Antibody-mediated rejection (AMR) is a major cause of kidney allograft failure. Its molecular mechanisms are multifaceted and may include a role of complement activation via the classical pathway. Here, we investigated whether noninvasive complement monitoring adds predictive power to the diagnosis of AMR in the setting of donor-specific antibody (DSA) positivity.In this cross-sectional study, 741 kidney transplant recipients with stable graft function ≥180 days posttransplantation were screened for the presence of human leukocyte antigen (HLA) alloantibodies. Eighty-three of 111 DSA-positive recipients underwent protocol biopsies and were tested for blood and urinary levels of complement proteins  and activation products .ρ = 0.44–0.64; P < 0.001). Analysis of death-censored graft survival over a median of 60 months revealed no independent associations with levels of complement markers in blood or urine.Forty-seven recipients were diagnosed with AMR, and 21 were C4d-positive. While biopsy-confirmed AMR (and C4d) associated with DSA-binding strength , tested complement markers did not have any predictive value for rejection (area under the receiver operating characteristic curve: 0.49–0.56). There were, however, tight correlations between complement activation products in urine and protein/creatinine ratio (Complement patterns in blood and urine failed to identify AMR in late biopsies and may have no relevant diagnostic value in this particular context. The pathophysiology of AMR is multifaceted and may include a contribution of a variety of complement-dependent and -independent (Fc gamma receptor-triggered) mechanisms.16 These results, however, were not confirmed in a subsequent study, and urinary C4d excretion was interpreted as a marker of unspecific glomerular injury.17 Such controversial results may have been due to small sample sizes or differences in case selection and rejection criteria. Moreover, one may argue that distinct CP activation markers reflecting activation of defined steps within the cascade may subtly differ in their diagnostic sensitivity and specificity. Furthermore, as diverse events like ischemia/reperfusion, rejection, or glomerulonephritis may activate the CP, the sole detection of complement markers may not be able to dissect reliably the pathophysiology of allograft dysfunction.Given the presumed pathogenetic role of intra-graft CP activation, a potential noninvasive strategy to dissect the clinical relevance of a given HLA antibody pattern may be the detection of CP function and complement products in peripheral blood or urine. Indeed, in an earlier study, detection of CP split product C4d in urine (but not C5b-9) was found to be associated with capillary C4d staining and rejection.4 which included an in-depth analysis of DSA characteristics and morphological/molecular AMR features.The primary objective of the present study was to determine whether the detection of complement components and split products in the blood and urine of DSA-positive kidney transplant recipients is able to predict AMR in concomitant protocol biopsies. Our study was performed in the context of the cross-sectional screening phase of the BORTEJECT trial,www.clinicaltrials.org: NCT01873157), which was designed to assess the effect of bortezomib on the course of late AMR.18 The trial was approved by the institutional ethics committee of the Medical University of Vienna (EK1515/2012) and conducted in accordance with the Declarations of Helsinki and Istanbul. During the screening period (between October 2013 and February 2015), 1165 kidney transplant recipients were registered at the Vienna Transplant Unit (outpatient clinic of the nephrology department)  were classified as DSA-positive and, following the study protocol, 86 of these patients underwent protocol biopsies. Twenty-five patients had no biopsy, either because of a lack of consent or the presence of one or more exclusion criteria defined in the protocol.4 For 83 of the 86 patients subjected to biopsy, adequate material for detailed evaluation of complement products in both peripheral blood (serum or plasma) and urine was available , prior transplantation, HLA mismatch, and cytotoxic panel reactivity. With the exception of more frequent desensitization among DSA-positive patients, groups did not significantly differ with respect to baseline data and immunosuppressive therapy . Multilayering of basement membranes of PTC and glomerular basement membranes was assessed by electron microscopy. For 3 of the 83 biopsies, no ultrastructural work-up was available. One of these biopsies fulfilled none of the histomorphological and immunohistochemical criteria of AMR, and 2 were classified as chronic active AMR with moderate or high grade cg. As previously described in detail,21 a proportion of 1 biopsy core was stabilized in RNALater and shipped to the Alberta Transplant Applied Genomics Centre for microarray-based gene expression analysis (Molecular Microscope Diagnostic System). A classifier related to AMR was generated using a recently published reference set of 1208 biopsy specimens.22 AMR was defined following the Banff 2013 consensus,20 based on histomorphological, immunohistochemical (C4d), ultrastructural (high-grade multilayering of basement membranes of PTC), and serological (DSA detection) criteria, as well as a thoroughly validated molecular classifier for AMR (Molecular Microscope Diagnostic System molecular AMR score ≥0.2), respectively. The latter differed significantly between AMR (median: 0.62 [IQR: 0.36–0.86]) and no AMR cases (0.06 [IQR: 0.02–0.13] P < 0.001).All 83 DSA-positive study patients underwent protocol biopsies, in median 23 days  after antibody screening. AMR-typical lesions, including C4d in peritubular capillaries (PTC), glomerulitis, peritubular capillaritis, and transplant glomerulopathy (cg), were defined and scored following the Banff 2013 scheme.9 Before alloantibody testing, serum samples were heat-inactivated  to prevent complement interference. The presence or absence of IgG type DSA (mean fluorescence intensity [MFI] threshold >1000) was determined in the context of serological and low- or high-resolution donor/recipient HLA typing . For assessment of the C1q-binding ability of DSA, C1qScreen assays (One Lambda) were used. For analysis of C4 or C3 activation and fixation (deposition of C4 and C3 split products to the bead surface),9 beads were first incubated with patient sera followed by an excess of serum obtained from a nonsensitized healthy volunteer (complement source). Beads were then washed and incubated with biotin-conjugated monoclonal antibodies against human C4d or C3d , and in a second step, phycoerythrin-conjugated Streptavidin. Test results were documented as the MFI of the immunodominant DSA (MFI_max) or the sum of DSA MFI (MFI_sum).HLA reactivity patterns were analyzed using LABScreen Single Antigen assays  as earlier described in detail.23 An enzyme-linked immunosorbent assay was applied to measure C1q serum concentrations24 (reference range: 60–180 mg/L). Serum concentrations of complement C3 (reference range: 0.9–1.8 g/L) and C4 (reference range: 0.15–0.55 g/L) were determined by turbidimetry . Complement activation split product C3a , C4d , C5a , and terminal pathway activation complex sC5b-9  levels were determined with commercial kits , according to the manufacturer’s instructions in ethylenediaminetetraacetic acid (EDTA) anticoagulated plasma or mid-stream urine samples. The methods, handling, and preparation of the urine samples were detailed previously.26 In brief, fresh urine was mixed (9:1 ratio) with 10 mM Tris buffer, pH 8.6, with 0.05% Tween 20 and 0.01% of NaN3 containing protease inhibitors . After centrifugation . Supernatants were aliquoted and stored at −80°C and thawed only once before testing. For analysis of levels in urine, complement protein concentrations were corrected according to urinary creatinine concentration. Blood samples were processed immediately, and separated serum and EDTA plasma aliquots were stored at −80° C until use. For the complement assays employed in the present study, intra-assay and inter-assay variation coefficients were <7% and <17%, respectively.All samples were collected, handled, and stored at −80°C  following a uniform predefined protocol. To exclude any batch effects, individual complement measurements were performed using uniform batches of test kits. Individual complement assays were performed at a single time point for all included subjects. Samples were randomly allocated on the plates. Total complement activity of the CP (50% hemolytic complement activity [CH50] assay) in serum samples was determined by an in-house hemolytic-titration assay based on Mayer’s method (reference range: 48–103 U/mL).U or Kruskal-Wallis tests to compare continuous data, while nonparametric test was used for correlation analysis. For comparative analyses in relation to DSA status, propensity score matching was applied to create a matched DSA-negative control group. Variables were selected using a logit model. Variables with a P value <0.10 and/or confounding factors known to be associated with AMR were selected . One-to-one matching was conducted, and balance between the final groups was assessed by propensity score distribution and descriptive statistics. The nonparametric bootstrap method, resampling with replacement 1000 times on the matched dataset, was conducted to provide inner validation. Receiver operating characteristic (ROC) curves and their corresponding area under the curve (AUC) values were calculated to assess the sensitivity and specificity of different predictors. Kaplan-Meier analysis was applied for calculation of death-censored graft survival. Mantel-Cox Log-rank test was used for comparison of survival between groups. For bivariate analysis, Cox regression analysis was performed using the following confounders: detection of urinary C4d and PCR. Hazard ratios (HRs) are presented with 95% confidence intervals (95%CI). A 2-sided P value <0.05 was considered statistically significant. For statistical analysis, IBM SPSS Statistics 24  was used.Continuous data were expressed as the median and IQR (range from the 25th to the 75th percentile) and categorical variables as absolute and relative frequencies. Fisher exact tests were used to compare categorical data and Mann-Whitney 27 (cytotoxic crossmatch conversion in 8 patients). At the time of cross-sectional screening, 62 recipients were on triple and 21 on dual immunosuppression. Fifty patients were on tacrolimus-based immunosuppression and 72 recipients on steroids. Median eGFR was 54 mL/min/1.73 m2 and urinary PCR 200 mg/g (Table The study population included 83 DSA-positive kidney transplant recipients who underwent protocol biopsies after a median of 4.9 years posttransplantation. Characteristics of the DSA-positive study population (and a propensity score matched cohort of 106 DSA-negative recipients) are summarized in Table Patients were tested for overall CP activity (CH50), plasma/serum levels of C1q, C4, C4d, C3, C3a, and sC5b-9, and concentrations of creatinine-adjusted urinary complement activation products C4d, C3a, C5a, and sC5b-9, respectively. As shown in Table P < 0.0001). Groups, however, did not differ with respect to HLA class specificity and complement fixing capability of DSA in C1q, C4d, or C3d bead assays (Table As detailed in