimicrobial resistance by preventing infections and reducing antimicrobial use. To achieve this vision, we propose 3 goals with appropriate objectives  and prioObjective 1. Increase coverage of vaccines with impact on AMRObjective 2. Update recommendations and normative guidance in both the vaccine and AMR sectors to include the role of vaccines to control AMRObjective 3. Improve awareness and understanding of the role of vaccines in limiting AMR through effective communication, education, and trainingObjective 4. Bridge the funding gap for R&D of new vaccines with potential for global AMR impactObjective 5. Develop regulatory and policy mechanisms to accelerate approval and use of new vaccines that can reduce AMRObjective 6. Improve methodologies and increase collection and analysis of data to assess vaccine impact on AMR, including antimicrobial useObjective 7. Develop estimates of vaccine value to avert the full public health and socioeconomic burden of AMRAbbreviations: AMR, antimicrobial resistance; R&D, research and development.Expanding the use of licensed vaccines will require reaching current uptake targets and setting and achieving ambitious coverage targets for newly licensed vaccines with the potential impact on AMR.Maximizing the impact of immunization on AMR will depend on the successful implementation of a global strategy with an integrated Action Framework linking immunization to primary health care and universal health coverage.Haemophilus influenzae type B vaccine, rotavirus vaccine, and measles-containing vaccines as well as increasing coverage for influenza and TCV.1a: Countries should implement existing vaccine-related recommendations of the Global Action Plan on AMR. Priority should be given to completion of the full basic series of PCV, 1b: Donors, countries, and other health payers should maintain and expand immunization financing and strengthen capacities, ensuring affordable supply, functional delivery systems, and programmatic sustainability. These should also support vaccine safety and effectiveness monitoring.New activities are needed to expand the impact of vaccines on AMR. Expanding the benefits of immunization throughout the life course will play a major role. When research and epidemiologic data emerge that justify changes in optimal vaccine use, revised recommendations should be developed, including situations in which vaccines are used to protect the effectiveness of antimicrobials. Specific vaccine use recommendations could also be developed for vulnerable groups who, for medical reasons, use antibiotics chronically or frequently, or who are at increased risk of exposure to drug-resistant microbes, such as healthcare workers.2a: Where justified, normative guidance, regulatory indications, policy recommendations, and health regulations for vaccine use should be adapted to account specifically for the use of vaccines to impact AMR.2b: AMR national action plans and international organizations dedicated to AMR control should consistently include vaccines in the portfolio of interventions planned for use against AMR.2c: Immunization programs should be strengthened to reach children beyond the first year of life and immunization services broadened to support vaccination with impact on AMR throughout the life course.2d: As part of a “One Health” perspective, bodies such as WHO, Food and Agriculture Organization, and World Organization for Animal Health, in collaboration with the agricultural industry and animal health stakeholders, should update recommendations and regulations and develop an action plan to maximize the use of animal vaccines to reduce antibiotic use in animals.The full value of vaccines at the individual and population levels is not completely understood, contributing to low and decreasing confidence and coverage in vaccines in some areas. Communicating the additional benefit of the use of vaccines to fight AMR requires the development of carefully constructed and evaluated communication strategies and tools.3a: Countries, funders, and other stakeholders should include the role of vaccines in limiting AMR in their communication materials.3b: Institutions involved in the vaccine and AMR sectors should develop communication, education, and training materials about the role of vaccines in controlling AMR, targeting audiences ranging from the general public to infectious disease experts.New vaccine R&D is an integral part of the Global Action Plan on AMR . Few newThe development and use of new or improved vaccines is of particular importance to prevent diseases becoming difficult to treat or untreatable owing to antimicrobial resistance. Pathogen areas to be prioritized for investments into vaccine R&D should be informed by public value and feasibility assessments, taking into account alternative options such as phage-based medicine or microbiome interventions .Investment in the development of new vaccines to affect global health is often impeded by scientific hurdles leading to market failures and decades-long development, high clinical development costs, prolonged licensure, or implementation timelines, as well as lack of recommendations regarding use. These challenges create a perception that vaccines are unattractive business investments. Innovative financing mechanisms channelling substantial public sector funding and private sector investment, push-and-pull incentives, or subscription models may be needed to support new vaccine development, and to bring candidates from discovery through preclinical and clinical testing to licensure, adoption, and implementation in LMICs. Related activities should be monitored and evaluated, in line with the Global Action Plan monitoring and evaluation framework for new products and funding instruments.4a: Funders, industry, governments, nongovernmental and supranational organizations, academic institutions, and researchers should consider increasing investments in vaccine candidates with anticipated benefits for AMR.4b: Funders, including governments and nongovernmental organizations, product development sponsors and industry, should increase financing for late-stage vaccine evaluation, introduction, evaluation of new vaccine effectiveness and impact, and to ensure sufficient manufacturing capacity to meet global needs for vaccines expected to reduce AMR.WHO recommendations inform decision making at multiple levels, including international financing bodies supporting vaccine procurement and distribution. Regulators and policymakers engage in discussions with funders and vaccine developers to prioritize disease areas, product development, investments, and activities, and create scientific consensus. Throughout, specific modalities should be adopted to consider and facilitate vaccine impact on AMR, all along regulatory and policy-making pathways. Vaccines and other AMR-relevant prophylactic interventions  should be considered for inclusion in legislation that