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Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats

Current Medical Science 2024年第2期44卷 355-368页

作者： Shao-ze JING Shu-han YANG Yun-kun QU Hai-hu HAO hua wu Department of Orthopedics Third Hospital of Shanxi Medical UniversityShanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalTaiyuan 030032China Department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Osteoarthritis(OA)is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local inflammation.This study aimed to investigate the anti-OA effect of scutellarein(SCU),a single-unit flavonoid compound obtained from Scutellaria barbata D.Don,in rats.Methods:The extracted rat chondrocytes were treated with SCU and IL-1β.The chondrocytes were divided into control group,IL-1βgroup,IL-1β+SCU 50µmol/L group,and IL-1β+SCU 100µmol/L group.Morphology of rat chondrocytes was observed by toluidine blue and safranin O staining.CCK-8 method was used to detect the cytotoxicity of SCU.ELISA,qRT-PCR,Western blotting,immunofluorescence,SAβ-gal staining,flow cytometry,and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1βintervention.Additionally,anterior cruciate ligament transection(ACL-T)was used to establish a rat OA model.Histological changes were detected by safranin O/fast green,hematoxylin-eosin(HE)staining,and immunohistochemistry.Results:SCU protected cartilage and exhibited anti-inflammatory effects via multiple mechanisms.Specifically,it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its degradation.In addition,SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase(NF-κB/MAPK)pathway,thereby reducing inflammatory cytokine production in the joint cartilage.Furthermore,SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes,further highlighting its potential role in OA treatment.In vivo experiments revealed that SCU(at a dose of 50 mg/kg)administered for 2 months could significantly delay the progression of cartilage damage,which was reflected in a lower Osteoarthritis Research Society International(OARSI)score,and reduced expression of matrix metalloproteinase 13(MMP13)in cartilage.Conclusion:SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.

关键词： scutellarein osteoarthritis apoptosis mitogen-activated protein kinase(MAPK) nuclear factor kappa-B(NF-κB)

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Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1173-1189页

作者： Yan Lin Jiangnan wu Yong Zhuo Bin Feng Zhengfeng Fang Shengyu Xu Jian Li hua Zhao De wu Lun hua Lianqiang Che Key Laboratory of Animal Disease‑Resistance Nutrition Animal Nutrition InstituteSichuan Agricultural UniversityChengdu 611130SichuanChina

Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.

关键词： Ileum Intrauterine growth restriction Methyl donor Methylation Sows

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PACS gene family-related neurological diseases: limited genotypes and diverse phenotypes

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World Journal of Pediatrics 2024年第1期20卷 82-91页

作者： Han Zhang Kai Gao Shuang Wang Yue-hua Zhang Zhi-Xian Yang Ye wu Yu-wu Jiang Department of Pediatrics Peking University First Hospital.No.1 Xi'an Men StreetWest DistrictBeijing 100034China Bejing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases BeijingChina Children Epilepsy Center Peking University First HospitalBeijingChina Key Laboratory for Neuroscience Ministry of Education/National Health and Family Planning CommissionPeking UniversityBeijingChina Center of Epilepsy Beijing Institute for Brain DisordersBeijingChina

Background The PACS gene family has been demonstrated to be related to intracellular vesicular trafficking.The phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy,intellectual disability/developmental delay,and malformations,such as facial abnormalities.Methods We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation sequencing.Detailed information obtained from these patients was analyzed along with that obtained from previously reported patients.Results With the inclusion of the newly diagnosed cases in this study,103 cases with PACS gene family-related neurological diseases were reported,of which 43 were PACS2-related cases and the remaining were PACSI-related cases.Most patients had seizures,which have been reported to be effectively controlled by several types of anti-seizure medications(ASMs).The most efficacious and frequently prescribed ASMs included sodium valproate(43.3%,13/30),oxcarbazepine/carbamazepine(26.7%,8/30),and levetiracetam(20%,6/30).Almost all patients had intellectual disability/developmental delay.The most common pathogenic missense variants were PACSI p.Arg203Trp and PACS2 p.Glu209Lys.In addition,we report a patient carrying a likely pathogenic copy number variation(CNV)(de novo heterozygous deletion of chr14:105821380-106107443,286 kilobase,destroyed part of the furin-binding region domain and the protein structure after it)with more severe and refractory late-onset epilepsy.Conclusions The clinical phenotypes of the different PACS heterozygous missense variants were similar.The pathogenic variant sites of PACSI and PACS2 were quite limited but located in different regions.A CNV destroying part of the PACS2 gene might also be pathogenic.These findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family.

