Ordered Membrane Electrode Assembly with Drastically Enhanced Proton and Mass Transport for Proton Exchange Membrane Water Electrolysis.

In this work, an ordered membrane electrode assembly (MEA) based on a cone Nafion array with gradient Nafion distribution, tightly bonded catalytic layer/proton exchange membrane (CL/PEM) interface, and abundant vertical channels has been engineered by an anodic aluminum oxide template and magnetron sputtering method. Benefiting from a highly efficient CL/PEM interface, plentiful proton transfer highways, and rapid oxygen bubble release, this ordered MEA achieves an ultralow Ir loading of 20.0 µg cm-2 and a high electrochemical active area by 8.7 times compared to traditional MEA with Ir loading of 1.0 mg cm-2. It yields a mass activity of 168 000 mA mgIr-1 cm-2 at 2.0 V, which is superior to most reported PEM electrolyzers. Notably, this ordered MEA maintains excellent durability at a current density of 500 mA cm-2. This work opens a simple, cost-effective, and scalable route to design ordered MEAs for proton exchange membrane water electrolysis.

Multiscale Architectured Nafion Membrane Derived from Lotus Leaf for Fuel Cell Applications.

Hierarchically patterned proton-exchange membranes (PEMs) have the potential to significantly increase the specific surface area, thus improving the catalyst utilization rate and performance of proton-exchange membrane fuel cells (PEMFCs). In this study, we are inspired by the unique hierarchical structure of the lotus leaf and proposed a simple three-step strategy to prepare a multiscale structured PEM. Using the multilevel structure of the natural lotus leaf as the original template, and after structural imprinting, hot-pressing, and plasma-etching steps, we successfully constructed a multiscale structured PEM with a microscale pillar-like structure and a nanoscale needle-like structure. When applied in a fuel cell, the multiscale structured PEM resulted in a 1.96-fold increase in discharge performance and a significant improvement in mass transfer compared to the membrane electrode assembly (MEA) with a flat PEM. The multiscale structured PEM has the combined advantage of a nanoscale and a microscale structure, benefiting from the markedly reduced thickness, increased surface area, and improved water management inherited from the multiscale structured lotus leaf's superhydrophobic characteristic. Using a lotus leaf as a multilevel structure template avoids the complex and time-consuming preparation process required by commonly used multilevel structure templates. Moreover, the remarkable architecture of biological materials can inspire novel and innovative applications in many fields through nature's wisdom.

A New Integrated GDL with Wavy Channel and Tunneled Rib for High Power Density PEMFC at Low Back Pressure and Wide Humidity.

Proton exchange membrane fuel cells (PEMFCs) have garnered significant attention due to their high efficiency and low emissions. However, PEMFC always suffers mass transfer and water management in performance improvement. Herein, an integrated gas diffusion layer (GDL) with wavy channel and micro-tunneled rib is designed and prepared to achieve faster and gentler mass transfer and excellent water management capability by laser engraving. Outstandingly, the new integrated GDL can use the back pressure of air as low as 0 and 50 kPa to respectively achieve 80% and 90% of fuel cell performance realized under pure oxygen. Such high performance is mainly due to the turbulent flow caused by wavy channel and express removing pathway of liquid water provided by micro-tunneled rib. Moreover, the new integrated GDL also shows wide humidity tolerance from 40% to 100% and a very high specific volume power density of 16,300 W L-1 due to the thin thickness of new integrated GDL. This new integrated GDL is expected to be widely used in PEMFC and other energy conversion devices.

Integrated Gas Diffusion Electrode with High Conductivity Obtained by Skin Electroplating for High Specific Power Density Fuel Cell.

Smaller volume/weight and higher output power/energy density are always the goals of electrochemistry energy devices. Here, a simple strategy is proposed to prepare an integrated gas diffusion electrode (GDE) with high conductivity through skin electroplating. The skin electroplating is the combination of magnetron sputtering and spatial confinement electroplating. The electroplated metal obtained by skin electroplating is uniformly, continuously, and tightly attached to the surface of carbon paper like a layer of skin. Uniform and continuous electroplating metal layer endows the integrated electrode excellent conductivity with the square resistance as low as 27 mΩ sq-1 . In application, the self-breathing fuel cell with 1 cm2 active area can harvest ultrahigh volume specific power density (20.9 kW L-1 ). Additionally, the weight of the fuel cell stack (23 W) with the integrated electrode is only 20 g, which is only 7% of the commercial stack with the same power. The mass specific power density reaches 1150 W kg-1 , which is 15 times of the commercial stack. Outstandingly, the stack can charge 4 mobile phones at the same time. More importantly, the skin electroplating provides an effective strategy to improve the specific power density of other energy devices including Zn-air batteries, Li-air batteries, and so on.