incentivize the development of AMR products .5a: Vaccine development sponsors and regulatory authorities should systematically assess the potential to prevent and control AMR and related data packages generated in clinical development to expand knowledge of investigational product risk–benefit balance.5b: Vaccine development sponsors and regulators should discuss clinical research requirements for regulatory labelling to include specifications about impact on AMR and antimicrobial use.5c: Regulators and policymakers should develop means to accelerate access to vaccines of urgent medical need, including impacts on AMR, without jeopardizing the required confidence in safety and efficacy.5d: WHO, through its Product Development for Vaccines Advisory Committee and Strategic Advisory Group of Experts on Immunization, and other stakeholders who shape progress in vaccine R&D should include evaluation of AMR impact in their product landscape analyses and guidance.5e: Sponsors of postlicensure vaccine evaluations, such as health–economic impact studies, should discuss with regulators and policymakers, during the approval process, when and how to include evaluation of a vaccine’s potential to reduce antimicrobial use and AMR in these studies.Continuing research is needed to strengthen the knowledge base on the potential role of vaccines in prevention and control of AMR, and this knowledge disseminated to stakeholders. Better estimates of impact will improve policy making and rational prioritization of investments.There is an urgent need to increase data collection and analysis on the impact of vaccines on AMR . This is6a: Normative bodies should provide guidance for health technology assessment and evaluation of vaccine impact on AMR and antimicrobial use.6b: Funders and researchers should analyze existing datasets from epidemiologic studies, trials, and routine surveillance to estimate vaccine impact on AMR.6c: Where relevant, vaccine trials and studies should assess impact on AMR and/or antimicrobial use.6d: Public health authorities at the global, national, and subnational levels should enhance surveillance data systems to link vaccination data with antimicrobial use and resistance data with the greatest practicable level of geographic and demographic granularity. In resource-limited settings, building capacity for data collection and analysis should be included in immunization and AMR country action plans.6e: Researchers should continue to generate new evidence on:•how to use vaccines with the specific aim of controlling drug-resistant pathogens;•how vaccines can complement other infection control strategies and stewardship efforts to prolong or restore effective use of antibiotics against specific pathogens; and•socioeconomic and ethical aspects of vaccine impact on AMR.6f: Researchers and their sponsors should ensure that new data and evidence are made rapidly and publicly available through prompt public posting and scientific publications, preprints, and data-sharing platforms.Decisions about vaccine development, introduction, and use should be informed by estimates of the full value of vaccines, including not just disease impact but also AMR economic burden, antibiotic use, and impact on social justice and equity. Mathematical modelling, multicriteria decision analysis and other methodologies including empirical approaches can be used to inform investment decision making. Through an iterative process, modelling estimates should be regularly refined as empirical data emerge.7a: Research funders should support researchers to develop and improve methodologies to estimate impact of vaccines on AMR. Factors such as individual protection, herd immunity, transmission patterns, pathogen carriage rates, bacterial population dynamics, serotype replacement, vaccine-driven reductions in antibiotic use, and the various molecular drivers of resistance should be considered.7b: Health delivery payers and investors in R&D should develop and use standardized health technology assessments and value–attribution frameworks to inform the estimation of the full value of vaccines to prevent and control AMR.Vaccines are already contributing to the battle against AMR through prevention of infections and an associated decrease in antibiotic use. The priority activities outlined in this document provide the opportunity for vaccines to contribute fully, sustainably, and equitably to the prevention and control of AMR as a complementary approach to other AMR reduction efforts.Increased investments from the private, philanthropic, and public sectors are needed for existing vaccines to increase coverage and to develop new vaccines.Guidance provided to the AMR and immunization communities should be updated and strengthened to reflect the vision expressed here. Regulatory and policy frameworks should be adapted to support efficient decision making and to maximize vaccine-related opportunities and impact.Haemophilus influenzae type B, PCV, TCV, and influenza should be prioritized for impact on antibiotic use and AMR. Among disease areas for which proof-of-concept evidence suggests that vaccine development or improvement is technically feasible, tuberculosis constitutes a major public health emergency and priority for investment. Vaccines against gonococcal infections and enteric diseases resulting from Shigella, E coli, and nontyphoidal Salmonella also constitute priority R&D opportunities.Among available vaccines, increased uptake of Streptococcus. It may be possible to develop vaccines against other important AMR pathogens such as S aureus, Pseudomonas aeruginosa, E coli, Campylobacter, Helicobacter pylori, K pneumoniae, Acinetobacter baumannii, Enterococcus faecium, Clostridium difficile, Chlamydia, and Candida, but in each case technical feasibility remains to be demonstrated.Development should be accelerated of next-generation vaccines providing expanded strain coverage and durable protection against influenza and pneumococcus, as well as new vaccines against malaria, human immunodeficient virus, respiratory syncytial virus, and group A Across disease areas, key activities to maximize impact on AMR include: further development of innovative technologies, accelerated testing pathways, effectiveness evaluation through pilot implementation, new opportunities for immunization along the life course, access to high-risk groups, and market shaping.More and better collection and analysis of data on the role of vaccines against AMR across a variety of microbiological, health, and economic sectors are critical. Modelling provides important tools to estimate the full value of vaccines against AMR.Health interventions and policies depend on public confidence. Advocacy and targeted communication can contribute to increased knowledge and catalyze the action needed to better protect everyone against infections and curb the threat that AMR poses to individuals, societies, and global health.


