摘要：地点:克罗拉多州,丹佛,国家犹太人医学和研究中心微生物学实验室。 目的:评价吡嗪酰胺对人体单核细胞培养分化的正常和激活的巨噬细胞中结核分支杆菌的抗菌作用。 设计:将人体血中分离的单核细胞在塑料平皿中培养7天使其衍化成巨噬细胞单层。使用TNF-α或IFN-γ激活或未经过处理的巨噬细胞感染结核分支杆菌。次日加入不同浓度的吡嗪酰胺(PZA)、吗啉酰胺(MZA)或异烟肼(INH),并于第0、4、8天记数细胞内的活菌数。 结果:不论其浓度大小均未发现吡嗪酰胺的抑菌作用,而在同一实验模型中则观察到了随着MZA和异烟肼剂量增加其抑菌和杀菌作用也增加。 结论:PZA对人体单核细胞培养分化的巨噬细胞内滞留或繁殖的结核分支杆菌既无抑菌作用又无杀菌作用,关于人们所知道的该药对结核病人的效力可能与所推测的该药对细胞内菌群的抗菌作用无关。

摘要：针对将形状指数(SI)应用于三维图像时缺乏对应的推广形式,常通过计算三维图像的3个截面的SI来组合表达,导致在肠道肿瘤检测等应用中造成了大量的误检的问题,研究了三维情形SI的推广.首先选取球坐标系表达的单位球面以消除灰度变化尺度的影响;然后分析了球面的6个等价区域,并选取其一作为灰度变化的表征区域;由于SI原有的表达式不利于推广到三维空间,因此推导了一种等价的表达式,并通过分析此表达式在三维情形的推广,得到了描述三维图像局部灰度变化的指标——密度指数(DI).通过研究DI所表征区域的几何特性,得到了一条具有重要性质的曲线——逆Z线,并分析了其上典型特征点所对应的灰度变化模式.仿真实验结果表明,对于肠道肿瘤检测的典型情况,使用DI检测的误检率明显低于SI.

摘要：Conductive and adhesive hydrogels are promising materials for designing *** satisfy the high conductivity of bioelectronic devices,metal nanomaterials have been used to fabricate composite ***,the fabrication of a conductive-nanomaterial-incorporated hydrogel with high performance is a great challenge because of the easy aggregation nature of conductive nanomaterials making processing ***,we report a kind of adhesive aero-hydrogel hybrid conductor(AAHC)with stretchable,adhesive and anti-bacteria properties by in situ formation of a hydrogel network in the aerogel-silver nanowires(AgNWs)*** AgNWs with good conductivity are wellintegrated on the inner-surface of shape-memory chitosan aerogel,which created a conductive framework to allow hydrogel *** by the aerogel-silver makes the hybrid hydrogel tough and *** groups from the hydrogel allow strong adhesion to wet tissues through molecular *** inherent bacteria-killing ability of silver ions endows the conductive hydrogel with excellent anti-bacteria *** proposed facile strategy of aerogel-assisted assembly of metal nanomaterials with hydrogel opens a new route to incorporate functional nanoscale building blocks into hydrogels.

摘要：目的探讨基于CD4立体构型设计的新型免疫抑制剂(J2)在小鼠体内的免疫抑制作用以及其作用机制。方法将羧基荧光素二醋酸琥珀酰亚胺酯(CFSE)标记的C57BL/6(H-2b)小鼠的淋巴细胞4×10~6～6×10~6经尾静脉注入经^(60)钴照射(900拉德)后的DBA/2(H-2d)小鼠体内构建模型。将DBA/2小鼠随机分为5组,每组5只,模型建立后即刻腹腔注射J2,每天1次。对照组注射生理盐水、CsA组注射环孢素A(10mg/kg体重);实验组J2A组(1mg/kg体重)、J2B组(4 mg/kg体重)、J2C组(8mg/kg体重)。给药3d后分组处死DBA/2小鼠取脾制备淋巴细胞,用CD3、CD4、CD8单抗分别标记受检T细胞,FACS流式细胞仪检测CD4^+T细胞和CD8^+T细胞在小鼠体内分裂增殖的情况,并检测CD4^+T细胞的凋亡情况。结果CFSE标记C57BL/6小鼠的脾淋巴细胞着染率大于99%。对照组分裂的CD4^+ T细胞(75.4±1.58)%、分裂的CD8^+ T细胞(83.48±1.25)%明显多于CsA组和实验组(P0.05),但J2A组多于CsA组(P<0.05)。对照组CD4^+ T细胞早期凋亡的比例(41.1±3.4)%明显高于其他各组(P<0.01)。J2A组(35.6±4.1)%、J2B组(24.0±3.7)%和J2C组(13.6±2.3)%CD4^+ T细胞早期凋亡的比例显著高于CsA组(7.4±1.9)%(P<0.05)。结论J2可能抑制T细胞亚群CD4^+ T细胞的活化,从而进一步抑制CD8^+ T细胞的分裂增殖而具有免疫抑制作用。

摘要：In vaccine development,broadly or cross-type neutralizing antibodies(bnAbs or cnAbs)are frequently targeted to enhance *** immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization ***,the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly *** this study,we discovered a cross-type neutralizing monoclonal antibody,13H5,against human papillomavirus 6(HPV6)and *** nAb exhibited a marked preference for HPV6,demonstrating superior binding activity to virus-like particles(VLPs)and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum(90%vs.31%).Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex,we delineated the epitope as spanning four segments of amino acids(Phe42-Ala47,Gly172-Asp173,Glu255-Val275,and Val337-Tyr351)on the L1 surface *** interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and *** Ser341 with alanine,which is the residue type present in HPV11 L1,almost completely abolished binding activity to *** swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1(Ser341,Thr338,and Thr339),we engineered chimeric HPV11-6HI ***,the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human *** approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