关键词： Developmental delay Epilepsy Intellectual disability PACSI PACS2

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Artificial selection shapes the lower genomic diversity and higher selective pressures on the sex chromosomes of domestic animals

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Science China(Life Sciences) 2024年第5期67卷 1072-1075页

作者： Meiming wu Dongfeng Wang Meng-hua Li Fenghua Lv College of Animal Science and Technology China Agricultural UniversityBeijing 100193China CAS Key Laboratory of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of Science(CAS)Beijing 100101China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Sanya Institute of China Agricultural University Sanya 572024China

Dear Editor,Sheep and goats were among the earliest domestic animals(Zeder,2008).During the transition from being hunted to being herded,excess males not involved in propagation were slaughtered at young ages under th... 详细信息

关键词： earliest harvest young

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Aldehyde oxidase mediated enantioselective metabolic health risk of dinotefuran

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Science China Chemistry 2024年第6期67卷 2079-2091页

作者： Liwei Xu Xinxin Xu hua Kuang Chuanlai Xu Xiaoling wu State Key Laboratory of Food Science and Resources Jiangnan UniversityWuxi214122China International Joint Research Laboratory for Biointerface and Biodetection and School of Food Science and Technology Jiangnan UniversityWuxi214122China Collaborative Innovation center of Food Safety and Quality Control in Jiangsu Province Jiangnan UniversityWuxi214122China

Chiral pollutants often pose significant differential environmental health risks.In this study,the biotransformation of chiral dinotefuran(DIN)and its enantioselective metabolic toxicity mechanisms have been systemically investigated.Firstly,reversedphase chromatography-high resolution mass spectrometry was developed to quantify the content of DIN R/S chiral enantiomer with pg level sensitivity,revealing a lower elimination rate constant(K_(e))of S-DIN(0.730 h^(-1))than R-DIN(0.746 h^(-1)).Secondly,the interaction mechanism between DIN metabolism and important endogenous bioactive molecules,such as aldehyde oxidase(AOX)and neurotransmitters,was revealed.The DIN nitro-group was converted into a guanidine group by the reducing site of nearby flavin adenine dinucleotide(FAD)in AOX with the preferred higher affinity of S-configuration.Meanwhile,the endogenous tryptophan(Trp)aldehyde metabolic intermediate,5-hydroxyindoleacetaldehyde(5-HIAL),provides a persistent electron donor for DIN reduction via the oxidation-catalyzed site in AOX,resulting in remarkable up-regulation of monoamine neurotransmitters such as serotonin and dopamine.Thirdly,the higher level of neurotransmitters further mediated dysregulation of oxylipin homeostasis via the serotonergic pathway,where S-DIN exhibited more pronounced liver lipid damage and environmental health risk with the accumulated lipid biomarkers,oxidized triglyceride(OxTG)and oxidized sphingomyelin(OxSM).This study elucidates the AOX-mediated enantioselectivity metabolic pathway of DIN,providing a new analytical method for chiral pollutants and paves the way for their health risk assessments.

关键词： neonicotinoid dinotefuran enantiomer aldehyde oxidase metabolomics health risk

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Synergistic Interdecadal Evolution of Precipitation over Eastern China and the Pacific Decadal Oscillation during 1951-2015

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Advances in Atmospheric Sciences 2024年第1期41卷 53-72页

作者： Minmin wu Rong-hua ZHANG Junya HU Hai ZHI Key Laboratory of Ocean Circulation and Waves Institute of OceanologyChinese Academy of SciencesQingdao 266071China School of Marine Sciences Nanjing University of Information Science and TechnologyNanjing 210044China Laosan Laboratory Qingdao 266237China School of Atmospheric Sciences Nanjing University of Information Science and TechnologyNanjing 210044China University of Chinese Academy of Sciences Beijing 100029China