Mn = 400–4000 gmol−1). In this regard, polycaprolactone diol (PCL) was selected as the soft segment, and 4,4′-cyclohexamethylene diisocyanate (H12MDI) and 1,6-hexanediol (HDO) were chosen as the hard segments. The films were prepared by curing polymer on Teflon surfaces. Fourier transform infrared spectroscopy (FTIR) was utilized for functional group identification in the prepared elastomers. FTIR peaks indicated the disappearance of −NCO and −OH groups and the formation of urethane (NHCOO) groups. The morphological behavior of the synthesized polymer samples was also elucidated using scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques. The AFM and SEM results indicated that the extent of microphase separation was enhanced by an increase in the molecular weight of PCL. The phase separation and degree of crystallinity of the soft and hard segments were described using X-ray diffraction (XRD). It was observed that the degree of crystallinity of the synthesized polymers increased with an increase in the soft segment’s chain length. To evaluate hydrophilicity/hydrophobicity, the contact angle was measured. A gradual increase in the contact angle with distilled water and diiodomethane (38.6°–54.9°) test liquids was observed. Moreover, the decrease in surface energy (46.95–24.45 mN/m) was also found to be inconsistent by increasing the molecular weight of polyols.In this study, we evaluated the morphological behavior of polyurethane elastomers (PUEs) by modifying the soft segment chain length. This was achieved by increasing the soft segment molecular weight ( The importance of PU elastomers is increasing because of their broad range of properties and increasing number of applications ,2,3. ThePolyurethane elastomers demonstrated microphase separation due to thermodynamic immiscibility between the polyol (soft segment) and urethane (hard segment). This double-phase microdomain structure shown by PUEs provides them with their better mechanical properties ,4,8,9.Importantly, the phase separation of the microdomain structure is not only influenced by the diisocyanate structure, molecular weight, cross-linking density, and ratio of the macrodiol and the chain extender ,5,10, buTo elucidate the relationships between morphology, chemical structural design, and the chemical properties of polymers, different physiochemical techniques were utilized . It was Mn = 400, 750, 1000, 2000, 3000 and 4000 gmol−1), which were utilized as soft segments (SSs). The H12MDI and HDO were used as ingredients to develop urethane linkage as hard segments (HSs) using the pre-polymer method. The reaction chemistry, influence of structure on morphological behavior, process ability and reactivity of the final product were studied. To the best of our knowledge, there are no other reports about this kind of polymer. Moreover, efforts have been made to elucidate the surface properties, crystallinity and hydrophilicity of polymeric materials through FTIR, SEM, AFM, XRD, contact angle and surface energy technologies. Meanwhile, our published article discusses the consequential effect of increasing the molecular weight of PCL on thermomechanical properties, assessed using TGA, DSC and DMTA; molecular characterization, assessed using FTIR; and the shape memory behavior of these polymers [The present study enforces the morphological analyses of PUEs. The morphological effect on the material’s behavior was evaluated by characterizing the prepared material. As PUEs are formed by combining hard (isocyanate) and elastic (polyol) parts, modification of these parts gives the polyurethane elastomers novel qualities. The PUEs were synthesized by using a wide range of molecular weights for the PCL polyols (polymers .12MDI) (2 mol), 1,6-hexanediol (HDO) (1.2 mol) and polycaprolactone diols (ranges Mn 400–4000 (0.8 mol)), were used to synthesize polyurethanes elastomers using step-growth polymerization  was conducted to obtain the NCO contents of the polymer. The synthesis of the pre-polymer was confirmed using FTIR spectroscopy.The PUEs were stirred in a four-necked round-bottom flask, and the polycaprolactone diol was added and stirred for a few minutes at 60–70 °C. Hthesized . FinallyBy changing the molecular weight of the polycaprolactone diols in the PU pre-polymer, eight samples were synthesized by following the above-mentioned procedure. −1, generated using attenuated total reflection (ATR) assembly. X-ray diffractograms of the PUEs were attained in dispersion range (2θ) of 5–70° by a Siemens D-5000 diffractometer with Cu-Ka radiations  at 25 °C. Two test liquids (double-distilled water and diiodomethane) were used to calculate the contact angle with the Krüss G10 contact angle measuring system. Surface tension was measured using Wu’s method. The surface topography of the fractured side was studied using scanning electron microscopy (SEM) at 2 kx, 5 kx and 15 kx after it was covered with a thin, gold layer using AFM (Germany) in tapping mode.The Equinox 55 Fourier Transform Infrared (FTIR) spectrometer  produced FTIR spectra of the prepared PUEs with a range of 750–4000 cm−1 for −NH− stretching, as reported in [−1, and the peaks at 2851–2862 and 2921–2935 cm−1 were attributed [2– groups (symmetric and asymmetric stretching vibrations), respectively [−1 (–NH– deformations), 1442–1465 cm−1 (–CH2– bending vibration), 1412–1431 cm−1 (–CH– bending vibration) and 1306–1362 cm−1 (–CH2– wagging), which verified the new synthesized products as having formed –NHCOO– groups. Using the above-discussed peak values, it is clear that all polyurethanes were successfully synthesized; the appearance of –NH– peaks showed complete consumption of –NCO-terminated pre-polymers. It was noted that the MW of polycaprolactone diol and the peak intensity of –NH– stretching vibration showed reciprocal trends, and the sharpness of the urethane carbonyl