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Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1

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International Journal of Oral Science 2022年第3期14卷 396-409页

作者： Yu Jin zhen Liu zhenxia Li Hairui Li Cheng Zhu Ruomei Li Ting zhou Bing fang Department of Orthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghaiChina

Osteoarthritis(OA)is a prevalent joint disease with no effective treatment strategies.Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis.Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies,the epigenetic control of OA remains unclear.Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes,including cell differentiation,proliferation,autophagy,and apoptosis.However,the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown.In this work,we confirmed the upregulation of JMJD3 in aberrant forceinduced cartilage injury in vitro and in vivo.Functionally,inhibition of JMJD3 by its inhibitor,GSK-J4,or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury.Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression.Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis,cartilage degeneration,extracellular matrix degradation,and inflammatory responses.In vivo,anterior cruciate ligament transection(ACLT)was performed to construct an OA model,and the therapeutic effect of GSK-J4 was validated.More importantly,we adopted a peptide-si RNA nanoplatform to deliver si-JMJD3 into articular cartilage,and the severity of joint degeneration was remarkably mitigated.Taken together,our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression.Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-si RNA nanocomplexes.

关键词： Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1

SlGH9-15 regulates tomato fruit cracking with hormonal and abiotic stress responsiveness cis-elements

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Journal of Integrative Agriculture 2023年第2期22卷 447-463页

作者： LIN Hao-wei WU zhen zhou Rong CHEN Bin ZHONG Zhao-jiang JIANG fang-ling College of Horticulture Nanjing Agricultural University/Key Laboratory of Horticultural Plant Biology and Germplasm Innovation in East ChinaMinistry of AgricultureNanjing 210095P.R.China

Fruit cracking occurs easily during the late period of fruit development when plants encounter an unsuitable environment,dramatically affecting fruit production and marketing.This study conducted the bulked segregant RNA-Seq(BSR)to identify the key regulatory gene of fruit cracking in tomatoes.BSR-Seq analysis illustrated that two regions associated with irregularly cracking were located on chromosomes 9 and 11,containing 127 candidate genes.Further,through differentially expression analysis and qRT-PCR in cracking-susceptible and cracking-resistant genotypes,the candidate gene SlGH9-15(Solyc09g010210)with significantly differential expression levels was screened.Bioinformatics analysis of the GH9 gene family revealed that 20 SlGH9 genes were divided into three groups.The phylogenetic analysis showed that SlGH9-15 was closely related to cell wall construction-associated genes AtGH9B1,AtGH9B6,OsGH9B1,and OsGH9B3.The cis-acting elements analysis revealed that Sl GH9-15 was activated by various hormones(ethylene and ABA)and abiotic stresses.The expression pattern indicated that 13 SlGH9 genes,especially SlGH9-15,were highly expressed in the cracking-susceptible genotype.Its expression level gradually increased during fruit development and achieved maximum value at the red ripe stage.Additionally,the cracking-susceptible tomato showed higher cellulase activity and lower cellulose content than the cracking-resistant tomato,particularly at the red ripe stage.This study identified SlGH9-15 as a key gene associated with fruit cracking in tomatoes for the first time and gives new insights for understanding the molecular mechanism and complex regulatory network of fruit cracking.

关键词： tomato irregular cracking BSR-Seq GH9-15

Influence of Selective Laser Melting Process Parameters on Microstructure and Properties of a Typical Ni-Based Superalloy

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Acta Metallurgica Sinica(English Letters) 2022年第10期35卷 1673-1687页

作者： zhen Lu Chengcai Zhang Nana Deng Haiping zhou Ruirui fang Kuidong Gao Yukuo Su Hongbin Zhang School of Materials Science and Engineering Harbin Institute of TechnologyHarbin150001China College of Mechanical and Electronic Engineering Shandong University of Science and TechnologyQingdao266590China Jier Machine-Tool Group Co.Ltd Jinan250022China

The influence of selective laser melting(SLM)process parameters on the microstructure and mechanical properties of a typical Ni-based superalloy was researched.The optimum parameters of P=170 W,V=0.8 m/s were determined,under which the SLMed samples exhibited both the largest relative density of 99.57%and the best mechanical properties,including the microhardness(329.3±3.8 HV),yield strength(726±8.1 MPa),ultimate tensile strength(900±5.9 MPa)and elongation((31.9±0.24)%).The average grain size ranges of SLMed samples are from 15.2 to 17.4μm,with a typical mixed grain structure.Owing to the high cooling rate and remelting during SLM process,a large number of low-angle grain boundaries(LAGBs),dislocations and sub-grains were formed,and the fraction of LAGBs reached above 65%.At the same time,the content of low-Σcoincidence site lattice(CSL)boundaries was mostly less than 1%,while there was almost noγ′phase precipitated in the matrix.The texture of SLMed samples was weak,and there was no obvious preferred growth direction.Combining with the microstructure characterization,both grain refinement strengthening and dislocation strengthening were considered as the main strengthening mechanisms.Moreover,the fracture mechanism of the optimum sample belonged to ductile fracture.

