静电纺树枝状聚偏氟乙烯纳米纤维膜的制备

通过向聚偏氟乙烯(PVDF)纺丝液中添加有机支化盐四丁基六氟磷酸铵(TBAHP),采用一步静电纺丝法制备了PVDF树枝状纳米纤维膜。探讨了TBAHP添加量、静电纺丝工艺参数及溶剂体积比对纤维树枝状形貌的影响,同时研究了TBAHP添加量对纤维膜力学性能、孔径和孔隙率的影响。结果表明,TBAHP摩尔浓度为0.05 mol/L、N,N-二甲基甲酰胺(DMF)与丙酮(ACE)体积比为7:3、电压为27 kV、接收距离为12 cm时,制备的纳米纤维膜分支纤维较多,呈现形貌良好的树枝状结构,其断裂强度达4.93 MPa,远大于纯PVDF纳米纤维膜的1.82 MPa,孔径仅0.2μm,孔隙率达90%,在过滤、油水分离、电化学及膜蒸馏等领域具有很好的应用前景。

Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies

Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles(PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxelfatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cistrans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.

Effect of a compound starter cultures inoculation on bacterial profile and biogenic amine accumulation in Chinese Sichuan sausages

Effects of a starter culture composed of Lactobacillus sakei,Pediococcus pentosaceus,Staphylococcus xylosus and S.carnosus at the ratios(m/m)of 1:1:1:1 on bacterial profile and biogenic amine accumulation in Chinese Sichuan sausages were demonstrated.In starter culture-inoculated sausages,Lactobacillus spp.,Pediococcus spp.and Staphylococcus spp.were predominant bacterial genus and their relative abundances ranged from 70.14%to 25.98%,57.66%to 14.08%,and 15.71%to 13.40%during fermentation,respectively.Accordingly,Lactobacillus spp.and Weissella spp.were predominant bacterial genus and their relative abundances ranged from 63.14%to 24.70%and 49.40%to 11.96%during spontaneous fermentation,respectively.Furthermore,the abundances of undesirable microorganisms such as Yersinia spp.,Enterobacter spp.,Acietobacter spp.and Psychrobacter spp.were lower than that of the control.The levels of histamine,putrescine,tyramine and cadaverine in Chinese Sichuan sausages with starter cultures inoculation were significantly lower(P<0.05)than that of the control,and were decreased by 83.09%,69.38%,51.87%and 57.20%,respectively,at the end of the ripening.These results revealed that the starter cultures inoculation was a better alternative for microbial quality improvement and biogenic amine reduction of Chinese Sichuan sausages with good sensory attributes.

Hopf Bifurcations in a Predator-Prey System of Population Allelopathy with Discrete Delay

A delayed Lotka-Volterra two-species predator-prey system of population allelopathy with discrete delay is considered. By linearizing the system at the positive equilibrium and analyzing the associated characteristic equation, the asymptotic stability of the positive equilibrium is investigated and Hopf bifurcations are demonstrated. Furthermore, the direction of Hopf bifurcation and the stability of the bifurcating periodic solutions are determined by the normal form theory and the center manifold theorem for functional differential equations (FDEs). Finally, some numerical simulations are carried out for illustrating the theoretical results.

Purification and Characterization of Hyaluronate Lyases Produced by Two Types of Bacteria

Hyaluronate lyases were obtained from two types of naturally isolated bacterial strains Paenibacillus yunnanensis and Paennarthrobacter nicotinovorans.PyHL(form P.yunnanensis)in the culture supernatant of the bacteria was purified by two steps of column chromatography.The enzyme showed the molecular mass of 74 kDa by SDS-PAGE and the maximal activity at pH 5.0,35℃.PyHL maximally degraded hyaluronate by an endo-type manner,and showed low degradation activity toward chondroitin sulfates.Dermatan sulfate was not the substrate.PnHL(from P.nicotinovorans)in the culture supernatant of the bacteria was purified by two steps of column chromatography.The enzyme showed the molecular mass of 70 kDa by SDS-PAGE and the maximal activity at pH 6.0,30℃.Genomic analysis of P.nicotinovorans on the bases of the internal amino acid sequences of PnHL.

