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Brain regulates weight bearing bone through PGE2 skeletal interoception: implication of ankle osteoarthritis and pain

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Bone Research 2024年第1期12卷 107-121页

作者： Feng Gao Qimiao Hu Wenwei Chen Jilong Li Cheng Qi Yiwen Yan Cheng Qian mei wan James Ficke Junying Zheng Xu Cao Department of Orthopedic Surgery Johns Hopkins University School of MedicineBaltimoreMaryland 21205USA Department of Biomedical Engineering Johns Hopkins University School of MedicineBaltimoreMaryland 21205USA

Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.

关键词： pain elevated PGE2

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Predictors of Adverse Pregnancy Outcomes Following Traumatic Injuries

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Current Medical Science 2024年第3期44卷 642-647页

作者： wan-rong LU Ping WU Gong SONG mei-qi GU Zhe XU Li HE National Clinical Research Center for Gynecology and Obstetrics Cancer Biology Research CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Traumatic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective After traumatic injury in pregnant women,providing timely and appropriate management for high-risk patients is crucial for both pregnant women and fetuses.This study aimed to identify risk factors that predict adverse pregnancy outcomes after traumatic injury.Methods A retrospective cohort study including 317 pregnant patients who experienced trauma was conducted.The collected data included general demographics,injury mechanisms and adverse pregnancy outcomes.Patients were divided into two subgroups based on the absence or presence of trauma-related adverse pregnancy outcomes.Univariate and multivariate logistic regressions were conducted to estimate the associations between clinical variables and adverse pregnancy outcomes.Results A total of 41(12.93%)patients experienced adverse pregnancy outcomes within the first 24 h post-trauma.This study revealed that age>35 years(OR=14.995,95%CI:5.024–44.755,P<0.001),third trimester trauma(OR=3.878,95%CI:1.343–11.204,P=0.012),abdominal pain(OR=3.032,95%CI:1.221–7.527,P=0.017),vaginal bleeding(OR=3.226,95%CI:1.093–9.523,P=0.034),positive scan in focused assessment with sonography for trauma(FAST)positive(OR=8.496,95%CI:2.825–25.555,P<0.001),9≤injury severity score(ISS)<16(OR=3.039,95%CI:1.046–8.835,P=0.041)and ISS≥16(OR=5.553,95%CI:1.387–22.225,P=0.015)increased the probability of posttraumatic adverse pregnancy outcomes.Maternal age,gestational age at delivery,vaginal bleeding and positive FAST results were risk factors for abnormal delivery.Conclusion Advanced maternal age,third trimester,and positive FAST results should alert multidisciplinary trauma teams to closely monitor patients to prevent adverse pregnancy outcomes.

关键词： adverse pregnancy outcomes predictive factors abnormal delivery trauma

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Large Deviations for a Critical Galton-Watson Branching Process

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Acta Mathematicae Applicatae Sinica 2024年

作者： Dou-dou LI wan-lin SHI mei ZHANG College of Statistics and Data Science Faculty of Science Beijing University of Technology Laboratory of Mathematics and Complex Systems (Ministry of Education) School of Mathematical SciencesBeijing Normal University Department of Mathematics and Physics North China Electric Power University

In this paper, a critical Galton-Watson branching process{Zn}is considered. Large deviation rates of SZn:=∑i=1ZnXiare obtained, where{Xi, i≥1}is a sequence of independent and identically distributed random variables and X1is in the domain of attraction of an α-stable law with α∈(0, 2). One shall see that the convergence rate is determined by the tail index of X1and the variance of Z1. Our results can be compared with those ones of the supercritical case.

