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Mulberry leaves are a well-known traditional Chinese medicine herb, and it has been observed since ancient times that leaves collected after frost have superior medicinal properties. Therefore, understanding the changes in critical metabolic components of mulberry leaves, specifically Morus nigra L., is essential. In this study, we conducted widely targeted metabolic profiling analyses on two types of mulberry leaves, including Morus nigra L. and Morus alba L., harvested at different times. In total, we detected over 100 compounds. After frost, 51 and 58 significantly different metabolites were identified in the leaves of Morus nigra L. and Morus alba L., respectively. Further analysis revealed a significant difference in the effect of defrosting on the accumulation of metabolites in the two mulberries. Specifically, in Morus nigra L., the content of 1-deoxynojirimycin (1-DNJ) in leaves decreased after frost, while flavonoids peaked after the second frost. In Morus alba L., the content of DNJ increased after frost, reaching its peak one day after the second frost, whereas flavonoids primarily peaked one week before frost. In addition, an analysis of the influence of picking time on metabolite accumulation in two types of mulberry leaves demonstrated that leaves collected in the morning contained higher levels of DNJ alkaloids and flavonoids. These findings provide scientific guidance for determining the optimal harvesting time for mulberry leaves.

Predicting the properties of materials prior to their synthesis is of great significance in materials science. Optical materials exhibit a large number of interesting properties that make them useful in a wide range of applications, including optical glasses, optical fibers, and laser optics. In all of these applications, refraction and its chromatic dispersion can directly reflect the characteristics of the transmitted light and determine the practical utility of the material. We demonstrate the feasibility of reconstructing chromatic-dispersion relations of well-known optical materials by aggregating data over a large number of independent sources, which are contained within a material database of experimentally determined refractive indices and wavelength values. We also employ this database to develop a machine-learning platform that can predict refractive indices of compounds without needing to know the structure or other properties of a material of interest. We present a web-based application that enables users to build their customized machine-learning models; this will help the scientific community to conduct further research into the discovery of optical materials.

To meet the anti-interference and multi-function requirements of the antenna, a compact 8-states frequency reconfigurable ultra-wideband (UWB) monopole antenna is proposed. The antenna consists of a coplanar waveguide structure (CPW), defected ground structure (DGS), rectangular radiation patch, and stepped feed line. Band rejections at the C band, WLAN, and X band are generated by two C-slots and inverted U-slot, respectively. Three PIN diodes are connected across the C-slots and inverted U-slot. By controlling the on/off state of PIN diodes to realize notch reconfiguration. The antenna size is only 22 mm $\times 13$ mm $\times0.8$ mm. The measured results show that the antenna can work in 8 states. The impedance bandwidth of UWB mode is 2.82-13.25 GHz, the relative bandwidth is 129.8%. The notch band is 3.19-4.58 GHz, 5.26-6.21 GHz, and 7.87-8.73 GHz, respectively. The antenna has stable gain, good omnidirectional radiation performance, and can switch freely between UWB mode and each notch band mode.

This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators.Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

The ability to auto-generate databases of optical properties holds great potential for advancing optical research, especially with regards to the data-driven discovery of optical materials. An optical property database of refractive indices and dielectric constants is presented, which comprises a total of 49,076 refractive index and 60,804 dielectric constant data records on 11,054 unique chemicals. The database was auto-generated using the state-of-the-art natural language processing software, ChemDataExtractor, using a corpus of 388,461 scientific papers. The data repository offers a representative overview of the information on linear optical properties that resides in scientific papers from the past 30 years. Public availability of these data will enable a quick search for the optical property of certain materials. The large size of this repository will accelerate data-driven research on the design and prediction of optical materials and their properties. To the best of our knowledge, this is the first auto-generated database of optical properties from a large number of scientific papers. We provide a web interface to aid the use of our database.

Purpose: This study aimed to use proteomics methods to investigate the changes in serum protein levels after high- and low-flux hemodialysis (HD). Methods: Before and after HD, serum samples were obtained from two selected patients who were treated with a Polyflux 140 H high-flux dialyzer and a Polyflux 14 L low-flux dialyzer during two continuous therapy sessions. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to identify the proteins. Results: A total of 212 and 203 serum proteins were identified after high-flux and low-flux HD, respectively. After high-flux HD, 21 proteins increased, and 132 proteins decreased. After low-flux HD, 87 proteins increased, and 45 proteins decreased. High-flux HD led to a significantly greater reduction in protein levels than low-flux HD (0.73 ± 0.13 vs. 0.84 ± 0.18, p = .00). Among the increased and decreased proteins, the isoelectric point (pI) values mainly ranged from 5 to 7, and the molecular weights (Mws) were mostly smaller than 30 kDa. The serum proteins showed no difference in pI or Mw for high- and low-flux HD. Gene ontology (GO) analysis showed that the detected proteins were related to immune system processes and complement activation. Conclusions: Serum protein levels differentially changed after high- and low-flux HD. Long-term effects should be observed in future studies.

The complications of hemodialysis accompanied the hemodialysis and threaten the patients life. Besides the loss of nutrient substance, such as amino acid and vitamin, we found new clues that the adsorbed proteins on common-used polysulfone-based dialysis membrane might be the reason according to the qualitative proteomic study by ionic liquid assisted sample preparation method. Our results indicated that the adsorbed proteins on the membrane were related with complement activation, blood coagulation, and leukocyte-related biological process. The quantitative proteome further demonstrated some significant changes of signal proteins in the post-dialysis plasma after the hemodialysis, such as beta-2-microglobulin and platelet factor-4, which would further verify these new clues.