peaks was observed to continuously increase as the molecular weight of the SS increased. In PU with high molecular weight PCL, the number of ester linkages gradually increased without any change in –NH groups. As such, the relative peak intensity of the −NH group decreased as compared with that of the –C=O group. In addition, by increasing the length of the polycaprolactone diol, the relative amount of –NH groups also decreased per unit weight of PU.FTIR spectra of the isocyanate, −NCO-terminated pre-polymer, 1,6-hexanediol (HDO) chain extender and PU are presented to explain the structural characterization . The peaorted in , the uretributed  to –CH2–ectively . The oth2) units affected the crystallinity of the polymer, and this increased with the increasing PCL chain length X was found by using the following Equation:CA, and the total area of amorphous and crystalline peaks is T.ATo determine the dependence of the crystalline structure on the molecular weight of polyols, XRD analysis was used. Phase separation and the degree of crystallinity of the SS and HS were evaluated using XRD. In segmented polyurethanes, the phase separation is dependent upon the thermodynamic incompatibility and structural regularity of soft segments. XRD investigations showed that in the polyurethane backbone, the number of methylene , liquid surface tension (γL), and solid–liquid interfacial tension (γSL) using Young’s Equation:Surface tension with polar and dispersive portions was calculated using Wu’s method . A decreThe results in The morphology of the matrix system was examined using SEM . MicrophAtomic force microscopy (AFM) was utilized for the visualization of surface microstructure and polymer flexibility. The present study showed the morphology of PUE8 films. which can be seen in −1) provided ordered and compact arrangements of the soft and hard phases. However, various factors can be responsible for phase segregation in PU, such as the dimensions of SS and HS, the polarity of groups, the chemical nature of PU and molecular weight [Moreover, in regard to polyurethane composition, it was also reported  that hydr weight . Furtherr weight .12MDI (diisocyanate) and HDO chain extenders were synthesized and analyzed using FTIR. The appearance of −NH peaks along with the disappearance of –NCO and –OH aligned with the proposed polyurethane structures. Morphological analysis is an important tool for correlating the structure–property relationship of PUEs. SEM and AFM techniques provided topographical images of the samples, with the low molecular weight PCL samples displaying a clear, smooth and homogeneous microstructure without any deformation. In addition, clear phase segregation was observed in the high molecular weight PCL samples. This significant change in phase segregation is due to the soft and hard domains. Micrographs demonstrated that phase segregation depended upon the increasing molecular weight of the macrodiol. It was observed that the high molecular weight of PCL helped with the order and free arrangement of soft and hard segments. XRD was used to study the crystalline behavior of polyurethane films and demonstrated increasing crystallinity with successive increases in the macrodiol chain length. Furthermore, the reciprocal trend of contact angle increasing as surface energy decreased exhibited the active relationship between hydrophilicity and flexible segment length. As such, the investigation of the morphological behavior of synthesized elastomers explained the dependence of phase segregation, crystallinity and hydrophilicity on the molecular weight of polyol in the PUE backbone.Various samples of polyurethane elastomers (PUEs) with low-to-high molecular weights of PCL (macrodiol), H


Functionalized polyacrylonitrile (PAN) nanofibers were used in the present investigation to enhance the fracture behavior of carbon epoxy composite in order to prevent delamination if any crack propagates in the resin rich area. The main intent of this investigation was to analyze the efficiency of PAN nanofiber as a reinforcing agent for the carbon fiber-based epoxy structural composite. The composites were fabricated with stacked unidirectional carbon fibers and the PAN powder was functionalized with glycidyl methacrylate (GMA) and then used as reinforcement. The fabricated composites’ fracture behavior was analyzed through a double cantilever beam test and the energy release rate of the composites was investigated. The neat PAN and functionalized PAN-reinforced samples had an 18% and a 50% increase in fracture energy, respectively, compared to the control composite. In addition, the samples reinforced with functionalized PAN nanofibers had 27% higher interlaminar strength compared to neat PAN-reinforced composite, implying more efficient stress transformation as well as stress distribution from the matrix phase (resin-rich area) to the reinforcement phase (carbon/phase) of the composites. The enhancement of fracture toughness provides an opportunity to alleviate the prevalent issues in laminated composites for structural operations and facilitate their adoption in industries for critical applications. Laminated composites, i.e., carbon/epoxy composites, have been extensively utilized in a variety of structural applications owing to their superior mechanical qualities, manufacturability, and corrosion resistance when compared to traditional materials such as metals. In a variety of structural applications, such as vehicles, aerospace, ground, and wind turbines, they are considered ideal metal substitutes ,2,3,4,5.IC was obtained at 547 and 749 J m−2 for the control composite (without nanofibers) and for the composites reinforced with poly (e-caprolactone) (PCL) nanofiber, with a 210 nm diameter, respectively. Therefore, the incorporation of PCL nanofiber led to a 37% improvement in GIC Brugo and Palazzetti [Dzenis and Reneker devised a nanotechnology-based approach for strengthening composites. Since its conception, the approach has sparked a lot of scientific attention. The researchers used an electrospun nanofiber thin film between the reinforcement layers to improve resin-rich layers’ mechanical characteristics . The uselazzetti  employedThe surface functionalization of electrospun carbon nanofibers was carried out by Chen et al. to improve the properties of the epoxy resins and the hybrid multi-scale traditional carbon/epoxy composites, including flexural properties, interlaminar shear strength, as well as impact energy absorption . GlycidyThe overarching aim of this study is to observe the effect of the addition of functionalized PAN nanofibers on the fracture toughness of a traditional carbon/epoxy composite. The GMA-grafted PAN polymer used in this study was created by a free radical reaction. The epoxy groups on the backbone of PAN nanofibers provide a better coupling site for crosslinking with other active groups in the matrix, such as amines ,29. Howe−2 traditional unidirectional carbon fiber fabric. Hexion Inc.  provided the epoxy resin (EPONTM Resin 828) as well as the curing agent (EPIKURETM Curing Agent F205).Chemicals such as polyacrylonitrile (Mw = 150 kDa), N-dimethylformamide , glycidyl methacrylate , and benzoyl peroxide (BPO) were procured from Sigma-Aldrich . Jinsor-Tech Industrial Co.  provided a 300 g mThe functionalized PAN was created using the procedures described in Neisiany et al. . Using fIn order to prepare the electrospinning solution, 10 wt% of functionalized PAN was dissolved in DMF, while the magnetic stirring was kept for 24 h at room temperature. A 5 mL blunt syringe with a needle gauge of 21 was used to inject the solution. Before the electrospinning, the unidirectional carbon fiber fabrics were firstly wrapped around a cylindrical grounded drum with a diameter of 20 cm. Next, the electrospun functionalized PAN nanofibers were deposited directly on the surfaces of the unidirectional carbon fiber fabric. A reliable electrospinning procedure is required to produce consistent nanofibers free of beads. As a result, the process parameters were changed to match the prior work of Neisiany et al. . The depHand layup was used to make the carbon/epoxy composite panels, and then a Vacuum Assisted Resin Transfer Molding (VARTM) approach was used to optimize the wetting mechanism of the nanofibers and carbon fiber textiles. The epoxy resin and its curing agent were mixed with a mass ratio of 100:58.Twelve layers of uniaxial carbon fiber were used to strengthen the epoxy matrix. The reinforced epoxy matrix was held in a parallel alignment by composite panels. The nanofiber embedded panel had 11 layers of functionalized PAN nanofibers, whereas the control composite had no nanofibers at all . During The morphology of deposited electrospun nanofibers on the surfaces of unidirectional carbon fiber textiles, the thickness of nanofiber layers, and the surfaces of cracked composites were investigated using electron microscopy. After sputter coating the sample surfaces with a thin layer of gold, the images were captured using a Hitachi S-4300 field emission scanning electron microscope (FE-SEM) .Ic (MBT).Water jet cut samples with lengths of 130 mm, widths of 25 mm, and crack lengths of 45 mm were obtained from composite panels for a double cantilever beam (DCB) experiment. To apply the load, steel hinges were firstly fastened to both tips of the cut test specimens. The DCB fracture tests were conducted according to ASTM D 5528 . The Mod® Series 40 Electromechanical Universal Test machine  in triplicate under quasi-static stress using a 5 kN load cell. The displacement rate was set at 3 mm.min−1 while the relative humidity and temperature were kept at 60% and 20 °C, respectively. During testing, a digital camera ) was utilized in order to track the crack growth at 5 s intervals.In this equation, P and δ are the load and the load point displacement, respectively, while b and a are the specimen’s width and the delamination length, respectively. The DCB tests were carried out by an MTS Criterion −2 of the functionalized PAN nanofibers on the surfaces of unidirectional carbon fiber fabric. The functionalized PAN nanofibers were found to be randomly deposited on the surface of carbon fiber textiles. Furthermore, the nanofiber orientation was unaffected by collection rotation or transverse needle movement. FE-SEM micrographs were also collected to evaluate the thickness of the functionalized PAN nanofiber mat following complete deposition of them on carbon fiber fabric, which was 1 g·m−2. −2 nanofiber on the carbon fiber surfaces will provide the highest fracture toughness enhancement.The average diameter of the functionalized PAN nanofiber was 416 nm with a standard deviation of 93 nm, as mentioned in the previous study . The mor−1, respectively. The PAN-reinforced samples had an 18% increase in fracture energy compared to the control samples, while the functionalized PAN-reinforced samples had 50% and 27% increase in comparison with the control and neat PAN-reinforced composites, respectively. Nonetheless, the fracture energy improvement of functionalized PAN-reinforced CFRP samples was greater than that of the PAN-nanofiber-reinforced CFRP samples, which could be attributable to the distinct failure processes in the samples. The improvement was reported to be 37% and 11% for PCL [To determine the R-curves for various crack lengths of the samples, fracture energy was calculated. The fluctuations in fracture energy during crack propagation are depicted in  for PCL  and Nylo for PCL  nanofibeThe failure mechanisms in various reinforcing configurations have been studied using SEM images of fracture surfaces. The addition of Nylon 6.6 nanofibers to unidirectional samples had an