Thoughts on Cultivation of Top-notch Innovative Talents of Food Subject in Local Universities

The cultivation of top-notch innovative talents is one of the most prominent tasks in China s universities in the new era,and also an opportunity and challenge for local universities.Taking the food subject of local universities as an example,some suggestions were put forward from the aspects of security measures,teacher team construction,talent selection and management,and talent cultivation,in order to provide reference for the exploration and practice of cultivating top-notch innovative talents in the food subject of local universities.

DNA methylation drives a new path in gastric cancer early detection:Current impact and prospects

Gastric cancer(GC)is one of the most common and deadly cancers worldwide.Early detection offers the best chance for curative treatment and reducing its mortality.However,the optimal population-based early screening for GC remains unmet.Aberrant DNA methylation occurs in the early stage of GC,exhibiting cancer-specific genetic and epigenetic changes,and can be detected in the media such as blood,gastric juice,and feces,constituting a valuable biomarker for cancer early detection.Furthermore,DNA methylation is a stable epigenetic alteration,and many innovative methods have been developed to quantify it rapidly and accurately.Nonetheless,large-scale clinical validation of DNA methylation serving as tumor biomarkers is still lacking,precluding their implementation in clinical practice.In conclusion,after a critical analysis of the recent existing literature,we summarized the evolving roles of DNA methylation during GC occurrence,expounded the newly discovered noninvasive DNA methylation biomarkers for early detection of GC,and discussed its challenges and prospects in clinical applications.

Boosting CAR-T cell therapy with CRISPR technology

Chimeric antigen receptor(CAR)-T cell therapy has made remarkable breakthroughs in treating cancers,especially hematologic malignancies,yet its broader application in cancer treatment is hindered by multiple challenges.Meanwhile,the development of clustered regularly interspaced short palindromic repeats(CRISPR)and its derived technologies has provided unprecedentedly efficient tools for genomic and cellular reprogramming,offering potential advantages for developing CAR-T cell therapy.There is hence a rapidly increasing interest in applying CRISPR to engineer CART cells.Here,we present a review of recent research utilizing CRISPR to boost CAR-T cell therapy by enhancing its safety or effectiveness.We first provide an overview of CAR-T cell therapy and CRISPR technology,followed by discussions on how CRISPR and its related technologies can be adopted to tackle various issues associated with CAR-T cell therapy,either via knockout/knockin of specific genes or CRISPR-based screening.We also summarize clinical trials involving CRISPR-edited CAR-T cells.Lastly,we address the potential risks of applying CRISPR in CAR-T cell engineering.

口腔鳞癌细胞系HLAI类分子异常表达及其机制探讨

为探讨两个口腔鳞癌细胞系 (KB和Tca81 1 3)中HLAI类抗原的表达水平及其异常的分子机制。利用流式细胞术、Westernblot检测细胞系中HLAI类抗原在蛋白水平的表达 ;RT PCR检测细胞系在转录水平的表达。结果两个口腔鳞癌细胞系中HLAI类抗原蛋白水平的表达下调 ;RT PCR结果显示Tca81 1 3细胞系中A、B、C、LMP2、LMP7、LMP1 0基因的mRNA表达下调 ;在KB细胞系中除了A、B、C、LMP7、LMP1 0基因的mRNA表达下调 ,LMP2、PA2 8α基因的mRNA表达显著减少或缺失 ;而TAP1、TAP2、Tapasin基因在mRNA水平的表达无改变。IFN γ诱导后纠正了多个基因在mRNA水平的异常表达。两个口腔鳞癌细胞系中HLAI类抗原表达下调 。

The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1- and Pgc-1α-mediated regulation of Glut2

Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly downregulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover,β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions.