We recently reported the identification and characterization of a novel small chemical molecule designated FL118. FL118 selectively inhibits multiple cancer survival and proliferation-associated antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and eliminates small and large human tumor xenografts in animal models (Ling et al., PLoS One 2012, 7, e45571). Here, we report a follow-up study on the structure-activity relationship (SAR) of the hydroxyl group in the lactone ring of FL118. We found that the superior antitumor efficacy of FL118 heavily depends on its steric configuration through comparing the antitumor activity of FL118 with FL113 (the racemic mixture of FL118). Consistently, FL118 proved much more effective in inhibiting the expression of survivin, Mcl-1, and cIAP2, both in vitro and in vivo, compared to FL113. Additionally, Tet-on controlled induction of survivin or forced expression of Mcl-1 protects cancer cells from FL118-mediated growth inhibition and cell death. To further explore the SAR, we synthesized seven position 20-esterifiable FL118 and FL113 derivatives. Studies on these seven new compounds revealed that keeping a free hydroxyl group of FL118 is also important for high antitumor efficacy. Together, these studies confirm the superior anticancer activity of FL118 and narrow the window for further SAR studies to generate novel analogues based on FL118 core structure on its other potential chemical positions.

High-performance unipolar n-type polymer semiconductors are critical for advancing the field of organic electronics, which relies on the design and synthesis of new electron-deficient building blocks with good solubilizing capability, favorable geometry, and optimized electrical properties. Herein, two novel imide-functionalized thiazoles, 5,5'-bithiazole-4,4'-dicarboxyimide (BTzI) and 2,2'-bithiazolothienyl-4,4',10,10'-tetracarboxydiimide (DTzTI), are successfully synthesized. Single crystal analysis and physicochemical study reveal that DTzTI is an excellent building block for constructing all-acceptor homopolymers, and the resulting polymer poly(2,2'-bithiazolothienyl-4,4',10,10'-tetracarboxydiimide) (PDTzTI) exhibits unipolar n-type transport with a remarkable electron mobility (μe ) of 1.61 cm2 V-1 s-1 , low off-currents (Ioff ) of 10-10 -10-11 A, and substantial current on/off ratios (Ion /Ioff ) of 107 -108 in organic thin-film transistors. The all-acceptor homopolymer shows distinctive advantages over prevailing n-type donor-acceptor copolymers, which suffer from ambipolar transport with high Ioff s > 10-8 A and small Ion /Ioff s < 105 . The results demonstrate that the all-acceptor approach is superior to the donor-acceptor one, which results in unipolar electron transport with more ideal transistor performance characteristics.

Tissue kallikrein, generally existing in living bodies as prokallikrein, is a serine proteinase that has proven of great significance to treat hypertension, cardiopathy and nephropathy. Although the extraction of tissue kallikrein from human urine is the most commonly used method to obtain such a protein, not only the yield is very little, but also the procedure is rather complex. Furthermore, the biological safety is uncertain. Therefore, the preparation of such a protein by genetic engineering method, including gene expression, cell culture, separation and purification, is very important. In this paper, a new method to obtain purified tissue prokallikrein excreted from insect cells by liquid chromatography has been proposed. In contrast to the previously published papers, the purification procedure is simplified to only three steps with the final yield of 57% and the purity of 95%, which is not only convenient, but also low-cost and suitable for the large-scale preparation of such a protein. The purified protein is further validated as prokallikrein by high performance liquid chromatography-mass spectrometry and amino acid sequencing.

Hemodialysis is one of the most important therapies for patients with uremia, and the dialysis membrane is the predominant factor that impacts the efficiency of dialysis. Here, a protein adsorption on two different membranes is investigated to provide a basis for improving dialysis materials. Two cases treated with the Polyflux 14L low-flux dialyzer and the Polyflux 140H high-flux dialyzers during two continuous therapies are selected. Four used dialyzers from selected patients are infused with C12Im-Cl to elute the adsorbed proteins. Then labeled digested proteins adsorb by Polyflux 140H and Polyflux 14L with 13 CD2 O and NaCNBD3 (light labeling, L) and CD2 O and NaCNBH3 (heavy labeling, H), respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to identify the proteins. According to the ratio (Light labeling/Heavy labeling), the eluted proteins are divided into three groups: significantly higher, significantly lower, and no significant differences with a ratio of >2, 2), 320 proteins are retained more by the Polyflux 14L membrane (ratio

Tangential flow affinity membrane cartridge (TFAMC) fs a new model of immunoadsorption therapy for hemoperfusion. Recombinant Protein A was immobilized on the membrane cartridge through Schiff base formation for extracorporeal IgG and immune complex removal from blood. Flow characteristics, immunoadsorption capacity and biocompatibility of protein A TFAMC were studied. The results showed that the pressure drop increased with the increasing flow rate of water, plasma and blood, demonstrating reliable strength of membrane at high now rare. The adsorption capacities of protein A TFAMC for IgG from human plasma and blood were measured. The cartridge with 139 mg protein A immobilized on the matrix (6 mg protein A/g dry matrix) adsorbed 553 mg IgG (23.8 mg IgG/g dry matrix) from human plasma and 499.4 mg IgG (21.5 mg IgG/g dry matrix) from human blood, respectively. The circulation time had a major influence on IgG adsorption capacity, but the flow rate had little influence. Experiments in vitro and in vivo confirmed that protein A TFAMC mainly adsorbed Ige and Little of other plasma proteins, and that blood cell damage was negligible. The extracorporeal circulation system is safe and reliable. Copyright (C) 1999 John Wiley & Sons, Ltd.