Table ys Table .P < 0.0001) and IgG MFI_sum  were significantly higher in C4d-positive than in C4d-negative patients. In parallel, levels of C1q (but not C4d or C3d) fixation were significantly different  but no significant correlations for C1q-, C4d-, and C3d-fixation . Concentrations of other tested complement (split) products in blood or urine did not correlate with DSA characteristics , showing a stepwise increase of complement levels with increasing proteinuria  (data not shown).Creatinine-adjusted urinary C4d, C3a, C5a, and sC5b9 levels were found to correlate tightly with PCR (C4d: P = 0.87), C3 (P = 0.76), C4 (P = 0.78), CH50 (P = 0.30), C3a (P = 0.70), and sC5b-9 (P = 0.37), respectively. In contrast, detection of C4d in urine was associated with inferior death-censored graft survival (P = 0.034), which paralleled a highly significant outcome effect of urinary protein excretion  and C5a (P=0.019), while for sC5b-9 only a trend towards adverse survival was observed (P = 0.11) (data not shown). Bivariate Cox regression analysis revealed a significant outcome effect of proteinuria at screening , however, failed to demonstrate an independent effect of urinary C4d . Similar results were obtained for urinary C3a and C5a, respectively (data not shown).Study patients were followed for a median of 60 (IQR: 55–62) months. Overall, death-censored graft survival after index biopsy was 99% and 85% at 12 and 60 months, respectively. As shown in Figure 28 A prominent finding, however, was that, in absence of any association with rejection, CP activation products in urine were tightly associated with levels of proteinuria (which were related to cg), indicating that their detection might rather nonspecifically mirror the extent of glomerular injury. While blood markers of complement were not associated with graft survival, univariate analysis revealed significant associations for complement detection in urine. However, bivariate analysis including proteinuria as a co-variable failed to demonstrate independent outcome effects.A major result of this cross-sectional cohort study was that blood and urine markers of complement function and activation did not show any diagnostic value in conjunction with DSA detection late after kidney transplantation. Our detailed analysis of 83 stable DSA-positive recipients revealed that none of the tested parameters were able to identify ongoing AMR and thus dissect the pathogenicity and clinical relevance of a given HLA antibody pattern. There was even no relationship with capillary C4d deposition, which is known to specifically reflect local CP activation triggered by endothelium-bound DSA.29 and this may provide a theoretical basis for the use of complement monitoring to dissect the relevance of a given DSA pattern. Complement activation triggered by preformed or de novo DSA may result in a sequence of events, including the release of anaphylatoxins , opsonin deposition , and in a final step, formation of the membrane attack complex (C5b-9). All these steps may promote the recruitment and activation of inflammatory cells, release of cytokines and chemokines, direct damage or activation  of the endothelium, vasodilation, and finally, activation of components of adaptive immunity.29 Several observations are in support of a role of CP activation in clinical transplantation. A prominent example is the finding of C4d staining in transplant capillaries, a marker of intra-graft CP activation found to strongly associate with graft survival.28 Moreover, detection of complement (C1q or C3d)-fixing DSA was reported to associate with rejection and graft failure,30 and there are data suggesting that complement-triggered transplant injury may be associated with a distinct pattern of gene expression that could even reflect the efficiency of complement inhibitory treatment.31A variety of experimental data and clinical observations are in support of a pathogenic role of the CP of complement as a trigger of rejection in organ transplantation,12 Strong support for complement independent mechanisms of injury come from microarray analysis of graft biopsies with subsequent pathway analysis which pointed to a dominant role of NK cell-triggered injury.32 Complement-independent transplant injury is supported by the frequent finding of C4d-negative phenotypes of rejection, especially in the late phase after transplantation.33 For example, in our cohort, only 21 of the biopsies were found to stain C4d positive, and, even when using a low threshold  for defining a positive staining, >50% of the AMR cases turned out to be C4d negative. In this respect, it may also be of interest that C4d itself was shown to exert distinct immunomodulatory effects, via interaction with atypical complement receptors on monocytes that might modulate the secretion of tumor necrosis factor-α or interleukin-6.34 The ability of antibodies to fix and activate complement, as can be quantified on HLA-coated microbeads, may critically depend not only on the distribution of involved immunoglobulin (sub)classes35 but also on antibody-binding strength, as to some extent reflected by the MFI recorded in bead assays,36 and one may speculate that the binding strength of a given HLA antibody may also directly relate to its ability to trigger complement-independent injury.However, in recent years, there has been emerging evidence for a role of complement-independent injury mechanisms, in particular, Fc gamma receptor–mediated cellular activation.9 the predictive accuracy of MFI even exceeded that of levels of complement fixation in different assay variants. As shown for capillary C4d, which was tightly related to DSA MFI (and complement-fixing ability), we found no association with complement split products in urine and blood. These data reinforce that measurement of complement in peripheral blood may not, as in other disease states , mirror complement activation in affected tissue: in our patients, the transplant microvasculature. We have no good explanation for this observation, but in silent cases of late AMR, levels of complement consumption and levels of released split products may be too low to be visible in the circulation. The same was true for urinary complement patterns, perhaps also due to the fact that in AMR the endothelial surface, rather than the tubular system, is the primary site of antibody-antigen interaction. Moreover, urine levels of C activation products were a priori very often below the detection threshold, and there was a strong overlap of the effects of proteinuria which may have made the detection of subtle differences impossible. In this respect, a major finding was that applying bivariate Cox regression analysis, including protein excretion as a co-variable, we were unable to demonstrate an independent impact of urinary complement levels on death-censored graft survival.In this respect, an interesting finding was a prominent association of DSA MFI with AMR and C4d detection. As already reported in a previous study,17 found that, as in our analysis, complement split product C4d in urine was tightly associated with proteinuria, but not with capillary C4d staining. These and our data support the view that complement product detection in the urine may be an unspecific measure of glomerular injury leading to protein excretion, independent of complement activation in the graft. At first sight, our data may be in contrast to a study by Bechtel et al,16 who found a relationship between urinary C4d (as well as ICAM-1 and VCAM-1) levels and rejection. However, levels were elevated particularly in patients with steroid-resistant rejection when compared with cases of steroid-sensitive or chronic rejection. They found no association at all for excretion of C5b-9; however, data on proteinuria were not provided.In an earlier study, Hönger et al38 In a recent observational study of 90 clinically indicated biopsies obtained from 87 kidney transplant patients with a DSA result, Jordan et al39 found high positive and negative predictive values of dd-cfDNA (at a threshold of 1%) in relation to the diagnosis of active AMR, both exceeding 80%. The positive predictive value of DSA detection alone was only 48%, suggesting that dd-cfDNA evaluation may effectively supplement DSA testing as a noninvasive diagnostic tool.39Our data reinforce the need for defining innovative new approaches to improve noninvasive AMR monitoring. In the specific context of DSA monitoring, one promising example may be the detection of donor-derived cell-free DNA (dd-cfDNA), the level of which may reflect the extent of immunologic transplant injury.2 However, complement levels were similar in a group of matched DSA-negative patients, indicating that there might be no discrimination of DSA status. Our study focused on a cohort of patients who presented with stable graft function late after transplantation. According to defined inclusion criteria, subjects with acute deterioration of graft function and early cases of rejection were not included, and our results do not exclude some diagnostic value in more severe manifestations of acute AMR, in which CP activation may be more pronounced and perhaps visible in peripheral blood or urine. Finally, one may argue that even a detailed biopsy work-up, which was based on different diagnostic criteria, including molecular analysis, may not allow for a clear-cut differentiation between AMR and no AMR, even though this was supported by a substantial and highly significant difference with respect to molecular AMR scores. For example, for 3 of the 83 biopsies, no ultrastructural analysis was available, and in 1 case classified as no rejection, discrete cg visible by electron microscopy only cannot be excluded. Moreover, our biopsies were evaluated following the rules of the Banff 2013 scheme. More recently, AMR diagnosis was in some aspects modified in the Banff 2017 scheme,2 and a major modification may be that C4d staining or expression of validated transcripts/classifiers may now substitute for DSA. Following our study design, however, only DSA-positive cases were subjected to biopsies, and a possible role of DSA-negative AMR was not studied in our cohort.We are aware of the limitations of our study. One limitation may be that patient screening included only a single snapshot of testing without any information regarding the kinetics of complement components in relation to the clinical course and serial biopsy findings. Accordingly, using an arbitrary MFI threshold, our study design cannot exclude fluctuating DSA results in some of our patients (either in DSA-positive or DSA-negative subjects). Moreover, according to our screening protocol, only DSA-positive patients were considered for protocol biopsy, and therefore no data on the prevalence of rejection in absence of DSA were available, a possibility now considered in the revised Banff 2017 scheme.The strengths of our study were a systematic prospective design, comparatively large number of cases recruited upon screening of >700 recipients, and a detailed characterization of DSA properties and biopsies.Altogether, our study results indicate that noninvasive complement analysis in conjunction with DSA detection does not improve the diagnosis of silent AMR late after kidney transplantation. Our data reinforce the need for alternative concepts to noninvasively dissect the relevance of a given DSA pattern in this specific context.


