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BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/ Stat3 pathway in mesenchymal stem cells

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Genes & Diseases 2024年第3期11卷 468-483页

作者： Jie Zhang Jinhai Jiang hang Liu Shiyu Wang Kaixin Ke Siyuan Liu Yue Jiang Lu Liu Xiang gao Baicheng he Yuxi Su Department of Pharmacology School of PharmacyChongqing Medical UniversityChongqing 400016China Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing Chongqing Medical UniversityChongqing 400016China Department of Orthopedics Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China orthopedics Department Children's Hospital of Chongqing Medical UniversityChongqing 400014China China International Science and Technology Cooperation Base of Child Development and Critical Disorders Jiangxi Hospital Affiliated Children's Hospital of Chongqing Medical UniversityJiangxi 330000China National Clinical Research Center for Child health and Disorders China

Bone defects and non-union are prevalent in clinical orthopedy,and the outcomes of current treatments are often suboptimal.Bone tissue engineering offers a promising approach to treating these conditions effectively.Bone morphogenetic protein 9(BMP9)can commit mesenchymal stem cells to osteogenic lineage,and a knowledge of the underlying mechanisms may help advance the field of bone tissue engineering.Leucine-rich repeats con-taining G protein-coupled receptor 4(LGR4),a member of G protein-coupled receptors,is essential for modulating bone development.This study is aimed at investigating the impact of LGR4 on BMP9-induced osteogenesis in mesenchymal stem cells as well as the underlying mechanisms.Bone marrow stromal cells from BMp9-knockout mice exhibited diminished LGR4 expression,and exogenous LGR4 clearly restored the impaired osteogenic potency of the bone marrow stromal cells.Furthermore,LGR4 expression was increased by BMP9 in C3H10T1/2 cells.LGR4 augmented the benefits of BMP9-induced osteogenic markers and bone formation,whereas LGR4 inhibition restricted these effects.Meanwhile,the BMP9-induced li-pogenic markers were increased by LGR4 inhibition.The protein levels of Raptor and p-Stat3 were elevated by BMP9.Raptor knockdown or p-Stat3 suppression attenuated the osteoblastic markers and LGR4 expression brought on by BMP9.LGR4 significantly reversed the blocking ef-fect of Raptor knockdown or p-Stat3 suppression on the BMP9-induced osteoblastic markers.Raptor interacts with p-Stat3,and p-Stat3 activates the LGR4 promoter activity.In conclusion,LGR4 boosts BMP9 osteoblastic potency in mesenchymal stem cells,and BMP9 may up-regulate LGR4 via the mTORC1/Stat3 signal activation.

关键词： BMP9 LGR4 mTORC1 Osteogenic differentiation Stat3

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Increased long-distance and homo-trans interactions related to H3K27me3 in Arabidopsis hybrids

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Journal of Integrative Plant Biology 2024年第2期66卷 208-227页

作者： Zhaoxu gao Yanning Su Le Chang Guanzhong Jiao Yang Ou Mei Yang Chao Xu Pengtao Liu Zejia Wang Zewen Qi Wenwen Liu Linhua Sun Guangming he Xing Wang Deng hang he School of Advanced Agriculture Sciences and School of Life Sciences State Key Laboratory of Protein and Plant Gene ResearchPeking UniversityBeijing 100871China College of Grassland Science Beijing Forestry UniversityBeijing 100083China Peking University Institute of Advanced Agricultural Sciences Shandong Laboratory of Advanced Agricultural Sciences in WeifangWeifang 261325China

In plants,the genome structure of hybrids changes compared with their parents,but the effects of these changes in hybrids remain elusive.Comparing reciprocal crosses between Col×C24 and C24×Col in Arabidopsis using high-throughput chromosome conformation capture assay(Hi-C)analysis,we found that hybrid three-dimensional(3D)chromatin organization had more long-distance interactions relative to parents,and this was mainly located in promoter regions and enriched in genes with heterosis-related pathways.The interactions between euchromatin and heterochromatin were increased,and the compartment strength decreased in hybrids.In compartment domain(CD)boundaries,the distal interactions were more in hybrids than their parents.In the hybrids of CURLY LEAF(clf)mutants clfCol×clfC24and clfC24×clfCol,the heterosis phenotype was damaged,and the long-distance interactions in hybrids were fewer than in their parents with lower H3K27me3.ChIP-seq data revealed higher levels of H3K27me3 in the region adjacent to the CD boundary and the same interactional homo-trans sites in the wild-type(WT)hybrids,which may have led to more long-distance interactions.In addition,the differentially expressed genes(DEGs)located in the boundaries of CDs and loop regions changed obviously in WT,and the functional enrichment for DEGs was different between WT and clf in the longdistance interactions and loop regions.Our findings may therefore propose a new epigenetic explanation of heterosis in the Arabidopsis hybrids and provide new insights into crop breeding and yield increase.

