Fundamental Study on Alkali-Activated Slag System with Sodium Carbonate or Calcium Hydroxide

Cement as a building material, has high fluidity, compressive strength, and durability, but carbon dioxide emissions during cement production are a major problem. As one of the countermeasures, alkali-activated cement using blast furnace slag powder with alkaline stimulants is considered to be a very promising solution for reducing carbon dioxide emissions, but there is a lack of information about the fundamental properties of alkali-activated materials. This study presents an experimental investigation of the fundamental properties of an alkali-activated slag system with sodium carbonate (NC) and calcium hydroxide (CH). The effects of calcium sulfo-aluminate (CSA) and shrinkage reducing agent (SRA) on the properties of blast furnace slag (BFS) based alkali-activated mixture were also investigated. In the experiments, fundamental characteristics including compressive strength, drying shrinkage, and water penetration tests of mortar were evaluated. Porosity, pH, and ignition loss were measured to verify the effectiveness of the materials. The experimental investigation revealed that the compressive strength was increased with the increasing replacement rates of NC in the BFS mortar, and in the case of water to BFS ratio of 0.45 with sodium carbonation addition contents 10 wt.%, the compressive strength for 28 days of curing reaches more than 50 MPa. Low water to BFS ratio and higher addition ratio of NC had a positive effect on the compressive strength development of mortar. Incorporating NC into BFS would affect the decrease in porosity and increase in ignition loss, leading to higher compressive strength. There was a negligible change to the compressive strength, porosity, pH, and ignition loss of BFS samples made with CH, thus, the addition rates of CH to BFS have no or little significant effect on the fundamental properties of alkali-activated cement. From the results of drying shrinkage and water penetration tests, the addition of NC and CH only to BFS exhibited poor drying shrinkage and water penetration characteristics. However, these problems may be overcome due to the use of CSA or SRA in the alkali-activated system made with NC or CH.

Microfluidic field strategy for enhancement and scale up of liquid-liquid homogeneous chemical processes by optimization of 3D spiral baffle structure

Due to the scale effect, the uniform distribution of reagents in continuous flow reactor becomes bad when the channel is enlarged to tens of millimeters. Microfluidic field strategy was proposed to produce high mixing efficiency in large-scale channel. A 3D spiral baffle structure(3SBS) was designed and optimized to form microfluidic field disturbed by continuous secondary flow in millimeter scale Y-shaped tube mixer(YSTM). Enhancement effect of the 3SBS in liquid-liquid homogeneous chemical processes was verified and evaluated through the combination of simulation and experiment. Compared with 1 mm YSTM, 10 mm YSTM with 3SBS increased the treatment capacity by 100 times, shortened the basic complete mixing time by 0.85 times, which proves the potential of microfluidic field strategy in enhancement and scale-up of liquid-liquid homogeneous chemical process.

事件–状态语义学:一个关于英语时体时态句的形式语义

英语中与时间相关的表达不仅有时态,还有时体,二者是英语时间表达的两个维度,共同形成了多种时体时态句。时态逻辑、区间语义学、RK理论给出了部分时态句的形式语义解释。如何理解时体维度,给出时体时态句的全面解释,是自然语言的形式语义研究的待解之题。对此事件–状态语义学放弃了时态逻辑的绝对时间框架,构建了以事件和状态为基本要素的相对时间框架。在此框架下,部分时体时态句得到了形式刻画。这一结果显示了事件–状态语义学对于英语时体时态句理解的合理性和处理潜力。其他部分的形式语义刻画将在现有工作的基础上通过进一步增加新的要素加以解决。

