摘要：Tissue engineering is an interdisciplinary field promising new therapeutic means for replacing lost or severely damaged tissues or organs. However, the fabrication of complex engineered tissues has been hampered due to the lack of vascularization to provide sufficient blood supply after implantation. In this article, we propose using rapid prototyping technology to prefabricate a scaffold with an inside hollowed vascular system including an arterial end, a venous end and capillary networks between them. The scaffold will be ''printed'' layer by layer. When printing every layer, a ''low-melting point'' material will be used to form a blood vessel network and a tissue-specific material will be used outside it. Hereafter the ‘low-melting point’ material will be evacuated by vaporization to ensure a hollowed vessel network. Then the inside hollowed capillary network can be endothelialized by using autologous endothelial cells in a cycling bioreactor while the outside material can be embedded with tissue-special cells. In the end, the new vascularized autologous grafts could be transferred to the defect site by using microsurgical techniques to connect the grafts with the host artery and vein. The strategy would facilitate construction of complex tissue engineering if the hypothesis proved to be practical.

摘要：Human rhinoviruses(HRVs)are the predominant infectious agents for the common cold *** HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma.3C protease,a highly conserved enzyme,cleaves the viral polyprotein during replication and assists the virus in escaping the host immune *** key roles make 3C protease an important drug target.A few structures of 3Cs complexed with an irreversible inhibitor rupintrivir have been *** structures shed light on the determinants of drug *** we describe the structures of HRV-C153C in free and inhibitor-bound *** volume-decreased S1'subsite and half-closed S2 subsite,which were thought to be unique features of enterovirus A 3C proteases,appear in the HRV-C 3C *** assumes an“intermediate”conformation in the complex,which might open up additional avenues for the design of potent antiviral *** of the features of the three-dimensional structures and the amino acid sequences of 3C proteases suggest new applications for existing drugs.

摘要：Fuel cells have attracted extensive attention due to their high conversion efficiency and environmental ***,their wider application is limited by the poor activity and high cost of platinum(Pt),which is widely used as the cathode catalyst to overcome the slow kinetics associated with oxygen reduction reaction(ORR).Pt‐based composites with one‐dimensional(1D)nanoarchitectures demonstrate great advantages towards efficient ORR *** review focuses on the recent advancements in the design and synthesis of 1D Pt‐based ORR *** introducing the fundamental ORR mechanism and the advanced 1D architectures,their synthesis strategies(template‐based and template‐free methods)are ***,their morphology and structure optimization are highlighted,followed by the superstructure assembly using 1D Pt‐based ***,the challenges and perspectives on the synthesis innovation,structure design,physical characterization,and theoretical investigations are proposed for 1D Pt‐based ORR *** anticipate this study will inspire more research endeavors on efficient ORR nanocatalysts in fuel cell application.

摘要：Objective To observe the value of deep learning (DL) models for automatic classification of echocardiographic views. Methods Totally 100 patients after heart transplantation were retrospectively enrolled and divided into training set, validation set and test set at a ratio of 7 ∶ 2 ∶ 1. ResNet18, ResNet34, Swin Transformer and Swin Transformer V2 models were established based on 2D apical two chamber view, 2D apical three chamber view, 2D apical four chamber view, 2D subcostal view, parasternal long-axis view of left ventricle, short-axis view of great arteries, short-axis view of apex of left ventricle, short-axis view of papillary muscle of left ventricle, short-axis view of mitral valve of left ventricle, also 3D and CDFI views of echocardiography. The accuracy, precision, recall, F1 score and confusion matrix were used to evaluate the performance of each model for automatically classifying echocardiographic views. The interactive interface was designed based on Qt Designer software and deployed on the desktop. Results The performance of models for automatically classifying echocardiographic views in test set were all good, with relatively poor performance for 2D short-axis view of left ventricle and superior performance for 3D and CDFI views. Swin Transformer V2 was the optimal model for automatically classifying echocardiographic views, with high accuracy, precision, recall and F1 score was 92.56%, 89.01%, 89.97% and 89.31%, respectively, which also had the highest diagonal value in confusion matrix and showed the best classification effect on various views in t-SNE figure. Conclusion DL model had good performance for automatically classifying echocardiographic views, especially Swin Transformer V2 model had the best performance. Using interactive classification interface could improve the interpretability of prediction results to some extent.

