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The ascent of immune checkpoint inhibitors： is the understudy ready for a leading role？

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Cancer Biology & Medicine 2017年第4期14卷 341-347页

作者： amy l. Cummings Edward B. Garon Department of Hematology and Oncology David Geffen School of Medicine at the University of California Los Angeles 90095 USA

The recent approval of pembrolizumab as second-line treatment for any solid tumor with high-level microsatellite instability or mismatch repair deficiency agnostic of tissue and origin1 has shattered a glass ceiling for immune checkpoint *** longer bound to a specific cancer diagnosis but rather a biomarker,pembrolizumab has heightened a burgeoning optimism towards the drug *** how these agents should carve out additional

关键词： PD The ascent of immune checkpoint inhibitors:is the understudy ready for a leading role PFS OS ORR IHC

Variability and trends of near-surface wind speed over the Tibetan Plateau:The role played by the westerly and Asian monsoon

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Advances in Climate Change Research 2024年第3期15卷 525-536页

作者： Gang-Feng ZHANG Cesar AZORIN-MOlINA Deliang CHEN Tim RMCVICAR Jose AGUIJARRO Kai-Qiang DENG lorenzo MINOlA Jaeyeon lee Seok-Woo SON Heng MA Pei-Jun SHI State Key laboratory of Earth Surface Processes and Resource Ecology Beijing Normal UniversityBeijing 100875China Engineering Center of Desertification and Blown-Sand Control of Ministry of Education Faculty of Geographical ScienceBeijing Normal UniversityBeijing 100875China Key laboratory of Environmental Change and Natural Disaster of Ministry of Education Beijing Normal UniversityBeijing 100875China Centro de Investigaciones Sobre Desertificaci'on Consejo Superior de Investigaciones Cientı'ficas(CIDECSIC-UV-Generalitat alenciana)ClimateAtmosphere and Ocean Laboratory(Climatoc-Lab)Moncada 46113Spain Regional Climate Group Department of Earth SciencesUniversity of GothenburgGothenburg 40530Sweden CSIRO Environment CanberraACT 2600Australia Australian Research Council Centre of Excellence for Climate Extremes CanberraACT 2600Australia State Meteorological Agency Balearic Islands OfficePalma de Mallorca 07015Spain School of Atmospheric Sciences Sun Yat-sen UniversityZhuhai 519082China Interuniversity Department of Regional and Urban Studies and Planning(DIST) Politecnico and University of TurinTurin 10125Italy School of Earth and Environmental Sciences Seoul National UniversitySeoul 08826South Korea Atmospheric and Oceanic Sciences Program Princeton UniversityPrinceton NJ 08544USA Geophysical Fluid Dynamics laboratory NOAAPrinceton NJ 08544USA

Near-surface wind speed exerts profound impacts on many environmental issues,while the long-term(≥60 years)trend and multidecadal variability in the wind speed and its underlying causes in global high-elevation and mountainous areas(e.g.,Tibetan Plateau)remain largely ***,by examining homogenized wind speed data from 104 meteorological stations over the Tibetan Plateau for 1961-2020 and ERA5 reanalysis datasets,we investigated the variability and long-term trend in the near-surface wind speed and revealed the role played by the westerly and Asian *** results show that the homogenized annual wind speed displays a decreasing trend(-0.091 m s^(−1)per decade,pltidecadal variability of wind speed,which manifested in an prominent increase in 1961-1970,a sustained decrease in 1970-2002,and a consistent increase in *** observed decadal variations are likely linked to large-scale atmospheric circulation,and the correlation analysis unveiled a more important role of westerly and East Asian winter monsoon in modulating near-surface wind changes over the Tibetan *** potential physical processes associated with westerly and Asian monsoon changes are in concordance with wind speed change,in terms of overall weakened horizontal air flow(i.e.,geostrophic wind speed),declined vertical thermal and dynamic momentum transfer(i.e.,atmospheric stratification thermal instability and vertical wind shear),and varied Tibetan Plateau *** indicates that to varying degrees these processes may have contributed to the changes in near-surface wind speed over the Tibetan *** study has implications for wind power production and soil wind erosion prevention in the Tibetan Plateau.

