摘要：The female reproductive system consists of the ovaries,the female gonads,and the reproductive tract organs of the fallopian tubes,uterus,cervix,and *** functions to provide hormonal support and anatomical structure for the production of new offspring.A number of endogenous and exogenous factors can impact female reproductive health and fertility,including genetic vulnerability,medications,environmental exposures,age,nutrition,and *** date,due to the ethical concerns of using human subjects in biomedical research,the majority of studies use in vivo animal models and 2D cell/tissue culture models to study female ***,the complexity and species difference of the female reproductive system in humans make it difficult to compare to those of ***,the monolayered cells cultured on flat plastics or glass lose their 3D architecture as well as the physical and/or biochemical contacts with other cells in ***,all reproductive organs do not work alone but interconnect with each other and also with non-reproductive organs to support female reproductive,endocrine,and systemic *** facts suggest that there is an urgent and unmet need to develop representative,effective,and efficient in vitro models for studying human female *** prodigious advancements of bioengineering(e.g.,biomaterials,3D printing,and organ-on-a-chip)allow us to study female reproduction in an entirely new ***,we review recent advances that use bioengineering methods to study female reproduction,including the bioengineering models of the ovary,fallopian tube,uterus,embryo implantation,placenta,and reproductive disease.

摘要：The growth of biotechnology in recent decades and the dual-use nature of most bioscience research are making their misuse,or accidental misuse or release,more likely and present as threats to biosecurity.A proactive approach is through educating the next generation of scientists to be more security ***,current educational and professional programs in biosecurity are *** this perspective,we recommend that biosecurity educational opportunities should be implemented and expanded for undergraduate and graduate students who will likely use one or more methods in the field of *** then propose that biosecurity education is a key factor in a path toward sustainable and safe ***,a set of 17 biosecurity competencies organized into 6 distinct themes is outlined.

摘要：Background:When patients with cirrhosis develop ascites,it is associated with sharply increasedmortality and healthcare utilization with decreased quality of *** salt restriction is first-line therapy for ascites but it is limited by poor ***:We will recruit 40 patients with cirrhosis and ascites who have received a recent paracentesis or hospitalization for a 1:1 randomized trial of standard care(education on salt restriction)versus home-delivered *** primary outcome is the number of paracenteses needed over 12 *** outcomes include hospital-bed days,health-related quality of life(HRQOL,Ascites Symptom Inventory-7 and Visual Analogue Scale)and performance on batteries of physical function including hand grip(kg)and walk speed(m/s).All subjects follow up through a series of calls where any paracenteses,hospital readmissions,weight changes and diuretic dosage changes are *** a final Week 12 visit,knowledge of dietary sodium intake,quality of life and frailty are reassessed,and satisfaction with the meal-delivery program is *** comparison testing will be conducted between the two ***:A nutritionally standardized meal-delivery program for patients with cirrhosis and ascites post discharge has a variety of potential patient-based benefits,including the effective management of ascites,reduction of healthcare utilization and improvement of *** have three core ***,patients will report interest in and satisfaction with a home-delivered meals ***,subjects on a salt-restricted(2 g sodium)meal-delivery program will have fewer therapeutic paracenteses and all-cause readmissions than subjects receiving standard of ***,subjects on a saltrestricted(2 g sodium)meal-delivery program will report increased HRQOL compared to subjects receiving standard of care.

摘要：Resource-scarce regions with serious COVID-19 outbreaks do not have enough ventilators to support critically ill patients,and these shortages are especially devastating in developing *** help alleviate this strain,we have designed and tested the accessible low-barrier in vivo-validated economical ventilator(ALIVE Vent),a COVID-19-inspired,cost-effective,open-source,in vivo-validated solution made from commercially available *** ALIVE Vent operates using compressed oxygen and air to drive inspiration,while two solenoid valves ensure one-way flow and precise cycle *** device was functionally tested and profiled using a variable resistance and compliance artificial lung and validated in anesthetized large *** functional test results revealed its effective operation under a wide variety of ventilation conditions defined by the American Association of Respiratory Care guidelines for ventilator *** large animal test showed that our ventilator performed similarly if not better than a standard ventilator in maintaining optimal ventilation *** FiO2,respiratory rate,inspiratory to expiratory time ratio,positive-end expiratory pressure,and peak inspiratory pressure were successfully maintained within normal,clinically validated ranges,and the animals were recovered without any *** regions with limited access to ventilators,the ALIVE Vent can help alleviate shortages,and we have ensured that all used materials are publicly *** this pandemic has elucidated enormous global inequalities in healthcare,innovative,cost-effective solutions aimed at reducing socio-economic barriers,such as the ALIVE Vent,can help enable access to prompt healthcare and life saving technology on a global scale and beyond COVID-19.

摘要：IntroductionA rapidly increasing need for organ transplantation and short list of donated organs have led to the development of new materials and technologies for organ manufacturing. Although some simple organs, such as skin and cartilage, have been successfully fabricated and commercialized, it is still difficult to make tissues and organs with high complexity. Engineered tissues have other biomedical applications, such as drug screening models and bio-actuators. Threedimensional （3D） bioprinting has become a great tool to fabricate tissue constructs on demand for transplantation and other biomedical applications.