Effects of Wuling Powder Mediating Notch Pathway on Mice with Nephrotic Syndrome

[Objectives]This study was conducted to investigate the renal protective effects of Wuling Powder on mice with nephrotic syndrome(NS)based on Notch pathway.[Methods]Sixty KM mice were randomly divided into normal group,model group,prednisone acetate positive group,high-dose Wuling Powder group,medium-dose Wuling Power group and low-dose Wuling Power group,with 10 mice in each group.Three days after prophylactic administration,a comprehensive nephropathy model was prepared by injecting 1 mg/ml doxorubicin hydrochloride solution(7.5 mg/kg)into the tail vein.After successful modeling,prednisone acetate and Wuling SAN were given high,medium and low doses for intervention for 28 d,respectively.After that,urinary protein and creatinine contents of mice in each group were detected,and pathological damage of renal tissue was observed by HE and Masson staining.The mRNA levels of Notch1,Jagged1 and Hes1 in mouse kidney tissues were detected by RT-PCR,and the expression levels of Notch1,Jagged1 and Hes1 proteins were detected by Western blot.[Results]Wuling Powder could effectively reduce the contents of urine protein(P<0.01)and Scr(P<0.01)in NS mice,and alleviate the pathological injury of kidney.Compared with the model group,the prednisone acetate group and various Wuling Powder groups could down-regulate the expressions of Notch1,Jagged1 and Hes1 mRNA in the kidney tissue of mice(P<0.01),and the expression of Notch1 protein in the renal tissue of mice decreased(P<0.01).The contents of Hes1 in the prednisone acetate group and the high-and medium-dose Wuling Powder groups significantly decreased(P<0.05).[Conclusions]Wuling Powder could protect the kidneys in mice with NS through Notch pathway.

Effects of Panax notoginseng saponins in a rat model of Alzheimer's disease

BACKGROUND： Modem pharmacological studies have demonstrated that Panax notoginseng saponins （PNS） can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and behavior of rats with Alzheimer＇s disease （AD） remains unclear. OBJECTIVE： Based on a Morris water maze test, this study aimed to measure improvements of spatial learning and memory by PNS in a rat model of AD, and to compare effects with huperzine A. DESIGN： A completely randomized grouping design, controlled animal experiment. SETTING： Center of Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University. MATERIALS： Ninety healthy Wistar rats of both genders, 15-month-old （n =75） and 3-month-old rats as young controls （n =15）, were used for this study. The study was performed in accordance with animal ethics guidelines for the use and care of animals. PNS was provided by Weihe Pharmaceutical Co., Ltd （permission No. Z53021485, Yuxi, Yunan Province, China）. Morris water maze equipment was provided by the Institute of Physiology, Chinese Academy of Science. METHODS： This study was performed at the Center of Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University from June 2003 to April 2005. Of the included rats, 15 healthy aged rats were randomly chosen as aged controls, and the remaining 60 aged rats were randomly divided into 4 groups with 15 rats in each： model group, PNS high- and low-dose groups, and an huperzine A group. Rats in the model group and the 3 treated groups were treated with intraperitoneal infusion of 9.6 g/L D-galactose （5 mL/kg） every day for 6 weeks successively to induce a subacute aging model. During week 7, animals received 1 μ L ibotenic acid （5 g/L） bilaterally into the nucleus basalis of Meynert to create a rat model of AD. The young and old rat controls received, in parallel, a corresponding volume of saline. Two weeks later, rats in the PNS high- and low-dose groups were gavaged with 200 and 100 mg/kg PNS suspension, respectively. Huperzine A suspension （0.3 mg/kg） was used in the huperzine A group. Rats in the other 3 groups were gavaged with a corresponding volume of normal saline. In each group, administration was carried out once per day for 4 consecutive weeks. MAIN OUTCOME MEASURES： After administration, learning and memory abilities were measured by place navigation and spatial probe tests. Recording indices consisted of escape latency （time-to-platform）, number of times to find the platform within 2 minutes, number of times the animal crosses the original platform location, and the percent of swimming time in each quadrant. RESULTS： Several rats died due to inflammatory reactions following brain lesion or intragastric administration; therefore, 61 rats were included in the final analysis. Results of spatial navigation test： Escape latency of rats in the model group was significantly prolonged, and number of times to find the platform within 2 minutes were significantly reduced compared with other groups （both P 〈 0.05）. No significant differences in these two indices were measured among the administration groups （all P 〉 0.05）. Results of spatial probe test： Times for crossing the original platform location and percent of time spent in the quadrant of original platform location were significantly less in the model group than in the other groups （P 〈 0.05）. There were no significant differences in these two indices among the administration groups （P 〉 0.05）. CONCLUSION： PNS can remarkably improve spatial learning and memory abilities of rats with AD. The therapeutic effect of PNS is not dose-dependent and is equivalent to the effect of huperzine A.