关键词： Tibetan Plateau Wind speed Decadal change Atmospheric circulation Physical processes

The need for pre-emptive control strategies for mpox in Asia and Oceania

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Infectious Disease Modelling 2024年第1期9卷 214-223页

作者： Gregory Gan AJanhavi Guan Tong Jue Tao lim Borame l.Dickens Saw Swee Hock School of Public Health National University of SingaporeSingapore lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore

Introduction:The transmission dynamics of the recent mpox outbreak highlights the lack of infrastructure available to rapidly respond to novel STI outbreaks,of which Asia and Oceania remains particularly ***,we simulate outbreaks in this setting and propose the use of pre-emptive vaccination within the men who have sex with men(MSM)community before the arrival and establishment of the *** and methods Using data driven heterogeneous sexual contact networks,we simulated outbreaks of mpox in Singapore,Hong Kong,and *** individual based SEIR compartmental model was used to simulate epidemic trajectories and the impact of different vaccination uptakes was assessed in their ability to avert or suppress outbreaks upon the arrival of mpox within the MSM ***:The highly dense sexual networks of Singapore and Sydney experience rapid outbreaks,with infection peaks occurring at day 41 and 23 respectively,compared to Hong Kong which occurs at day *** the simulations with no vaccination,68.2%–89.7%of the MSM community will become infected with mpox across the different cities,over a simulation period of 1 *** implementing vaccination strategies,the infection rate across the cities can be reduced to as low as 3.1%of the population(range:3.1%–82.2%)depending on the implementation and uptake of the *** is also extremely effective in slowing the start of the epidemic,delaying the epidemic peak by 36–50 days in Hong Kong,or even preventing the outbreak of ***:With extremely dense and well-connected sexual contact networks,where 65.2%–83.2%of the population are connected to a super-spreader in the different contact networks,pre-emptive or immediate vaccination upon identification of the first case is strongly recommended to help better manage the outbreak of mpox and prevent potential straining of healthcare systems.

关键词： Monkeypox virus Modelling Network model Mpox Contact matrix Sexual contact

Dual inhibition of sirtuins 1 and 2:reprogramming metabolic energy dynamics in chronicmyeloid leukemia as an immunogenic anticancer strategy

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Cancer Communications 2024年第8期44卷 921-925页

作者： Michael Schnekenburger Anne lorant Sruthi Reddy Gajulapalli Ridhika Rajora Jin-Young lee Aloran Mazumder Haeun Yang Christo Christov Hyoung Jin Kang Bernard Pirotte Marc Diederich laboratoire de Biologie Moleculaire et Cellulaire du Cancer LuxembourgLuxembourg Research Institute of Pharmaceutical Sciences&Natural Products Research Institute College of PharmacySeoul National UniversitySeoulRepublic of Korea Faculte de Medecine Universite de LorraineVandoeuvre-les-NancyFrance Department of Pediatrics Seoul National University College of MedicineSeoul National University Cancer Research InstituteSeoul National University Children’s HospitalSeoulRepublic of Korea laboratory of Medicinal Chemistry Center for Interdisciplinary Research on Medicines(CIRM)University of LiegeLiegeBelgium

Chronicmyeloid leukemia(CMl)is a lethal hematopoietic malignancy with a global incidence primarily attributed to the breakpoint cluster region-Abelson(BCR-ABl1)fusion oncogene in over 95%of *** introduction of tyrosine kinase inhibitors(TKIs)has revolutionized CMl management;however,a subset of patients encounters challenges such as resistance and relapse,hindering the achievement of complete *** these challenges in CMl also requires addressing persistent leukemia stem cells(lSCs)with inherent resistance *** regulators of lSC metabolism,proliferation,and survival,as well as genetic and epigenetic alterations,provide potential targets[1].

关键词： metabolism myeloid alterations

Cardiovascular health awareness,risk perception,behavioural intention and INTERHEART risk stratification among middle-aged adults in Malaysia

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Asian Pacific Journal of Tropical Medicine 2024年第2期17卷 61-70页

作者： Siew-Keah lee Ang-lim Chua Clement Heng Yew Fong Ban Hao Brian Cong Wen ling Ng Jing Feng Kong Yik-ling Chew Kai Bin liew Yang Shao M.Kandiah Faculty of Medicine and Health Sciences Universiti Tunku Abdul RahmanMalaysia Faculty of Medicine Universiti Teknologi MARAMalaysia Faculty of Pharmaceutical Sciences UCSI UniversityMalaysia Faculty of Pharmacy University of CyberjayaMalaysia The First Affiliated Hospital of Hainan Medical University China

Objective:To investigate the interrelationship between cardiovascular health awareness,risk perception,behavioural intention,and INTERHEART risk stratification in a middle-aged adult population in ***:A cross-sectional survey with convenience sampling was conducted during November 2022 and January *** completed validated questionnaires assessing cardiovascular health awareness,risk perception of cardiovascular diseases,behavioural intention towards adopting healthy habits,and INTERHEART risk stratification score(IHRS)based on established risk factors.A total of 602 respondents were included in the final *** were analysed with independent t-test/one-way ANOVA or Mann-Whitney/Kruskal-Wallis to test the differences,Pearson correlation or linear regression test to analyze the association of independent and dependent ***:There was a significant positive correlation between medical knowledge related to cardiovascular disease(CVD)and knowledge related to CVD risk prevention,risk perception,behavioural intention and IHRS(Plation).Notably,individuals with higher IHRS tended to have lower knowledge related to CVD and CVD risk prevention,risk perception,and behavioural ***,laborers,active/former smokers,individuals with lower household income and educational levels,those involved in occupations not related to the healthcare sector,and those who did not receive the CVD health brochure or are unaware of health self-assessment tools are likely to have lower levels of knowledge,risk perception,and poorer behavioural intention regarding cardiovascular health(Ple educational level,smoking status,awareness about CVD poster,self-assessment tools were repeatedly significantly associated with knowledge related to CVD and CVD risk prevention,risk perception,behavioral intention and/or IHRS(Plinear regression).Conclusions:These findings underscore the importance of promoting car

关键词： Cardiovascular risk Knowledge Risk perception Behavioural intention INTERHEART Middle-aged lifestyle Physical activity Psychosocial stress

Discrimination of polysorbate 20 by high-performance liquid chromatography-charged aerosol detection and characterization for components by expanding compound database and library

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Journal of Pharmaceutical Analysis 2024年第5期14卷 722-732页

作者： Shi-Qi Wang Xun Zhao li-Jun Zhang Yue-Mei Zhao lei Chen Jin-lin Zhang Bao-Cheng Wang Sheng Tang Tom Yuan Yaozuo Yuan Mei Zhang Hian Kee lee Hai-Wei Shi Jiangsu Institute for Food and Drug Control Nanjing210019China School of Pharmacy China Pharmaceutical UniversityNanjing211112China School of Pharmacy Nanjing University of Chinese MedicineNanjing210046China Chinese Pharmacopoeia Commission Beijing100061China Nanjing Well Pharmaceutical Group Co. Ltd.Nanjing210018China School of Environmental and Chemical Engineering Jiangsu University of Science and TechnologyZhenjiangJiangsu212003China University of Massachusetts Amherst Amherst01003USA Department of Chemistry National University of SingaporeSingapore117543Singapore

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual *** similar structures and polarities of PS20 components make accurate separation,identification,and quantification *** this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPlC)with charged aerosol detection(CAD)to separate 18 key components with multiple *** separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPlC-Q-TOF-MS)with an identical gradient as the HPlC-CAD *** polysorbate compound database and library were expanded over 7-time compared to the commercial *** method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process ***-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different *** method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to ***-CAD and UHPlC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

关键词： Polysorbate 20 Component Database Discrimination Degradation

Inhibiting scar formation via wearable multilayer stacked electret patch:Self-creation of persistent and customizable DC electric field for fibrogenic activity restriction

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InfoMat 2024年第3期6卷 66-80页

作者： Sung-Won Kim Sumin Cho Donghan lee Jiyu Hyun Sunmin Jang Inwoo Seo Hyun Su Park Hee Jae Hwang Hyung-Seop Han Dae Hyeok Yang Heung Jae Chun Suk Ho Bhang Dongwhi Choi School of Chemical Engineering Sungkyunkwan UniversitySuwonRepublic of Korea Department of Mechanical Engineering(Integrated Engineering Program) Kyung Hee UniversityYonginGyeonggiRepublic of Korea Biomaterials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)SeoulRepublic of Korea Department of Medical life Sciences College of MedicineInstitute of Cell and Tissue EngineeringThe Catholic University of KoreaSeoulRepublic of Korea

