摘要：AIM: The transcription factor EGR-1 (early growth response gene-1) plays an important role in cell growth, differentiation and development. It has identified that EGR-1 has significant transformation suppression activity in some neoplasms, such as fibrosarcoma, breast carcinoma. This experiment was designed to investigate the role of egr-1 in the cancerous process of hepatocellular carcinoma (HCC) and esophageal carcinoma (EC), and then to appraise the effects of EGR-1 on the growth of these tumor cells. METHODS: Firstly, the transcription and expression of egr-1 in HCC and EC, paracancerous tissues and their normal counterpart parts were detected by in situ hybridization and immunohistochemistry, with normal human breast and mouse brain tissues as positive controls. Egr-1 gene was then transfected into HCC (HHCC, SMMC7721) and EC (ECa109) cell lines in which no egr-1 transcription and expression were present. The cell growth speed, FCM cell cycle, plate clone formation and tumorigenicity in nude mice were observed and the controls were the cell lines transfected with vector only. RESULTS: Little or no egr-1 transcription and expression were detected in HCC, EC and normal liver tissues. The expression of egr-1 were found higher in hepatocellular paracancerous tissue (transcription level P=0.000; expression level P=0.143, probably because fewer in number of cases) and dysplastic tissue of esophageal cancer (transcription level P=0.000; expression level P=0.001). The growth rate of egr-1-transfected HHCC (HCC cell line) cells and ECa109 (EC cell line) cells was much slower than that of the controls. The proportion of S phase cell, clone formation and tumorigenicity were significantly lower than these of the controls' (decreased 45.5% in HHCC cells and 34.1% in ECa109 cells; 46.6% and 41.8%; 80.4% and 72.6% respectively). There were no obvious differences between SMMC7721 (HCC) egr-1-transfected cells and the controls with regard to the above items. CONCLUSION: The dec

摘要：Objective: As one of the most popular designs used in genetic research, family-based design has been well recognized for its advantages, such as robustness against population stratification and admixture. With vast amounts of genetic data collected from family-based studies, there is a great interest in studying the role of genetic markers from the aspect of risk prediction. This study aims to develop a new statistical approach for family-based risk prediction analysis with an improved prediction accuracy compared with existing methods based on family history. Methods: In this study, we propose an ensemble-based likelihood ratio(ELR) approach, Fam-ELR, for family-based genomic risk prediction. Fam-ELR incorporates a clustered receiver operating characteristic(ROC) curve method to consider correlations among family samples, and uses a computationally efficient tree-assembling procedure for variable selection and model building. Results: Through simulations, Fam-ELR shows its robustness in various underlying disease models and pedigree structures, and attains better performance than two existing family-based risk prediction methods. In a real-data application to a family-based genome-wide dataset of conduct disorder, Fam-ELR demonstrates its ability to integrate potential risk predictors and interactions into the model for improved accuracy, especially on a genome-wide level. Conclusions: By comparing existing approaches, such as genetic risk-score approach, Fam-ELR has the capacity of incorporating genetic variants with small or moderate marginal effects and their interactions into an improved risk prediction model. Therefore, it is a robust and useful approach for high-dimensional family-based risk prediction, especially on complex disease with unknown or less known disease etiology.

摘要：囊膜病毒可能采用相似的病毒 宿主细胞膜融合机制 ,即病毒表面糖蛋白结合到宿主细胞受体后 ,启动了病毒融合蛋白的一系列构象变化 ,根据囊膜蛋白构象变化特征 ,囊膜病毒可采用两种以上的方式发生膜融合 ,并据此分为两类 :Ⅰ型病毒膜融合和Ⅱ型病毒膜融合 .Ⅱ型病毒膜融合以黄病毒为代表 ,其分子机制与Ⅰ型病毒膜融合不同 ,但不很清楚 .而Ⅰ型病毒膜融合中 ,如艾滋病毒 ,流感病毒等 ,在囊膜蛋白变构形成稳定折叠的发夹三聚体结构时 ,拉近了两膜之间的距离 ,此过程释放出来的能量进一步促使两膜融合 .膜融合使病毒蛋白及病毒RNA基因组释放到宿主细胞内而感染宿主 .以上述研究为基础设计的C肽 /N肽小分子抑制子 ,可以在病毒糖蛋白中间体构象形成的短时间内 ,高效、特异地竞争结合其配体 ,从而阻止糖蛋白的进一步折叠 ,达到抑制病毒入侵的目的 ,为病毒疾病的防治提供了新思路和策略 .针对艾滋病毒设计的C肽 ,即T2 0或Enfuvirtide在临床应用效果很好 .以艾滋病毒和流感病毒为例 。

摘要：Obesity has become a global threat to health;however,the available drugs for treating obesity are *** investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative *** short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte ***,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore ***,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse ***-ATS showed higher specificity for adipocyte targetability without obvious ***-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS *** conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.

