摘要：The acrosome reaction （AR）, an absolute requirement for spermatozoa and egg fusion, requires the influx of Ca2＋ into the spermatozoa through voltage-dependent Ca2＋ channels and store-operated channels. Maitotoxin （MTx）, a Ca2＋-mobilizing agent, has been shown to be a potent inducer of the mouse sperm AR, with a pharmacology similar to that of the zona pellucida （ZP）, possibly suggesting a common pathway for both inducers. Using recombinant human ZP3 （rhZP3）, mouse ZP and two MTx channel blockers （U73122 and U73343）, we investigated and compared the MTx- and ZP-induced ARs in human and mouse spermatozoa. Herein, we report that MTx induced AR and elevated intracellular Ca2＋ （[Ca2＋]~） in human spermatozoa, both of which were blocked by U73122 and U73343. These two compounds also inhibited the MTx-induced AR in mouse spermatozoa. In disagreement with our previous proposal, the AR triggered by rhZP3 or mouse ZP was not blocked by U73343, indicating that in human and mouse spermatozoa, the AR induction by the physiological ligands or by MTx occurred through distinct pathways. U73122, but not U73343 （inactive analogue）, can block phospholipase C （PLC）. Another PLC inhibitor, edelfosine, also blocked the rhZP3- and ZP-induced ARs. These findings confirmed the participation of a PLC-dependent signalling pathway in human and mouse zona protein-induced AR. Notably, edelfosine also inhibited the MTx-induced mouse sperm AR but not that of the human, suggesting that toxin-induced AR is PLC-dependent in mice and PLC-independent in humans.

摘要：The expression of human α-1,2-fucosyltransferase (HT) or complement regulatory proteins has been proved as an strategy to overcome hypercute rejection in discordant xenogeneic organ transplantation. In this study, we examined whether peripheral blood mononuclear cells (PBMCs) from polytransgenic mice expressing the human HT, and complement regulatory proteins (DAF and CD59), can provide more effective protection against xenograft rejection. Transgenic mice were produced by co-injection of gene constructs for human HT, DAF and/or CD59. Flow Cytometry (FCM) was used to screen the positive transgenic mice. PBMCs from transgenic mice were incubated with 15% human serum to evaluate natural antibody binding, complement activation and expression of adhesion molecules. Three transgenes were strongly expressed in PBMCs of transgenic mice, and HT expression signifi- cantly reduced expression of the major xenoepitope galactose-α-1,3-galactose (α-Gal). Functional studies with PBMCs showed that co-expression of HT and DAF or CD59 markedly increased their re- sistance to human serum-mediated cytolysis when compared with single transgenic PBMCs. Moreover, the combined expression of triple transgenes in PBMCs led to the greatest protection against human serum-mediated cytolysis, avoided hyperacute rejection and reduced expression of adhesion mole- cules. Strong co-expression of triple transgenes was completely protected from xenograft hyperacute rejection and partially inhibited acute vascular rejection. The studies suggest that engineering mice to express triple molecules represents an critical step toward prolonging xenograft survival and might be more suitable for xenotransplantation.

摘要：Congenital bilateral absence of vas deferens （CBAVD） is a manifestation of the mildest form of cystic fibrosis （CF） and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator （CFTR） gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach： （i） first, a reverse dot-blot analysis was performed to detect mutations with regional impact; （ii） next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and （iii） finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%.

摘要：Candida albicans （C. albicans） infection has a high mortality rate in immunocompromised patients. Owing to the inefficiency of the current diagnostic system and the absence of licensed vaccines against candidiasis, the prevention of C. albicans infection remains a challenge. C. albicans infection can be evaluated and prevented by the anti-secreted aspartyl proteinase 2 antibody （anti-Sap2 IgG） and Hsp90 antibody （anti-Hsp90 IgG）. In this study, to explore a new agent for the improvement of the diagnosis and the prevention of C. albicans infection, an engineered fd bacteriophage, which is considered a human-safe virus nanofiber, was designed and prepared with two epitopes that could induce and capture anti-Sap2 IgG and anti-Hsp90 IgG. The dual-display phage was employed as a novel capture probe to develop a new enzyme-linked immunosorbent assay （ELISA） method, which significantly improved the detection rate compared with those of the ELISA in which recombinant protein Sap2 was used as coating antigen to capture the spedfic antibodies （rSap2-ELISA） and the ELISA in which recombinant protein Hsp90 was used as coating antigen to capture the specific antibodies （rHsp90-ELISA）. In addition, the nanofibers acted as a potential vaccine to immunize mice, as well as recombinant proteins, more efficiently mediated humoral and cellular immune responses, decreased levels of C. albicans colonization, and increased the survival rates in C. albicans-infected mice. Therefore, the phage dual-display nanofiber has been shown to be a powerful bifunctional agent for protection against and sensitive detection of clinical infections, which has the potential to be widely used in the life sciences, clinical medicine, and environmental sciences.