关键词： 3D chromatin organization H3K27me3 homo-trans hybrids long-distanceinteractions

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Patterns and drivers of plant sexual systems in the dry-hot valley region of southwestern China

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Plant Diversity 2024年第2期46卷 158-168页

作者： Rong Ma Qi Xu Yongqian gao Deli Peng hang Sun Bo Song State Key Laboratory of Plant Diversity and Specialty Crops/Yunnan Key Laboratory for Integrative Conservation of Plant Species with Extremely Small Populations Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China College of Life Sciences Shaanxi Normal UniversityXi'an 710119China Yunnan Forestry Technological College Kunming 650224China School of Life Science/Key Laboratory of Yunnan for Biomass Energy and Biotechnology of Environment Yunnan Normal UniversityKunming 650500YunnanChina

Sexual systems play important roles in angiosperm evolution and exhibit substantial variations among different floras. Thus, studying their evolution in a whole flora is crucial for understanding the formation and maintenance of plant biodiversity and predicting its responses to environmental change. In this study, we determined the patterns of plant sexual systems and their associations with geographic elements and various life-history traits in dry-hot valley region of southwestern China, an extremely vulnerable ecosystem. Of the 3166 angiosperm species recorded in this area, 74.5% were hermaphroditic,13.5% were monoecious and 12% were dioecious, showing a high incidence of diclinous species. Diclinous species were strongly associated with tropical elements, whereas hermaphroditic species were strongly associated with temperate and cosmopolitan elements. We also found that hermaphroditism was strongly associated with showy floral displays, specialist entomophily, dry fruits and herbaceous plants.Dioecy was strongly associated with inconspicuous, pale-colored flowers, generalist entomophily, fleshy fruits, and woody plants, whereas monoecy was strongly associated with inconspicuous, pale-colored flowers, anemophily, dry fruits, and herbaceous plants. In addition, hermaphroditic species with generalist entomophily tended to flower in the dry season, whereas diclinous species with specialist entomophily tended to flower in the rainy season. However, independent of sexual systems, plants that produce dry fruits tended to flower in the rainy season and set fruits in the dry season, but the opposite pattern was found for fleshy fruit-producing plants. Our results suggest that in the dry-hot valleys, plant sexual systems are associated with geographic elements as well as various life-history traits that are sensitive to environmental change.

关键词： Floral traits Fruit type Growth form Pollination system Reproductive phenology

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Semi-implantable device based on multiplexed microfilament electrode cluster for continuous monitoring of physiological ions

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Bio-Design and Manufacturing 2024年第1期7卷 88-103页

作者： Shuang Huang Shantao Zheng Mengyi he Chuanjie Yao Xinshuo Huang Zhengjie Liu Qiangqiang Ouyang Jing Liu Feifei Wu hang gao Xi Xie Hui-jiuan Chen State Key Laboratory of Optoelectronic Materials and Technologies Guangdong Province Key Laboratory of Display Material and TechnologySchool of Electronics and Information TechnologySun Yat-Sen UniversityGuangzhou 510006China Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument School of Biomedical EngineeringSun Yat-Sen UniversityShenzhen 518107China The First Affiliated Hospital of Sun Yat-Sen University Guangzhou 510080China Pazhou Lab Guangzhou 510335China Institute of Microelectronics of the Chinese Academy of Sciences Beijing 100029China

Modern medicine is increasingly interested in advanced sensors to detect and analyze biochemical indicators.Ion sensors based on potentiometric methods are a promising platform for monitoring physiological ions in biological subjects.Current semi-implantable devices are mainly based on single-parameter detection.Miniaturized semi-implantable electrodes for multiparameter sensing have more restrictions on the electrode size due to biocompatibility considerations,but reducing the electrode surface area could potentially limit electrode sensitivity.This study developed a semi-implantable device system comprising a multiplexed microfilament electrode cluster(MMEC)and a printed circuit board for real-time monitoring of intra-tissue K^(+),Ca^(2+),and Na^(+)concentrations.The electrode surface area was less important for the potentiometric sensing mechanism,suggesting the feasibility of using a tiny fiber-like electrode for potentiometric sensing.The MMEC device exhibited a broad linear response(K^(+):2–32 mmol/L;Ca^(2+):0.5–4 mmol/L;Na^(+):10–160 mmol/L),high sensitivity(about 20–45 mV/decade),temporal stability(>2weeks),and good selectivity(>80%)for the above ions.In vitro detection and in vivo subcutaneous and brain experiment results showed that the MMEC system exhibits good multi-ion monitoring performance in several complex environments.This work provides a platform for the continuous real-time monitoring of ion fluctuations in different situations and has implications for developing smart sensors to monitor human health.