The First High-quality Reference Genome of Sika Deer Provides Insights into High-tannin Adaptation

Sika deer are known to prefer oak leaves,which are rich in tannins and toxic to most mammals;however,the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear.In identifying the mechanism responsible for the tolerance of a highly toxic diet,we have made a major advancement by explaining the genome of sika deer.We generated the first high-quality,chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments.Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food,especially the expansion of the UGT family 2 subfamily B of UGT genes.The first chromosome-level assembly and genetic characterization of the tolerance to a highly toxic diet suggest that the sika deer genome may serve as an essential resource for understanding evolutionary events and tannin adaptation.Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis

The recent outbreak of COVID-19 has been rapidly spreading on a global scale.To date,there is no specific vaccine against the causative virus,SARS-CoV-2,nor is there an effective medicine for treating COVID-19,thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19.By extracting and analyzing all available published clinical data,we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19.Specifically,preexisting chronic conditions such as hypertension,cardiovascular disease,chronic kidney disease,and diabetes are strongly associated with an increased risk of developing severe COVID-19;surprisingly,however,we found no correlation between chronic liver disease and increased disease severity.In addition,we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality.Given the high risk of comorbidity and the high mortality rate associated with tissue damage,organ function should be monitored closely in patients diagnosed with COVID-19,and this approach should be included when establishing new guidelines for managing these high-risk patients.Moreover,additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe,potentially fatal complications,and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease.Taken together,these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.

YAP regulates the liver size during the fasting-refeeding transition in mice

Liver is the central hub regulating energy metabolism during feeding-fasting transition.Evidence suggests that fasting and refeeding induce dynamic changes in liver size,but the underlying mechanisms remain unclear.Yes-associated protein(YAP)is a key regulator of organ size.This study aims to explore the role of YAP in fasting-and refeeding-induced changes in liver size.Here,fasting significantly reduced liver size,which was recovered to the normal level after refeeding.Moreover,hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting.Conversely,refeeding promoted hepatocyte enlargement and proliferation compared to fasted state.Mechanistically,fasting or refeeding regulated the expression of YAP and its downstream targets,as well as the proliferation-related protein cyclin D1(CCND1).Furthermore,fasting significantly reduced the liver size in AAV-control mice,which was mitigated in AAV Yap(5SA)mice.Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation.Besides,the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice.Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation.In summary,this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition,which provides new evidence for YAP in regulating liver size under energy stress.

Actively separated microneedle patch for sustained-release of growth hormone to treat growth hormone deficiency

Growth hormone deficiency(GHD)has become a serious healthcare burden,and presents a huge impact on the physical and mental health of patients.Here,we developed an actively separated microneedle patch(PAA/NaHCO_(3)^(-)Silk MN)based on silk protein for sustained release of recombinant human growth hormone(rhGH).Silk protein,as a friendly carrier material for proteins,could be constructed in mild full-water conditions and ensure the activity of rhGH.After manually pressing PAA/NaHCO_(3)^(-)Silk MN patch to skin for 1 min,active separation is achieved by absorbing the interstitial fluid(ISF)to trigger HCO_(3)^(-)in the active backing layer to produce carbon dioxide gas(CO_(2)).In rats,the MN patch could maintain the sustained release of rhGH for more than 7 days,and produce similar effects as daily subcutaneous(S.C.)injections of rhGH in promoting height and weight with well tolerated.Moreover,the PAA/NaHCO_(3)^(-)Silk MN patch with the potential of painless self-administration,does not require cold chain transportation and storage possess great economic benefits.Overall,the PAA/NaHCO_(3)^(-)Silk MN patch can significantly improve patient compliance and increase the availability of drugs,meet current unmet clinical needs,improve clinical treatment effects of GHD patients.