关键词： Selective laser melting Ni-based superalloy Relative density Microstructure Mechanical property

Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1αaxis and insulin sensitivity

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Animal Nutrition 2022年第4期11卷 25-37页

作者： Yuan Luo Wenhao zhou Ruixin Li Samwel MLimbu fang Qiao Liqiao Chen Meiling Zhang zhen-Yu Du LANEH School of Life SciencesEast China Normal UniversityShanghai 200241China University of Dar Es Salaam Department of Aquaculture TechnologyDar Es Salaam 60091Tanzania UDSM-ECNU Joint Research Center for Aquaculture and Fish Biology(JRCAFB) Dar Es Salaam 60091Tanzania ECNU-UDSM Joint Research Center for Aquaculture and Fish Biology(JRCAFB) Shanghai 200241China

Pyruvate dehydrogenase kinases(PDKs)-pyruvate dehydrogenase E1αsubunit(PDHE1α)axis plays an important role in regulating glucose metabolism in mammals.However,the regulatory function of PDKsPDHE1α axis in the glucose metabolism of fish is not well known.This study determined whether PDKs inhibition could enhance PDHE1αactivity,and improve glucose catabolism in fish.Nile tilapia fingerlings(1.90±0.11 g)were randomly divided into 4 treatments in triplicate(30 fish each)and fed control diet without dichloroacetate(DCA)(38% protein,7% lipid and 45% corn starch)and the control diet supplemented with DCA,which inhibits PDKs through binding the allosteric sites,at 3.75(DCA3.75),7.50(DCA7.50)and 11.25 g/kg(DCA11.25),for 6 wk.The results showed that DCA3.75,DCA7.50 and DCA11.25significantly increased weight gain,carcass ratio and protein efficiency ratio(P<0.05)and reduced feed efficiency(P<0.05)of Nile tilapia.To investigate the effects of DCA on growth performance of Nile tilapia,we selected the lowest dose DCA3.75 for subsequent analysis.Nile tilapia fed on DCA3.75significantly reduced the mesenteric fat index,serum and liver triglyceride concentration and total lipid content in whole fish,and down-regulated the expressions of genes related to lipogenesis(P<0.05)compared to the control.The DCA3.75 treatment significantly improved glucose oxidative catabolism and glycogen synthesis in the liver,but significantly reduced the conversion of glucose to lipid(P<0.05).Furthermore,the DCA3.75 treatment significantly decreased the PDK2/4 gene and protein expressions(P<0.05),accordingly stimulated PDHE1αactivity by decreasing the phosphorylated PDHE1αprotein level.In addition,DCA3.75 treatment significantly increased the phosphorylated levels of key proteins involved in insulin signaling pathway and glycogen synthase kinase 3β(P<0.05).Taken together,the present study demonstrates that PDK2/4 inhibition by using DCA promotes glucose utilization in Nile tilapia by activating PDHE1αand improving insulin sensitivity.Our study helps

关键词： Dichloroacetate Glucose utilization Insulin sensitivity Nile tilapia PDK2/4-PDHE1αaxis

Synthesis of waterborne polyurethane using snow as dispersant:Structures and properties controlled by polyols utilization

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Journal of Materials Science & Technology 2019年第7期35卷 1491-1498页

作者： Changqing fang Shaofei Pan zhen Wang Xing zhou Wanqing Lei Youliang Cheng Faculty of Printing Packaging Engineering and Digital Media TechnologyXi'an University of TechnologyXi'an710048China School of Mechanical and Precision Instrument Engineering Xi'an University of TechnologyXi'an710048China

waterborne polyurethane (WPU) dispersions have gained attention towards environm entally-friendly synthesis. In this article, a series of waterborne polyurethane em ulsions was successfully synthesized and extensively characterized in terms of thermal, mechanical properties, hydrophilic behavior and morphology. Snowwas chosen as dispersant instead of comm only used water. Preparation param eters such as intrinsic properties and molecular weight of polyols were discussed systematically. A chain structure was confirmed by Fourier transform infrared (FT-IR) spectroscopy. when com paring the nature of the polyols (PPG, PEG and PNA, 2000g/mol) of this study, as-synthesized polyether waterborne polyurethane provided higher solid content, viscosity and water-resistance. However, polyester waterborne polyurethane perform ed differently and it exhibited higher therm al stability and crystallinity. When com paring the samples (WPU-N210, WPU-N220, WPU-N230 and WPU-N240) with different molecular weight of the same polyol (PPG) used as soft segment, the emulsion WPU-N220 with molecular weight of 2000g/mol PPG provided the highest solid content and lowest viscosity. It was observed th at particle size was uniform and highly dispersed for all sam ples from TEM images. Therm ogravim etric, differential scanning calorim etry (DSC) and X-ray diffraction results dem onstrated that the emulsion WPU-N230 with m olecular weight of 3000 g/mol PPG possessed higher therm al stability and crystallinity than the other samples. The reason was that the Tg and thermal stability were increased with increasing molecular weight. when molecular weight increased, the arrangem ent of soft segm ent became more regular and so did the regularity of the molecular chains. This work demonstrated that different polyols as soft segment applied could lead to great differences in the structure and property of the resulting WPU.