Nanosized Proton Conductor Array with High Specific Surface Area Improves Fuel Cell Performance at Low Pt Loading.

The use of ordered catalyst layers, based on micro-/nanostructured arrays such as the ordered Nafion array, has demonstrated great potential in reducing catalyst loading and improving fuel cell performance. However, the size (diameter) of the basic unit of the most existing ordered Nafion arrays, such as Nafion pillar or cone, is typically limited to micron or submicron sizes. Such small sizes only provide a limited number of proton transfer channels and a small specific area for catalyst loading. In this work, the ordered Nafion array with a pillar diameter of only 40 nm (D40) was successfully prepared through optimization of the Nafion solvent, thermal annealing temperature, and stripping mode from the anode alumina oxide (AAO) template. The density of D40 is 2.7 × 1010 pillars/cm2, providing an abundance of proton transfer channels. Additionally, D40 has a specific area of up to 51.5 cm2/cm2, which offers a large area for catalyst loading. This, in turn, results in the interface between the catalyst layer and gas diffusion layer becoming closer. Consequently, the peak power densities of the fuel cells are 1.47 (array as anode) and 1.29 W/cm2 (array as cathode), which are 3.3 and 2.9 times of that without array, respectively. The catalyst loading is significantly reduced to 17.6 (array as anode) and 61.0 µg/cm2 (array as cathode). Thus, the nanosized Nafion array has been proven to have high fuel cell performance with low Pt catalyst loading. Moreover, this study also provides guidance for the design of a catalyst layer for water electrolysis and electrosynthesis.

A Recyclable Standalone Microporous Layer with Interpenetrating Network for Sustainable Fuel Cells.

The commercialization of fuel cells inevitably brings recycling problems. Therefore, achieving high recyclability of fuel cells is particularly important for their sustainable development. In this work, a recyclable standalone microporous layer (standalone MPL) with interpenetrating network that can significantly enhance the recyclability and sustainability of fuel cells is prepared. The interpenetrating network enables the standalone MPL to have high strength (17.7 MPa), gas permeability (1.55 × 10-13  m2 ), and fuel-cell performance (peak power density 1.35 W cm-2 ), providing the basic guarantee for its application in high-performance and highly recyclable fuel cells. Additionally, the standalone MPL is highly adaptable to various gas-diffusion backings (GDBs), providing high possibility to select highly recyclable GDBs. Outstandingly, anode standalone MPLs and GDBs can be easily detached from the spent membrane electrode assembly (MEA). This not only saves >90 vol% solvent in the recovery of the catalyst-coated membrane (CCM), but also extends the service life of the GDBs and the anode standalone MPL at least 138 times (2 760 000 h assuming 20 000 h of CCM) comparing to CCM. Therefore, the standalone MPL significantly enhances the recyclability and sustainability of fuel cells and is promising to be an indispensable component in the next-generation fuel cells.

Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies.

BACKGROUND: Pulmonary fibrosis (PF) is a devastating disease characterized by remodeling of lung architecture and abnormal deposition of fibroblasts in parenchymal tissue and ultimately results in respiratory failure and death. Preclinical studies suggest that mesenchymal stem cell (MSC) administration may be a safe and promising option in treating PF. The objective of our meta-analysis is to assess the efficacy of MSC therapy in preclinical models of PF. METHODS: We performed a comprehensive literature search in PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to March 17, 2021. Studies that assessed the efficacy of MSC therapy to animals with PF were included. The SYRCLE bias risk tool was employed to evaluate the bias of included studies. The primary outcomes included survival rate and pulmonary fibrosis scores. Meta-analysis was conducted via Cochrane Collaboration Review Manager (version 5.4) and Stata 14.0 statistical software. RESULTS: A total of 1120 articles were reviewed, of which 24 articles met inclusion criteria. Of these, 12 studies evaluated the survival rate and 20 studies evaluated pulmonary fibrosis scores. Compared to the control group, MSC therapy was associated with an improvement in survival rate (odds ratios (OR) 3.10, 95% confidence interval (CI) 2.06 to 4.67, P < 0.001, I2 = 0%) and a significant reduction in pulmonary fibrosis scores (weighted mean difference (WMD) 2.05, 95% CI -2.58 to -1.51, P < 0.001, I2 = 90%). CONCLUSIONS: MSC therapy is a safe and effective method that can significantly improve the survival and pulmonary fibrosis of PF animals. These results provide an important basis for future translational clinical studies.

Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 1: SAR of the aryl region.

A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin dependant kinase. Inhibitory activities against the enzyme ranged from 34nM to >20microM and were dependant upon both the nature of the aryl group and the hydrogen bond donating potential of the maleimide ring. Key interactions with the kinase ATP site and hinge region were found to be consistent with homology modeling predictions.

Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 2: SAR of the amine tether.

A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin-dependant kinase. Inhibitory activities against the enzyme ranged from 34nM to >20microM and were dependant upon both the nature of the aryl group and the tether joining the basic amine to the indolyl maleimide core. Key interactions with the kinase ATP site and hinge region, predicted by homology modeling, were confirmed.

Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 3: Importance of the indole orientation.

A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin dependant kinase. Inhibitory activities against the enzyme ranged from 10nM to >20microM and were dependant upon both the nature of the aryl group and the tether joining the basic amine to the indolyl maleimide core of the inhibitors. Key interactions with the kinase ATP site and hinge region, predicted by homology modeling, were confirmed.

Pyrimidine-based inhibitors of CaMKIIdelta.

Non-ATP competitive pyrimidine-based inhibitors of CaMKIIdelta were identified. Computational studies were enlisted to predict the probable mode of binding. The results of the computational studies led to the design of ATP competitive inhibitors with optimized hinge interactions. Inhibitors of this class possessed improved enzyme and cellular activity compared to early leads.

Tra2β Enhances Cell Proliferation by Inducing the Expression of Transcription Factor SP1 in Cervical Cancer / 生物医学与环境科学（英文）

OBJECTIVE@#In this study, the role and potential mechanism of transformer 2β (Tra2β) in cervical cancer were explored.@*METHODS@#The transcriptional data of Tra2β in patients with cervical cancer from Gene Expression Profiling Interactive Analysis (GEPIA) and cBioPortal databases were investigated. The functions of Tra2β were evaluated by using Western blot, MTT, colony formation, Transwell assays, and nude mouse tumor formation experiments. Target genes regulated by Tra2β were studied by RNA-seq. Subsequently, representative genes were selected for RT-qPCR, confocal immunofluorescence, Western blot, and rescue experiments to verify their regulatory relationship.@*RESULTS@#The dysregulation of Tra2β in cervical cancer samples was observed. Tra2β overexpression in Siha and Hela cells enhanced cell viability and proliferation, whereas Tra2β knockdown showed the opposite effect. Alteration of Tra2β expression did not affect cell migration and invasion. Furthermore, tumor xenograft models verified that Tra2β promoted cervical cancer growth. Mechanically, Tra2β positively regulated the mRNA and protein level of SP1, which was critical for the proliferative capability of Tra2β.@*CONCLUSION@#This study demonstrated the important role of the Tra2β/SP1 axis in the progression of cervical cancer in vitro and in vivo, which provides a comprehensive understanding of the pathogenesis of cervical cancer.

Characteristics and clinical significance of mitochondrial injury of T lymphocyte subsets in patients with autoimmune hepatitis / 中国医师进修杂志

Objective:To study the characteristics and clinical significance of mitochondrial injury of T lymphocyte subsets in patients with autoimmune hepatitis (AIH).Methods:The clinical data of 57 patients with AIH (AIH group) from June to December 2021 in Hangzhou Xixi Hospital were retrospectively analyzed, while 60 healthy physical examiners were included as healthy group. The peripheral blood T lymphocyte subsets (CD 8+ T lymphocyte count and CD 4+ T lymphocyte count) were detected by flow cytometry, and matched mitochondrial staining value according to certain algorithm was used to determine the mitochondrial damage of helper T lymphocyte (Th cell) and suppressor T lymphocyte (Ts cell). The levels of IgG, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using a Roche E170 automatic electrochemiluminescence immunoassay. Anti-nuclear antibody (ANA) titer was measured by immunofluorescence. Multivariate Logistic regression was used to analyze the independent risk factors of mitochondrial damage of Th cell and Ts cell in patients with AIH. Results:The ALT, AST, IgG, positive rate of ANA titer, CD 4+ T lymphocyte count, CD 8+ T lymphocyte count, rate of Th cell mitochondrial injury and rate of Ts cell mitochondrial injury in AIH group were significantly higher than those in healthy group: (118.90 ± 37.61) U/L vs. (30.96 ± 14.37) U/L, (102.40 ± 36.51) U/L vs. (31.12 ± 14.06) U/L, (18.40 ± 3.71) g/L vs. (13.89 ± 1.98) g/L, 96.49% (55/57) vs. 16.67% (10/60), 438 (323, 637) × 10 6/L vs. 398 (272, 469) × 10 6/L, 296 (211, 296) × 10 6/L vs. 270 (193, 322) × 10 6/L, 61.40% (35/57) vs. 8.33% (5/60) and 82.46% (47/57) vs. 11.67% (7/60), and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that the AST elevated and CD 8+ T lymphocyte count reduced were the independent risk factors of Ts cell mitochondrial injury in patients with AIH ( OR = 1.06 and 0.99, 95% CI 1.01 to 1.10 and 0.99 to 1.00, P<0.05); the ALT elevated and IgG elevated were the independent risk factors of Th cell mitochondrial injury in patients with AIH ( OR = 1.08 and 1.66, 95% CI 1.02 to 1.14 and 1.11 to 2.48, P<0.05). Conclusions:It is of positive clinical significance to measure the T lymphocyte subtype mitochondrial injury in patients with AIH. The probability of mitochondrial injury of T lymphocyte subtype can be predicted by biochemical indexes such as ALT, AST and IgG, so as to indirectly evaluate the liver cell necrosis.