insignificant influence on the samples, according to a study by Brugo and Palazzetti . The autIc The PAN-reinforced samples had an 18% increase in fracture energy compared to the control samples, while the functionalized PAN-reinforced samples had a 50% and 27% increase in comparison with control and neat PAN-reinforced composites, respectively. Furthermore, FE-SEM micrographs demonstrated that, compared to control samples, the microcracks created in functionalized PAN-reinforced composites were forced to disrupt/shatter a considerable amount of matrix during the propagation stage, needing more energy to extend. The improvement of fracture toughness for laminated structural composites will aid in the containment of cracks and prevent further fracture. This could be critical in stopping sudden and brittle failure in structures when cracks are present in the system and provide a warning so that necessary precautions can be taken.The effect of integrating functionalized PAN nanofibers between carbon fiber fabrics on the laminated structural composite delamination characteristics was examined in this study. PAN nanofibers were functionalized to increase the nanofibers and epoxy resin matrix interaction, and therefore the reinforced panel’s delamination strength. Both types of reinforced panels demonstrated a considerable increase in fracture energy, but the samples reinforced with functionalized nanofibers had higher delamination strengths than the neat PAN nanofiber-reinforced samples. The presence of nanofibers delayed crack initiation by acting as a matrix reinforcement, as evidenced by the increased interlaminar fracture energy G


The cognitive control dilemma describes the necessity to balance two antagonistic modes of attention: stability and flexibility. Stability refers to goal-directed thought, feeling, or action and flexibility refers to the complementary ability to adapt to an ever-changing environment. Their balance is thought to be maintained by neurotransmitters such as dopamine, most likely in a U-shaped rather than linear manner. However, in humans, studies on the stability-flexibility balance using a dopaminergic agent and/or measurement of brain dopamine are scarce.The study aimed to investigate the causal involvement of dopamine in the stability-flexibility balance and the nature of this relationship in humans.18F-DOPA-PET, dopamine availability in the striatum was examined at baseline to investigate its relationship to the RT distractor effect and to the L-DOPA-induced change of the RT distractor effect.Distractibility was assessed as the difference in reaction time (RT) between distractor and non-distractor trials in a visual search task. In a randomized, placebo-controlled, double-blind, crossover study, 65 healthy participants performed the task under placebo and a dopamine precursor (L-DOPA). Using There was a pronounced RT distractor effect in the placebo session that increased under L-DOPA. Neither the RT distractor effect in the placebo session nor the magnitude of its L-DOPA-induced increase were related to baseline striatal dopamine.L-DOPA administration shifted the stability-flexibility balance towards attentional capture by distractors, suggesting causal involvement of dopamine. This finding is consistent with current theories of prefrontal cortex dopamine function. Current data can neither confirm nor falsify the inverted U-shaped function hypothesis with regard to cognitive control.The online version contains supplementary material available at 10.1007/s00213-022-06077-w. According to the dual-state theory of PFC function, a relatively stronger activation of dopamine D1 receptors in the PFC is thought to uphold a “closed state” that is goal-directed and resistant to distraction by background stimuli while a D2-dominated “open state” is associated with increased cognitive flexibility   is currently the best available in vivo approach in humans to do so. PET parameters for dopamine uptake, turnover, and washout have proven to be valuable for that purpose  in the ventral (nucleus accumbens) and dorsal striatum (caudate nucleus and putamen) were specified. Critically, prefrontal ROIs were not examined, as the 18F-DOPA signal in the PFC is likely to be highly susceptible to measurement error and therefore results are not reliable , effective distribution volume ratio (EDVR), and washout rate (kloss) were assessed.In this study, we examined the pharmacological effect of L-DOPA on a behavioral marker of distractibility  in 65 human individuals . We used a visual singleton feature search task Theeuwes . Partici18F-DOPA PET parameters and the magnitude of the RT distractor effect in the placebo session: (a) a U-shaped relation, that is, greater distractibility in participants with comparatively low or high baseline striatal dopamine . This hypothesis rested on the assumption that dopamine levels were most likely distributed around an “optimum” in most of the healthy young adults, and excess dopamine would promote a D2-dominated “open-state” in the PFC . The project aimed to investigate the effects of a dopaminergic challenge on the balance between behavioral flexibility and stability with respect to three different domains: (i) updating versus goal shielding, (ii) goal-directed versus habitual instrumental responding, and (iii) background-monitoring versus goal-directed attention. The latter domain is addressed in the study at hand. For a detailed and complete outline of the study procedures and flow of participants, we would like to refer to earlier publications  and by the German Federal Office for Radiation Protection (Bundesamt für Strahlenschutz). The experimental protocol was performed in accordance with relevant guidelines and regulations. All participants provided written informed consent and were invited to three or four study visits in total: (1) a baseline