摘要：Background： Smokeless tobacco is widely used by athletes to enhance performance. Nicotine is a central nervous system stimulant and acts on cardiocirculatory and metabolic systems, involving tissue blood flow and circulatory vasoreactivity. The aim of this study was to investigate the effects of the oral smokeless tobacco （Swedish snus （SS）） on the perception of fatigue and time to exhaustion （TTE） during moderate-intensity aerobic exercise. Methods： Fourteen healthy non-tobacco male users were recruited for a double-blind, controlled crossover design （SS vs. snus placebo （SP））. Subjects were tested for 3 sessions： experimental session 1 （Exp 1） consisted of an incremental test to determine the maximal aerobic power out-put （Wmax）, whereas Exp2 and Exp3 consisted of exercising at 65%Wmax until exhaustion in SS or SP conditions. During Exp2 and Exp3, muscle and cerebral oxygenation was assessed by means of near-infrared spectroscopy, and the rating of perceived exertion （RPE） was recorded. Results： Comparing SS with SP tests, significant differences （p 〈 0.05） were found in the values of cerebral （-3%） and muscular tissues oxygenation （-4%） in the first 30 min of exercise. The RPE values were not significantly different between the 2 conditions （SS vs. SP）. No significant difference was found in TTE （SS： 54.25 ± 21.84 min; SP： 50.01 ± 17.03 min）. Conclusion： This study showed that muscular and cerebral oxygenation increased significantly with snus administration during an endurance exercise until exhaustion, but this did not affect fatigue perception and TTE. The results showed that snus could not be considered an ergogenic substance in non-tobacco users.2018 Published by Elsevier B.V. on behalf of Shanghai University of Sport. This is an open access article under the CC BY-NC-ND license. （http：//***/licenses/by-nc-nd/4.0/）.

摘要：The repair of osteochondral defects is one of the major clinical challenges in ***-established osteochondral tissue engineering methods have shown promising results for the early treatment of small ***,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the *** this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion *** developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite *** microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle *** 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage *** histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control *** genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control *** findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.

摘要：Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical *** has also been employed in various advanced industrial *** development of intelligent biomedical engineering has raised the requirements for 3D printing,such as flexible manufacturing processes and technologies,biocompatible constituents,and alternative ***,state-of-the-art 3D printing mainly involves inorganics or polymers and generally focuses on traditional industrial fields,thus severely limiting applications demanding biocompatibility and *** this regard,peptide architectonics,which are self-assembled by programmed amino acid sequences that can be flexibly functionalized,have shown promising potential as bioinspired inks for 3D ***,the combination of 3D printing and peptide self-assembly poten-tially opens up an alternative avenue of 3D bioprinting for diverse advanced ***,a small but innovative nation,has significantly contributed to 3D bioprinting in terms of scientific studies,marketization,and peptide architectonics,including modulations and applications,and ranks as a leading area in the 3D bioprinting *** review summarizes the recent progress in 3D bioprinting in Israel,focusing on scientific studies on printable components,soft devices,and tissue *** paper further delves into the manufacture of industrial products,such as artificial meats and bioinspired supramolecular architectures,and the mechanisms,physicochemical properties,and applications of peptide ***,Israel contributes significantly to the field of 3D bioprinting and should thus be appropriately recognized.

摘要：对一个国家来说,噪声导致的失聪是一种巨大的社会和经济损失,是以前未曾遇到过的医疗卫生问题,现在这个问题有了一种解决办法。美国农业部(FDA)近年来没有批准任何预防噪声导致失聪的新产品。在美国,这类产品(包括耳塞和耳罩)的市场价值大约为2.43亿美元,其中约75%来自耳塞的销售。对听力的物理防护可以降低声压水平,但若噪声过强,这种物理防护并不能完全保证听力不受损害。而且,这类"屏蔽"方法也会损害需要通过听、说进行交流来保证的个人安全性。近十年来我们对应激、病理和年龄因素在决定细胞生存和死亡的分子和生化机制方面有了明显深入的了解和认识。我们可以确定导致细胞死亡的凋亡或坏死途径,以及对这些途径起调节作用的外部环境或内源性遗传启动因子、基因及转导因子。用这些新知识,我们开始设计新的干预方法来减轻或防止细胞死亡,使我们第一次能够预防或治疗以前不能预防或治疗的疾患,失聪即是其中一种。

摘要：背景:1992年纽约市医院耐两种或更多种药物的活动性结核病情况。目的:检查纽约市1992年结核发病高峰期间,经鉴定命名为公共卫生研究所(PHRI)W株的具有高度耐药且有17条IS6110印迹带的结核菌在全市的分布情况。同时还将此W株与其它纽约市常见菌株加以比较。设计:应用双盲回归法对保存的结核菌培养物进行限定性片段长度多态性(RFLP)DNA指纹分析。结果:1992年中,我们在21所医院的住院病人中共分离112株W印迹株和8个变株。几乎所有的分离株均对四种一线药物和卡那霉素(KAN)耐药。1992年此单一菌株至少占纽约市多种耐药(MDR)结核病的22％,远高于其它任何一株。几乎所有的W株病例均是AIDS患者。该菌群为纽约市耐药程度最高且迄今为止与其它地区比较所鉴定出的最大的具有IS6110指纹相似性的菌群。结论:由于推荐的四药化疗方案对此高度耐药的菌群不能有效杀灭,因此90年代初在纽约AIDS患者中发生因W株感染而引起的结核暴发流行。其它常见菌株并非呈现高度耐药,甚至于令人惊奇的是表现为全敏感。单一多种耐药菌株能够在AIDS和结核均常见的地区引起广泛的播散。