摘要：目的探讨共识指南及循证指南的证据质量与推荐强度是否一致。研究设计经验性分析。数据来源美国心脏病学会/美国心脏协会(ACC/AHA)和美国临床肿瘤学会(ASCO)于2021年3月27日前制订的指南。指南选择纳入推荐意见符合以下标准的指南:明确报告循证或共识意见、推荐意见独立于指南全文、报告证据质量和推荐强度。数据提取由2名研究人员独立提取资料,提取内容包括:推荐意见类型(共识意见或循证意见)、制订推荐意见的分级系统、推荐强度和证据质量。研究团队统计了低质量证据强推荐和不合理的低质量证据强推荐(不符合GRADE标准)的数量。结果本研究共纳入12部ACC/AHA指南中的1434条推荐意见以及69部ASCO指南中的1094条推荐意见。ACC/AHA指南共有504条基于低质量证据的推荐意见,其中200条(40%)是共识意见,304条(60%)是循证意见;ASCO指南中包含404条基于低质量证据的推荐意见,其中292条(72%)是共识意见,112条(28%)是循证意见。ACC/AHA和ASCO制订的指南中,共识指南比循证指南出现了更多基于低质量证据的强推荐,ACC/AHA[比值比(0R)=2.1,95%可信区间(CI)(1.5-3.1)],ASCO[OR=2.9,95%CI(1.1-7.8)],以及更多不合理的低质量证据强推荐,ACC/AHA[OR=2.6,95%CI(1.7-3.7)],ASCO[OR=5.1,95%CI(1.6-16.0)]。结论与循证指南相比,共识指南更容易形成不符合循证医学基本原则的推荐意见。确保证据质量与推荐强度的一致性和合理性是制订可信赖指南的关键。

摘要：Background RNA interference （RNAi） is a potential cure for amyotrophic lateral sclerosis （ALS） caused by dominant, gain-of-function superoxide dismutase 1 （SOD1） mutations. The success of such therapy relies on the functional small interfering RNAs （siRNAs） that can effectively deliver RNAi. This study aimed to design the functional siRNAs targeting ALS-associated mutant alleles. Methods A modified dual luciferase system containing human SOD1 mRNA target was established to quantify siRNA efficacy. Coupled with validated siRNAs identified in the literature, we analyzed the rationale of siRNA design and subsequently developed an asymmetry rule-based strategy for designing siRNA. We then further tested the effectiveness of this design strategy in converting a naturally symmetric siRNA into functional siRNAs with favorable asymmetry for gene silencing of SOD1 alleles. Results The efficacies of siRNAs could vary tremendously by one base-pair position change. Functional siRNAs could target the whole span of SOD1 mRNA coding sequence as well as non-coding region. While there is no distinguishable pattern of the distribution of nucleobases in these validated siRNAs, the high percent of GC count at the last two positions of siRNAs （P18 and P19） indicated a strong effect of asymmetry rule. Introducing a mismatch at position 1 of the 5＇ of antisense strand of siRNA successfully converted the inactive siRNA into functional siRNAs that silence SOD1 with desired efficacy. Conclusions Asymmetry rule-based strategy that incorporates a mismatch into siRNA most consistently enhances RNAi efficacy and guarantees producing functional siRNAs that successfully silence ALS-associated SOD1 mutant alleles regardless target positions. This strategy could also be useful to design siRNAs for silencing other disease-associated dominant, gain-of-function mutant genes.

摘要：该项目旨在为美国德克萨斯州休斯顿市的一处商业区制定一项综合性总体规划,该规划以可持续都市主义为设计原则。其主要设计目标是建立一个宜居且可持续的城市商业中心,以促进当地经济增长;同时推广一项街景设计指南,以提升该地块对行人和骑行者的友好度。

摘要：化疗依然是包括手术、放疗、以及靶向疗法在内的最重要的抗癌手段之一。尽管高效细胞毒素很多,但癌细胞和健康细胞之间微小的差别限制了这些抗癌化合物因为毒副作用在临床上的广泛应用。鉴于抗肿瘤单克隆抗体对肿瘤细胞表面抗原的特异性,抗体药物已经成为肿瘤治疗的标准疗法,但单独使用时疗效经常不尽人意。抗体药物偶联物(antibody drug conjugate,ADC)把单克隆抗体和高效细胞毒素完美地结合到一起,充分利用了前者靶向、选择性强,后者活性高,同时又消除了前者疗效偏低和后者副作用偏大等缺陷。其中抗体是ADC的制导系统,能够靶向性地把效应分子输送到肿瘤细胞,有效地提高了抗体本身对癌细胞的杀伤力。ADC包括抗体、接头(linker)和细胞毒素(也经常称为效应分子)三个组成部分。通过靶向特定抗原,ADC有效地渗透到肿瘤组织,并被肿瘤细胞吞噬进入酶溶体,释放效应分子。尽管ADC新药的开发已经获得前所未有的成功,技术上仍然有待进一步优化,其中包括被肿瘤细胞吞噬的效率、细胞毒素的活性以及效应分子的释放等。本文简单介绍ADC领域的研究进展,并试图从抗体、接头和效应分子三个方面,讨论提高ADC分子在循环系统的稳定性等一系列优化ADC分子特征的策略。对当前ADC领域技术上存在的问题,以及中国公司进入这个领域要面临的挑战进行深度分析,并提出一些积极的应对方案。

摘要：本文主要综述了近5年(2005-2009年)来芯片电色谱(μCEC)的新发展。详细描述了芯片设计制作、进样富集,色谱柱填充技术,电渗流(EOF)操控与电色谱分离机制等最新研究进展,也包含μCEC的一些新应用;此外,对μCEC技术的发展趋势和前景进行了展望。