visit; (2–3) two fMRI visits including the VST, which was performed outside the MRI scanner; (4) a PET visit for a subset of participants. Based on attendance hours, participants received compensation of approximately 100 €. Data was collected from February 2014 to February 2016 at the Neuroimaging Center of the TUD and the PET Center of the Department of Nuclear Medicine at the TUD.SD) = 9). Each participant completed the task under L-DOPA and placebo  used to study dopaminergic modulation of the stability-flexibility balance in cognitive control. The VST was performed on each of the two fMRI visits, which were 13 days apart on average  were adN = 15,778) were screened. Participants included in the study (1) were 30 to 40 years of age, (2) had no history of neuropsychiatric disorders according to the Screening Version of the Structured Clinical Interview for DSM-IV  = 36.2, SD = 3.7). Of these 65 participants, a subset of 43 participants received a PET scan and a subset of 49 participants had serum dopamine levels analyzed.Eighty-nine participants completed the VST in both fMRI visits. Twenty-four of these participants had to be excluded (see supplement). Sixty-five participants were eligible for VST data analysis . The VST was implemented using E-Prime presentation software, Version 2.0 . Participants were asked to carry out the task with their dominant hand.The VST had a fixed duration of 15 min with a group average of 394 trials for each visit  and accuracy were recorded. Each participant that was included for analysis reached more than 50% accuracy per trial type (target/distractor) and drug (L-DOPA/placebo). Responses with RTs greater than 2000 ms, and misses were recorded as error trials. Error trials were excluded before calculating mean RTs. Trials with an RT smaller than 200 ms were excluded from all further analyses. Within-subject trimming of RTs  or a matched placebo was administered in tablet form about 80 min after the begin of each fMRI visit. A booster dose of Madopar (75 mg L-DOPA + 18.75 mg benserazide) or a matched placebo was administered 100 min after the first dose and 75 min prior to the VST  for a subset of 49 participants. Serum levels during three timepoints T1 to T3) were used to descriptively assess the course of drug exposure during the entire experimental session  MBq was administered intravenously at the start of the PET scan. The PET scan followed a 4-h acquisition protocol . This parameter describes the extent of vesicular storage of fluorodopamine , compared with a reference region in the occipital cortex. kocc therefore reflects the uptake of dopamine within a region. Second is the the 18F-DOPA washout rate (kloss). This parameter indicates the rate at which dopamine is deaminated, and both FDA and its metabolites are cleared from the brain into the plasma. kloss therefore reflects the loss of vesicular dopamine. Third is the effective distribution volume ratio (EDVR), which is the inverse of dopamine turnover (EDVR = kocc / kloss). EDVR reflects the amount of dopamine available at steady state for vesicular storage. PET measures were acquired as averaged within three striatal region of interests (ROIs) defined in each individual’s native space: putamen, nucleus accumbens (Nacc), caudate. Data were averaged across hemispheres in each ROI. PET measures were not assessed within prefrontal ROIs, because the 18F-DOPA signal in these cortical regions is likely to be more susceptible to measurement error and therefore results are less reliable  were employed, among others. For all statistical tests, the level of significance was defined at 5% (α = 0.05). Figures were created using the afex_plot function from the afex package version 0.26–0 (https://cran.r-project.org/package=afex), the ggscatter and ggarrange function from the ggpubr package version 0.2.5 (https://cran.r-project.org/package=ggpubr), and the ggplot function from the ggplot2 package version 3.2.1 (https://cran.r-project.org/package=ggplot2), among others.All statistical analyses were performed in R version 3.6.2  in the placebo session using a paired two-sample t-test. Reliability of the VST was assessed as for similar interference tasks in previous studies  was calculated by adjusting split-half correlations between odd and even trials with the Spearman-Brown prophecy formula . Mean RTs, median RTs, and standard deviations (SD) per drug (L-DOPA/placebo) and trial type (target/distractor) were computed. Density plots for RT distributions in each individual were created using the gghistogram function from the ggpubr package.First, we assessed the RT distractor effect  and trial type (target/distractor) using the aov_car function from the afex package. The working memory capacity composite (WMC) score was included as a covariate. ANOVAs were separately performed for RTs, accuracy, and IES. Results of the 2 × 2 factorial repeated measures ANOVAs were consistent for RT and IES . In addition to these analyses, we assessed the correlation between L-DOPA serum levels and the magnitude of the L-DOPA-induced change in the RT distractor effect (see supplement).More complex ANOVA models did not show a significant main or interaction effect of either gender or administration order (L-DOPA first session/L-DOPA second session) on RTs  in three different ROIs  using the lm function from the stats package. To test a linear relationship, we fitted linear instead of quadratic functions. In addition, we investigated a U-shaped relationship between the PET data and mean RTs on distractor trials (instead of the RT distractor effect) in the placebo session.Third, we tested the association between the 18F-DOPA PET parameters and the magnitude of the L-DOPA-induced change in the RT distractor effect. We separately fitted a linear function to the L-DOPA-induced change in the RT distractor effect as compared to the three