关键词： Multiplexed microfilament electrode cluster Physiological ion sensing Subcutaneous and brain experiment Wearable platform for multi-ion detection Continuous real-time monitoring system

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Effectiveness of Acupoint Application in Patients with Pharyngeal Pain: Evidence from CHUNBO, A Prospective Real-World Study

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Chinese Journal of Integrative Medicine 2024年第1期30卷 18-24页

作者： MA hang-kun WANG Yi-ming GUO Man-ping LI Chen-fei LI Rui gao Rui Emergency Department Xiyuan Hospital Affiliated to China Academy of Chinese Medical SciencesBeijing(100091)China National Medical Products Administration for Laboratory of Clinical Research and Evaluation of Traditional Chinese Medicine Beijing(100091)China National Clinical Research Center for Chinese Medicine Cardiology Beijing(100091)China Postdoctoral Workstation of Yabao Pharmaceutical Group Co. Ltd.YunchengShanxi Province(044602)China

Objective: To assess the outcomes after acupoint application in patients with pharyngeal pain in a real-world settings, and analyze the characteristics of effective population and prescription characteristics of acupoint application. Methods: Based on CHUNBO platform, patients with pharyngeal pain who were candidates for acupoint application on the basis of physician-evaluation, were enrolled in a nationwide, prospective, 69-week multicenter observational study from August 2020 to February 2022. Propensity score matching(PSM) was used to match the confounding factors and the association rules were used to analyze the characteristics of effective population and prescription characteristics of acupoint application. Outcome assessments included the disappearance rate of pharyngeal pain(within 3, 7, and 14 days), disappearance time of pharyngeal pain, as well as adverse events. Results: Of 7,699 enrolled participants, 6,693(86.9%) received acupoint application and 1,450(21.7%) with non-acupoint application. After PSM, there were 1,004 patients each in the application group(AG) and non-application group(NAG). The disappearance rate of pharyngeal pain in the AG at 3, 7, and 14 days were all higher than those in the NAG(Phe disappearance time of pharyngeal pain in the AG were shorter than that in the NAG(logrank Phe median age of effective cases was 4 years, mainly 3–6 years old(40.21%). The disappearance rate of pharyngeal pain in the application group with tonsil diseases was 2.19 times higher than that in the NAG(Phe commonly used acupoints for the effective cases were Tiantu(RN 22), Shenque(RN 8) and Dazhui(DU 14). The commonly used herbs for the effective cases were Natrii sulfas, Radix et Rhizoma Rhei, and herba Ephedrae. Among them, Natrii sulfas was applied to RN 8 most frequently(support 84.39%). A total of 1,324(17.2%) patients experienced AEs, and mainly occurred in the AG, with significant difference in the incidence of AEs be

关键词： acupoint application Chinese medicine pharyngeal pain multicentre effectiveness characters real-world study

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Preparation, Crystallization and Mechanical Properties of Potassium Aluminosilicate Glass-ceramics

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Journal of Wuhan University of Technology(Materials Science) 2024年第3期39卷 587-595页

作者：郑伟宏黄猛 gao Zipeng Zhang hang YUAN Jian TIAN Peijing PENG Zhigang State Key Laboratory of Silicate Materials for Architectures Wuhan University of TechnologyWuhan 430070China Shahe Research Institute of Glass Technology Shahe 054100China