关键词： Waterborne polyurethane (WPU) Snow Soft segment Polyester Polyether

强化公共属性,助力城市发展:德国慕尼黑城市公园建设及启示

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中国园林 2022年第3期38卷 51-55页

作者：王贞方舟华中科技大学建筑与城市规划学院武汉430074

广泛的国际经验研究可为中国的公园城市建设提供科学、有效的策略支撑,并推动其相关理论的完善。系统梳理了德国慕尼黑在不同历史时期城市公园的发展脉络,总结了其城市公园系统的分级、分类与分布特征,解析了慕尼黑公园建设中表达其公... 详细信息

广泛的国际经验研究可为中国的公园城市建设提供科学、有效的策略支撑,并推动其相关理论的完善。系统梳理了德国慕尼黑在不同历史时期城市公园的发展脉络,总结了其城市公园系统的分级、分类与分布特征,解析了慕尼黑公园建设中表达其公共属性的4项特征,即全员化的运动场地设置、全方位的社会服务供给、丰富多样的文娱活动,以及灵活高效的功能转换。这些宝贵的经验将为我国新时期的城市发展建设提供有益的借鉴与启示。

关键词：风景园林城市公园公园城市公园系统公共属性慕尼黑

Global Solutions of the Evolutionary Faddeev Model with Small Initial Data

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Acta Mathematica Sinica,English Series 2011年第2期27卷 309-328页

作者： zhen LEI fang Hua LIN Yi zhou School of Mathematical Sciences LMNS and Shanghai Key Laboratory for Contemporary Applied Mathematics Fudan University Shanghai 200433 P. R. China Courant Institute of Mathematics New York University NY 10012 USA

We consider the Cauchy problem for evolutionary Faddeev model corresponding to maps from the Minkowski space R^1＋n to the unit sphere S2, which obey a system of non-linear wave equations. The nonlinearity enjoys the null structure and contains semi-linear terms, quasi-linear terms and unknowns themselves. We prove that the Cauchy problem is globally well-posed for sufficiently small initial data in Sobolev space.

关键词： Faddeev model global existence quasi-linear wave equations semi-linear wave equations

Wake-Promoting Effect of Bloodletting Puncture at Hand Twelve Jing-Well Points in Acute Stroke Patients:A Multi-center Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2021年第8期27卷 570-577页

作者： YU Nan-nan XU Zhi-fang GAO Yang zhou Zhi-liang ZHAO Xue zhou Dan WANG zhen-guo CHEN Ze-lin PAN Xing-fang GUO Yi Department of Traditional Chinese Medicine Xijing Hospitalthe Air Force Medical UniversityXi’an710032China Acupuncture Research Center Tianjin University of traditional Chinese MedicineTianjin301617China Acu-moxibustion and Tuina Department Tianjin University of Traditional Chinese MedicineTianjin301617China Department of Acupuncture and Moxibustion the First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin300193China Department of Acupuncture and Moxibustion the Second Affiliated Hospital of Tianjin University of Traditional Chinese MedicineTianjin300150China The Third Department of Encephalopathy Xi’an Encephalopathy Hospital of Traditional Chinese MedicineXi’an710032China Department of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin301617China

Objective To assess the effect and safety of bloodletting puncture at hand twelve Jing-Well points(HTWPs)in acute stroke patients with conscious disturbance.Methods In this multi-center and randomized controlled trial,360 patients suffered from ischemic or hemorrhagic stroke with conscious disturbance within 48 h from the onset of symptom were divided into bloodletting(180 cases)and control(180 cases)groups using a block randomization.Patients in both groups received routine Western medicine,and patients in the bloodletting group received additional bloodletting puncture at HTWPs on admission immediately before conventional treatment.The primary outcome measure was Glasgow Coma Scale(GCS)score and the secondary outcomes included blood pressure,respiratory rate and pulse rate.All variables were evaluated at baseline(before bloodletting),0(after bloodletting immediately),15,30,50 and 80 min post bloodletting.Results At 80 min post bloodletting,the proportion of patients with improved consciousness in the bloodletting group was greater than the control group(P0.05).Conclusion The bloodletting puncture at HTWPs was safe and could improve conscious levels of ischemic stroke patients,highlighting a first-aid intervention for acute stroke.

关键词： acute stroke bloodletting Jing-Well point conscious disturbance randomized controlled trial

Excellent effects and possible mechanisms of action of a new antibody–drug conjugate against EGFR-positive triple-negative breast cancer

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Military Medical Research 2022年第4期9卷 419-431页

作者： Dan-Dan zhou Wei-Qi Bai Xiao-Tian Zhai Li-Ping Sun Yong-Su zhen Zhuo-Rong Li Qing-fang Miao NHC Key Laboratory of Biotechnology of Antibiotics Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNo.1 Tiantan XilBeijing 100050China Department of Organic Chemistry Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNo.1 Tiantan XiliBeijing 100050China

Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to d

关键词： Triple-negative breast cancer Epidermal growth factor receptor Antibody–drug conjugate Targeted therapy Antitumor effect