Metal organic frameworks (MOFs) have been exploited for various applications in science and engineering due to the possibility of forming different mesoscopic frameworks and pore structures. To date, further development of MOFs for practical applications in areas such as energy storage and conversion have encountered tremendous challenge owing to the unitary porous structure  and conventional morphology . More recently, one-dimensional (1D) MOFs/nanofibers composites emerged as a new molecular system with highly engineered novel structures for tailored applications. In this mini-review, the recent progress in the development of MOFs-based 1D nanofibers via electrospinning will be elaborated. In particular, the promising applications and underlying molecular mechanism of electrospun MOF-derived carbon nanofibers are primarily focused and analyzed here. This review is instrumental in providing certain guiding principles for the preparation and structural analysis of MOFs/electrospun nanofibers (M-NFs) composites and electrospun MOF-derived nanomaterials.  The design flexibility of MOF in terms of highly variable geometry and functionality based on the choices of incorporated constituents has attracted increasing attentions from researchers in catalysis, energy, and electronics. The main advantage of MOFs in comparison with conventional porous materials is the achievement of specific structure and tunable porosity at the molecular level by adjusting both metal species and organic ligands. For instance, the typical porosity of MOFs is higher than 50% of the total solid volume while the surface area of MOFs generally ranges from 1000 to 10,000 mUntil now, most studies in MOF have been steered towards the development of potential applications in important technological areas, such as catalysts ,3,4, carIn order to expand the applications of MOFs, more attention has been paid to the design and fabrication of 1D MOFs/nanofibers composites and their derivatives . For exaMaterials Horizons solely discussed the applications of MOF-derived porous or hollow carbon-based nanofibers for energy storage and conversion [While various methods have been introduced for the synthesis of MOFs/nanofibers composites and their derivatives, it is worthwhile to mention that electrospinning has emerged as the most reliable technique for preparing MOFs/electrospun nanofibers (M-NFs). In general, electrospinning applies a strong electric field upon a polymer solution or polymer melt under active dispensation to nanofibers of 2 nm to several micrometers in diameter onto designated substrates ,16. Elecnversion . Only a nversion . Due to Zeolitic imidazolate frameworks (ZIFs) are a typical class of MOFs characterized by its porous crystalline structure extending into 3D space by bridging each tetrahedral metal ion with multiple imidazolate (Im) groups. Due to the flexibility of metal ions and organic blocks, the structure and properties of zeolites can be forged with interesting properties for challenging applications in molecular catalysis and separation . As such(I) In situ growth method by preparing electrospun nanofibers that are incorporated with contain metal ions (or ligands), followed by in situ growth of MOF nanoparticles on electrospun nanofibers; (II) Co-electrospinning synthesis by mixing MOF nanoparticles with a polymer solution to form a precursor followed by formation of M-NFs via electrospinning. 2), PAN, and poly-(vinylpyrrolidone) (PVP) are mixed in N,N-Dimethylformamide (DMF) to obtain an electrospun precursor solution. Then Zn(acac)2/PVP/PAN fibers are prepared by electrospinning immediately followed by immersion in mixed with 2-methylimidazole (mIM) solution within a Teflon-lined container and kept at 120 °C for 12 hours. Because PVP is more hydrophilic than PAN, PVP can be extracted from Zn(acac)2/PVP/PAN fibers in accompany by the generation of pore structure by hydrothermal treatment /polyacrylonitrile (PAN) nanofibers is introduced as a model M-NFs by in situ growth method (Ⅰ) was highlighted . Specifireatment b. It wasreatment c. IntereAN@ZIF-8 . Additio2+, which serves as the coordination center of the ZIF-8 nanocrystal to be eventually distributed in high concentration on the PU nanofibers. Moreover, BET surface area of ZIF-8/PU decreases with the amount of ZIF-8 nanocrystal. Although the loading of the MOFs nanoparticles was increased by activating the surface of the fiber and the like, which brought about an occlusion of the pores and attenuate the adverse effects of the one-dimensional morphology of the nanofibers. Therefore, it is not advisable to increase the load blindly, various factors such as the ‘bearing capacity of the nanofibers’ should be comprehensively considered in the preparation of M-NFs. Apart from in situ-grown ZIF-8/PAN, other types of Z-NFs prepared have been prepared by in situ growth method. Zhou and co-workers reported the first time in situ crystal growth of ZIF-8 on electrospun polyurethane (PU) nanofibers (ZIF-8/PU) . More sp2O3/ZnO2 nanofibers instead of Zn2+ coated PU nanofiber was applied as a source of Zn2+ for serving as a template for the in situ growth of ZIF-8, an In2O3/ZIF-8 core–shell complex was successfully produced with the effective loading of ZIF-8. It is also noteworthy that the transformation from ZnO particles to metal centers coordinated with organic ligands may likely lead to the formation of structural defects between linkers, thus enlarging the pore size of metal–organic framework ZIF-8 [In addition to pre-treating the materials during in-situ growth to optimize the structure of the M-NFs, different metal sources can also be used to obtain different structures and performances. Different types of materials can be selected as the source of metal ions or as templates for the growth of ZIFs crystal. By introducing other materials into the crystal growth process, a variety of composites with unique structures and physical properties can be obtained. Activation of the fiber surface and continued addition of ligand or metal ion solution during in situ growth can promote the ZIFs crystal growth. When Inrk ZIF-8 ,37. In a(a)ZIFs nanoparticles are evenly loaded in the fiber matrix and the degree of loading is adjustable, which effectively avoid the large-scale agglomeration of ZIFs nanoparticles;(b)Defects, mesopores, etc. can be formed during electrospinning;(c)Nanofibers can enhance the mechanical properties and stability of Z-NFs due to its support and protection of ZIFs nanoparticles.While the in situ growth method is being developed, another method known co-electrospinning has received increasing attentions. Again, ZIF-67/PAN is used as a typical example to cover the co-electrospinning method in detail . SchematZ-NFs is not only the most representative type of material in M-NFs, but also the earliest and most widely studied materials. With the development of Z-NFs, more MOF materials other than sole ZIFs have been produced through the fabrication of nanofiber composites by electrospinning . M-NFs are prepared in a similar way compared to Z-NFs, while larger range of structural and physical properties of M-NFs are revealed, due to the significant variability among different metal centers and organic ligands ,45,46,472 adsorption on the HKUST-1/PAN nanofibers are mainly at the open metal sites /PAN nanofibers by combining co-electrospinning and in situ growth, which promoted multiple growth and activation processes . The actal sites a. The asal sites b. As shoameworks . In addiameworks ,50. Multiple activations and growths can enhance the loading of MOF nanoparticles and the binding force of MOF particles and nanofibers to obtain more stable and more active composites. Besides, similar performance can be achieved by selecting the appropriate polymer with a target group which can form a strong bonding with the organic functional groups or ions in MOFs. Recently, Peng and co-workers have reported a UiO-66/PVA  nanofiber networks via co-electrospinning . The hyd3(BDC)2) metal organic frameworks (paper@MOF-5) materials [2 coatings deposited on polyamide-6 (PA-6) nanofibers by atomic layer deposition (ALD) to form Zr-based MOF thin films (PA-6@TiO2@UiO-66-NH2). Moreover, certain MOF–nanofiber textile composites can achieve ultra-fast degradation of chemical warfare agents (CWAs) [The polymers related to M-NFs which were reported in recent years are mainly PAN, PVP, PVA, PS, etc. However, many other polymers  are also important materials for preparing M-NFs. Laurila et al. reported the in situ crystal growth of HKUST-1 on electrospun cellulose nanofibers . Yang etaterials . Zhao ets (CWAs) . Wu et as (CWAs) . Recentls (CWAs) . Rosal as (CWAs) . Similars (CWAs) . Table 2Electrospun MOFs-derived carbon nanofibers (M-CNFs) are generally prepared by heat treatment and reduction of M-NFs that obtained via electrospinning. After M-NFs are obtained, the heat treatment of composites can be roughly classified into two categories: (I) The composites are directly subjected to high temperature carbonization under an air atmosphere to obtain a target product . The structure and properties of the target product can be controlled by changing the temperature, heating rate, and calcination time. 2 (or Ar) atmosphere .(II) Preheating the composites in an air atmosphere at lower temperature and then transferring the composites to high temperature carbonization under N2 NTs after the calcination at 600 °C for 1 h in air atmosphere under the heating rate of 10 °C min−1 [x-N-C via the pyrolysis process that includes stabilization and carbonization. The progress of stabilization was implement in air at 280 °C for 2 h. Carbonization step was conducted in a N2 atmosphere at temperature up to 800 °C for 1 h [In the direct calcination method, pure phase metal oxides can be obtained at higher temperatures. Recently, Kim and co-workers have reported that the as-spun Pd@ZIF-8/PVP/Sn composite NFs were transformed to PdO@ZnO-SnO°C min−1 . Some po for 1 h .The wide application of M-CNFs is attributed to its attractive structures such as one-dimensional nanofibrous morphology and hollow tubular structure. MOFs-derived carbon nanofibers have been considered as excellent electrode materials in energy conversion and storage devices ,64,65. M• Lithium/sodium ion battery3O4/graphene composites as electrode of battery [3O4@C) via solvothermal reaction of manganese acetate monohydrate and polyvinylpyrrolidone [3O4 with electrospun carbon (Co3O4/C) prepared by annealing the ZIF-67/PAN templates, the Co3O4/C shows a capacity of 1024.1 mAh g −1 after 100 cycles [The difference in physical properties of electrode material directly affects the performance of the battery. Poor battery performance is mainly attributed to two aspects: (1) Its extremely low intrinsic electrical conductivity; (2) Volume expansion of the material during charging/discharging, which causes particle comminution and spalling . Many st battery . Althougrolidone . However0 cycles . 