PET measures  in three different ROIs  using the lm function from the stats package.Fourth, we tested the association between the SD) per drug (L-DOPA/placebo) and trial type (target/distractor) are presented in the supplement (Table N = 49) and (ii) in that levels were higher after L-DOPA compared to placebo administration .Sixty-five participants had complete VST data and received both verum and placebo. Of these 65 participants, a subset of 43 participants received a PET scan and a subset of 49 participants had serum dopamine levels analyzed in the verum session. Mean RTs, median RTs, and standard deviations  in the placebo session (16 ms) (t(64) = 5.64, p < 0.001). Internal consistency of the VST in the placebo session was excellent for mean RTs across target trials (Cronbach’s α = 0.99) and distractor trials (Cronbach’s α = 0.99). Internal consistency was much lower for the interference score ; Cronbach’s α = 0.55). Note that mathematically, classical reliability of a difference score decreases with an increasing correlation between the “raw” scores . In addition, an attenuation of the reliability coefficient for the interference score may be due to a combined measurement error from the two trial types (congruent and incongruent presentations)  = 4.64, p = 0.035, η2G = 0.0004, η2P = 0.07) (Table t(64) = 7.51, p < 0.001) and 16 ms in the placebo session (t(64) = 5.64, p < 0.001) . However, there was no statistical difference in RTs on distractor trials between the L-DOPA and placebo session (t(66.4) = 0.41, p = 0.680). Also, there was no statistical difference in RTs on target trials between the L-DOPA and placebo session (t(66.4) =  − 0.29, p = 0.777). Follow-up exploratory analyses on inter-trial effects revealed that the L-DOPA-induced increase of the RT distractor effect was highly significant for trials that followed a distractor trial, but was not detectable for trials that followed a target trial (see supplement). The numerical differences in RTs with respect to current and previous trial type indicated adaptive attentional inhibition of distractors after distractor trials in the placebo session, whereas such adaptation did not occur in the L-DOPA session  = 7.80, p = 0.007, η2G = 0.09, η2P = 0.11)  and trial type (target/distractor)  Fig. . The eff1) Table . Working1) Table .Table 1Fkocc, EDVR, kloss) in any ROI  sufficiently explained the variance in the RT distractor effect. That is, there was neither any quadratic model fit  in any ROI  significantly correlated with the L-DOPA induced change in the RT distractor effect  and flexibility (distractibility). It has been suggested, but scarcely verified in humans, that this balance is maintained by neurotransmitters such as dopamine. Also, research indicates a U-shaped or linear relationship between dopamine availability in the brain and behavioral markers of the stability-flexibility balance. The nature of the relationship appears to differ among different brain regions and cognitive domains. Here, we used a visual search task (VST) as a behavioral marker of the stability-flexibility balance. The task was performed both after administration of the dopamine precursor L-DOPA and after placebo. PET striatal imaging is currently the best available in vivo approach in humans to assess central nervous dopamine and was employed in the current design to examine the nature of the brain dopamine to behavior relationship for visual selective attention. As hypothesized  . A significant quadratic relationship between striatal 18F-DOPA-PET indices and a behavioral marker of the stability-flexibility balance would have confirmed the “inverted U-shaped” function hypothesis. A linear relationship would have confirmed a constant change in distractibility with increasing tonic dopamine in the brain. However, because dopamine effects in the PFC and striatum are sometimes thought to behave in opposite fashion, the exact direction of the relationship between PET data and behavior could not be predicted with certainty. Regardless of this matter, we found neither a quadratic nor a linear relationship in the current data. That is, participants with comparatively high or low striatal dopamine did not show a pronounced RT distractor effect. At the same time, participants’ distractibility also did not change linearly with the extend of dopamine availability.The extended PET assessment in the current study permitted the calculation of three PET indices (instead of one) for the striatum . The use of extended The L-DOPA effect of increased distractibility in the visual search task can be explained with regard to three theoretical models, although direct evidence from neuroimaging is lacking. First, the effect is in line with the dual-state theory of PFC dopamine function  goes along with a much larger RT distractor effect (up to 200 ms) compared with moderate  or high frequency (up to 80%)  the lack of neuroimaging data for both sessions, (ii) no assessment of prefrontal dopamine metabolism, (iii) no assessment of individual dopamine receptor density, (iv) low specificity of the dopaminergic intervention, and (v) a lack of separate task sessions under varying drug dose. On the one hand, future projects could address these limitations, and a stepwise approach would likely be most promising. Studies could first identify a task with a robust behavioral marker of the stability-flexibility balance that is substantially, specifically and preferably bidirectionally modulated by a pharmacological intervention. Agents such as bromocriptine (selective dopamine D2 receptor agonist), amisulpride and sulpiride (selective dopamine D2 receptor antagonists), and PDE10A inhibitors  have proven to be suitable candidates . Ultimately, these core mechanisms may be targeted in treatment.Supplementary file1 (DOCX 961 KB)Below is the link to the electronic supplementary material.