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A human monoclonal antibody neutralizes SArS-CoV-2 Omicron variants bytargeting the upstream region of spike protein Hr2 motif

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hLife 2024年第3期2卷 126-140页

作者： Hang Su jun Zhang Zhenfei Yi Sajid Khan Mian Peng Liang Ye Alan Bao Han Zhang Guangli Suo Qian Li Housheng Zheng Dandan Wu thomas j.Kipps Lanfeng Wang Zhenghong Lin Suping Zhang Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies Guangdong Key Laboratory for Genome Stability andHuman Disease PreventionDepartment of PharmacologySchool of Basic Medical SciencesBase for International Science and TechnologyCooperation:Carson Cancer Stem Cell Vaccines R&D CenterInternational Cancer CenterShenzhen University Medical SchoolShenzhenUniversityGuangdongChina School of Life Sciences Chongqing UniversityChongqingChina The Center for Microbes Development and HealthCAS Key Laboratory of Molecular Virology&ImmunologyShanghai Institute of Immunityand InfectionChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina College of Life Sciences University of Chinese Academy of SciencesBeijingChina Department of Critical Care Medicine Shenzhen Luohu People’s HospitalGuangdongChina University of California BerkeleyCaliforniaUSA Xenta Biomedical Science Co. LtdGuangdongChina CAS Key Laboratory of Nano-Bio Interface Suzhou Institute of Nano-Tech and Nano-BionicsChinese Academy of SciencesJiangsuChina Center of Novel Therapeutics University of CaliforniaSan DiegoCaliforniaUSA

The continuous emergence of new severe acute respiratory syndrome coronavirus 2(SArS-CoV-2)variants meansthere is a need to explore additional strategies to develop broad-spectrum vaccines or therapeutics for individuals remaining at risk of coronavirus disease 2019(COVID-19).Neutralizing monoclonal antibody(mAb)that binds to theconserved S2 subunit of the SArS-CoV-2 spike(S)protein alone,or in combination with mAb that binds to the receptor-binding domain(rBD)of S protein,might be effective in eliciting protection from infection by a variety of SArS-CoV2 *** high-throughput single-cell immunoglobulin sequencing of B cells from COVID-19-convalescent donors,we identified a high-affinity S2-specific mAb-39,that could inhibit original SArS-CoV-2 strain,Omicron BA.1,BA.2.86,BA.4,BA.5,and EG.5.1 S protein-mediated membrane fusion,leading to the neutralization of these ***,mAb-39 could also improve the neutralizing activity of anti-rBD antibody against the highlyneutralization-resistant Omicron *** docking and point mutation analyses revealed that mAb-39 recognized epitopes within the conserved upstream region of the heptad repeat 2(Hr2)motif of the S2 ***,these findings demonstrate that targeting the conserved upstream region of the Hr2 motif(e.g.,using mAbs)provides anovel strategy for preventing the infection of SArS-CoV-2 and its variants.

关键词： coronavirus disease 2019(COVID-19) severe acute respiratory syndrome coronavirus 2(SArS-CoV-2)Omicron variants monoclonal antibody upstream region of heptad repeat 2(Hr2) immunoglobulin repertoiresequencing

Surgical techniques for the management of male infertility

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Asian journal of Andrology 2012年第1期14卷 94-102,177页

作者： Natalya A Lopushnyan thomas j Walsh Department of Urology University of Washington Seattle WA 98195 USA

Evaluation and surgical treatment of male infertility has evolved and expanded, now leading to more precise diagnoses and tailored treatments with diminished morbidity and greater success. Surgeries for male infertility are divided into four major categories：（i） diagnostic surgery; （ii） surgery to improve sperm production; （iii） surgery to improve sperm delivery; and （iv） surgery to retrieve sperm for use with in vitrofertilization and intracytoplasmic sperm injection （IVF-ICSI）. While today we are more successful than ever in treating male infertility, pregnancy is still not always achieved likely due to factors that remain poorly understood. Clinicians treating infertility should advocate for couple-based therapy, and require that both partners have a thorough evaluation and an informed discussion before undergoing specific surgical therapies.

关键词： male infertility testis varicocele

Foreword： varicocele - unraveling the enigma

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Asian journal of Andrology 2016年第2期18卷 159-160页

作者： Anthony j thomas Cleveland Clinic Lerner College of Medicine of CaseWestern University Cleveland Ohio USA.

It was more than 40 years ago, as a first-year Urology resident, that I performed my first varicocele ligation （a palomo procedure under the watchful eye and able hands of my staff physician. I dutifully read all I could the night before the procedure and became familiar with the names of Barfield, Macomber and Sanders, Tulloch, MacLeod, Ivanissevich, Palomo, Amelar and Dubin and others who had written about varicoceles being associated with abnormal semen parameters and a potentially surgically correctable cause of male infertility.