2-Co3O4 NFs with ZIF-67 (which contains Co ions and mIM) as a template [2-Co3O4 NFs are shown in 2-Co3O4 NFs was formed via electrospinning and subsequent calcination process form a large number of mesoporous structures. The results shows that the introduction of the ZIF-67 framework not only causes the material to form a large number of oxygen vacancies, but also enhances the conductivity of the material, inducing more active sites for Li storage in lithium-ion batteries (LIBs). As such SnO2-Co3O4 NFs maintain a reversible capacity of 1287 mAh g−1 after 300 cycles at a current density of 500 mA g–1. Similarly, the authors have prepared hollow porous SnO2-CuO composite nanotubes by electrospinning and calcination [2-MxOy  nanocomposites (nanofibers) display a porous (mesoporous) structure as well as a large number of defects and oxygen vacancies, which solves the problems of poor cycle stability, low ionic conductivity, and low reversible capacity of SnO2. In addition to the introduction of MOF framework into SnO2 system by electrospinning and heat treatment to form SnO2-MxOy porous nanofibers, many reports have focused on the formation of metal oxide/carbon nanofibers composites formed by co-electrospinning of MOF nanoparticles and polymer and the subsequent heat treatment as electrode materials for batteries. Yang et al. have reported a yolk–shell MnOx carbon nanofiber composite (ysMnOx@NC) based on Mn-MOF [−1). Double buffering of nanofibers and the yolk–shell structure can reduce the activity due to material loss during cycling, thereby increasing the reversible capacity of the battery.Electrospun MOFs-derived one-dimensional carbon nanofibers are ideal materials for battery electrode materials due to their high specific surface area, good electrical conductivity, and well-defined porous structure. For instance, Cheong et al. have prepared one dimension SnOtemplate . Schematcination . After tn Mn-MOF . The yol2O4/NiO/carbon nanofibers) based on Co/Ni-ZIF, which was prepared via successive carbonization and oxidation heat-treatments [−1 after 200 cycles (100 mA g−1). Zhang et al. have also prepared carbon fibers with uniformly distributed Co3O4 hollow nanoparticles (NPs) by electrospinning of ZIF-67 NPs and thermal treatment [Preparing materials with special structure (porous or yolk shell structures) is a way to improve the performance of M-CNFs as battery materials. Besides, preparation of bimetallic or polymetallic composite materials is also an important method to optimize the performance of M-CNFs. The improvement in performance is mainly due to the synergy between bimetallic or polymetallic. Sodium-ion batteries (SIBs) are also of much interests. Recently, Li and co-workers have reported a kind of hierarchical heteroatom-doped carbon nanofibers decorated with several nanocomposites  The MOF framework will form excess oxygen vacancies and defects, thereby increasing the active site of the material during post-treatments; (b) The porous interwoven network of MOF derivative carbon nanofiber can improve the mass/charge transport and the conductivity of the material, support the composite system, and adapt the cyclic change of the material to reduce the loss of activity of the material for achieving high lithium (sodium) storage capacity;(c) Synergistic interaction between polymetallic and between metal and carbon nanofiber networks can improves material performance;(d) Anisotropic materials with hollow and porous structures have large specific surface area and strong carrying capacity.• Metal-air batteryZn-air battery is the most widely studied and used battery in the metal-air battery category. MOFs are considered as a suitable material for Zn-air battery due to its tunable structure and inherent heteroatoms that promote electron transfer. However, MOF-derived carbon catalysts are generally susceptible to evolution into isolated nanoparticles, which greatly reduces conductivity and thus weakens its electrochemical properties. One-dimensional porous conductive networks of carbon nanotubes or carbon fibers have been shown to improve the conductivity and electron transfer of materials, which has aroused widespread interest among researchers. It is worth mentioning that composite materials like M-CNFs with hierarchical structure and hybrid nanostructures provide additional channels for material diffusion, promoting exposure of active reactive sites . 2 g−1) by activated carbon fiber prepared [−1, the specific capacitance was maintained at 146.7 F g−1 [−1 at 0.5 A g−1 [According to different energy storage mechanisms (SCs), supercapacitors can be divided into two categories: electric double layer capacitors (EDLCs) and Faraday quasi capacitors. EDLCs has received much attention for its outstanding advantages . Carbon prepared  The intrprepared ,83. M-CN.7 F g−1 . Recentl.5 A g−1 .3 NFs is shown in the 3 via electrospinning, which promotes electron conduction and sensing performance of Pd@ZnO-WO3 NFs. Kim and co-workers have conducted further research on the basis of this work and prepared the PdO@ZnO dual catalysts-loaded hollow SnO2 NTs (PdO@ZnO-SnO2 NTs) via electrospinning and the subsequent calcination [2 NTs can ensure the uniform loading of a large amount of precious metal particles, and the active sites are also increased correspondingly. The hollow PdO@ZnO-SnO2 NTs exhibited high acetone response (Rair/Rgas = 5.06 at 400 °C@1 ppm). Guo et al. have prepared the Pt-ZnO-In2O3 composite nanofibers with ZIF-8 as a template by electrospinning [2O3 NFs is related to the n-n heterojunctions between ZnO and In2O3 and p-n heterojunction formed between p-type PtO2 and n-type In2O3 (ZnO). Precious metal particles can be uniformly dispersed in the network structure formed by electrospun nanofibers and MOF frames, which can effectively solve the deterioration of sensing performance caused by agglomeration of metal particles. After heat treatment, a variety of heterojunctions formed in the material can enhance the conductivity and the synergy among the metal oxides, and a large number of oxygen vacancies can improve the sensing performance.Nowadays, air pollution is getting more serious, the monitoring of volatile organic pollutants such as acetone is receiving more attentions. MOFs have many attractive features, including the ability to encapsulate precious metal nanoparticles  . Hermes cination . The holspinning . The excFuel cells are receiving more attentions with the development of clean energy technologies ,93. In gX-N-C), which were prepared by electrospinning and carbonization with ZIF-67 used as a template [X-N-C exhibited excellent discharge specific capacity (610 mAh g−1) and discharge voltage, which are comparable to 20 wt % Pt/C and RuO2. Moreover, Wu et al. have reported that hierarchical porous Fe-N-doped carbon nanofibers (Fe-NHCFs) can be fabricated via carbonization of MOF nanofibers [−2 and an output peak power density of 61 mW cm−2. Application performances or properties of representative electrospun MOF-derived carbon nanofibers are shown in Bimetall zeolitic imidazolate frameworks (ZIFs) grown on the surface of MIM/PAN electrospun nanofibers via electrospinning, that is Zn-Co-ZIF-n(shell)/PAN(core) nanofibers (n refers to the molar ratio of Zn/Co before carbonization). After subsequent calcination, Zn/Co@C-NCNFs with layered network structure and high surface area are prepared, whose core layer is nitrogen-doped carbon nanofibers (NCNFs) and the shell layer is Zn/Co bimetallic nanoparticles coated with graphitic carbon layer (Zn/Co@C). Preparative process of Zn/Co@C-NCNFs is shown in template . The Co/nofibers . Fe-N doMOF-derived carbon-based materials doped with heteroatom can exhibit electrocatalytic properties comparable to those of Pt, which mainly due to the following aspects:2 in the system (promoting mass transfer); (a) The inherent MOF framework and pore canals formed by interweaving the electrospun fibers with the organic framework during the carbonization process provide additional channels for O(b) Highly graphitized and one-dimensional porous conductive networks improve the conductivity and electron transfer of materials; (c) Metal-heteroatom doping in the system induces the formation of a large number of active sites.Due to the existence of heterojunction between MOF nanoparticles and nanofibers, the stability of the materials are enhanced while active sites are increased in number. In addition, the anxiety regarding the difficulty of recycling and easy agglomeration of the nanoparticle can be relieved with the adoption of the electrospun fibers support. After calcination, the mesoporous structure, defects and oxygen vacancies may be formed in the electrospun MOF-derived nanomaterials , which is beneficial for the improvement of the performance of the obtained composite nanofibers. However, further efforts in the field are still needed to address the following issues: (1) For M-NFs composite materials: (a) the activity and specific surface area of the material decrease compared to their constituent MOFs nanoparticles; (b) The loading of MOFs particles in the electrospinning method is less controllable and the stable growth of MOFs particles on the fibers is hard to be achieved during in situ growth process. (2) For the electrospun MOF-derived nanomaterials, the mechanical properties of the fibers after heat treatment are significantly reduced, hindering its further application. (3) More research should focus on the relationship between performance and structure. In other words, M-NFs and their derivatives obtained by electrospinning have great potential in many emerging applications.


Although the Kaposi sarcoma (KS) is one of the AIDS defining entity and seen in almost one third of HIV infected patients with low CD4 cell counts, it is not uncommon in HIV seronegative persons, but genital KS is rare, particularly in people without risk factors for HIV infection. Isolated penile KS is an unusual manifestation, especially as solitary nodule with ulceration, in HIV seronegative patient.We report such a case of Kaposi sarcoma showing HHV-8 positivity in an elderly male Arabian patient with a delay in prompt diagnosis, but treated successfully with 3 3 years follow-up after limited local surgical excision.The general practitioners, venereologists and urologists should think of KS as a possibility in such lesion and consider early biopsy. Though Moritz Kaposi in 1872 described 5 cases of aggressive forms of sarcoma with mortality within 3 years, the incidence rate of Kaposi sarcoma increased with the discovery of HIV during early 1980s and its association with this vascular tumor. But the real causation of Kaposi sarcoma has been linked with HHV-8 in 1994 [A 63 year old man was referred from a primary health center with a penile lesion of 8 months duration. The lesion started as a small, pruritic, slightly thickened brown discoloration on glans penis, for which a topical corticosteroid cream was prescribed with a clinical suspicion as lichen planus. But it continued to grow to reach the present size with recent surface ulceration.There was no history of any systemic disease except he has been on diet for glucose intolerance.No history of exposure to risk factors of sexually transmitted diseases obtained. There was history of mild intermittent voiding and post void dribbling. No history of fever, weight loss or any other skin diseases. Local examination revealed an ulcerated firm, reddish brown, slightly tender nodule of 8 mm. on glans penis near corona on the ventral aspect of the penis Fig. a.Fig. 1No other similar lesions seen in genitalia. No inguinal lymphadenopathy noted. Dermatologic examination also did not reveal any skin or oral lesions.The laboratory investigations for CBC, serum creatinine, serum PSA and complete urine analysis including urine culture did not show abnormal result. Swab culture from ulcer was negative. The blood HbA1c was 5.8%. The serological tests for HIV, HBsAg and RPR were negative. The pelvic ultrasound showed moderately enlarged prostate (size of 45 g.), but otherwise normal study.After a signed consent, the patient underwent an excisional biopsy with the clinical impression of pyogenic granuloma. The initial histopathology report revealed atypical spindle cell proliferation with clear resection margins and advised immunohistochemical studies for final diagnosis. The immunostains revealed the spindle cells were immunoreactive for CD31, CD34 &HHV8 LANA-1 and non-reactive for SMA. (Fig. On consultation, uro-oncologist advised close clinical follow - up for any recurrence. No local recurrence or systemic lesions observed during last three years of follow up.Kaposi sarcoma is considered as a borderline malignant tumor derived from lymphatic endothelial cells and is common in advanced HIV infection with low CD4 cell count. There are 5 categories which include classic, endemic, epidemic, iatrogenic and non-epidemic types .Though the common denominator is the underlying immunosuppression in majority of patients, it is known to be caused by HHV-8 in almost all cases, even in immunocompetent persons . The genMany cases of penile KS presents as multiple macules or papules or nodules confining only to.penis or genital area, but more commonly as part of cutaneous lesions elsewhere.The first genital Kaposi sarcoma in Saudi Arabia was reported in 1994, with multiple papules on penis and scrotum . In 2016In one study, 13 patients of penile KS were managed with local excision, but 4 of them showed local recurrence . Our patThe sporadic Kaposi sarcoma can present in an unusual manner in rare sites without any known risk factors. The atypical features in the current case are KS manifesting as only penile single ulcerative nodule resembling pyogenic granuloma and demonstrating HHV8 LANA-1 immunoreactivity in HIV negative elderly person, with no recurrence after proper excision. The general practitioners, venereologists and urologists should think of KS as a possibility in such lesion and consider early biopsy. The proper early treatment and regular follow -up will facilitate better health care.