原发性血小板增多症合并局灶增生性IgA肾病1例及相关文献复习

原发性血小板增多症(essential thrombocythemia,ET)是一种费城染色体阴性骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN),年发病率约为1.1~2/10万人口[1]。

Modularly engineered prodrug-nanoassemblies for cancer therapy:Nonpharmacological moiety dominating delivery fates

Self-engineered small-molecule prodrug-nanoassemblies have emerged as promising nanomedicines for cancer treatment.Modular design of prodrug molecules is crucial to guarantee the favorable assembly stability,tumor-specific prodrug activation,and satisfactory antitumor effect.However,too much attention has been paid to the pharmacophores and chemical linkages in prodrug molecules while neglects the vital roles of nonpharmacological moieties.Herein,we found that iso-carbon fatty acids with different number,position,and cis-trans configuration of double bonds dramatically affect the nanoassembly feature and drug delivery fates of thioether-linked paclitaxel prodrug-nanoassemblies.Particularly,the number and cis-trans configuration of double bonds in fatty acid moieties not only dominate the self-assembly ability and colloidal stability of prodrugs,but also exert significant influences on the pharmacokinetics,prodrug activation,and antitumor activity of prodrug-nanoassemblies.Finally,oleic acid with one cis double bond stands out as the optimal nonpharmacological moiety for thioether-linked paclitaxel prodrugnanoassemblies.This study elucidates the crucial roles of nonpharmacological moieties in prodrugs,and provides new insights into the modular design of prodrug-based nanomedicines for cancer therapy.

Space view of the decadal variation for typical air pollutants in the Pearl River Delta （PRD） region in China

The Pearl River Delta （PRD） is one of the most industrialized, urbanized and populated regions in China, and thus has been long suffering from severe air pollutions. Space data provide a unique perspective for investigating the atmospheric environment at a regional scale. By utilizing multiple satellite retrievals from 2005 to 2013, this study presented, for the first time, the spatial patterns and temporal trends of typical air pollutants over PRD and its vicinity. As viewed from space, aerosol optical depth （AOD）, NO2 and SO2 all had their higher values at the central part of PRD, and showed clear descending gradients as moving to the outskirt of this region. As to the inter-annual variation, all these pollutants had decreasing trends in PRD during the study period, which generally agreed with the relevant in situ measurements. However, the satellite retrievals differed from ground measurements when addressing NO2 and SO2 in the vicinity of PRD. This work also provides the inter-comparison among PRD and three other metropolitan clusters in China： PRD had relatively high AOD, moderate NO2 and low SO2 levels, and it was the only region achieving the effective reduction of NO2 and SO2 during last decade. Unlike the previous three pollutants, HCHO observed by satellite showed very special patterns： it had a relatively homogeneous spatial distribution over both of PRD and its vicinity, and presented an opposite increasing trend from 2005 to 2010. Moreover, PRD had the highest HCHO level among all the metropolitan clusters, hinting a considerable contribution of biogenic origins of HCHO in PRD.

Oxidized Dopamine Acrylamide Primer to Achieve Durable Resin-Dentin Bonding

The durability of the resin-dentin bonding interface is a key issue in clinical esthetic dentistry.Inspired by the extraordinary bioadhesive properties of marine mussels in a wet environment,we designed and synthetized N-2-(3,4-dihydroxylphenyl)acrylamide(DAA)according to the functional domain of mussel adhesive proteins.DAA’s properties of collagen cross-linking,collagenase inhibition,inducing collagen mineralization in vitro,and as a novel prime monomer for clinical dentin adhesion use,its optimal parameters,and effect on the adhesive longevity and the bonding interface’s integrity and mineralization,were evaluated in vitro and in vivo.The results showed that oxide DAA can inhibit the activity of collagenase and cross collagen fibers to improve the anti-enzymatic hydrolysis of collagen fibers and induce intrafibrillar and interfibrillar collagen mineralization.As a primer used in the etch-rinse tooth adhesive system,oxide DAA can improve the durability and integrity of the bonding interface by anti-degradation and mineralization of the exposed collagen matrix.Oxidized DAA(OX-DAA)is a promising primer for improving dentin durability;using 5%OX-DAA ethanol solution and treating the etched dentin surface for 30 s is the optimal choice when used as a primer in the etch-rinse tooth adhesive system.