Effects of dissolved oxygen and nutrients from the Kuroshio on hypoxia off the Changjiang River estuary

The intrusion of the Kuroshio into the East China Sea(ECS)aff ects the development of hypoxia off the Changjiang(Yangtze)River estuary;however,quantitative analysis of its impacts is lacking.In this study,the Regional Ocean Modeling Systems(ROMS)model coupled with the Carbon,Silicate and Nitrogen Ecosystem(CoSiNE)model was used to investigate the relative importance of dissolved oxygen(DO)and diff erent nutrients(silicate,nitrate,and phosphate)in the Kuroshio on hypoxia in the ECS.Results show that changes in DO concentrations in the Kuroshio modify the distribution and intensity of hypoxia through direct onshore transport by hydrodynamic processes.An increase in Kuroshio DO concentration by 25%or 50%would result in a decrease of the maximum hypoxia extent(MHE)in the ECS by 76%or 86%,respectively,while a 25%decrease in Kuroshio DO would increase the MHE by up to 219%.The contribution of DO in the Taiwan Strait is almost negligible.In contrast to Kuroshio DO,nutrients aff ect hypoxia in the ECS through onshore transport by hydrodynamic and biochemical processes.Changes in phosphate and nitrate concentrations by 25%in the Kuroshio would change the MHE by up to 30%and 18%,respectively,accompanied by apparent changes in surface chlorophyll-a concentrations.The eff ect of silicate on hypoxia is negligible because a 25%change in silicate concentrations in the Kuroshio would result in less than 1%change in the MHE.Our results reveal a hierarchical rank of importance for environmental variables in the Kuroshio(i.e.,DO>phosphate>nitrate>silicate)in modifying the development of hypoxia in the ECS.

Observations on a magnetotactic bacteria-grazing ciliate in sediment from the intertidal zone of Huiquan Bay,China

Magnetotactic bacteria(MTB)are a group of prokaryotes having the ability to orient and swim along geomagnetic field lines because they contain intracellular magnetosomes that are synthesized through a biomineralization process.Magnetosomes have recently also been found in unicellular eukaryotes,which are referred to as magnetically responsive protists(MRPs).The magnetosomes have three origins in MRPs.In this study,we characterized a MTB-grazing ciliated MRP that was magnetically collected from intertidal sediment of Huiquan Bay,Qingdao,China.Based on 18S rRNA gene sequence analysis,the ciliated MRP was tentatively identified as Uronemella parafi lificum HQ.Using transmission electron microscopy,we observed that magnetosomes having 2-3 shapes were randomly distributed within this ciliate.Energydispersive X-ray spectroscopy and high-resolution transmission electron microscopy images of the magnetosomes were consistent with them being composed of magnetite.Magnetosomes having the same shape and mineral composition were also detected in MTB that occurred in the same environment as the ciliated MRP.Statistical analysis showed that the size and shape of the magnetosomes in the ciliated MRP were similar to those in MTB.The results suggest that this ciliated MRP can graze,ingest,and digest various types of MTB.It is certainly worth noting that this is the first record of MRPs in Asian aquatic sediment and suggesting they might be widely distributed.These results also support the assertion that MRPs probably contribute to the ecological cycles of iron,and expand possibilities for research into the mechanism of magnetoreception in eukaryotes.

Characterization and diversity of magnetotactic bacteria from sediments of Caroline Seamount in the Western Pacific Ocean

Magnetotactic bacteria(MTB)are a group of microorganisms capable of orientating and swimming along magnetic fields because they contain intracellular biomineralized magnetosomes composed of magnetite(Fe 3 O 4)or/and greigite(Fe_(3)S_(4)).They are ubiquitous in freshwater,brackish,and marine habitats,and are cosmopolitan in distribution.However,knowledge of their occurrence and distribution in seamount ecosystems is limited.We investigated the diversity and distribution of MTB in the Caroline Seamount(CM4).The abundance of living MTB in 12 stations in depth varying from 90 to 1545 m was 1.1×10^(3)-43.7×10^(3) inds./dm 3.Despite diverse shapes of MTB observed,magnetotactic cocci were the dominant morphotype and could be categorized into two types:1)typical cocci that appeared to have peritrichous fl agella;and 2)those characterized by having a drop-shaped form and one bundle of fl agella located at the thin/narrow end of the cell.Transmission electron microscopy(TEM)analysis revealed that the magnetosomes formed by those magnetotactic cocci are magnetite(Fe 3 O 4)with octahedral crystal habit.A total of 41 operational taxonomic units(OTUs)of putative MTB(2702 reads)were acquired from nine stations,based on high-throughput sequencing.Of these,40 OTUs belonged to the Proteobacteria phylum and one belonged to the Nitrospirae phylum.We found apparent connectivity between the MTB populations on the Caroline and Kexue(Science in Chinese)seamounts,although the diversity of MTB on Caroline was much richer than on the Kexue Seamount.Our results imply that the unique topography of seamounts and other as-yet unclear environmental factors could lead to evolution of different fl agella arrangements in magnetotactic cocci,and the occurrence of octahedral magnetite magnetosomes.