摘要：The low temperature,high salt content,and bacterial composition of a seawater environment can induce severe infections in open wounds,thus impeding wound *** date,numerous wound dressings have been developed for injuries and various antibacterial ***,ordinary antibacterial strategies could not provide long-term resistance to infections and could not promote wound ***,we proposed a strategy for enhancing resistance to seawater immersion wound infection by killing bacteria and delivering bacterial antigens in ***,MXene-embedded tannin-Eu^(3+)(M@TA-Eu)particles were constructed to effectively alleviate injuries infected through seawater immersion and persistently fight infection by forming in situ bacterial vaccines and immune *** the particle,the platform composed of TA and Eu3+exhibited provascularization and antigen presentation *** with near-infrared photothermal effect were introduced to kill the bacteria,promote the recruitment of antigen presentation cells,and ultimately enhance vaccination *** results showed that the particles not only effectively accelerated the healing of injuries by relieving wound inflammation and inhibiting bacteria but also produced a potent vaccination by forming in situ bacterial ***,the M@TA-Eu particles are novel materials for high-grade anti-infection dressing.

摘要：多数发表的科研结果都是错误的,这一观点受到越来越多的关注。科研成果正确与否取决于多种因素,如:研究的把握度和偏倚,研究同一问题的小组数量,更重要的是研究所得的“真实关联”与“无关联”的比率。如果研究规模较小,效应尺度较小,被测关联的数量较大而预选量较少,设计、定义、结局和分析方式的灵活性越大,过多考虑财政和其他利益等都会减小研究成果的真实几率。对多数科研领域而言,研究成果仅仅是对主要偏倚的精确估量。

摘要：Immune evasion behavior and immunosuppressive characteristics of tumor extensively impedethe immune initiation effect of therapy triggered immunogeniccell death (ICD). In this work, a carrier-adjuvantedimmunostimulator (designated as CoCeC) is developed toboost photodynamic immunotherapy by downregulatingprogrammed death ligand 1 (PD-L1) and impairing adenosinetriphosphate (ATP) hydrolysis. Among these, the crosslinkedchitosan oligosaccharide is applied as the drug carrier fordelivery of Ce6 and Ceritinib, which also serves as an immuneadjuvant to downregulate PD-L1. Meanwhile, the robustphotodynamic therapy (PDT) of CoCeC exhibits lethal toxicityagainst tumor cells to induce ICD and release damage-associated molecular patterns (DAMPs), which can also impairATP hydrolysis by blocking CD39. In vitro and in vivo resultsdemonstrate the robust therapeutic efficacy of CoCeC tosuppress primary tumor growth and activate a superior immune elimination against lung metastasis by amplifying theimmune initiation of ICD with the assistance of immune *** work provides a self-adjuvanted strategy to enhance the immune response of therapy induced ICD, which ispromising to activate systemic antitumor immunity in consideration of the complicated immunosuppressive factors.

摘要：Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the *** elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains *** this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature ***,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic ***,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the ***,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain *** conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.

摘要：As surgical procedures transition from conventional resection to advanced tissue-regeneration technologies,human disease therapy has witnessed a great leap *** particular,three-dimensional(3D)bioprinting stands as a landmark in this setting,by promising the precise integration of biomaterials,cells,and bioactive molecules,thus opening up a novel avenue for tissue/organ *** by the editorial board of Bio-Design and Manufacturing,this review brings together a cohort of leading young scientists in China to dissect the core functionalities and evolutionary trajectory of 3D bioprinting,by elucidating the intricate challenges encountered in the manufacturing of transplantable *** further delve into the translational pathway from scientific research to clinical application,emphasizing the imperativeness of establishing a regulatory framework and rigorously enforcing quality-control ***,this review outlines the strategic landscape and innovative achievements of China in this field and provides a comprehensive roadmap for researchers worldwide to propel this field collectively to even greater heights.

摘要：Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain ***,we explored the bone regeneration promotion effect of allo-BMSCs in 3D-printed autologous bone particle(ABP)***,we concurrently printed scaffolds with polycaprolactone,ABPs,and allo-BMSCs for appropriate support,providing bioactive factors and seed cells to promote *** vitro studies showed that ABP scaffolds promoted allo-BMSC osteogenic *** vivo studies revealed that the implantation of scaffolds loaded with ABPs and allo-BMSCs into canine skull defects for nine months promoted *** experiments suggested that only a small portion of implanted allo-BMSCs survived and differentiated into vascular endothelial cells,chondrocytes,and *** implanted allo-BMSCs released stromal cell-derived factor 1 through paracrine signaling to recruit native BMSCs into the defect,promoting bone *** study contributes to our understanding of allo-BMSCs,providing information relevant to their future application.