Electrical stimulation has recently received attention as noninvasive treatment in skin wound healing with its outstanding biological property for clinical set***,the complexity of equipment for applying appropriate electrical stimulation remains an ongoing ***,we proposed a strategy for skin scar inhibition by providing electrical stimulation via a multilayer stacked electret(MS-electret),which can generate direct current(DC)electric field(EF)without any power supply *** addition,the MS-electret can easily control the intensity of EFs by simply stacking electret layers and maintain stable EF with the surface potential of 3400 V over 5 days owing to the injected charges on the electret *** confirmed inhibition of type 1 collagen andα-SMA expression of human dermal fibroblasts(hDFs)by 90%and 44%in vitro,indicating that the transition of hDFs to myofibroblasts was restricted by applying stable electrical *** further revealed a 20%significant decrease in the ratio of myofibroblasts caused by the MS-electret in *** findings present that the MS-electret is an outstanding candidate for effective skin scar inhibition with a battery-free,physiological electrical microenvironment,and noninvasive treatment that allows it to prevent external infection.

关键词： DC electric field dermal fibroblasts electret scar formation restriction self-creation of electrical stimulation

Variation in floral form of CRISPR knock-outs of the poplar homologs of lEAFY and AGAMOUS after FT heat-induced early flowering

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Horticulture Research 2023年第8期10卷 183-193页

作者： amy l.Klocko Estefania Elorriaga Cathleen Ma Steven H.Strauss Department of Biology University of Colorado Colorado SpringsColorado SpringsCO 80918USA Department of Forest Ecosystems and Society Oregon State UniversityCorvallisOR 97331USA

Plant migration and gene flow from genetically modified or exotic trees to nearby lands or by crossing with wild relatives is a major public and regulatory *** genetic strategies exist to mitigate potential gene flow;however,the long delay in onset of flow-ering is a severe constraint to research *** used heat-induced FT overexpression to speed assessment of the expected floral phenotypes after CRISPR knockout of poplar homologs of the key floral genes,lEAFY and *** selected events with previously characterized CRISPR-Cas9 induced biallelic changes then re-transformed them with the Arabidopsis thaliana FlOWERING lOCUS T(AtFT)gene under control of either a strong constitutive promoter or a heat-inducible *** successfully obtained flowering in both a male and female clone of poplar,observing a wide range of inflorescence and floral forms among flowers,ramets,and insertion ***,flowers obtained from the selected lFY and AG targeted events were consistent with what would be predicted for loss-of-function of these ***-targeted events showed small catkins with leaf-like organs,AG-targeted events had nested floral organs consistent with reduction in floral determinacy and absence of well-formed carpels or *** findings demonstrate the great developmental plasticity of Populus flowers during genetically accelerated flowering,which may be of horticultural *** also provide an informative early view of floral phenotypes and apparent sterility from knockouts of both these gene targets.

关键词： AGAMOUS flowers organs

High-yield and rapid isolation of extracellular vesicles by flocculation via orbital acoustic trapping:FlOAT

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Microsystems & Nanoengineering 2024年第1期10卷 313-323页

作者： Joseph Rufo Peiran Zhang Zeyu Wang Yuyang Gu Kaichun Yang Joseph Rich Chuyi Chen Ruoyu Zhong Ke Jin Ye He Jianping Xia Ke li Jiarong Wu Yingshi Ouyang Yoel Sadovsky luke P.lee Tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA Department of Biomedical Engineering Duke UniversityDurhamNCUSA Department of Obstetrics Gynecologyand Reproductive SciencesMagee-Womens Research InstituteUniversity of PittsburghPittsburghPAUSA Department of Microbiology and Molecular Genetics School of MedicineUniversity of PittsburghPittsburghPAUSA Renal Division and Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA Department of Bioengineering Department of Electrical Engineering and Computer ScienceUniversity of CaliforniaBerkeleyBerkeleyCAUSA Department of Biophysics Institute of Quantum BiophysicsSungkyunkwan UniversitySuwonKorea

Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various ***,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low ***,we report a high-yield(>90%)and rapid(lation method called Flocculation via Orbital Acoustic Trapping(FlOAT).The FlOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid *** adding a thermoresponsive polymer flocculant,nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the *** demonstrate the ability of FlOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid *** to its high-yield nature,FlOAT reduces biofluid starting volume requirements by a factor of 100(from 20 ml to 200µl),demonstrating its promising potential in point-of-care diagnostics.

关键词： trapping utilize separating