In this study,transparent K_(2)O-Al_(2)O_(3)-SiO_(2)(KAS)glass-ceramics with leucite as the main crystalline phase were prepared by melting-quench method and two-step heat treatment.The effects of SiO_(2)/Al_(2)O_(3) ratio and heat treatment on crystallization and mechanical properties were studied.The crystallization kinetics and X-Ray Diffraction(XRD)results showed that SiO_(2)/Al_(2)O_(3) ratio and heat treatment system had a direct impact on the crystallization behavior of potassium aluminosilicate glass-ceramics.When heat-treated at 680℃/2 h and 780℃/1 h,cracks generated on the surface of the sample with the addition of SiO_(2)/Al_(2)O_(3)=4.8(in mol)due to the huge difference in the coefficient of thermal expansion between glass matrix and surface.When the addition of SiO_(2)/Al_(2)O_(3)(in mol)was 4,the sample with leucite as the main crystalline phase showed an excellent fracture toughness(1.46 MPa·m^(0.5))after the heat treatment of 680℃/2 h and 780℃/5 h.And there was a phase transformation from kaliophilite to leucite.The crystalline phases of the sample heat-treated at 680℃/8 h and 780℃/1 h were leucite and kaliophilite,which resulted in the visible light transmittance of 63%and the fracture toughness of 0.91 MPa·m^(0.5).Furthermore,after the heat treatment of 680℃/2 h and 780℃/5 h,the main crystalline phase of the sample with SiO_(2)/Al_(2)O_(3)=3.2(in mol)was still kaliophilite.Because leucite only grows on the surface of the sample and is hard to grow inward,it is hard to achieve the bulk crystallization of leucite in the sample with SiO_(2)/Al_(2)O_(3)=3.2(in mol).

关键词： leucite glass-ceramic kaliophilite crystallization kinetics

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Exploring precursor effect in in-situ reconstruction of Bi metal organic-frameworks during CO_(2)electroreduction reaction to tailor formate selectivity towards 100%

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Science China Chemistry 2024年第7期67卷 2190-2198页

作者： Zhida Liu Qikui Fan hang Huo Fanglei Yao Xiaoping gao Jin Wang College of Materials Science and Engineering Shenzhen UniversityShenzhen 518071China College of Physics and Optoelectronic Engineering Shenzhen UniversityShenzhen 518060China Key Laboratory of Functional Molecular Solids Ministry of EducationCollege of Chemistry and Materials ScienceAnhui Normal UniversityWuhu 241002China hefei National Research Center for Physical Sciences at the Microscale University of Science and Technology of ChinaHefei 230026China

Bi-based metal-organic frameworks(Bi-MOFs)as efficient catalysts for the CO_(2)electroreduction reaction(CRR)have been extensively investigated.It has been established that Bi-MOFs usually undergo in-situ transformation during the CRR,ultimately converting into Bi nanostructures.However,the effect of the MOF precursors on the structure of the derived Bi catalysts and consequently on their electrocatalytic properties has not been clearly elucidated.In this work,we prepared four variants of a novel Bi-MOF with different morphologies and dimensions,and explored the effects of the precursors on the resulting Bi catalysts and their CRR performance.A precursor-dependent in-situ transformation and its profound impact on tuning the CO_(2)-formate FE towards~100%have been revealed.Among the four examined variants,Bi-MOF with nanocube-like morphology(BiMOF-NC)is transformed into thin and flat Bi nanosheets capable of successfully enveloping the fibers of carbon paper(working electrode),while the other three variants with increased size and dodecahedral/octahedral geometry have been transformed into Bi nanoflowers,exposing a fair portion of the carbon fibers in the working electrode.Furthermore,the transformation rate was found to be dependent on the precursors and BiMOF-NC exhibited the highest rate of reconstruction compared with other samples.Consequently,the Bi catalyst derived from BiMOF-NC delivered a selectivity for the formate product of nearly 100%at-1.2 V(vs.reversible hydrogen electrode(Rhe))and of over 95%in a wide potential range due to efficient suppression of the competing hydrogen evolution reaction(heR)over carbon fibers.The in-situ transformed BiMOFNC also demonstrated equivalently high formate selectivity at large current densities(≥100 mA cm^(-2))in flow cell reactors as that in H-type reactors,underscoring its potential for industrial applications.This work highlights the necessity of finely tuning the structural features of MOF precursors to achieve optimized electrocatalytic performance.

关键词： Bi-MOFs precursor effect in-situ transformation Bi nanosheets CO2-to-formate

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Ultra‑Efficient and Cost‑Effective Platinum Nanomembrane Electrocatalyst for Sustainable Hydrogen Production

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Nano-Micro Letters 2024年第6期16卷 95-110页

作者： Xiang gao Shicheng Dai Yun Teng Qing Wang Zhibo Zhang Ziyin Yang Minhyuk Park hang Wang Zhe Jia Yunjiang Wang Yong Yang Department of Mechanical Engineering College of EngineeringCity University of Hong KongTat Chee AvenueKowloon TongKowloonHong KongPeople’s Republic of China State Key Laboratory of Nonlinear Mechanics Institute of MechanicsChinese Academy of SciencesBeijingPeople’s Republic of China School of Engineering Science University of Chinese Academy of SciencesBeijingPeople’s Republic of China Laboratory for Microstructures Institute of MaterialsShanghai UniversityShanghaiPeople’s Republic of China School of Materials Science and Engineering Jiangsu Key Laboratory for Advanced Metallic MaterialsSoutheast UniversityNanjingPeople’s Republic of China Department of Materials Science and Engineering College of EngineeringCity University of Hong KongTat Chee AvenueKowloon TongKowloonHong KongPeople’s Republic of China