Advances in new microfluidic chips for enrichment and detection of circulating tumor cells / 中华检验医学杂志

Due to the characteristics such as high capture, high recovery and precise control with fluid, the microfluidic chip has attracted much attention in the research field of circulating tumor cells (CTCs). The developed microfluidic system mainly included three types based on the captured principles such as biological affinity tag microfluidic chip, free label microfluidic chip and rely on biological affinity with the physical properties of integrated microfluidic chip.

Ezrin Promotes the Proliferation, Migration, and Invasion of Ovarian Cancer Cells / 生物医学与环境科学（英文）

Objective@#The underlying mechanism of Ezrin in ovarian cancer (OVCA) is far from being understood. Therefore, this study aimed to assess the role of Ezrin in OVCA cells (SKOV3 and CaOV3) and investigate the associated molecular mechanisms.@*Methods@#We performed Western blotting, reverse transcription-quantitative polymerase chain reaction, MTT, cell colony, cell wound healing, transwell migration and invasion, RhoA and Rac active pull down assays, and confocal immunofluorescence experiments to evaluate the functions and molecular mechanisms of Ezrin overexpression or knockdown in the proliferation and metastasis of OVCA cells.@*Results@#The ectopic expression of Ezrin significantly increased cell proliferation, invasiveness, and epithelial-mesenchymal transition (EMT) in OVCA cells. By contrast, the knockdown of endogenous Ezrin prevented OVCA cell proliferation, invasiveness, and EMT. Lastly, we observed that Ezrin can positively regulate the active forms of RhoA rather than Rac-1 in OVCA cells, thereby promoting robust stress fiber formation.@*Conclusion@#Our results indicated that Ezrin regulates OVCA cell proliferation and invasiveness by modulating EMT and induces actin stress fiber formation by regulating Rho-GTPase activity, which provides novel insights into the treatment of the OVCA.

Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin K.

We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.

Evaluation of the consistency and detection capability of seven domestic 2019-nCoV nucleic acid detection kits / 中华检验医学杂志

Objective:To compare the consistency and detection capability of seven 2019-nCoV nucleic acid detection kits, and provide reference for detection method selection of clinical laboratory and diagnosis of new coronavirus pneumonia.Methods:Two batches of pharyngeal swab samples were collected from tenpatients with confirmed infection of 2019-nCoV and 10 suspected patients with negative 2019-nCoV test results during January 29 to February 5, 2020 in Shenzhen Luohu People′s Hospital. Seven kinds of kits were labeled as ato g and used for nucleic acid detection respectively to evaluate the consistency of the test results of the clinical samples. A 2019-nCoV positive specimen was selected and diluted to 5-concentration gradient plates (Level-1 to 5) with RNase-free water. The positive detection rate and intra-batch repeatability of different brands of kits were compared.Results:The negative and positive coincidence rates of twenty clinical samples tested by six kinds of kits were 100%, and the positive and negative coincidence rate was 8/10 and 10/10 for the other kit, respectively. The results of intra-batch repeatability showed the CVs of viral loads tested by these seven kits were all less than 5%. In the concentration range of Level-1 to 3, the detection capability for open reading frame (ORF)1ab gene of Kit b,d and f was lower than Kit a,c,e and g, and the detection capability of kit e and g was the highest (14/15). The detection capability for N gene of Kit a (15/15) was higher than the other 5 kits. The comprehensive analysis of the detection capability for ORF1ab and N gene showedthat Kit d had the lowest detection capability (ORF1ab:40%,N:53%), and there was no significant difference in the detection capability of Kit a, b, c, e, and f.Conclusions:There was no significant difference in the accuracy and repeatability of the seven kits for positive samples with high viral loads, and the detection performance was good; but some kits had poor detection capability for weak positive samples. It is suggested that the weak positive samples should be rechecked by at least two manufacturers′ kits to ensure the accuracy of the results.