Genomic analysis of a pure culture of magnetotactic bacterium Terasakiella sp.SH-1

Magnetotactic bacteria(MTB)display magnetotaxis ability because of biomineralization of intracellular nanometer-sized,membrane-bound organelles termed magnetosomes.Despite having been discovered more than half a century,only a few representatives of MTB have been isolated and cultured in the laboratory.In this study,we report the genomic characterization of a novel marine magnetotactic spirillum strain SH-1 belonging to the genus Terasakiella that was recently isolated.A gene encoding haloalkane dehalogenase,which is involved in the degradation of chlorocyclohexane,chlorobenzene,chloroalkane,and chloroalkene,was identified.SH-1 genome contained cysCHI and soxBAZYX genes,thus potentially capable of assimilatory sulfate reduction to H_(2)S and using thiosulfate as electron donors and oxidizing it to sulfate.Genome of SH-1 also contained genes encoding periplasmic dissimilatory nitrate reductases(napAB),assimilatory nitrate reductase(nasA)and assimilatory nitrite reductases(nasB),suggesting that it is capable of gaining energy by converting nitrate to ammonia.The pure culture of Terasakiella sp.SH-1 together with its genomic results off ers new opportunities to examine biology,physiology,and biomineralization mechanisms of MTB.

Distribution characteristics of wave energy in the Zhe-Min coastal area

A 10-year(2003–2012)hindcast was conducted to study the wave field in the Zhe-Min coastal area(Key Area OE-W2)located off Zhejiang and Fujian provinces of China.Forced by the wind field from a weather research and forecasting model(WRF),high-resolution wave modelling using the SWAN was carried out in the study area.The simulated wave fields show a good agreement with observations.Using the simulation results,we conducted statistical analysis of wave power density in terms of spatial distribution and temporal variation.The effective duration of wave energy in the sea area was discussed,and the stability of wave energy was evaluated using the coefficient of variation of wave power density.Results indicate that the wave energy resource in the study area was about 4.11×10^(6) kW.The distribution of wave energy tends to increase from the north(off Zhejiang coast)to the south(off Fujian coast),and from near-shore area to the open sea.The sea areas with wave power density greater than 2 kW/m are mostly distributed seaward of the 10-m isobath,and the contours of the wave power density are almost parallel to the shoreline.The sea areas around the islands that are far from the mainland are rich in wave energy,usually more than 6 kW/m,and therefore are of obvious advantages in planning wave energy development and utilization.The effective duration of wave energy in the offshore area shows an increasing trend from north(off Zhejiang coast)to south(off Fujian coast),with values of∼3500 h in the north and∼4450 h in the south.The coefficient of variation of wave energy in this region is mostly in the range of 1.5–3.0,and gradually decreases from the north to the south,suggesting that the wave energy in the south is more stable than that in the north.

A Rapid, Non-invasive Method for Anatomical Observations of Tadpole Vertebrae in Vivo

The tadpole is a critical stage in the amphibian life cycle and plays an important role during the transition from the aquatic to the terrestrial stage. However, there is a large gap in tadpole research, which represents a vital component of our understanding of the diversity and complexity of the life history traits of amphibians, especially their developmental biology. Some aspects of this gap are due to limited research approaches. To date, X-ray microcomputed tomography （micro-CT） has been widely used to conduct osteology research in adult amphibians and reptiles, but little is known about whether this tool can be applied in tadpole studies. Thus, we compared the results of two methods （the bone-cartilage double-staining technique and micro-CT） to study vertebrae in tadpole specimens. The results revealed no significant difference between the two methods in determining the number of vertebrae, and micro-CT represents a rapid, non-invasive, reliable method of studying tadpole vertebrae. When scanning tadpoles, voltage is the most critical of the scanning parameters （voltage, current and scan time）, and moderate scanning parameters are recommended. In addition, micro-CT performed better using specimens stored in 70% ethanol than those preserved in 10% formalin. Finally, we suggest that micro-CT should be more widely applied in herpetological research to increase specimen utilization.