Recently, several classes of non-insulin glucose-lowering drugs, such as dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1-RA), and sodium glucose co-transporter-2 inhibitors (SGLT2i), have been approved to treat type 2 diabetes. Clinical trials have shown that GLP1RA and SGLT2i confer cardiovascular benefit, while DPP4i do not have such benefit; these drugs do not seem to increase the risk of hypoglycemia. However, due to underrepresentation of older adults with frailty and lack of frailty assessment in clinical trials, little is known about how the effectiveness and safety of these drugs change across different levels of frailty. In this symposium, we present the real-world evidence from Medicare data April 2013-December 2016 on the utilization trends of newly approved diabetes drugs (Dr. Dave) and comparative effectiveness and safety of SGLT2i vs sulfonylurea (Dr. Pawar), SGLT2i vs DPP4i (Dr. Kim), and SGLT2i vs GLP1-RA (Dr. Patorno). The outcomes were 1) composite cardiovascular endpoint of mortality, myocardial infarction, stroke, or heart failure; and 2) severe hypoglycemia, defined as emergency department visits or hospitalizations due to hypoglycemia. We applied a validated claims-based frailty index (CFI) to estimate the treatment effectiveness and safety in non-frail (CFI<0.10), pre-frail (CFI 0.10-0.19), or frail individuals (CFI≥0.20). Following individual presentations, Dr. Munshi and presenters will lead an interactive discussion about clinical implications and methodological challenges in conducting geriatric pharmacoepidemiologic studies using Medicare data. This symposium will demonstrate the utility of CFI in claims-based pharmacoepidemiologic studies and provide health care providers with new evidence to tailor diabetes pharmacotherapy based on frailty.


Here, we prepared TiO2 nanofibers with different crystal phase contents by electrospinning followed via calcination at different temperatures. The TiO2 nanofibers were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectrometry, transmission electron microscopy (TEM), and photocatalytic performance testing. The results showed that the phases of TiO2 nanofibers were layered, that surface crystal phase transition rate was faster than that of internal layers contributed the difference in the ratio of anatase and rutile in the outer and inner layer of TiO2 nanofibers. The TiO2 nanofibers obtained at 575 °C had the best photocatalytic activity, taking only 25 min to degrade Rhodamine B. At 575 °C, the rutile content of the sample surface was about 80 wt.%, while the internal rutile content was only about 40 wt.%. Subsequently, we prepared two different structures of anatase–rutile core-shell TiO2 nanofibers. The core-shell structure can be clearly seen by TEM characterization. The photocatalytic activity of two kinds of core-shell TiO2 nanofibers was tested. The results showed that the photocatalytic activity was close to that of the pure phase TiO2 nanofibers, which corresponded with the surface phase. This further proves that the photocatalytic activity of the material is mainly affected by its surface structure.The crystal phases and surface states of TiO Among them, the anatase and rutile phases are extensively used in photocatalytic reactions [2 have a significant effect on carrier transfer in photocatalytic applications. For example, it is widely recognized that P25 powder, which contains 20% rutile and 80% anatase, is a good photocatalyst [2 can be critical to the photocatalytic activity. For instance, the amount of surface absorption of water and hydroxyl determined by anatase and rutile plays an important role in adsorbing molecules to a great extent [2, which is directly exposed to light and the reactants, contributes to photocatalysis because the photocatalytic reaction takes place only when photoinduced electrons and holes are available on the surface [With the acceleration of industrial modernization, people have discharged large amounts of production waste water into the environment they live in, which contain many toxic pollutants such as pesticides and industrial dyes. These toxic pollutants pose a great threat to human health ,2,3. Mortoxicity ,9,10,11.eactions . It is reactions ,14,15. Teactions . Howevercatalyst  as the ccatalyst . In addit extent . The sur2 and ZnO. In recent years, many studies have been established on the photocatalytic performance of mixed crystal TiO2 nanofibers via electrospinning [2/ZnO nanofibers with different ratios of anatase/rutile and their results showed that TiO2/ZnO nanofibers with optimal anatase/rutile ratio (48:52) had the highest photocatalytic efficiency in the degradation of Rhodamine B under visible irradiation [2 nanofibers, when calcined at 650 °C. The TiO2 nanofibers exhibited the best photocatalytic performance with the anatase/rutile phase ratio of 83:17 under UV irradiation [2 nanofiber crystal phase and its photocatalytic mechanism in detail. The surface crystal phases are particularly important for photocatalysis. Therefore, it is expected that if the proportion of anatase/rutile in the inner and outer layers of TiO2 nanofibers could be tunable, then the interaction between rutile and anatase phases can exert a variable influence on the surface structure and properties of TiO2 nanofibers, which would be important for designing superior photocatalysts and for further understanding of the photocatalysis processes.Nanofibrous photocatalysts are attractive for practical applications in environmental purification due to their greater surface-to-volume ratio and a three-dimensional open structure, which allows its surface-active sites to be more easily and effectively accessed by the reactants ,22,23. Sspinning ,28. For adiation . Riaz etadiation . However2 nanofibers with different crystal ratios by adjusting the calcination temperature, and discussed the process of TiO2 phase transition at high temperature. At the same time, we studied the photocatalytic properties of TiO2 nanofibers where the inner and outer layers contained different anatase/rutile ratios and discussed the relationship between crystal structure and its photocatalytic performance in detail. In order to prove that the surface morphology of TiO2 nanofibers plays a decisive role in its photocatalytic activity, the core-shell TiO2 nanofibers with different crystal structures were prepared by the hydrolysis treatment of TiO2 nanofibers, and the photocatalytic properties of the core-shell nanofibers were studied.In this work, we prepared TiOTetrabutyl titanate (>95%), ethanol (>95%) and acetic acid (>95%) were of analytical grade and purchased from Tianjin Chemical Company . Poly(vinyl pyrrolidone)  and titanium isopropoxide  were purchased from Sigma-Aldrich . Concentrated nitric acid and Rhodamine B were purchased from Beijing Chemical Company . The above chemical reagents were used without further purification.2 nanofibers with different crystal forms according to the previously reported method [In a typical procedure, 0.45 g of poly(vinyl pyrrolidone) (PVP) was mixed with 7.5 mL of ethanol and stirred at room temperature for 6 hours until the PVP was completely dissolved. Another 1.5 g of tetrabutyl titanate was added to a mixed solvent of 3 mL of ethanol and 3 mL of acetic acid, stirred for 15 min to fully dissolve, and then quickly poured into the previously prepared PVP solution, vigorously stirred for 15 min. The mixture was loaded into the glass syringe for electrospinning, and 15 kV high-voltage was provided between the syringe and aluminum foil at a distance of 20 cm. The nanofibers were collected onto the aluminum foil and left in air for 24–48 hours to ensure that they sufficiently hydrolyzed, and subsequently calcinated at different temperature (400–850 °C in air for 5 h) to obtain TiOd method .2 nanofibers. A suitable amount of well-prepared rutile TiO2 nanofibers calcinated at 850 °C was dispersed in a mixture of 80 mL of water, 20 mL of ethanol, 20 mL acetic acid, and 1 mL of concentrated nitric acid under vigorous stirring at 38 °C for 15 min. Then, 5 mL of titanium isopropoxide was added into the premixed solution. The system was mixed vigorously for 16 h at 38 °C with a magnetic stirrer. The rutile–anatase core-shell TiO2 nanofibers were recovered by centrifugation and washed three times with water. The washed nanofibers were then allowed to dry in an oven for 24 h before characterization.A hydrolysis method was used to prepare rutile–anatase core-shell TiO2 nanofibers. A suitable amount of well-prepared anatase TiO2 nanofibers calcinated at 400 °C was dispersed in 125 mL of nitric acid solution (pH 1.2) under vigorous stirring at 60 °C for 15 min. Then, 3 mL of titanium isopropoxide and 5 mL of isopropanol were mixed and added into the premixed solution. The system was mixed using a magnetic stirrer until the solution became opaque and then aged for 6 h at 60 °C. Anatase–rutile core-shell TiO2 nanofibers were recovered by centrifugation and washed three times with water. The washed nanofibers were then allowed to dry in an oven at 60 °C for 24 h before characterization.A modified alkoxide method was used to prepare anatase–rutile core-shell TiONanofibers were characterized by means of scanning electron microscope , transmission electron micrographs , X-ray diffraction , UV/visible spectrometer , high-resolution full-band micro-area Raman spectrometer ), confocal Raman microscope ), and a box type high temperature resistance furnace .2 nanofibers. First, a dilute solution of 20 mg/L Rhodamine B was configured, then 50.0 mg of the catalyst was weighed into 50.0 mL of 20 mg/L Rhodamine B solution. The reaction system was stirred for 30 min in the dark to achieve an adsorption–desorption equilibrium before UV irradiation. The reaction system was then transferred to a photocatalytic reaction chamber and stirring was continued under ultraviolet light. The temperature of the system was maintained at 35 °C using condensed water and an air-cooling device. During the reaction, a sample solution was taken every 5 min for UV–Vis spectroscopy to determine the concentration change of the Rhodamine B solution.Rhodamine B was used as a reference for organic pollutants to evaluate the photocatalytic activity of the TiO2 nanofibers after calcination, we used SEM to characterize them as shown in 2 nanofibers was significantly reduced after 500 °C calcination, which might be caused by the loss of moisture and organic matter during calcination.In order to observe the morphology changes of the TiO2 nanofibers prepared at different temperatures. The results are shown in 2 nanofibers obtained at 450 °C were the pure anatase phase (JCPDS: 84-1286); and the TiO2 nanofibers obtained at 800 °C were classified as the pure rutile phase (JCPDS: 88-1175); TiO2 nanofibers prepared at 500, 550, 575, 600, 650, and 700 °C were all mixed phases. The weight percentage of each crystal phase was calculated from the individual diffraction peaks on the basis of formulas reported in the literature [AW and RW represent the weight fraction of the anatase and rutile TiO2 phases, respectively; AI and RI represent the diffraction intensities of the anatase (101) and rutile (110) peaks. With