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Evaluating the Compatibility Mechanism of Shengxian Decoction Based on an Excretion Study of 18 Bioactive Constituents in Rat Biosamples

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 40-52页

作者： Tao Pang Nan Weng Yong Chen Cui-Yun Huang mei Sun Feng Zhang wan-Sheng Chen Department of Pharmacy Changzheng HospitalNaval Medical University(Second Military Medical University)ShanghaiChina Department of Pharmacognosy Shenyang Pharmaceutical University ShenyangLiaoning ProvinceChina Traditional Chinese Medicine Resource and Technology Center Shanghai University of Traditional Chinese MedicineShanghaiChina

Introduction:The Shengxian decoction(SXT),a Chinese herbal medication used to treat heart failure,is composed of Astragali Radix,Anemarrhenae Rhizoma,Bupleuri Radix,Cimicifuage Rhizoma,and Platycodonis Radix.Knowledge of the excretion of the active compounds in this herbal medication is vital for investigating the underlying mechanisms behind its compatibility.However,this remains unclear.Methods:Liquid chromatography coupled with mass spectrometry was performed in both positive and negative modes to assay 18 constituents of SXT from rat urinary,fecal,and biliary samples.Results:The methodology was validated and showed good linearity(r≥0.9),precision,stability,repeatability,and recovery.The relative standard deviations and relative errors for the precision and accuracy did not exceed 15%.The recoveries of all the compounds ranged from 77.37%to 114.82%,and the matrix effect was between 82.53%and 105.71%.The results suggested that,when combined with Platycodonis Radix,the levels of 14 constituents from the four herbs were reduced in the urine,while the levels of six constituents were reduced in the feces.Conclusions:The comparative excretion results indicated that Platycodonis Radix reduced the excretion of compounds in SXT,demonstrating the compatibility mechanism and holistic properties of these compounds,favoring the pharmacological effects of SXT.

关键词： Compatibility excretion liquid chromatography coupled with mass spectrometry Platycodonis Radix Shengxian decoction

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Thiazoloisoindigo-based Polymer Semiconductors: Synthesis,Structure-Property Relationship, Charge Carrier Polarity, and Field-Effect Transistor Performance

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Chinese Journal of Polymer Science 2024年第1期42卷 24-31,I0006页

作者： Bo-Wen Li Miao Xiong mei-Hua Liu Zhi-Gao Li Long Sang Zi-Han Xiong Biao Xiao Jian Pei Xiao-Bo wan Key Laboratory of Optoelectronic Chemical Materials and Devices Ministry of EducationSchoolofOptoelectronic Materials&TechnologyJianghan UniversityWuhan430056China Bejing National Laboratoryfor Molecular Sciences the Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of EducationCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

Developing new polymeric semiconductors with excellent device performance is essential for organic electronics. Herein, we synthesized two new thiazoloisoindigo(Tz II)-based polymers, namely, P(Tz II-d Th-d Th) and P(Tz II-d Th-d Tz), by copolymerizing thiophene-flanked Tz II with bithiophene and bithiazole, respectively. Owing to the more electron-deficient nature of bithiazole than bithiophene, P(Tz II-d Th-d Tz)possesses deeper LUMO/HOMO levels of-3.45/-5.47 e V than P(Tz II-d Th-d Th)(-3.34/-5.32 e V). The organic field-effect transistor(OFET) devices based on P(Tz II-d Th-d Th) exhibited p-type behaviors with an average hole mobility value as high as 1.43 cm^(2)·V^(-1)·s^(-1), while P(Tz II-d Th-d Tz)showed typical ambipolar characteristics with average hole and electron mobilities of 0.38 and 0.56 cm^(2)·V^(-1)·s^(-1). In addition, we compared the performances of both polymers with other Tz II-based polymers reported in our previous work, and showed that the charge carrier polarity can be manipulated by adjusting the number of the thiophene units between the acceptor unit. As the increase of the number of thiophene rings,charge carrier polarity shifts from electron-dominated ambipolar transport to hole-dominated ambipolar transport and then to unipolar hole transport in OFETs, which provides an effective molecular design strategy for further optimization of polymer OFET performance.