The effect of membrane protein NMHC ⅡA on invasion and metastasis of bladder cancer cells / 国际检验医学杂志

Objective Non-muscle myosin heavy chain ⅡA (NMHC ⅡA ) plays a significant role in tumor progression and metastasis .Our prior study showed that the expression of NMHC ⅡA was much higher in human bladder cancer sample than that in adjacent tissue .The increased level of NM HC ⅡA expression was correlated with worse prognosis .However ,the role of NMHC ⅡA is unknown in the invasion and metastasis of bladder cancer .Methods RT-PCR and western blotting were used to examine NMHC ⅡA expression lev-els in normal bladder epithelial cells and bladder cancer cell lines .T he migration and invasion ability of cells was tested by wound healing assay and Transwell invasion assay ,respectively .Results Our study showed that knockdown of NMHC ⅡA inhibited migration and invasion in bladder cancer cell line .Conclusion The study indicated that NM HC ⅡA expression increased the invasion and metastasis ability of bladder cancer cell line in vitro .

Study on fingerprint of Saxifraga stolonifera herbs and determination of five components by HPLC / 中草药

Objective To establish a method to research the fingerprint and determine the ingredients of Saxifraga stolonifera by HPLC, which aimed at providing reference for the quality control of Saxifraga stolonifera. Methods Agilent Eclipse XDB-C18 (150 mm × 4.6 mm, 5 μm) column was used as the stationary phase, and the mobile phase consisted of acetonitrile (A)-0.1% phosphoric acid with gradient elution at the flow rate of 1.0 mL/min. The detection wavelength was 254 nm, and the column temperature was maintained at 35 ℃. The result would be analyzed by SOP of Similarity evaluation system for chromatographic fingerprint of TCM. Results The results obtained by the method of fingerprint analysis are good. In the fingerprints, 11 peaks were selected as the common peaks to evaluate the similarities among 21 batches of S. stolonifera collected from different regions, and five contents of them were indentified as protocatechuic acid, gallic acid, bergenin, quercetin-5-O-β-D-glucoside, and quercitrin. The similarities between standard herb and each determined herb showed a lot of differences from others. The determination method showed that there weregood linear relationships of five figured contents in the range of 0.052 8-0.844 8, 0.020 96-0.335 36, 0.241 6-3.865 6, 0.130 8-2.092 8, and 0.023 68-0.378 88 μg. Moreover, the recoveries rates of five figured contents are 96.64%, 100.72%, 96.62%, 103.71%, 96.75%,and all RSDs were lower than 2%. The contents of 5 components in the gathered herbs were determined by external standard method in the range of 0.07-0.40, 0.19-4.36, 1.42-5.98, 0.42-6.86, and 0.11-1.51 mg/g. Conclusion The method established in this study is simple, reliable and durable, which can provide a scientific basis for the quality control of S. stolonifera.

Factors related to use of emergency medical services in patients with acute stroke / 中华急诊医学杂志

Objective To examine the availability of emergency medical services(EMS) for patients with acute stroke and to investigate influential factors affecting the preference of patients'to EMS.Methods Consecutive information of patients with acute stroke who presented to the emergency department of Zhongnan Hospital of Wuhan University from June 1, 2014 to December 31, 2015 were analyzed.Gender, age of patients, transport modality, risk factors in cerebrovascular diseases, initial symptoms, stroke types, onset and admission time were included to make analysis in retrospective study.The participants were divided into two groups based on the preference of patients, namely EMS group and self-transport group.Wilcoxon rank sum test or Chi-squared test was used to statistical analysis as appropriate.A multiple binary logistic regression was used to determine the relationship between various patient-related factors with probability whether patients chose EMS or not.Results Among the 240 patients, only 29.2%of them asked for the EMS at the onset of symptoms (EMS group, n=70), and the rest patients called for other services(self-transport group, n=170).Logistic regression analysis revealed that the patients with the symptom of altered consciousness or convulsion (95%CI:0.107-0.403,OR=0.208,P<0.01) were more likely to use EMS.The time consumed from onset to visit of patients with acute stroke to emergency physician was significantly shorter in EMS group (M, 60 min vs.180 min,P<0.01).Conclusion The symptom of altered consciousness or convulsion was the independent factor to determine whether patients with acute stroke preferred EMS or not.