By using the multi-taper method(MTM)of singular value decomposition(SVD),this study investigates the interdecadal evolution(10-to 30-year cycle)of precipitation over eastern China from 1951 to 2015 and its relationship with the North Pacific sea surface temperature(SST).Two significant interdecadal signals,one with an 11-year cycle and the other with a 23-year cycle,are identified in both the precipitation and SST fields.Results show that the North Pacific SST forcing modulates the precipitation distribution over China through the effects of the Pacific Decadal Oscillation(PDO)-related anomalous Aleutian low on the western Pacific subtropical high(WPSH)and Mongolia high(MH).During the development stage of the PDO cold phase associated with the 11-year cycle,a weakened WPSH and MH increased the precipitation over the Yangtze River Basin,whereas an intensified WPSH and MH caused the enhanced rain band to move northward to North China during the decay stage.During the development stage of the PDO cold phase associated with the 23-year cycle,a weakened WPSH and MH increased the precipitation over North China,whereas an intensified WPSH and the weakened MH increased the precipitation over South China during the decay stage.The 11-year and 23-year variabilities contribute differently to the precipitation variations in the different regions of China,as seen in the 1998flooding case.The 11-year cycle mainly accounts for precipitation increases over the Yangtze River Basin,while the 23-year cycle is responsible for the precipitation increase over Northeast China.These results have important implications for understanding how the PDO modulates the precipitation distribution over China,helping to improve interdecadal climate prediction.

关键词： MTM-SVD PDO SST anomalies interdecadal variability precipitation over China

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The RNA-binding domain of DCL3 is required for long-distance RNAi signaling

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aBIOTECH 2024年第1期5卷 17-28页

作者： Jie Li Bo-Sen Zhang hua-Wei wu Cheng-Lan Liu Hui-Shan Guo Jian-hua Zhao State Key Laboratory of Plant Genomics Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China CAS Center for Excellence in Biotic Interactions University of the Chinese Academy of SciencesBeijing 100049China Qilu Zhongke Academy of Modern Microbiology Technology Jinan 250022China

Small RNA(sRNA)-mediated RNA silencing(also known as RNA interference,or RNAi)is a conserved mechanism in eukaryotes that includes RNA degradation,DNA methylation,heterochromatin formation and protein translation repression.In plants,sRNAs can move either cell-to-cell or systemically,thereby acting as mobile silencing signals to trigger noncell autonomous silencing.However,whether and what proteins are also involved in noncell autonomous silencing have not been elucidated.In this study,we utilized a previously reported inducible RNAi plant,PDSi,which can induce systemic silencing of the endogenous PDS gene,and we demonstrated that DCL3 is involved in systemic PDS silencing through its RNA binding activity.We confirmed that the C-terminus of DCL3,including the predicted RNA-binding domain,is capable of binding short RNAs.Mutations affecting RNA binding,but not processing activity,reduced systemic PDS silencing,indicating that DCL3 binding to RNAs is required for the induction of systemic silencing.Cucumber mosaic virus infection assays showed that the RNA-binding activity of DCL3 is required for antiviral RNAi in systemically noninoculated leaves.Our findings demonstrate that DCL3 acts as a signaling agent involved in noncell autonomous silencing and an antiviral effect in addition to its previously known function in the generation of 24-nucleotide sRNAs.

关键词： RNAi signaling DCL3 RBD RNAs Cucumber mosaic virus

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Development of antibody-drug conjugates in cancer:Overview and prospects

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Cancer Communications 2024年第1期44卷 3-22页

作者： Dan-Yun Ruan Hao-Xiang wu Qi Meng Rui-hua Xu Department of Clinical Research Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer Chinese Academy of Medical SciencesGuangzhouGuangdongP.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China

In recent years,remarkable breakthroughs have been reported on antibody-drug conjugates(ADCs),with 15 ADCs successfully entering the market over the past decade.This substantial development has positioned ADCs as one of the fastest-growing domains in the realm of anticancer drugs,demonstrating their efficacy in treating awide array of malignancies.Nonetheless,there is still an unmet clin-ical need forwider application,better efficacy,and fewer side effects of ADCs.An ADC generally comprises an antibody,a linker and a payload,and the combina-tion has profound effects on drug structure,pharmacokinetic profile and efficacy.Hence,optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side effects.In this review,we comprehen-sively reviewed the current development and the prospects of ADC,provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China,highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies,and also discussed the new related technologies,possibility of next-generation ADCs and the directions of clinical research.