关键词： Field-effect transistor Charge carrier polarity Thiazoloisoindigo

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Sialylation of TLR2 initiates osteoclast fusion

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Bone Research 2022年第2期10卷 286-296页

作者： Ce Dou Gehua Zhen Yang Dan mei wan Nathachit Limjunyawong Xu Cao Department of Orthopedic Surgery Institute of Cell Engineering and Department of Biomedical EngineeringJohns Hopkins University School of MedicineBaltimoreMDUSA The Solomon H.Snyder Department of Neuroscience Johns Hopkins University School of MedicineBaltimoreMDUSA

The molecular control of osteoclast formation is still not clearly elucidated. Here, we show that a process of cell recognition mediated by Siglec15-TLR2 binding is indispensable and occurs prior to cell fusion in RANKL-mediated osteoclastogenesis. Siglec15 has been shown to regulate osteoclastic bone resorption. However, the receptor for Siglec15 has not been identified, and the signaling mechanism involving Siglec15 in osteoclast function remains unclear. We found that Siglec15 bound sialylated TLR2 as its receptor and that the binding of sialylated TLR2 to Siglec15 in macrophages committed to the osteoclast-lineage initiated cell fusion for osteoclast formation, in which sialic acid was transferred by the sialyltransferase ST3 Gal1. Interestingly, the expression of Siglec15 in macrophages was activated by M-CSF, whereas ST3 Gal1 expression was induced by RANKL. Both Siglec15-specific deletion in macrophages and intrafemoral injection of sialidase abrogated cell recognition and reduced subsequent cell fusion for the formation of osteoclasts, resulting in increased bone formation in mice. Thus, our results reveal that cell recognition mediated by the binding of sialylated TLR2 to Siglec15 initiates cell fusion for osteoclast formation.

关键词： osteoclast TLR2 injection

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Effect of slow shot speed on externally solidified crystal,porosity and tensile property in a newly developed high-pressure die-cast Al-Si alloy

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China Foundry 2024年第1期21卷 11-19页

作者： Wen-ning Liu Wei Zhang Peng-yue wang Yi-xian Liu Xiang-yi Jiao Ao-xiang wan Cheng-gang wang Guo-dong Tong Shou-mei Xiong School of Materials Science and Engineering Tsinghua UniversityBeijing 100084China Key Laboratory for Advanced Materials Processing Technology Tsinghua UniversityBeijing 100084Beijing China FAW Group Co. Ltd.Changchun 130013China China FAW Foundry Co. Ltd.Changchun 130013China

The effect of slow shot speed on externally solidified crystal(ESC),porosity and tensile property in a newly developed high-pressure die-cast Al-Si alloy was investigated by optical microscopy(OM),scanning electron microscopy(SEM)and laboratory computed tomography(CT).Results showed that the newly developed AlSi9MnMoV alloy exhibited improved mechanical properties when compared to the AlSi10MnMg alloy.The AlSi9MnMoV alloy,which was designed with trace multicomponent additions,displays a notable grain refining effect in comparison to the AlSi10MnMg alloy.Refining elements Ti,Zr,V,Nb,B promote heterogeneous nucleation and reduce the grain size of primaryα-Al.At a lower slow shot speed,the large ESCs are easier to form and gather,developing into the dendrite net and net-shrinkage.With an increase in slow shot speed,the size and number of ESCs and porosities significantly reduce.In addition,the distribution of ESCs is more dispersed and the net-shrinkage disappears.The tensile property is greatly improved by adopting a higher slow shot speed.The ultimate tensile strength is enhanced from 260.31 MPa to 290.31 MPa(increased by 11.52%),and the elongation is enhanced from 3.72%to 6.34%(increased by 70.52%).