摘要：设计合成了一种四足针尖状铁钯纳米颗粒(简称TFPs),分别通过诱导乳腺癌细胞自噬和巨噬细胞释放促炎因子,实现在光声成像引导下的乳腺肿瘤细胞铁死亡协同免疫治疗.首先,该新型TFPs具有优异的光学吸收和较高的光热转换效率,是良好的光声成像造影剂.其次,TFPs具有过氧化物酶/谷胱甘肽氧化酶模拟酶性能,能原位催化肿瘤区过表达过氧化氢,产生羟基自由基,并同时下调胞内谷胱甘肽水平,协同诱导细胞铁死亡.此外,其独特的针状形态可以进一步触发肿瘤细胞自噬,加快铁蛋白降解,释放铁离子,进而增效铁死亡;同时,特殊的尖状结构能触发巨噬细胞释放促炎细胞因子,增效放大免疫效应,在与PD-L1检查点抑制剂联合使用后,取得最强的抗肿瘤效果.这项工作不仅开发了一种高效的铁死亡诱导剂,也为在纳米尺度调控肿瘤细胞自噬/免疫功能提供了一种全新的策略.

摘要：Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory ***,the development of a model for effective drug screening is urgently *** the established therapeutic testing models for CCA are often ineffective,we fabricated an enabling three-dimensional(3D)-bioprinted CCA-on-a-chip model that to a good extent resembled the multicellular microenvironment and the anatomical microstructure of the hepato-vascular-biliary system to perform high-content antitumor drug ***,cholangiocytes,hepatocytes,and vascular endotheliocytes were employed for 3D bioprinting of the models,allowing for a high degree of spatial and tube-like microstructural ***,it was possible to observe CCA cells attached to the surfaces of the gelatin methacryloyl(GelMA)hydrogelembedded microchannels and overgrown in a thickening manner,generating bile duct stenosis,which was expected to be analogous to the in vivo *** 4000 differentially expressed genes were detected in the CCA cells in our 3D coculture model compared to the traditional two-dimensional(2D)*** screening revealed that the CCA cells grown in the 3D traditional model were more sensitive to the antitumoral prodrug than those in the 2D monoculture due to drug biotransformation by the neighboring functional *** study provides proof-of-concept validation of our bioprinted CCA-on-a-chip as a promising drug screening model for CCA treatment and paves the way for potential personalized medicine strategies for CCA patients in the future.

摘要：3-Hydroxymethyl-4-methyl-DCK(3,HMDCK)was discovered previously as a potent HIV non-nucleoside reverse transcriptase inhibitor(NNRTIs)(EC_(50):0.004 μM,TI:6225)with a novel mechanism of *** exerts anti-HIV activity by inhibiting the production of HIV-1 double-stranded viral DNA from a single-stranded DNA intermediate,rather than blocking the generation of single-stranded DNA from a RNA template,which is the mechanism of action of current HIV-1 RT ***,the insufficient metabolic stability of 3 limits its further clinical *** the current study,a series of ester prodrugs of 3 was designed and synthesized to explore the new drug candidates as *** L-alanine ester prodrug 10 exhibited desirable pharmacokinetic properties in vitro and in vivo and showed improved oral bioavailability of 26%in rat,and would be a potential clinical candidate as a new anti-AIDS drug.

