摘要：Background:Handan Eye Study (HES),a large population-based cohort study in rural area of northern China,was one of the few studies focusing on the major eye diseases of rural Chinese *** aim of this study was to introduce the design,methodology and to assess the data quality of the follow-up phase of ***:All participants were recruited in Yongnian county of Handan city between 2012 and *** outcomes were measured by visual quality scales and ocular *** performed the Chi-square test to make comparison of categorical data among groups,One-way analysis of variance and Kruskal-Wallis test was applied to make comparison of continuous data among groups,a post-hoc test was done to make further pairwise ***-class correlation coefficients (ICCs) and Kappa coefficients were used to evaluate the consistency between different *** regression was used to explore the influence factors of death,odds ratio (OR) and 95% confidence interval (CI) were used to estimate the effect size of each influence ***:The follow-up rate was 85.3%.Subjects were classified into three groups:the follow-up group (n =5394),the loss to follow-up group (n =929),and the dead group (n =507),comparison of their baseline information was *** with the other two groups,age of the dead group (66.52 ± 10.31 years) was the oldest (Z =651.293,P < 0.001),male proportion was the highest (59.0 %)(x2 =42.351,P < 0.001),only 65.9 % of the dead finished middle school education (Z =205.354,P < 0.001).The marriage percentage,body mass index (BMI),best-corrected visual acuity (BCVA),and intra-ocular pressure of the dead group was the lowest *** equivalent error (SER) of the dead group was the ***,history of smoking,hypertension,diabetes,and heart disease were more common in the dead *** analysis showed that age (OR =1.901,95% CI:1.074-1.108),gender (OR =0.317,95% CI:0.224-0.448),and BCVA (OR =0.282,95%

摘要：Focal adhesion kinase(FAK)is an intracellular tyrosine kinase that plays a critical role in the occurrence,development,and metastasis of cancer through both its kinase-dependent catalytic functions and kinase-independent scaffolding *** kinase inhibitors target only its catalytic activity,leaving the scaffolding functions ***,proteolysis targeting chimeras(PROTACs)offers a promising approach by degrading the entire FAK protein,thereby inhibiting both functions *** this study,we designed and synthesized novel PROTAC degraders,utilizing a defactinib derivative(compound 12)as the FAK ligand and a lenalidomide analog as the E3 ligase *** structures of these compounds were confirmed through^(1)H NMR,^(13)C NMR,and high-resolution mass spectrometry(HRMS).Among the synthesized compounds,the optimized compound 16b exhibited potent degradation activity against FAK protein in A549 cells,with a DC_(50)of 6.16±1.13 n M,significantly inhibiting the proliferation and colony formation of these *** to defactinib,16b showed enhanced inhibition of A549 cell migration and ***,our research demonstrated that the rapid and effective FAK degradation induced by 16b was mediated by a CRBN-dependent proteasome mechanism.

摘要：A plant fermentation was carried out by Yeast and Lactobaccilli against fermented black turmeric, Kaempferia parviflora (FBT). These materials were proved by as safe in animal safety experiment. We tried to investigate changes of immune-competent cells that commonly utilized FBT, including after administration of immno-suppressed animals, the effects by FBT on the regulated effect on the cells were evaluated. Our results showed that FBT augmented the level of lymphocytes in number, while FBT regulated the level of granulocytes in both number and function. In our clinical study with 20 healthy volunteers, granulocyte and lymphocyte ratio suggesting their constitution as neutral in peripheral blood were increased significantly 30 days after the administration of FBT in rodents, and compromised host was prepared with cancer chemotherapeutic agent (Mytomycin-C). Our observations showed against intracellular parasite, and that FBT augmented intercellular pathogen through humoral immunity. We discussed the significance and mechanism of FBT on the level of leukocyte subsets in number and function that were considered to be potential indicators for the activation of the compromised host. We also proposed an idea that FBT exhibited tonic effects via activating complement components. The evidences were shown by immune-electrophoretic method. Moreover, we tried to access further to the anti-oxidative activities of this FBT. This modification brought to the significant lift up for antibody producing cells and anti-oxidative activity for phagocytic cells.

摘要：Cryobioprinting has tremendous potential to solve problems to do with lack of shelf availability in traditional bioprinting by combining extrusion bioprinting and *** order to ensure the viability of cells in the frozen state and avoid the possible toxicity of dimethyl sulfoxide(DMSO),DMSO-free bioink design is critical for achieving successful cryobioprinting.A nontoxic gelatin methacryloyl-based bioink used in cryobioprinting is composed of cryoprotective agents(CPAs)and a buffer *** selection and ratio of CPAs in the bioink directly affect the survival of cells in the frozen ***,the development of universal and efficient cryoprotective bioinks requires extensive *** first compared two commonly used CPA formulations via experiments in this *** show that the effect of using ethylene glycol as the permeable CPA was 6.07%better than that of *** datasets were obtained and four machinelearning models were established to predict experimental *** predictive powers of multiple linear regression(MLR),decision tree(DT),random forest(RF),and artificial neural network(ANN)approaches were compared,suggesting an order of ANN>RF>DT>*** final selected ANN model was then applied to another *** reveal that this machine-learning method can accurately predict the effects of cryoprotective bioinks composed of different *** also suggest that the formulations presented here have *** findings are likely to greatly accelerate research and development on the use of bioinks for cryobioprinting.

