Efficient and chemoselective alkylation of amines/amino acids using alcohols as alkylating reagents under mild conditions

We report a mild and environmentally benign method for the synthesis of tertiary amines using alcohols as the alkylating reagents. Not only secondary amines such as piperazines but also amino acids and amino alcohols can be N-alkylated selectively. For N,O-benzyl protected amino alcohols, both N,O-de-benzylation and N-methylation were achieved in one-pot.NSF of China [20832005]; National Basic Research Program (973 Program) of China [2010CB833200

Quantitative Proteomic Study of Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Acquired by Laser Capture Microdissection

Objective. To investigate the differential protein profile of human lung squamous carcinoma (HLSC) and normal bronchial epithelium (NBE) and provide preliminary results for further study to explore the carcinogenic mechanism of HLSC. Methods. Laser capture microdissection (LCM) was used to purify the target cells from 10 pairs of HLSC tissues and their matched NHBE, respectively. A stable-isotope labeled strategy using iTRAQ, followed by 2D-LC/Q-STAR mass spectrometry, was performed to separate and identify the differential expression proteins. Results. A total of 96 differential expression proteins in the LCM-purified HLSC and NBE were identified. Compared with NBE, 49 proteins were upregulated and 47 proteins were downregulated in HLSC. Furthermore, the expression levels of the differential proteins including HSPB1, CKB, SCCA1, S100A8, as well as S100A9 were confirmed by western blot and tissue microarray and were consistent with the results of quantitative proteomics. Conclusion. The different expression proteins in HLSC will provide scientific foundation for further study to explore the carcinogenic mechanism of HLSC

Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition)

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.Improving the Ability of Diagnosis and Treatment of Difficult Disease

Efficacy, Safety, and Immunogenicity of an Escherichia coliProduced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial

HPV是一种常见的生殖道感染病毒，高危型HPV持续性感染能够导致几乎所有的宫颈癌，其中HPV 16型和18型危害最大，可导致约70%的宫颈癌。预防性HPV疫苗有望减少甚至最终消灭由疫苗型别导致的宫颈癌，降低HPV相关的疾病负担。该研究是在全国4个中心5个现场的18-45岁健康女性中进行的多中心、随机、双盲、对照（戊肝疫苗）的三期临床试验，该研究结果证实我校自主研发的双价人乳头瘤病毒疫苗（大肠杆菌）具有良好的安全性、免疫原性和免疫持久性，可有效地预防HPV 16型和/或18型相关的宫颈高度癌前病变及持续性感染。 该论文报告了我校和厦门万泰沧海生物技术有限公司自主研发的双价人乳头瘤病毒疫苗（大肠杆菌）三期临床试验的期中分析结果。这是第一个进入临床试验并提交药品注册申请的国产人乳头瘤病毒疫苗（HPV疫苗），有望成为世界上第四个上市的HPV疫苗，受到世界卫生组织和盖茨基金会等国际组织的高度关注。 中国医学科学院肿瘤医院乔友林教授、我校吴婷教授、广西壮族自治区疾病预防控制中心李荣成主任医师、江苏省疾病预防控制中心胡月梅主任医师、北京大学人民医院魏丽惠教授、中国食品药品检定研究院李长贵研究员、中国医学科学院肿瘤医院陈汶教授为该论文的共同第一作者，我校张军教授、夏宁邵教授和中国医学科学院肿瘤医院乔友林教授为该论文的共同通讯作者。【Abstract】Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase 3 clinical trial was conducted to evaluate the efficacy, safety and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multi-centre, randomized, double-blind trial started on November 22, 2012, in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receiving 3 doses of the test or control (hepatitis E) vaccine at months 0, 1 and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received 3 doses of the vaccine. This report presents data from a pre-specified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval [CI] = 55.6% to 100.0%, 0/3306 in the vaccine group vs. 10/3296 in the control group) and 97.8% (95% CI = 87.1% to 99.9%, 1/3240 vs. 45/3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The Escherichia coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18 associated high-grade genital lesions and persistent infection in women.This work was supported by grants from the Chinese National High-tech R&D Program (863 program, 2012AA02A408), the Chinese National Major Scientific and Technological Special Project for “Significant New Drug Development” (2018ZX09308010 and 2012ZX09101316), the National Natural Science Foundation of China (81673240 and U1705283), the Fujian Provincial Major Scientific and Technological Project (2015YZ0002), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS, 2017-I2M-B&R-03, and 2016-I2M-1-019) and Xiamen Innovax. 该研究获得了国家高技术研究发展计划（863计划）、新药创制国家科技重大专项、国家自然科学基金、福建省科技重大专项、中国医学科学院医学与健康科技创新工程基金以及厦门万泰沧海生物技术有限公司的资助

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead