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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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The current situation of semen analysis in China,based on a survey of 296 laboratories

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Asian Journal of Andrology 2024年第2期26卷 220-221页

作者： Long-Long Fu Ying Liu Xiao-Wei Wang Fang Zhou Ying Guo Wen-Hong Lu Yi-Qun Gu national health Commission Key Laboratory of Male Reproductive health Reproductive Health Research CenterNational Research Institute for Family PlanningBeijing 100081China institute of Pediatric research Children's Hospitalof Soochow UniversitySuzhou 215025China

Dear Editor,Semen analysis is a basic test to assess male fertility and is a fundamental test in assisted reproductive *** the first publication of World health Organization(WHO)Laboratory Manual of Human Semen and Sperm-Cervical Mucus Interaction in 1980,to the publication of the WHO Manual,6th edition in 2021,these 40 years have been recognized as providing a global standard that is widely used in research and clinical laboratories *** WHO Manual,6th edition in Chinese,which we have been authorized by the WHO to translate,will be published soon.

关键词： technology. analysis translate

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Importance of dietary supplementation of soluble and insoluble fibers to sows subjected to high ambient temperatures during late gestation and effects on lactation performance

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Animal Nutrition 2024年第1期16卷 73-83页

作者： Seung Min Oh Abdolreza Hosseindoust Sang Hun Ha Jun Young Mun Joseph Moturi Habeeb Tajudeen Yo Han Choi Su Hyup Lee Jin Soo Kim Gyeongbuk Livestock research institute Department of Animal Industry Convergence Kangwon National University Swine Division National Institute of Animal Science Rural Development Administration Department of Swine Science Korea National University of Agriculture and Fisheries

Heat stress adversely affects sows' performance, which can be improved by applying proper nutritional strategies. This study was conducted to investigate the interactive effects of dietary fiber levels and sources on sows' reproductive performance, metabolic response during gestation, and the carry-over influence on litter performance in the lactation period during heat stress(average room temperature of 27.1°C). Fifty-four multiparous sows(Landrace × Yorkshire; initial body weight of 236.3 ± 16 kg; 2, 3and 4 parities) at d 90 of gestation were assigned to a 2 × 3 factorial arrangement(9 sows/treatment),involving 2 dietary fiber levels(4.5% and 6% crude fiber) and 3 dietary fiber sources(wheat bran [WB],palm kernel meal [PK], and beet pulp [BP]). Sows fed the BP diet had highest(P < 0.01) feed intake and constipation index and lowest(P < 0.01) farrowing duration. Piglet weight(P = 0.041) and litter weight(P < 0.01) at weaning were higher in sows in the BP treatment compared to PK treatment. Sows in the BP treatment showed the greatest(P < 0.01) digestibility of crude protein and neutral detergent fiber. The fecal concentration of acetate was the lowest(P < 0.01) in the PK treatment. Total short-chain fatty acid production was increased in the WB and BP treatments compared with the PK. Sows in the BP treatment showed the lowest(P = 0.036) hair cortisol. The blood insulin concentration of sows was higher(P = 0.026) in the high fiber(6%) treatment compared with the low fiber(4.5%) treatment at 90 min and120 min after the meal. The concentration of phthalic acid, succinic acid, phenylethylamine, hydrocinnamic acid, iron, linoleic acid, glycerol, ketone, and formamide were increased(P < 0.05) in the BP treatment compared with the WB. The BP treatment with high soluble fiber content improved the constipation index, farrowing duration, and litter performance, while high insoluble fibers increased sows comfort and reduced stress factors including respiratory rate and rectal

关键词： Soluble fiber Insoluble fiber Beet pulp Wheat bran Palm kernel Metabolites

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Anti-epileptic and Neuroprotective Effects of Ultra-low Dose NADPH Oxidase Inhibitor Dextromethorphan on Kainic Acid-induced Chronic Temporal Lobe Epilepsy in Rats

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Neuroscience Bulletin 2024年第5期40卷 577-593页

作者： Jing-Jing Yang Ying-Xin Liu Yan-Fang Wang Bi-Ying Ge Ying Wang Qing-Shan Wang Sheng Li Jian-Jie Zhang Ling-Ling Jin Jau-Shyong Hong Sheng-Ming Yin Jie Zhao College of Basic Medical Sciences Dalian Medical UniversityDalian116044China Department of Neurology The First Affiliated Hospital of Dalian Medical UniversityDalian116011China national and Local Joint Engineering research Center for Drug research and development of Neurodegenerative Diseases Dalian116044China School of Public health Dalian Medical UniversityDalian116044China Neurobiology Laboratory National Institute of Environmental Health SciencesNational Institutes of HealthResearch Triangle ParkDurhamNC27709USA

Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy(TLE).We postulated that kainic acid(KA)-Induced status epilepticus triggers microglia-dependent inflammation,leading to neuronal damage,a lowered seizure threshold,and the emergence of spontaneous recurrent seizures(SRS).Extensive evidence from our laboratory suggests that dextromethorphan(DM),even in ultra-low doses,has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative *** results showed that administration of DM(10 ng/kg per day;subcutaneously via osmotic minipump for 4 weeks)significantly mitigated the residual effects of KA,including the frequency of SRS and seizure *** addition,DM-treated rats showed improved cognitive function and reduced hippocampal neuronal *** found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91^(phox) and p47^(phox) proteins in KA-induced chronic TLE ***,even after discontinuation of DM treatment,ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects,which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.

关键词： Temporal lobe epilepsy Dextromethorphan NADPH oxidase Ultra-low dose

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Modeling of multiphase flow in low permeability porous media:Effect of wettability and pore structure properties

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第4期16卷 1127-1139页

作者： Xiangjie Qin Yuxuan Xia Juncheng Qiao Jiaheng Chen Jianhui Zeng Jianchao Cai national Key Laboratory of Petroleum Resources and Engineering China University of PetroleumBeijing102249China research institute of Petroleum Exploration and development Beijing10083China

Multiphase flow in low permeability porous media is involved in numerous energy and environmental ***,a complete description of this process is challenging due to the limited modeling scale and the effects of complex pore structures and *** address this issue,based on the digital rock of low permeability sandstone,a direct numerical simulation is performed considering the interphase drag and boundary slip to clarify the microscopic water-oil displacement *** addition,a dual-porosity pore network model(PNM)is constructed to obtain the water-oil relative permeability of the *** displacement efficiency as a recovery process is assessed under different wetting and pore structure *** show that microscopic displacement mechanisms explain the corresponding macroscopic relative *** injected water breaks through the outlet earlier with a large mass flow,while thick oil films exist in rough hydrophobic surfaces and poorly connected *** variation of water-oil relative permeability is significant,and residual oil saturation is high in the oil-wet *** flooding is extensive,and the residual oil is trapped in complex pore networks for hydrophilic pore surfaces;thus,water relative permeability is lower in the water-wet *** the displacement efficiency is the worst in mixed-wetting systems for poor water *** negatively correlates with invading oil volume fraction due to strong capillary resistance,and a large microporosity corresponds to low residual oil *** work provides insights into the water-oil flow from different modeling perspectives and helps to optimize the development plan for enhanced recovery.

关键词： Low permeability porous media Water-oil flow Wettability Pore structures Dual porosity pore network model(PNM) Free surface model

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Fine description of unconventional clastic oil reservoirs

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Petroleum research 2024年第2期9卷 289-303页

作者： Huanqing Chen research institute of Petroleum Exploration&development PetroChinaChina

The latest researches reveal that studies on unconventional clastic oil reservoirs in China generally lag far behind those in other countries in respect of content and *** study presents the definition and classification of unconventional oil reservoirs and analyzes the problems in the fine description of unconventional oil *** key content of the fine description of unconventional oil reservoirs is summarized from four aspects:fine fracture characterization based on fine structure interpretation,reservoir architecture characterization based on sedimentary facies,characteristics of nanoscale microscopic pore structure of reservoir,and evaluation of source rock and“sweet spot zone”.Finally,this study suggests that development of fine description of unconventional clastic oil reservoirs in the future should focus on rock brittleness analysis and fracture modeling,geophysical characterization of unconventional clastic oil reservoirs,fluid description of tight reservoirs,and physical/numerical simulation experiments of unconventional oil reservoirs.

关键词： Unconventional clastic reservoir Fine reservoir description Oil sand Tight oilShale oil Fracture characterization Nanoscale microscopic pore structure Sweet spot

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State of the art of lightweight aggregates used in lightweight refractories for working lining of high-temperature furnaces

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Journal of Iron and Steel research(International) 2024年第6期31卷 1320-1343页

作者： Wei Zhang Wen-yong Dai Shenyang national Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016LiaoningChina research and development Department AGC Plibrico(Dalian)Industries Inc.Dalian 116600LiaoningChina

Lightweight refractories for the working lining of high-temperature furnaces play an important role in the smelting of advanced steels and *** prepare lightweight refractories for the working lining of high-temperature furnaces,the synthesis of lightweight aggregates is the ***,the research on the synthesis of lightweight aggregates with high service temperature,low thermal conductivity,high strength,and good slag resistance has received widespread *** available literature on the synthesis of lightweight aggregates was summarized,including corundum,mullite,mullite-corundum,spinel,corundum-spinel,cordierite,cordierite-mullite,calcium hexaluminate,corundum-calcium hexaluminate,bauxite,magnesia,magnesia-based,and forsterite-based ***,the future development trend of lightweight aggregates was proposed.

关键词： Lightweight aggregate Lightweight refractory Working lining Apparent porosity Closed porosity Thermal conductivity Pore-forming approach

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Active disturbance rejection distributed secondary control for DC microgrids

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High Voltage 2024年第1期9卷 241-251页

作者： Jianlin Li Honghao You Shuo Liu Xingchen Li Ziyang Ding Fei Zou national User-Side Energy Storage Innovation research and development Center North China University of TechnologyBeijingChina

A novel control scheme is presented to eliminate the negative effects of communication disturbances,which introduces active disturbance rejection control(ADRC)in the control strategy design to achieve the objectives of the restoration of the bus voltage and the sharing of the power even in the presence of disturbances and delays in ***,its dynamic disturbance decoupling feature is used to realise the decoupling between power and voltage,so that the proposed controller only exchanges power information with its neighbours,reducing the communication burden and simplifying control *** control performance of the strategy is verified by employing steady-state *** impact of controller parameters is studied by establishing a small signal ***,both simulation cases and experimental tests prove the feasibility of this scheme.

关键词： Active disturbance establishing

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Bispecific antibody drug conjugates:Making 1+1>2

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1965-1986页

作者： Yilin Gu Zhijia Wang Yuxi Wang Targeted Tracer research and development Laboratory Institute of Respiratory HealthFrontiers Science Center for Disease-Related Molecular NetworkNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China Frontiers Medical Center Tianfu Jincheng LaboratoryChengdu 610212China

Bispecific antibody‒drug conjugates(BsADCs)represent an innovative therapeutic category amalgamating the merits of antibody‒drug conjugates(ADCs)and bispecific antibodies(BsAbs).Positioned as the next-generation ADC approach,BsADCs hold promise for ameliorating extant clinical challenges associated with ADCs,particularly pertaining to issues such as poor internalization,off-target toxicity,and drug ***,ten BsADCs are undergoing clinical trials,and initial findings underscore the imperative for ongoing *** review initially delves into specific design considerations for BsADCs,encompassing target selection,antibody formats,and the linker–payload *** sections delineate the extant progress and challenges encountered by BsADCs,illustrated through pertinent case *** amalgamation of BsAbs with ADCs offers a prospective solution to prevailing clinical limitations of ***,the symbiotic interplay among BsAb,linker,and payload necessitates further optimizations and coordination beyond a simplistic“1+1”to effectively surmount the extant challenges facing the BsADC domain.

关键词： Bispecific antibody drug conjugates Antibody drug conjugates Bispecific antibody Targeted therapy Safety HER2 EGFR

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Resonance mechanism of flapping wing based on fluid structure interaction simulation

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Chinese Journal of Aeronautics 2024年第5期37卷 243-262页

作者： Yueyang GUO Wenqing YANG Yuanbo DONG Dong XUE national Key Laboratory of Science and Technology on Aerodynamic Design and research School of AeronauticsNorthwestern Polytechnical UniversityXi'an 710072China research&development institute of Northwestern Polytechnical University in Shenzhen Shenzhen 518063China Yangtze River Delta research institute of Northwestern Polytechnical University Taicang 215400China

Certain insect species have been observed to exploit the resonance mechanism of their *** order to achieve resonance and optimize aerodynamic performance,the conventional approach is to set the flapping frequency of flexible wings based on the Traditional Structural Modal(TSM)***,there exists controversy among researchers regarding the relationship between frequency and aerodynamic *** that the structural response of wings can be influenced by the surrounding air vibrations,an analysis known as Acoustic Structure Interaction Modal(ASIM)is introduced to calculate the resonant *** this study,Fluid Structure Interaction(FSI)simulations are employed to investigate the aerodynamic performance of flapping wings at modal frequencies derived from both TSM and ASIM *** performance is evaluated for various mass ratios and frequency ratios,and the findings indicate that the deformation and changes in vortex structure exhibit similarities at mass ratios that yield the highest aerodynamic ***,the flapping frequency associated with the maximum time-averaged vertical force coefficient at each mass ratio closely aligns with the ASIM frequency,as does the frequency corresponding to maximum ***,the ASIM analysis can provide an effective means for predicting the optimal flapping frequency for flexible ***,it enables the prediction that flexible wings with varying mass ratios will exhibit similar deformation and vortex structure *** paper offers a fresh perspective on the ongoing debate concerning the resonance mechanism of Flexible Flapping Wings(FFWs)and proposes an effective methodology for predicting their aerodynamic performance.

关键词： Flexible Flapping Wing(FFW) Acoustic Structure Interaction Modal(ASIM) Fluid Structure Interaction(FSI) Resonance mechanism Aerodynamic performance

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