关键词： companies breakthrough payload

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Counteracting effects on ENSO induced by ocean chlorophyll interannual variability and tropical instability wave-scale perturbations in the tropical Pacific

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Science China Earth Sciences 2024年第2期67卷 387-404页

作者： Rong-hua ZHANG Feng TIAN Qidong SHI Xiujun WANG Tongwen wu School of Marine Sciences Nanjing University of Information Science and TechnologyNanjing210044China Laoshan Laboratory Qingdao266237China Key Laboratory of Ocean Circulation and Waves Institute of OceanologyChinese Academy of SciencesQingdao266071China University of Chinese Academy of Sciences Beijing101408China Faculty of Geographical Sciences Beijing Normal UniversityBeijing100875China Earth System Modeling and Prediction Centre China Meteorological AdministrationBeijing100081China

Large perturbations in chlorophyll(Chl)are observed to coexist at interannual and tropical instability wave(TIW)scales in the tropical Pacific;at present,their combined effects on El Ni?o-Southern Oscillation(ENSO)through ocean biologyinduced heating(OBH)feedbacks are not understood well.Here,a hybrid coupled model(HCM)for the atmosphere and ocean physics-biogeochemistry(AOPB)in the tropical Pacific is adopted to quantify how ENSO can be modulated by Chl perturbations at interannual and TIW scales,individually or collectively,respectively.The HCM-based sensitivity experiments demonstrate a counteracting effect on ENSO:the bio-climate feedback due to large-scale Chl interannual variability acts to damp ENSO through its impact on upper-ocean stratification and vertical mixing,whereas that due to TIW-scale Chl perturbations tends to amplify ENSO.Because ENSO simulations are sensitively dependent on the ways Chl effects are represented at these different scales,it is necessary to adequately take into account these related differential Chl effects in climate modeling.A bias source for ENSO simulations is illustrated that is related with the Chl effects in the tropical Pacific,adding in a new insight into interactions between the climate system and ocean ecosystem on different scales in the region.These results reveal a level of complexity of ENSO modulations resulting from Chl effects at interannual and TIW scales,which are associated with ocean biogeochemical processes and their interactions with physical processes in the tropical Pacific.

关键词： Ocean chlorophyll Bio-climate feedbacks Interannual variability Tropical instability waves Counteracting effects A hybrid coupled model

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Buried interface management via bifunctional NH_(4)BF_(4)towards efficient CsPbI_(2)Br solar cells with a V_(oc)over 1.4 V

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Journal of Energy Chemistry 2024年第2期89卷 364-370,I0009页

作者： Fazheng Qiu Ming-hua Li Jinpeng wu Jin-Song Hu School of Materials Science and Engineering NingboTech UniversityNingbo 315100ZhejiangChina Beijing National Laboratory for Molecular Sciences(BNLMS) Institute of ChemistryChinese Academy of SciencesBeijing 100190China College of Chemical Engineering Beijing Advanced Innovation Center for Soft Matter Science and EngineeringBeijing University of Chemical TechnologyBeijing 100029China School of Chemical Sciences University of Chinese Academy of SciencesBeijing 100049China

CsPbI_(2)Br perovskite solar cells(PSCs)have drawn tremendous attention due to their suitable bandgap,excellent photothermal stability,and great potential as an ideal candidate for top cells in tandem solar cells.However,the abundant defects at the buried interface and perovskite layer induce severe charge recombination,resulting in the open-circuit voltage(V_(oc))output and stability much lower than anticipated.Herein,a novel buried interface management strategy is developed to regulate interfacial carrier dynamics and CsPbI_(2)Br defects by introducing ammonium tetrafluoroborate(NH_(4)BF_(4)),thereby resulting in both high CsPbI_(2)Br crystallization and minimized interfacial energy losses.Specifically,NH_(4)^(+)ions could preferentially heal hydroxyl groups on the SnO_(2)surface and balance energy level alignment between SnO_(2)and CsPbI_(2)Br,enhancing charge transport efficiency,while BF_(4)^(-)anions as a quasi-halogen regulate crystal growth of CsPbI_(2)Br,thus reducing perovskite defects.Additionally,it is proved that eliminating hydroxyl groups at the buried interface enhances the iodide migration activation energy of CsPbI_(2)Br for strengthening the phase stability.As a result,the optimized CsPbI_(2)Br PSCs realize a remarkable efficiency of 17.09%and an ultrahigh V_(oc)output of 1.43 V,which is one of the highest values for CsPbI_(2)Br PSCs.

关键词： Inorganic perovskite Buried interface Defect Stability Open-circuit voltage loss

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