关键词： hypoeutectic Al-Si alloy high pressure die casting porosity externally solidified crystal tensile property

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Self-assembled high-entropy nitride multilayer coating

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Rare Metals 2024年第6期43卷 2876-2883页

作者： Xiang-Yu Zhang Yan Liu Vasiliy Pelenovich Xiao-mei Zeng Jie Liu Qiang wan Alexander Pogrebnjak Long-Jian Xue Zhi-Wen Chen Yan Lei Bing Yang School of Power and Mechanical Engineering Wuhan University Hubei JiuFengShan Future Science and Technology Laboratory Institute of Technological Sciences of Wuhan University Hubei Key Laboratory of Electronic Manufacturing and Packaging Integration Wuhan University College of Engineering Huazhong Agricultural University Sumy State University Institute of Materials Science Slovak University of Technology in Bratislava Shenzhen Research Institute of Wuhan University

The development of advanced materials and construction of multilayer structure contribute to enhancing the performance of protective coatings,further improving the industrial productivity and conserving energy.In this paper,the self-assembled high-entropy nitride (HEN)AlCrNbSiTiN multilayer coating was designed by harnessing the plasma distribution characteristics and depos-ited by arc ion plating using single target.

关键词： Entropy

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Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2038-2059页

作者： Xiang-Hui wan Guo-Bing Jin Qun Yang Ji-Long Hu Zhi-Liang Liu Jun Rao Can Wen Peng-Ling Li Xi-mei Yang Bo Huang Xiao-Zhong wang Jiangxi Medical College Nanchang UniversityNanchang 330029Jiangxi ProvinceChina Department of Clinical Laboratory Jiangxi Cancer HospitalNanchang 330029Jiangxi ProvinceChina Jiangxi Key Laboratory of Translational Research for Cancer Jiangxi Cancer HospitalNanchang 330029Jiangxi ProvinceChina Department of Abdominal Surgery Jiangxi Cancer HospitalNanchang 330029Jiangxi ProvinceChina Department of Pathology Jiangxi Cancer HospitalNanchang 330029Jiangxi ProvinceChina Science and Education Section Jiangxi Cancer HospitalNanchang 330029Jiangxi ProvinceChina Department of Clinical Laboratory Jiangxi Children’s HospitalNanchang 330006Jiangxi ProvinceChina Department of Clinical Laboratory The Second Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina Jiangxi Province Key Laboratory of Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.AIM To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.METHODS Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b.The relationship between the expression values and the clinicopathological features of the patients was investigated.Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western blot.Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric assays.The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay.The Warburg effect was evaluated by glucose uptake and lactic acid production assays.RESULTS The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and IV.Furthermore,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification.HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 cells.However,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg effect.CONCLUSION These findings suggest that the novel miR-490-

关键词： Heterogeneous ribonucleoprotein A1-b MiR-490-3p Colon cancer Alternative splicing Warburg effect

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Neutralization of excessive levels of active TGF-β1 reduces MSC recruitment and differentiation to mitigate peritendinous adhesion

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Bone Research 2023年第2期11卷 368-383页

作者： Yu Sheng Li Xiao wang Bo Hu Qi Sun mei wan Andrew Carr Shen Liu Xu Cao Department of Orthopedic Surgery The Johns Hopkins University School of MedicineBaltimoreMD21205USA Nuffield Department of Orthopedics Rheumatology and Musculoskeletal SciencesBotnar Research CentreUniversity of OxfordWindmill RoadOxford OX 37 LDUK

PPeritendinous adhesion formation(PAF)can substantially limit the range of motion of digits.However,the origin of myofibroblasts in PAF tissues is still unclear.In this study,we found that the concentration of active TGF-β1 and the numbers of macrophages,mesenchymal stromal cells(MSCs),and myofibroblasts in human and mouse adhesion tissues were increased.Furthermore,knockout of TGF-β1 in macrophages or TGF-β1R2 in MSCs inhibited PAF by reducing MSC and myofibroblast infiltration and collagenⅠandⅢdeposition,respectively.Moreover,we found that MSCs differentiated into myofibroblasts to form adhesion tissues.Systemic injection of the TGF-β–neutralizing antibody 1D11 during the granulation formation stage of PAF significantly reduced the infiltration of MSCs and myofibroblasts and,subsequently,PAF.These results suggest that macrophage-derived TGF-β1 recruits MSCs to form myofibroblasts in peritendinous adhesions.An improved understanding of PAF mechanisms could help identify a potential therapeutic strategy.

关键词： inhibited injection MSC

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