Hydrogen production through hydrogen evolution reaction(heR)offers a promising solution to combat climate change by replacing fossil fuels with clean energy sources.However,the widespread adoption of efficient electrocatalysts,such as platinum(Pt),has been hindered by their high cost.In this study,we developed an easy-to-implement method to create ultrathin Pt nanomembranes,which catalyze heR at a cost significantly lower than commercial Pt/C and comparable to non-noble metal electrocatalysts.These Pt nanomembranes consist of highly distorted Pt nanocrystals and exhibit a heterogeneous elastic strain field,a characteristic rarely seen in conventional crystals.This unique feature results in significantly higher electrocatalytic efficiency than various forms of Pt electrocatalysts,including Pt/C,Pt foils,and numerous Pt singleatom or single-cluster catalysts.Our research offers a promising approach to develop highly efficient and cost-effective low-dimensional electrocatalysts for sustainable hydrogen production,potentially addressing the challenges posed by the climate crisis.

关键词： Platinum Hydrogen evolution reaction Lattice distortion heterogeneous strain

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Metagenomic analysis revealing the metabolic role of microbial communities in the free amino acid biosynthesis of Monascus rice vinegar during fermentation

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Food Science and Human Wellness 2024年第4期13卷 2317-2326页

作者： hang gao Jian Zhang Li Liu Lijun Fu Yan Zhao Germán Mazza Xin Zhang Beijing Academy of Food Sciences 100068 BeijingChina Institute for Research and Development in Process Engineering Biotechnology and Alternative Energies(PROBIENCONICET-UNCo)8300 NeuquénArgentina

Free amino acid(FAA)is the important component of vinegar that infl uences quality perception and consumer acceptance.FAA is one of the major metabolites produced by microorganisms;however,the microbial metabolic network on FAA biosynthesis remains unclear.Through metagenomic analysis,this work aimed to elucidate the roles of microbes in FAA biosynthesis during Monascus rice vinegar fermentation.Taxonomic profiles from functional analyses showed 14 dominant genera with high contributions to the metabolism pathways.The metabolic network for FAA biosynthesis was then constructed,and the microbial distribution in different metabolic pathways was illuminated.The results revealed that 5 functional genera were closely involved in FAA biosynthesis.This study illuminated the metabolic roles of microorganisms in FAA biosynthesis and provided crucial insights into the functional attributes of microbiota in vinegar fermentation.

关键词： Monascus rice vinegar Metagenomic analysis Free amino acid synthesis Metabolic pathway Microbial distribution

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Status and developmental trends in recombinant collagen preparation technology

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Regenerative Biomaterials 2024年第2期3卷 17-36页

作者： Xiaolei Guo Yuan Ma hang Wang Hongping Yin Xinli Shi Yiqin Chen Guobiao gao Lei Sun Jiadao Wang Yunbing Wang Daidi Fan Center for Medical Device Evaluation National Medical Products AdministrationBeijing 100081China State Key Laboratory of Tribology Tsinghua UniversityBeijing 100084China school of Life Science and Technology China Pharmaceutical UniversityNanjing 210009China National Engineering Research Center for Biomaterials&College of Biomedical Engineering Sichuan UniversityChengdu 610064China Biotech.&Biomed.Research Institute Northwest UniversityXi'an 710127China

Recombinant collagen is a pivotal topic in foundational biological research and epitomizes the application of critical bioengineer-ing technologies.These technological advancements have pro-found implications across diverse areas such as regenerative medicine,organ replacement,tissue engineering,cosmetics and more.Thus,recombinant collagen and its preparation methodologies rooted in genetically engineered celis mark pivotal milestones in medical product research.This article pro-vides a comprehensive overview of the current genetic engi-neering technologies and methods used in the production of recombinant collagen,as well as the conventional production process and gquality control detection methods for this material.Furthermore,the discussion extends to foresee the strides in physical transfection and magnetic control sorting studies,envisioning an enhanced preparation of recombinant collagen-seeded cells to further fuel recombinant collagen production.

关键词： recombinant collagen preparation genetic engineering collagen characterization physical transfection seed cell sorting

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