The Approach of Major Players in Retail in Expanding Their Operations into Developing Markets-Taking Walmart as an Example

This research investigates the expansion behavior of international(giant)retailers,with a specific focus on the determinants of the entry mode choice in emerging markets based on the performance of Walmart in its venture into less developed markets.This research investigates the approach in which major players in retail are expanding their operations into other developing markets,specifically focusing on how the entry mode decisions of giant retailers moderate the risks and difficulties in making business in emerging countries.The objective of this study is to analyze and evaluate the potential causes and antecedents of large merchants's entry mode(EM)choices by assessing Walmart's business performance in less advanced nations in recent years.

近红外荧光手术导航探针的研究进展

近红外荧光(near-infrared fluorescence, NIRF)成像技术已被证明是外科手术中定位肿瘤部位、识别肿瘤边界以及区分肿瘤细胞和正常组织的有效方法.开发高质量的NIRF探针对于肿瘤的完全减灭至关重要.然而,传统荧光探针在癌组织和健康组织中都能产生荧光信号并且无癌症靶向性,这导致了相对较高的背景信号和较差的特异性.近年来,人们通过纳米修饰、偶联肿瘤靶向配体以及生物标志物激活等方式,逐渐开发出了更具临床转化价值的荧光探针.此外,近红外二区(NIR-Ⅱ)荧光探针也逐渐成为研究热点.本文聚焦在荧光手术导航用荧光探针的结构与性能上,同时对被动靶向型、主动靶向型、可激活型荧光探针以及NIR-II荧光探针进行了全面阐述,分析其面临的挑战,探讨可能的解决思路,以期推动近红外荧光手术导航技术的临床应用.

LncRNA NKILA inhibits HBV replication by repressing NF-κB signalling activation

Hepatitis B virus(HBV)infection results in liver cirrhosis and hepatocellular carcinoma(HCC).HBx/nuclear factor(NF)-κB pathway plays a role in HBV replication.However,whether NF-κB-interacting long noncoding RNA(NKILA),a suppressor of NF-κB activation,regulates HBV replication remains largely unknown.In this study,gain-and-loss experiments showed that NKILA inhibited HBV replication by inhibiting NF-κB activity.In turn,HBV infection down-regulated NKILA expression.In addition,expression levels of NKILA were lower in the peripheral blood-derived monocytes(PBMCs)of HBV-positive patients than in healthy individuals,which were correlated with HBV viral loads.And a negative correlation between NKILA expression level and HBV viral loads was observed in blood serum from HBV-positive patients.Lower levels of endogenous NKILA were also observed in HepG2 cells expressing a 1.3-fold HBV genome,HBV-infected HepG2-NTCP cells,stable HBV-producing HepG2.2.15 and HepAD38 cells,compared to those HBV-negative cells.Furthermore,HBx was required for NKILA-mediated inhibition on HBV replication.NKILA decreased HBx-induced NF-κB activation by interrupting the interaction between HBx and p65,whereas NKILA mutants lack of essential domains for NF-κB inhibition,lost the ability to inhibit HBV replication.Together,our data demonstrate that NKILA may serve as a suppressor of HBV replication via NF-κB signalling.