摘要：目的评价基于CD4立体构型设计的新型免疫抑制物J2对小鼠胰岛移植后急性排斥反应的影响。方法将900～1000个DBA/2（H-2^d）小鼠的胰岛移植在糖尿病模型C57BL/6（H-2^b）小鼠肾被膜下。移植前用台盼蓝和双硫腙染色检测胰岛细胞活性和纯度。将C57BL/6小鼠随机分为5组,每组10只,在胰岛移植后第1～10天腹腔内注射J2,每天一次。对照组注射生理盐水、CsA组注射环孢素A（10 mg/kg）;实验组J2A组（1mg/kg）、J2B组（4 mg/kg）、J2C组（8 mg/kg）。术后监测不同时间各组小鼠的血糖变化及移植胰岛的存活时间,并观察移植胰岛在术后第三天及发生急性排斥反应时的组织病理学及免疫组化表现。结果获得的胰岛细胞的活性＞95%,纯度＞85%。胰岛移植术前各组糖尿病小鼠的血糖平均高于20.0mmol/L,术后前四天各组小鼠的血糖下降明显,均低于11.1 mmol/L,且各组之间比较差异无统计学意义（P＞0.05）。移植第7天以后,对照组、J2A组小鼠的血糖较术后前四天明显升高（P＜0.05）。术后第八天开始,对照组、J2A组小鼠血糖升高平均高于11.1 mmol/L;CsA组、J2B组、J2C组的血糖仍低于11.1 mmol/L,三组之间无明显差异,但明显低于对照组和J2A组（P＜0.05）。病理学检查示移植后第三天各组移植的胰岛细胞轻度水肿,形态大致正常;移植后第八天对照组、J2A组的移植胰岛出现急性排斥反应病理改变,其他组病理未见排斥表现,小鼠胰岛素抗体免疫组化结果显示胰岛素阳性。CsA组（21.6±2.1 d）、J2B组（19.0±2.7d）、J2C组（18.7±2.3d）的移植胰岛存活时间比较差异无统计学意义,但分别较对照组（8.1±0.56d）、J2A组（8.3±0.48d）显著延长（P＜0.01）。结论一定剂量的J2具有和CsA相似的免疫抑制作用,可明显抑制小鼠胰岛移植后排斥反应的发生,显著延长移植物的存活时间。

摘要：一般情况下,每年冬季是季节性流感高发季节,但在当前2019冠状病毒病(COVID-19)大流行期间,全球季节性流感活动呈“断崖式”下降。为应对即将到来的流感季节,亟需弄清这种前所未有的流感低水平流行的原因。本文中,我们探索了一种国家特异性推理模型,利用该模型估计中国、英国和美国这三个国家中佩戴口罩、人员流动变化(国际和国内)以及严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)干扰的影响。结果发现,在这些地区增加一周佩戴口罩的干预措施,流感活动可减少11.3%~35.2%。实施一周的限制人员流动措施对国际(1.7%~6.5%)和国内社区(1.6%~2.8%)的影响较小。2020年至2021年,仅佩戴口罩这一项干预措施就可使阳性率下降13.3%至19.8%。仅人员流动变化可使阳性率降低5.2%至14.0%,其中79.8%~98.2%归因于国际旅行限制。SARS-CoV-2干扰仅在2019年至2020年具有统计学显著效应。中国北方地区及英国的阳性百分比分别降低7.6%(2.4~14.4)和10.2%(7.2~13.6)。探索所得出的结果对了解非药物干预措施和其他呼吸系统疾病背景下的流感演变有一定意义,有助于制定卫生政策,并可为公共卫生措施的个性化设计提供信息。

摘要：The fragile antibody leads to a great challenge as a scaffold to fabricate the luminescent metal nanoclusters using one-pot *** study presents a stable single-chain anti-body(scFv57R-ATS)for the fabrication of luminescent gold nanoclusters(AuNCs@scFv57R-ATS)and a quick,sensitive rabies virus detection in living *** this paper,AuNCs@scFv57R-ATS was designed to specifically recognize antigen RV in modified HeLa cells,which promoted the demonstration of metal nanocluster fluorescent probes for antigen targeting and therapy.