an increase of the calcinated temperature, the content of rutile also increased. The phase compositions of the samples are summarized in XRD was used to study the phases of the TiOterature .WA = 1 1g (519 cm−1), 2B1g (399 and 519 cm−1), and 3Eg  and rutile has four Raman active modes: A1g (612 cm−1), B1g (236 cm−1), B2g (826 cm−1) and Eg (447 cm−1) [2 nanofibers obtained at 450 °C exhibited distinct peaks of the anatase phase. As the calcination temperature increased, the distinct peaks of rutile phase appeared gradually. When the temperature reached 800 °C, the characteristic peak of the anatase phase could hardly be observed as the TiO2 nanofibers  would have been completely converted into the rutile phase. For the visible Raman spectrum, the peak area ratio of the two characteristic peaks for anatase phase (395 cm−1) and rutile phase (445 cm−1) was linear with the content ratio (AW/RW) [2 nanofibers was different from the overall conversion rate. In order to further understand the differences, UV Raman spectroscopy was used to analyze TiO2 nanofibers in −1 (anatase phase) and 445, 612 cm−1 (rutile phase). The TiO2 nanofibers obtained at 450 °C exhibited distinct peaks of the anatase phase. As the sintering temperature increased, the characteristic peak of the rutile phase began to appear at 445 cm−1 in the spectrum, while the characteristic peak of the anatase phase at 638 cm−1 began to shift . With the further increase of temperature, the characteristic peak of anatase phase gradually weakened, the characteristic peak at 445 cm−1 gradually increased, and the characteristic peak displacement at 638 cm−1 was more obvious. When the temperature rose above 575 °C, the characteristic peak of the rutile phase at 445 cm−1 became the main characteristic peak, and the characteristic peak at 638 cm−1 was almost completely displaced to 612 cm−1, indicating that the crystal form was mainly composed of the rutile phase. When the temperature reached 650 °C, the characteristic peak of the anatase phase was hardly observed as the TiO2 nanofibers (surface) were all converted into the rutile phase. Similarly, the weight percentage of the rutile phase at different temperatures is shown in 2 nanofibers.UV Raman and visible Raman were used to further analyze the crystal phase. According to reports, UV Raman spectroscopy is more sensitive to the surface crystal phase of the sample, while visible Raman spectroscopy is more sensitive to the crystal phase inside the sample. As we know, the structures of both anatase (D4h 19(I41/amd)) and rutile (D4h 14(P42/mnm)) are tetragonal. Derived from the factor group analysis, anatase has six Raman-active modes: A47 cm−1) ,33. It c (WA/WR) . The wei2 nanofibers was significantly faster than the interior. As show in 2 nanofibers was preferentially converted to the rutile phase. When calcined at 650 °C, the surface anatase phase of the TiO2 nanofibers converted into the rutile phase completely, and there was still a certain amount of anatase phase inside the TiO2 nanofibers without complete conversion. When the temperature reached 800 °C, the anatase phase was completely converted into the rutile phase.The results obtained from XRD, UV Raman, and visible Raman spectroscopy suggest that the crystal transition rate of the surface of TiO2 nanofibers calcined at different temperatures by degrading Rhodamine B. The results are shown in 0 and C are the equilibrium concentrations of Rhodamine B in the reaction system before and after UV illumination. It can be seen that the TiO2 nanofibers had obvious catalytic degradation to Rhodamine B, but with the change of sintering temperature, the degradation rate had a significant difference. The pure anatase phase TiO2 nanofibers degraded rhodamine B completely for about 55 min, while the pure rutile phase TiO2 nanofibers degraded Rhodamine B much more slowly, in about 105 min. This indicates that the anatase phase TiO2 has higher photocatalytic activity than the rutile phase. It is generally believed that there are two main reasons for this difference: (1) The forbidden band width Eg of the anatase phase is 3.2 eV, which is slightly larger than the rutile phase TiO2 (Eg = 3.0 eV), and the conduction band of the rutile phase TiO2 correction hinders the reduction reaction of active oxygen, so the electron-hole pairs generated by the anatase phase TiO2 have stronger redox ability; (2) the anatase phase lattice contains more defects and dislocations, which can produce more oxygen vacancies to capture electrons, making photogenerated electrons and holes easier to separate [2 nanofibers had better photocatalytic efficiency than pure anatase phase. For example, the TiO2 nanofibers calcined at 500, 550, and 575 °C used less than 50 min, while the TiO2 nanofibers obtained at 575 °C only took 30 min.We studied the photocatalytic activity of TiOseparate . However2 nanofibers is caused by the synergistic effect produced by the interaction between the anatase phase and the rutile phase. It has been reported that the photocatalytic mechanism includes three aspects: (1) generation of photogenerated electrons and holes; (2) electron transitions to adjacent sites to reduce the combination with holes; and (3) electrons and holes transfer to the surface of the materials and conduct desired reactions  trap, leading to the separation of electron and hole pairs. Since the photocatalytic excitation process usually occurs on the surface, the electrons trapped inside occupy a small proportion. At the same time, only a small number of electrons trapped inside can reach the surface of the material due to the path and high bonding rate [2 nanofibers lead to the production of OH radicals, which will decompose pollutants in water [2 nanofibers causes less excitation of the electron-hole pair; but if the surface rutile phase increases, less of the anatase phase cannot promote the efficient separation of electrons and holes. The nanofiber surface obtained at 575 °C had a richer rutile phase and synergized with the anatase phase. We can recognize that the amount of rutile and anatase on the surface of the nanofibers obtained at this temperature only led to the efficient separation of electrons and holes and the sufficient reaction with small molecules on the surface [This excellent photocatalytic activity of the mixed phases of TiOing rate . Therefoin water . It is w surface ,37, ther2 nanofibers plays a decisive role in its photocatalytic activity, we developed unique rutile–anatase core-shell structured nanocrystalline TiO2 nanofibers. 2 nanofibers prepared by different methods. It can be seen that the surface of the anatase phase TiO2 nanofibers was evenly coated with a dense layer of needle-shaped TiO2 from 2 nanofiber was coated with a TiO2 layer composed of nanoparticles in In order to prove that the surface phase of TiO2 nanofibers are mixed phases. The TiO2 nanofibers of the anatase core@rutile shell structure still had anatase structure and contained a certain amount of the rutile phase; while the rutile core@anatase shell structure of TiO2 nanofibers mainly had a rutile structure. Then, we used Raman spectroscopy to analyze two core-shell TiO2 nanofibers and pure phase TiO2 nanofibers. 2 nanofibers of the core-shell structure exhibited a Raman spectrum similar to their internal. The rutile core@anatase shell structured nanofibers exhibited a complete rutile phase while the characteristic peak of the anatase phase was not observed from the figure. The anatase core@rutile shell nanofibers mainly exhibited an anatase structure, but weak rutile phase peaks could still be found, which indicates that the rutile phase content of the shell was higher, a property that cannot be ignored by the response of the visible Raman spectroscopy. The result of the UV Raman spectroscopy (as show in 2. On the contrary, although the inner nuclear layer of the rutile core@anatase shell fiber had a complete rutile phase, the surface was mainly of the anatase phase. The presence of a small amount of rutile phase could be seen in the spectrum, which was due to the thinner shell of the nanofibers. In addition, we used the previous method to calculate the crystal phase compositions under the three test results, as shown in As shown in 2 nanofibers with a core-shell structure by the photocatalytic degradation of Rhodamine B as a template reaction as shown in 2 nanofibers had a mixed phase, the photocatalytic activity was determined by the crystal structure of the surface. It took 95 min to degrade the Rhodamine B completely, which was similar to that of the pure rutile TiO2 nanofibers, while the photocatalytic activity of the rutile core@anatase shell fiber was close to that of pure anatase phase TiO2 nanofibers. The result further demonstrates that the photocatalytic activity is mainly determined by the surface crystal structure of the TiO2 nanofibers. On the other hand, we found that the photocatalytic activity of the core-shell TiO2 nanofibers was higher than that of the corresponding pure phase TiO2 nanofibers. The reason could be due to the synergistic effect at the interface between the core-shell structures, which contributed to the slight improvement of the photocatalytic activity. We also studied the photocatalytic activity of TiO2 nanofibers with different anatase/rutile content were prepared by controlling the sintering temperature. The whole, surface, and internal crystal structures of the TiO2 nanofibers were analyzed in detail by XRD, visible Raman, and UV Raman. The results showed that the phase of TiO2 nanofibers was layered, and there were some differences in the internal and surface crystal phase distribution during the phase transition. The surface phase transition rate was faster than the phase transition rate of the inner layer, thus causing the difference of the layers.Electrospun TiO2 nanofibers containing different proportions of crystal structure was tested. The TiO2 nanofibers produced at 575 °C had the best photocatalytic activity, which took only 25 min for the degradation of Rhodamine B under UV irradiation. At 575 °C, the rutile content of the sample surface was about 80 wt.%, while the internal rutile content was only about 40 wt.%. The surface rutile was slightly dominant and formed an effective interfacial synergistic effect with anatase. Since the rutile phase is more prone to light response, the electron-hole pair can be more effectively separated by the synergistic effect, thereby enhancing the photocatalytic activity.The photocatalytic activity of the TiO2 nanofibers. The core-shell structure could be clearly seen by TEM characterization. The XRD test showed that both core-shell fibers were mixed crystals. However, the Raman test results were biased toward the internal nuclear layer structure, and the UV Raman test results were biased toward the structure of the surface shell. The photocatalytic activity of two kinds of core-shell TiO2 nanofibers was tested. The results showed that the photocatalytic activity was close to that of the pure phase TiO2 nanofibers, which corresponded with the surface phase. This further proves that the photocatalytic activity of the material was mainly affected by its surface structure.Subsequently, we prepared two different structures of anatase–rutile core-shell TiO