Enhancement of catalytic activity for hydrogenation of nitroaromatic by anionic metal-organic framework

Nitroaromatic hydrogenation catalysis without precious metals remains a longstanding challenge.The rate of electron transfer is the crucial factor affecting hydrogenation catalysis.Herein,an ionic Cd-based metal-organic framework(I-Cd-MOF)exhibiting a unique structure with one-dimensional(1D)opening nanochannels and good electron transfer ability was synthesized for catalyzing hydrogenation of 4-nitrophenol(4-NP).The catalytic activity of the unique I-Cd-MOF without noble metals is detected,which is higher than most reported noble metal catalysts.Remarkably,the reaction rate of I-Cd-MOF(4.28 min^(-1))is about 47.6 times higher than that of the Cd-based neutral MOF(N-Cd-MOF)with the similar crystalline structure.Liquid chromatograph mass spectrometer(LC-MS)and theoretical results demonstrate that 4-NP and five intermediates are stabilized in the channels of I-Cd-MOF,which increases the possibility of contact with H^*and H_(2)g enerated at the Cd sites.The I-Cd-MOF was extended to other nitroaromatic hydrogenation catalysis,which still displays excellent activity.More importantly,the I-MOF@Filter membrane was successfully constructed for continuous hydrogenation catalytic reactions,which maintains a high catalytic performance after 7 cycles of recycling without washing.This work fills in the application of the I-MOFs in hydrogenation catalytic reactions and provides an effective way for the rapid and green degradation of nitroaromatic compounds.

Bright/dark switchable mode-locked fiber laser based on alcohol

A passively switchable erbium-doped fiber laser based on alcohol as the saturable absorber(SA)has been demonstrated.The SA is prepared by filling the gap between two optical patch cords with alcohol to form a sandwich structure.The modulation depth of the alcohol-SA is measured to be 6.4%.By appropriately adjusting the pump power and the polarization state in the cavity,three kinds of mode-locked pulse patterns can be achieved and switched,including bright pulse,bright/dark soliton pair,and dark pulse.These different soliton emissions all operate at the fundamental frequency state,with a repetition rate of 20.05 MHz and a central wavelength of~1563 nm.To the best of our knowledge,this is the first demonstration of a switchable soliton fiber laser using alcohol as the SA.The experimental results further indicate that organic liquid-like alcohol has great potential for constructing ultrafast lasers.

内皮粘蛋白抗体与肾移植术后抗体介导排斥反应和移植肾预后的研究

目的:探讨肾移植前内皮粘蛋白(EMCN)抗体与抗体介导排斥反应(ABMR)以及移植物预后的相关性。方法:选择2021~2022年在山西省第二人民医院进行移植肾穿刺活检诊断为ABMR或高度怀疑为ABMR的受者作为病例组,以2022年行肾移植且移植肾功能稳定的受者作为对照组。最终病例组纳入18例受者,对照组纳入37例受者;另有9例受者移植肾穿刺活检诊断为非ABMR,纳入移植物预后分析。比较两组移植前EMCN抗体水平差异,利用受试者工作特征(ROC)曲线确定移植前EMCN抗体预测术后ABMR的最佳截断值,分析移植前EMCN抗体对移植肾存活和功能恶化的影响,通过单因素和多因素Cox比例风险模型分析ABMR发生的危险因素。结果:病例组和对照组受者移植前EMCN抗体检测校正值分别为(0.87±0.64)和(0.41±0.31),差异有统计学意义(t=2.85,P<0.05)。移植前EMCN抗体水平对ABMR发生具有预测作用,ROC曲线下面积为0.7679(95%CI 0.64~0.90,P<0.05)。根据约登指数(0.41)确定截断值为0.4276,敏感度为70.59%,特异度为70.27%。移植前EMCN阳性受者和EMCN阴性受者移植肾存活率无统计学意义差异(P>0.05),EMCN阳性受者经移植肾穿刺活检确诊或高度怀疑ABMR的比例高于EMCN阴性受者(41.4%和14.3%),移植肾功能恶化比例亦高于EMCN阴性受者(48.3%和11.4%)(P均<0.05)。肾移植前EMCN抗体水平和HLA-DSA是术后发生ABMR的独立危险因素(HR=5.50和5.56,95%CI 1.89~16.06和1.08~28.63),供肾冷缺血时间越短ABMR风险越低(HR=0.41,95%CI 0.25~0.70)。结论:肾移植前EMCN抗体水平与术后ABMR和移植物功能恶化相关,对ABMR有预测作用,是ABMR发生的独立危险因素。

Improving tensile-shear properties of friction stir lap welded dissimilar Al/Mg joints by eliminating hook defect and controlling interfacial reaction