关键词： Foreword varicocele - unraveling the enigma

Synthesis and electronic properties of expanded 5-(hetero)arylthien-2-yl substituted 3-ethynyl quinoxalines with AIE characteristics

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Science China Chemistry 2018年第8期61卷 909-924页

作者： Franziska K.Merkt thomas j.j.Müller Institute of Organic Chemistry and Macromolecular Chemistry Heinrich Heine University Düsseldorf

Expanded 5-(hetero)aryl-thien-2-yl substituted 3-ethynyl quinoxaline dyes with variable substitution pattern on the peripheral thiophene ring were synthesized in moderate to very good yields by Suzuki and Buchwald-Hartwig coupling of the corresponding brominated 3-ethynyl quinoxalines. Dumbbell-shaped bis(thienyl 3-ethynyl quinoxalines) are also accessible by the Suzuki protocol. The photophysical properties were investigated by UV and fluorescence spectroscopy. Most of the obtained compounds display fluorescence in solution and some of them also in the solid state. Additionally, tuning of the emission color of the quinoxaline based chromophores can be conveniently accomplished by the remote substituent group. The determined absorption and emission maximum as well as the Stokes shifts strongly correlate with Hammett σp+parameters. Besides,photophysical properties of selected derivatives in the solid state, biphasic solutions, and PMMA films, along with their relationships, are comparatively investigated. Moreover, two 5-(hetero)aryl-thien-2-yl substituted 3-ethynyl quinoxaline dyes are aggregation induced emission(AIE) chromophores indicated by restriction of molecular motions. A covalently restricted 3-ethynyl quinoxaline supports that the inhibition of molecular rotation is responsible for the significant enhancement of fluorescence in acetonitrile/water mixtures.

关键词： absorption aggregation induced emission cross-coupling fluorescence heterocycles palladium

Quantitative model evaluation of organic carbon oxidation hypotheses for the Ediacaran Shuram carbon isotopic excursion

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Science China Earth Sciences 2017年第12期60卷 2118-2127页

作者： SHI Wei LI Chao thomas j.ALGEO State Key Laboratory of Biogeology and Environmental Geology China University of Geosciences State Key Laboratory of Geological Processes and Mineral resources China University of Geosciences Department of Geology University of Cincinnati

The largest global carbon-cycle perturbation in Earth history was recorded in the Ediacaran—a persistent negative shift in the global marine dissolved inorganic carbon(DIC) reservoir that lasted for ~25–50 million years, with a nadir of –12‰(i.e.,the Shuram Excursion, or SE). This event is considered to have been a result of full or partial oxidation of a large dissolved organic carbon(DOC) reservoir, which, if correct, provides evidence for massive DOC storage in the Ediacaran ocean owing to an intensive microbial carbon pump(MCP). However, this scenario was recently challenged by new hypotheses that relate the SE to oxidization of recycled continentally derived organic carbon or hydrocarbons from marine seeps. In order to test these competing hypotheses,this paper numerically simulates changes in global carbon cycle fluxes and isotopic compositions during the SE, revealing that:(1) given oxygen levels in the Ediacaran atmosphere-ocean of ≤40% PAL, the recycled continental organic carbon hypothesis and the full oxidation of oceanic DOC reservoir hypothesis are challenged by the atmospheric oxygen availability which would have been depleted in 4 and 6 million years, respectively;(2) the marine-seep hydrocarbon oxidation hypothesis is challenged by the exceedingly large hydrocarbon fluxes required to sustain the SE for >25 Myr; and(3) the heterogeneous(partial) DOC oxidation hypothesis is quantitatively able to account for the SE because the total amount of oxidants needed for partial oxidation(reservoir could have been met.

关键词： Carbon isotope Shuram Excursion Dissolved organic carbon Atmospheric oxygen Oceanic oxidation

The impact of macroalgae on mean and turbulent flow fields

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journal of Hydrodynamics 2015年第3期27卷 427-435页

作者： thomas robert E. MCLELLAND Stuart j. Department of Geography Environment and Earth Sciences University of Hull

In this paper, we attempt to quantify the mean and turbulent flow fields around live macroalgae within a tidal inlet in Norway. Two Laminaria digitata specimens - 0.50 m apart were selected for detailed study and a profiling ADV was used to collect 45 velocity profiles, each composed of up to seven 0.035 m-high profiles collected for 240 s at 100 Hz, at a streamwise spacing of 0.25 m and cross-stream spacing of 0.20 m. To quantify the impact of the macroalgae, measurements were repeated over a sparser grid after the region had been completely cleared of algae and major roughness elements.

关键词： dealiasing laminaria digitata turbulence vectrino profiler velocity profile

Analysis of PFAAs in American alligators part 2： Potential dietary exposure of South Carolina hunters from recreationally harvested alligator meat

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journal of Environmental Sciences 2017年第11期29卷 31-38页

作者： jessica j.Tipton Louis j.Guillette jr Susan Lovelace Benjamin B.Parrott thomas r.rainwater jessica L.reiner College of Charleston Charleston SC 29724 USA Medical University of South Carolina Department of Obstetrics and Gynecology Charleston SC 29425 USA University of Georgia Odum School of Ecology Savannah River Ecology Laboratory Jackson SC 29831 USA Torn Yawkey Wildlife Center & Belle W. Baruch Institute of Coastal Ecology and Forest Science Clemson University P.O. Box 59(5 Georgetown SC 29442 USA National Institute of Standards and Technology Chemical Sciences Division Hollings Marine Laboratory Charleston SC 29412 USA

Exposure to perfluorinated alkyl acids（PFAAs） has been linked to many harmful health effects including reproductive disorders, developmental delays, and altered liver and kidney function. Most human exposure to environmental contaminants, including PFAAs,occurs through consumption of contaminated food or drinking water. This study uses PFAA data from meat samples collected from recreationally harvested American alligators（Alligator mississippiensis） in South Carolina to assess potential dietary exposure of hunters and their families to PFAAs. Consumption patterns were investigated using intercept surveys of 23 hunters at a wild game meat processor. An exposure scenario using the average consumption frequency, portion size, and median perfluorooctane sulfonic acid（PFOS） concentration in alligator meat from all hunt units found the daily dietary exposure to be 2.11 ng/kg body weight per day for an adult human. Dietary PFOS exposure scenarios based on location of harvest suggested the highest daily exposure occurs with alligator meat from the Middle Coastal hunt unit in South Carolina. Although no samples were found to exceed the recommended threshold for no consumption of PFOS found in Minnesota state guidelines, exposure to a mixture of PFAAs found in alligator meat and site-specific exposures based on harvest location should be considered in determining an appropriate guideline for vulnerable populations potentially exposed to PFAAs through consumption of wild alligator meat.

关键词： Public hunt American alligator Dietary exposure PFOS Consumption advisory Contaminant consumption

Analysis of PFAAs in American alligators part 1： Concentrations in alligators harvested for consumption during South Carolina public hunts

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journal of Environmental Sciences 2017年第11期29卷 24-30页

作者： jessica j.Tipton Louis j.Guillette jr Susan Lovelace Benjamin B.Parrott thomas r.rainwater jessica L.reiner College of Charleston Charleston SC 29424 USA Medical University of South Carolina Department of Obstetrics and Gynecology Charleston SC 29425 USA University of Georgia Odum School of Ecology Savannah River Ecology Laboratory Jackson SC 29831 USA Tom Yawkey Wildlife Center & Belle W. Baruch Institute of Coastal Ecology and Forest Science Clemson University P.O. Box 596 Georgetown SC 29442 USA National Institute of Standards and Technology Chemical Sciences Division Hollings Marine Laboratory Charleston SC 29412 USA

Environmental contamination resulting from the production or release of harmful chemicals can lead to negative consequences for wildlife and human health. Perfluorinated alkyl acids（PFAAs） were historically produced as protective coatings for many household items and currently persist in the environment, wildlife, and humans. PFAAs have been linked to immune suppression, endocrine disruption, and developmental toxicity in wildlife and laboratory studies. This study examines the American alligator, Alligator mississippiensis,as an important indicator of ecosystem contamination and a potential pathway for PFAA exposure in humans. Alligator meat harvested in the 2015 South Carolina（SC） public hunt season and prepared for human consumption was collected and analyzed for PFAAs to determine meat concentrations and relationships with animal body size（total length）, sex, and location of harvest. Of the 15 PFAAs analyzed, perfluorooctane sulfonate（PFOS） was found in all alligator meat samples and at the highest concentrations（median 6.73 ng/g）. No relationship was found between PFAA concentrations and total length or *** of one or all compounds varied significantly across sampling locations, with alligators harvested in the Middle Coastal hunt unit having the highest PFOS concentrations（median 16.0 ng/g; p = 0.0001）. Alligators harvested specifically from Berkley County, SC（located in the Middle Coastal hunt unit） had the highest PFOS concentrations and the greatest number of PFAAs detected（p 〈 0.0001）. The site-specific nature of PFAA concentrations in alligator meat observed in this study suggests a source of PFAA contamination in Berkley County, SC.

关键词： Perfluorinated alkyl acids American alligators South Carolina Perfluorooctane sulfonate(PFOS) Dietary exposure

Evaluation of a model for providing cost effective,accessible continuing education to the forensic science community

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Forensic Sciences research 2021年第4期6卷 224-230页

作者： thomas j.Gluodenis Department of chemistry&Physics Lincoln UniversityLincoln UniversityPAUSA

This study presents a detailed model and its subsequent assessment for the development and optimized delivery of continuing education for the forensic science *** continuing education is on the rise as this modality of content dissemination allows for accessibility,convenience,and *** model,which includes an educational needs assessment,gap analysis,online content delivery and archival,was evaluated through the launch of a global training event/symposium *** four-year study of over 6000 participants representing>75 countries provides empirical support for the model based upon registration/attendance data and participant self-assessment *** practices are identified relative to content and format,operational excellence,technology,and financing of the *** directions along with opportunities to further enhance the model are also discussed.

关键词： Forensic sciences continuing education educational requirements online web-based certification