摘要：合成生物学是借助基因工具改造活细胞和生物体的学科,其经历了蓬勃发展阶段,在生物医学领域得到广泛应用,包括新型生物传感器和生物材料设计,以及最新临床治疗药物和疫苗的开发.纳米材料具有独特的物理、化学和生物特性,在拓展合成生物学的生物医学应用场景上具有巨大的潜力,可以提高治疗剂的生产效率,并增强改造生物体的功能.在此,我们简要概述了纳米材料应用于合成生物学领域的最新进展,主要涵盖纳米材料作为递送载体、信号转导器和功能增强剂的角色及其制备过程和性能特点.本综述首先强调了纳米材料作为基因载体的最新成果,包括有机、无机和仿生递送系统;其次,回顾了纳米材料介导的刺激响应型基因表达调控的研究;第三,总结了在可编程的杂化生物活性材料方面的开创性工作,包括纳米材料/细菌杂合系统和纳米材料/哺乳动物细胞杂合系统;最后,讨论了该领域当前面临的挑战,并从个人观点展望了未来的发展前景.

摘要：Acellular porcine small intestinal submucosa(SIS)has been used for esophagoplasty with success in a canine ***,it did not lead to complete *** better reconstruction,a cellular component is ***,promotion of angiogenesis with copper has been widely recognized by basic research as well as clinical *** this study,we have evaluated the feasibility and effectiveness of combined Cu and SIS(SIS-Cu patch)for the esophageal repair using a canine *** male beagle dogs were subjected to surgical resection to produce cervical esophageal defects(5 cm in length,180°in range).SIS with Cu(5 or 25μmol L 1copper)or without Cu was patched on the esophageal *** esophagram and histology exam were carried out to evaluate the effectiveness of the *** shown,the SIS-Cu graft promoted re-epithelialization,re-vascularization and muscular ***-Cu patch is more effective than SIS alone for esophageal repair,and the SIS+25μmol L 1Cu group demonstrated additional advantages over the SIS+5μmol L 1Cu.

摘要：The encapsulation of essential oil components in cyclodextrins(CDs)to form inclusion complexes(ICs)is an effective strategy for improving their stability and *** aim of the present study was to obtain a deeper understanding of the encapsulation behavior of multi-components inβ-*** molecules ofα-pinene,myrcene,and 3-carene,having the same molecular weight,formed ICs withβ-CD by a freeze-drying method.A simplex lattice mixture design with 28 experiments was carried *** analysis was applied to analyze the encapsulation behavior of guest components,and quantitative models of guest components in ICs were constructed by coupling with near-infrared(NIR)spectroscopy and chemometrics ***,the molecular docking technique was used to obtain the optimal conformation and explain the binding behavior of *** results suggested that the spatial structure and ratio of guest molecules were the key factors affecting the encapsulation effect.A non-destructive and rapid NIR analytical model for the guest component in ICs could be obtained by second derivative(2nd der)***,the encapsulation of guest components inβ-CD was differentiated,and NIR could be used as a rapid and non-destructive tool for quantitative analysis of ICs.

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：延长基于蛋白质治疗药物的半衰期可以提高药物疗效。然而,基因治疗本质上是长期表达所需的治疗性药物,药物半衰期对基因治疗疗效的影响尚不清楚。在这项腺相关病毒(adeno-associated virus,AAV)基因治疗研究中,通过与免疫球蛋白G1(immunoglobulin G 1,IgG1)可溶性单体Fc区(soluble monomeric IgG1 fragment crystallizable,sFc)或Fc区融合,设计了几种能够延长半衰期的蛋白质。研究表明,延长AAV递送的小分子双功能蛋白和成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)的半衰期显著增加了它们在血液循环中的浓度。此外,AAV递送FGF21延长其半衰期使2型糖尿病动物模型中肝损伤和血糖显著降低,并改善了葡萄糖耐量和胰岛素敏感性。这些结果证明了延长药物半衰期的基因治疗在应对人类疾病中的治疗潜力。

摘要：A good Ti-based joint implant should prevent stress shielding and achieve good bioactivity and anti-infection *** meet these requirements,the low-elastic-modulus alloy—Ti–35Nb–2Ta–3Zr—was used as the substrate,and functional coatings that contained bioceramics and Ag ions were prepared for coating on TiO_(2)nanotubes(diameter:(80±20)nm and(150±40)nm)using anodization,deposition,and spin-coating *** effects of the bioceramics(nano-β-tricalcium phosphate,microhydroxyapatite(micro-HA),and meso-CaSiO_(3))and Ag nanoparticles(size:(50±20)nm)on the antibacterial activity and the tribocorrosion,corrosion,and early in vitro osteogenic behaviors of the nanotubes were *** tribocorrosion and corrosion results showed that the wear rate and corrosive rate were highly dependent on the features of the nanotube ***-HA showed great wear resistance with a wear rate of(1.26±0.06)×10^(−3)mm^(3)/(N·m)due to adhesive and ***-CaSiO_(3)showed enhanced cell adhesion,proliferation,and alkaline phosphatase *** coatings that contained nano-Ag exhibited good antibacterial activity with an antibacterial rate of≥89.5%against Escherichia *** findings indicate that hybrid coatings may have the potential to accelerate osteogenesis.