To improve tensile-shear properties of fiction stir lap welded(FSLW) dissimilar Al/Mg joints, pin-tip profiles were innovatively designed and welding speed was optimized, and effects of them on formation, interface microstructure and mechanical properties of different FSLW joints were investigated. With increasing the welding speed, the tensile-shear load of FSLW joints produced by three pins presents an increasing firstly and then decreasing trend. Compared with Rpin, the hook and hole defect in the joints made by S-pin and T-pin are eliminated owing to additional eccentric force. Moreover, the joints obtained by T-pin at 75 mm/min have the highest tensile-shear load, and a maximum value of 3.425 kN is produced, which increases by 96.8%.Meanwhile, the pin-tip profile improves significantly the interface reaction depending on the welding temperature. For R-pin, thick brittle intermetallic compounds of about 6.9 μm Al3Mg2and 13.3 μm Al12Mg17layers at the welding interface derived from diffusion reaction are formed, resulting in continuous cracks. However, using T-pin can raise the interface temperature, and which makes the interface liquefy locally to generate only 2.2 μm Al3Mg2layer and dispersive(Al12-Mg17+Mg) eutectic structure. This can release high residual stress and remove welding crack, consequently enhancing the interface properties of T-pin joints.

Efficacy and Safety of Sofosbuvir-based Regimens in Hepatitis C Patients With Decompensated Cirrhosis:A Systematic Review and Meta-analysis

Background and Aims:Decompensated cirrhotic patients with hepatitis C(HCV)are often under-represented in clinical trials.We aimed to evaluate pooled data on the efficacy and safety of sofosbuvir(SOF)-based regimens in these patients.Methods:We conducted a systemic review and meta-analysis by searching multiple databases for studies published from October 2010 to October 2020.Outcomes of interest were sustained virologic response(SVR)and safety of SOFbased regimens in decompensated HCV patients.Two reviewers independently performed the study selection and data extraction.Results:We included 33 studies that enrolled 5,302 HCV patients.The pooled SVR rate in decompensated patients with SOF-based regimens was 85.1%(95%CI:82.8–87.3).Patients on SOF/velpatasvir±ribavirin achieved a significantly higher SVR(91.0%,95%CI:87.7–93.9)than that of SOF/ledipasvir±ribavirin[(86.3%,95%CI:84.6–87.8);p=0.004],or on SOF/daclatasvir±ribavirin(82.4%,95%CI:78.2–86.2%;p<0.001).Adding ribavirin to SOFbased regimens(pooled SVR 84.9%,95%CI:81.7–87.9)did not significantly increase the SVR[83.8%(95%CI:76.8–89.8%;p=0.76)]in decompensated patients,which was also true in subgroup analyses for each regimen within the same treatment duration.However,adding ribavirin significantly increased the frequency of adverse events from 52.9%(95%CI:28.0–77.1)to 89.2%(95%CI:68.1–99.9)and frequency of severe events.The pooled incidence of hepatocellular carcinoma and case-fatality of decompensated patients were 3.1%(95%CI:1.5–5.0)and 4.6%(95%CI:3.1–6.3),respectively.The overall heterogeneity was high.There was no publication bias.Conclusions:The analysis found that 12 weeks of SOF/velpatasvir without ribavirin is the preferred therapy,with a significantly higher SVR compared with other SOF-based regimens in decompensated HCV patients.

The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a severe global health crisis;its structural protein envelope(E)is critical for viral entry,budding,production,and induction of pathology which makes it a potential target for therapeutics against COVID-19.Here,we find that the E3 ligase RNF5 interacts with and catalyzes ubiquitination of E on the 63rd lysine,leading to its degradation by the ubiquitin-proteasome system(UPS).Importantly,RNF5-induced degradation of E inhibits SARS-CoV-2 replication and the RNF5 pharmacological activator Analog-1 alleviates disease development in a mouse infection model.We also found that RNF5 is distinctively expressed in different age groups and in patients displaying different disease severity,which may be exploited as a prognostic marker for COVID-19.Furthermore,RNF5 recognized the E protein from various SARS-CoV-2 strains and SARS-CoV,suggesting that targeting RNF5 is a broad-spectrum antiviral strategy.Our findings provide novel insights into the role of UPS in antagonizing SARS-CoV-2 replication,which opens new avenues for therapeutic intervention to combat the COVID-19 pandemic.