Daphnia, an important model organism, to investigate the effect(s) of selected CNS agents on heart rate. Dopamine’s effects onDaphnia’s heart has not been previously reported. Caffeine is a well-known and widely consumed stimulant. Ethanol is well known for its effects on both neurological and physiological processes in mammals. We tested the effect of dopamine on the heart rate ofDaphnia, and compared its effect with caffeine and ethanol alone and in combination. Both caffeine and dopamine were found to instantly increase the heart rate ofDaphnia in a dose-dependent manner. Interestingly, caffeine synergized with dopamine to increaseDaphnia’s heart rate. As ethanol decreased the heart rate ofDaphnia and dopamine increased the heart rate ofDaphnia, we wanted to test the effect of these molecules in combination. Indeed, Dopamine was able to restore the ethanol-induced decrease in the heart rate ofDaphnia.  Effects of these CNS agents onDaphnia can possibly be correlated with similar effects in the case of mammals.Dopamine is a key neurotransmitter, and is widely used as a central nervous system (CNS) agent.  Dopamine plays an important role in humans, including a major role in reward and motivation behaviour. Several addictive drugs are well known to increase neuronal dopamine activity. We selected Stimulation of the hypothalamus can lead to cardiovascular disturbances, indicating a direct connection between the heart and the CNS3. Different types of rewards are known to increase the level of dopamine in the brain4.Daphnia are small crustaceans commonly known as “water fleas”, and are found in water bodies5.Daphnia is an ideal organism for research, as it has short life span, and can easily be cultured6. These organisms can feed on algae, yeast and bacteria5. More importantly,Daphnia are transparent, thus allowing clear visualization of different organs, including the heart7. The organs are protected by a thin membrane that allows the penetration of different compounds; therefore assisting with heart rate monitoring in real time5. Using a microscope that has computer-aided real-time imaging capabilities, the effect of various compounds can be observed onDaphnia‘s heart in real time.Daphnia’s life span is 40–50 days, which varies in different species and also changed with environmental conditions, especially temperature. Male and femaleDaphnia can easily be differentiated, as femaleDaphnia have brood pouch that holds eggs. These eggs develop into embryos, leading to the production of juveniles that attain sexual maturity within ten days.Neurotransmitters are the key mediators of communication between nerve cells. Because of their effect on brain and spinal cord, central nervous system (CNS) agents can be used to control or treat variety of medical conditions8. Caffeine, by antagonizing adenosine A2A receptors, is known to augment dopamine signalling in the brain10. Even at routine doses, caffeine can enhance dopamine receptor accessibility in the mammalian CNS10. Caffeine has also been reported to normalize the heart rate ofDaphnia, which is decreased by atropine and atenolol11. Ethanol is known to cause progressive weakness, difficulty in walking, and lowered heart rate12. Ethanol also inhibits calcium dependent neurotransmitter release, and, excitatory and inhibitory postsynaptic potentials in cultured spinal cord neurons13.Dopamine is important for normal cardiopulmonary response to exercise and is necessary for optimal high-intensity exercise performance. Blocking dopamine receptors appears to be detrimental to exercise performanceDaphnia’s heart rate, alone and in combination of caffeine and ethanol. The rationale behind this research was that both caffeine and ethanol are known to affect nervous system functions14, and dopamine is a major neurotransmitter.The aim of the present study was to investigate the effect of Dopamine onDaphnia were isolated from Chitti Vai river of Punjab. For the isolation ofDaphnia, 0.5–2.0 litres of river water was collected and transported to laboratory. AdultDaphnia were manually identified as per the standard identification features15, and filtered out using muslin cloth. These adults were cultured in 300 ml glass jars containing river water that was filtered with muslin cloth.Daphnia culture was supplemented with 0.5% yeast culture, added every third day. Yeast culture, in this case, was used as a food forDaphnia. Algae, yeast or bacteria are preferred food forDaphnia. Although, many workers use river water forDaphnia culture presuming that it would have better mineral composition, in our case, we were also able to cultureDaphnia in aged tap water in the similar manner. Cultures were routinely monitored to ensure production of healthyDaphnia.Daphnia, real-time monitoring of changes in the heart rate ofDaphnia is required. We used a microscope equipped with computer-aided real-time imaging capability , and for each reading heart rate was initially counted without any treatment (control). Subsequently, changes in the heart rate was monitored after the addition of selected agents. EachDaphnia was placed on the glass slide with 100 ul of water. The slide was observed in real time under the microscope at 40x or 100x magnification, and heart rate was counted. To avoid the effect of temperature or other environmental factors, counting was done after five seconds of starting the microscope. Subsequently, the microscope was switched off for five seconds, cardiovascular agents were added . P<0.05 was considered significant.Daphnia’s heart has not been reported previously. We hereby report that dopamine instantly increases the heart rate ofDaphnia in a dose-dependent manner, and a significant increase (25.7%) in the heart rate was observed, even at a low dose of 0.8 mg/ml  was initially counted without any treatment (controls). Subsequently, changes in the heart rate was monitored after the addition of selected agents.Copyright: © 2018 Kundu A and Singh G2018Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).20. It is possible that these psychoactive agents can have similar or more drastic effects in humans. It is, therefore, very important to urgently investigate the effect of these psychoactive agents, alone or in combination, in humans. Such studies can provide crucial information that can be used in a variety of clinical settings. For example, cases of alcohol or caffeine intoxication can be managed by dopamine therapy, treatment(s) of cardiac disorders may be different for alcoholics or coffeeholics, and patients undergoing dopamine therapy need to be regularly monitored for cardiothoracic status, and alcohol/caffeine consumption.This fundamental investigation can be of enormous importance, as caffeine and ethanol are the most widely consumed psychoactive drugs, and dopamine is a master neurotransmitter that is known to be involved in variety of diseasesThe data referenced by this article are under copyright with the following copyright statement: Copyright: © 2018 Kundu A and Singh GData associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).Daphnia. Heart rates (beats per minute) was initially counted without any treatment (controls). Subsequently, changes in the heart rate was monitored after the addition of selected agents. DOI,10.5256/f1000research.12180.d19418921Dataset 1: Effect of dopamine, caffeine and ethanol on the heart rate of The study “Dopamine synergizes with caffeine to increase the heart rate of Daphnia” done by Aman Kundu and Gyanesh Singh, investigates the effect of dopamine, caffeine and alcohol on Daphnia’s heart rate. Also the combination of caffeine and ethanol was tested. The rationale of the paper was to use the Daphnia’s heart rate to test treatment(s) of cardiac disorders in high consumers of coffee or alcohol. The importance and objectives of the study are well explained and methods are well described, although some aspects of this manuscript should be really improved and corrected.  The statistical Analysis applied is not correct; consequently I have some doubts if the results would be the same applying a correct statistical analysis. Authors used t-paired test to evaluate a dose-dependence curve in which more than two concentrations are compared. I suggest to authors apply One-Way ANOVA followed by a post hoc test . Additionally, authors indicated that the experiments were done two times. I understand that this means that a duplicate of each experiment were performed, is it correct?. If this is the case, a mean ± SD should be used to compare data. Please, correct. Another important issue is about the synergism. Author concluded that dopamine synergizes with caffeine to increase the heart rate of Daphnia. But, synergism should be declared if a sub-threshold concentrations of DA and Caff is used. If not, only a potentiation is achieved. Please, correct the terminology of synergism or other experiments should be done using the combination of sub-threshold doses of DA and Caff. It would be very important to add positive controls to test Daphnia’s heart rate, for example, noradrenaline or atropine, both are prototypical substances that increase heart rate in vertebrate animals. In the conclusion: in addition to the purpose of this kind of assay, I wondering if Daphnia’s heart rate assay could be more suitable as a biomarker of toxicity instead of serve as a screening test of different drugs to alter Daphnia’s heart rate?I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. The original article written by Kundu and Singh focuses on the study of the effects of cardiovascular drugs of the heart rate of Daphnia. In this study the authors have used an interesting heart model of Daphnia. The article represents the synergistic effect of dopamine and caffeine to increase the heart rate in Daphnia, the tiny water fleas. Though, neither this model can be compare with mammals nor their organ function. The authors have tried to show some effects without mentioning the mechanism of effects. I think they should clarify the followings points: 1. Authors have analyzed the data with a simple t test. Why they didn’t they approach with ANOVA test?  Moreover, statistical analysis with only two observations is not sufficient. Observations should be made of at least four times for significance test. 2. In Figures, the vertical line given on top of each bar represents what? - SEM or SD? 3. Table 1 shows the lowest concentration of dopamine as 0.4mg/ml which is missing in the entire manuscript. Where is the result of 0.4 mg/ml? 4. Why did the authors choose 40µg or 120µg/ml instead of mg/ml that they have tested and represented in Figure 1. What is the reason of this sudden switch over? Nothing is clear to me! 5. In Figure 3 Why the authors have used the combination of lower concentration of caffeine (40µg/ml) with higher concentration of dopamine (1.6mg/ml) and higher concentration of caffeine (120 µg/ml) with lower concentration of dopamine (0.8mg/ml)? This needs clarification. 6. Figure 5 have the same queries like Figure 3 and it should be better in both the cases of combinations, keep one constant and vary the other one. 7. The Daphnia model does not directly resemble the mammalian system. The conclusion they have made in the manuscript requires rethinking and should be presented accordingly. 