摘要：The World Health Organization has declared the rapidly spreading coronavirus to be a global *** FDA is yet to approve a vaccine for human novel ***,we developed a peptide-based vaccine and used high-throughput screening by molecular dynamics simulation to identify T-cell-and p-cell-recognized epitopes for producing specific antibod-ies against *** construct~12 P'antigenic epitope peptides to develop a more effective vaccine and identify specific *** epitope peptides selectively presented the best antigen presentation scores for both human pMHC class I and II alleles to develop a strong binding *** antigens identified of SARS-nCoV-2 different proteins by each attached specific~1-7 L linker adaptor were used to construct a broad single peripheral peptide *** is expected to be highly antigenic with a minimum allergic *** a result of these exciting outcomes,expressing a vaccine using the intimated peptide was highly promising and positive to be highly proposed as epitope-based peptide vaccine of specific antibody against SARS-nCoV-2 by initiating T cells and β-*** in vitro study for the proposed peptide-based vaccine *** *** clinical trials are required to check the efficacy of this vaccine.

摘要：Recently, the anti-glycation and anticancer properties of curcumin longa and okra seed extract were studied alone and also in combination with the well-established drug metformin. The combined effect of curcumin with metformin and metformin with okra seed extract was found to be highly efficacious in inhibiting Advanced Glycation End-products （AGEs）. In order to understand the mechanistic implications of curcumin combined with metformin and its enhanced anti-glycation activity, a Curcumin-Metformin Adduct was chemically synthesized. This adduct was fully characterized by thin-layer chromatography, Nano Drop spectrophotometry and electrospray-ionization mass spectrometry. The adduct may be helpful not only in elucidating the mechanism of anti-glycation and anti-cancer activities but also in studying the role of curcumin in binding of AI3-oligomers and disaggregating fibrillar formation in Alzheimer＇s disease.

摘要：Animal models are increasingly gaining values by cross-comparisons of response or resistance to clinical agents used for ***,many disease mechanisms and drug effects generated from animal models are not transferable to *** address these issues,we developed SysFinder（http：//***/SysFinder）,a platform for scientists to find appropriate animal models for translational *** offers a ＂topic-centered＂ approach for systematic comparisons of human genes,whose functions are involved in a specific scientific topic,to the corresponding homologous genes of animal *** topic can be a certain disease,drug,gene function or biological *** calculates multi-level similarity indexes to evaluate the similarities between human and animal models in specified scientific ***,SysFinder offers species-specific information to investigate the differences in molecular mechanisms between humans and animal ***,SysFinder provides a userfriendly platform for determination of short guide RNAs（sgRNAs） and homology arms to design a new animal *** studies illustrate the ability of SysFinder in helping experimental *** is a useful platform for experimental scientists to carry out their research in the human molecular mechanisms.

摘要：The purpose of this review is to provide medical researchers,especially those without a bioinformatics background,with an easy-to-understand summary of the concepts and technologies used in microbiome ***,we define primary concepts such as microbiota,microbiome,and ***,we discuss study design schemes,the methods of sample size calculation,and the methods for improving the reliability of *** emphasize the importance of negative and positive controls in this ***,we discuss statistical analysis methods used in microbiome research,focusing on problems with multiple comparisons and ways to compare β-diversity between ***,we provide step-by-step pipelines for bioinformatics *** summary,the meticulous study design is a key step to obtaining meaningful results,and appropriate statistical methods are important for accurate interpretation of microbiome *** step-by-step pipelines provide researchers with insights into newly developed bioinformatics analysis methods.

摘要：As we navigate the transition from the Fourth to the Fifth Industrial Revolution,the emerging fields of biomanufacturing and biofabrication are transforming life sciences and *** sectors are benefiting from a synergy of synthetic and engineering biology,sustainable manufacturing,and integrated design *** techniques such as 3D bioprinting,tissue engineering,directed assembly,and self-assembly are instrumental in creating biomimetic scaffolds,tissues,organoids,medical devices,and biohybrid *** field of biofabrication in the United Kingdom and Ireland is emerging as a pivotal force in bioscience and healthcare,propelled by cutting-edge research and *** on the production of biologically functional products for use in drug delivery,in vitro models,and tissue engineering,research institutions across these regions are dedicated to innovating healthcare solutions that adhere to ethical standards while prioritising sustainability,affordability,and healthcare system benefits.

摘要：水痘带状疱疹病毒(VZV)初次感染可引发水痘并可长期潜伏在宿主神经节内,一旦再激活即可引起带状疱疹.VZV病毒具有疱疹病毒典型结构,从内向外依次是DNA核心、衣壳、皮层和囊膜.VZV皮层是核衣壳与囊膜之间一层无固定形状的蛋白层.VZV皮层由多种蛋白组成,但种类和功能仍未全部确定.本文综述了目前已发现的VZV皮层蛋白在病毒感染过程中发挥的多种作用,讨论了VZV皮层蛋白相关的蛋白-蛋白相互作用及其对病毒在SCID-hu人鼠嵌合感染模型中组织趋向性的影响,这将有助于更好地理解VZV皮层蛋白是如何帮助病毒DNA复制、逃避宿主免疫反应和致病.