8. In the manuscript the authors didn’t mention about the treatment procedure. How have they administered the dopamine, caffeine or alcohol? What is the route of administration of these compounds? Are those administered or given in the culture medium? Depending on the route of administration for this particular model, the author should discuss about the mechanism of action of these agents on Daphnia heart rate or cardiovascular system.  Suggestions: I think for indexing following works are needed to improve the manuscript: 1. Redesign the experiments as I suggested. 2. More observations (at least 4) for each experiment are needed. 3. Proper statistical analysis is essential. Simple t test is not enough as the experiment are in combination of different agents.I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. The original article by Kundu and Singh focuses on the study the effects of cardiovascular drugs on the heart rate of Daphnia. The authors have used an interesting heart model: Daphnia. This model has some advantages in comparison with classical animal models such as rats, mice, dogs, cats, and others. This model could be interesting for researchers from undeveloped countries. The study shows the effect of dopamine, caffeine, and alcohol on Daphnia heart rate (HR), which has been studied in other animal models. In this case, it is shown that dopamine and caffeine increase HR, and alcohol reduces HR. Interestingly, dopamine restores the low HR ethanol-induced. The authors claim that it’s probably similar effects of this agents in humans, however, the Daphnia heart does not represent a direct analog of mammalian cardiac function, so the interpretation of the results of the present study in terms of mammals is problematic.It is mentioned in the introduction, that atropine and atenolol decrease HR and this is not true in humans: Atenolol, a beta blocker reduces HR, but atropine, a cholinolytic agent, increase HR, so this statement must be revised.It could be useful if the authors add the how HR was performed. In general, after reading this submission, I consider that this is a short and interesting article about a simple model which will be useful for students, young researchers interested in alternatives to study cardiovascular function. After clarifying the comments the paper can be indexed. I have two comments/questions:I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


Sci., 2016, DOI: 10.1039/c6sc00011h.Correction for ‘High yielding synthesis of 2,2′-bipyridine macrocycles, versatile intermediates in the synthesis of rotaxanes’ by J. E. M. Lewis  The support of the Leverhulme Trust (RPG-2014-084) was regrettably omitted by the authors in the published manuscript. The updated acknowledgements section is as follows:The Royal Society of Chemistry apologises for this error and any consequent inconvenience to authors and readers.We thank Fluorochem for the gift of reagents, the EPSRC National Mass Spectrometry Service for HRMS analysis and the EPSRC (EP/L016621/1), Leverhulme Trust (RPG-2014-084), Queen Mary, University of London and the University of Southampton for funding. JEML is a European Commission Marie Skłodowska-Curie Fellow. SMG is a Royal Society Research Fellow. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 660731.


Kaposi sarcoma (KS) is the most common neoplasm associated with Acquired Immune Deficiency Syndrome (AIDS), but antiretroviral therapy has reduced its incidence dramatically. Endobronchial KS is usually associated with concurrent mucocutaneous lesions and is highly vascular; so biopsy generally is not recommended. The use of advanced bronchoscopic techniques for evaluation of endobronchial KS may mitigate the bleeding risks but has not been described previously. We describe an unusual case of KS, which presented as an isolated obstructing endobronchial tumor that was effectively resected using electrocautery snare and argon plasma coagulation (APC) during bronchoscopy. Kaposi sarcoma (KS) remains the most common neoplasm associated with Acquired Immune Deficiency Syndrome (AIDS), but antiretroviral therapy has reduced its incidence dramatically. Endobronchial KS, usually associated with concurrent mucocutaneous lesions, typically appears as slightly raised, sub-mucosal, violaceous lesions in the bronchial wall. Given the vascularity of these lesions, a biopsy is not recommended; however, the use of argon plasma coagulation (APC) or electrocautery may mitigate these risks, making it safer to biopsy and/or ablate the KS lesion. We describe an unusual case of KS, which presented as an isolated obstructing endobronchial tumor that was resected using electrocautery snare and APC during bronchoscopy, followed by cryotherapy ablation of the residual lesion.A 40-year-old Caucasian male, a non-smoker, was referred for evaluation of an endobronchial lesion diagnosed on thoracic imaging done for workup of four weeks of progressive cough, wheezing, and dyspnea. Past medical history was significant for allergic rhinitis and previously undisclosed Human Immunodeficiency Virus (HIV) for which he had not sought medical attention. Physical examination demonstrated bronchial breath sounds in the right mid-lung zone and no abnormal findings on the skin or oral mucosa. A CT of the thorax revealed a polypoid endobronchial tumor in the distal right mainstem bronchus extending into the bronchus intermedius (BI) without associated parenchymal abnormalities Figure . BronchoMild bleeding was well-controlled using APC. Cytologic examination revealed spindle-cell proliferation with mild cytologic atypia Figure . ImmunohTwo days later, a repeat bronchoscopy was performed due to newly reported fever and abnormal CT imaging Figure . InspectEndobronchial lesions associated with both endemic and immunosuppression-related KS are well-documented. The vast majority of them appear as flat-to-slightly-raised violaceous lesions, often located near minor carinae . DiffereThis case is unique both in its unusual presentation and its use of therapeutic bronchoscopic techniques not previously described for the treatment of endobronchial KS. Despite the unknown nature of the tumor at the initial presentation, its polypoid nature made it amenable to snare electrocautery resection. Its wide pedicle, suggesting endobronchial invasion, necessitated cryotherapy and subsequent APC to achieve hemostasis and to destroy residual malignant tissue. We chose electrocautery and APC because of its ease, good safety profile, the similar risk of iatrogenic endoluminal damage between electrocautery and Nd:YAG laser , and equKaposi sarcoma presenting as a localized, obstructing airway mass without concurrent mucocutaneous disease is extremely rare but should be considered in the differential diagnosis in patients with known immunocompromised state. While tumor manipulation risks bleeding, advanced endoscopic techniques in the hands of trained operators allow for safe and effective intervention. This article was originally published as an abstract: Papali A, Sachdeva A, Pickering E, Shah N: Electrocautery Snare Resection and Argon Plasma Coagulation of Endobronchial Kaposi Sarcoma Presenting as an Obstructing Tumor. Chest 2014, 146:7773A. 10.1378/chest.1993118


As a proof of principle, the controlled synthesis of the PAAC from l-arginine and N,N′-methylenebisacrylamide was performed up to a monodisperse product with 11 monomeric units and molecular weight 1840. This synthetic procedure was also tested with l-alanine. All intermediates were isolated and characterized. Noticeably, all of them were α,ω-difunctionalized with either acrylamides or sec-amines and were, in fact, building blocks with potential for preparing complex macromolecular architectures. In a first instance, copolymers with controlled sequences of amidoamine- and amidoamino acid units were prepared.Polyamidoamino acids (PAACs) are synthetic polymers prepared by the polyaddition of bisacrylamides with natural α-amino acids, which in the process maintain both their chirality and their amphoteric nature. This polymerization process is slow, but has the merits of taking place in water and of neither involving protection/de-protection steps nor releasing by-products. However, it leads to polydisperse polymers and, using α-amino acids mixtures, random copolymers. This paper presents a step-by-step polyaddition process leading to homo- and copolymeric PAACs with controlled sequences and controlled molecular weights. It exploits the much different rates of the two Michael addition steps of NH N-acryloyl- or N-methacryloyl α-aminoacids, are in fact polyacrylamides or polymethacrylamide-bearing carboxylated chiral substituents on the nitrogen  was prepared as [MArM-Pip]n by substituting MArMArM  for MArM. The reaction proceeded for 17 days; yield 37%. wM = 5270; w/MnM = 1.09. The 1H and 13C APT NMR spectra are reported in l-valine with hydroxymethyl-vinyl ketone, which prevailingly yields the monoadduct n) and 4500 ([MArMArM-Pip]n) were in good agreement with the SEC results. Therefore, besides having a controlled structure, these copolymers had narrow molecular weight distributions, approaching monodispersity. A possible explanation is that in these alternating PAAC-PAA copolymers the oligomeric PAAC blocks had a much higher molecular weight  than piperazine (86), and therefore on a weight-to-weight basis they constituted the by far prevailing portion . The polymerization degrees and number of molecular species of [MArM-Pip]n and [MArMArM-Pip]n present in samples of molecular weight of a few thousands was necessarily modest compared with that of a usual PAA or PAAC of similar molecular weight. During ultrafiltration, to be retained by- or to pass through the membrane was probably a matter of one or two building block units. For all these reasons, the fractionation proceeded through sharp molecular weight “jumps” and significantly narrowed polydispersity.[MArM-Pip]sec-amine groups. Therefore, they actually constitute macromonomers that can be used as building blocks to prepare PAAC–PAA copolymers in which the different units are regularly sequenced along the polymer chain. Both types of copolymers after a single ultrafiltration step are almost monodisperse, therefore, the use of intermediate oligomers as building blocks may constitute a facile short cut to PAAC-PAA copolymers with controlled sequences and with narrow polydispersity. As a final conclusion, the synthetic process devised has a wide potential for a new category of synthetic polymers with controlled sequence of monomer units and controlled molecular weight, prepared using natural α-amino acids or their stereoisomers as monomers.The results reported in this paper demonstrate that the controlled synthesis of linear PAACs both in terms of unit sequences and molecular weight is feasible. The step-by-step process devised is slow but has the advantages of simplicity and absence of secondary by-products. Moreover, all intermediates obtained in each step are alternatively α, ω-terminated by either acrylamide double bonds or