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Recent research progress from biological perspective on the mechanism of formation of osteoarthritis after anterior cruciate ligament injury
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作者 ZHOU Kai DU Xiu-pan WANG Guang-ji 《Journal of Hainan Medical University》 CAS 2024年第4期60-64,共5页
The anterior cruciate ligament(ACL)mainly plays a role in stabilizing the knee joint by limiting the forward translation of tibial force and rotational force at the tibial joint,and if this ligament is damaged,it will... The anterior cruciate ligament(ACL)mainly plays a role in stabilizing the knee joint by limiting the forward translation of tibial force and rotational force at the tibial joint,and if this ligament is damaged,it will cause joint pain,limited mobility,knee instability,etc.According to related studies,the incidence of traumatic osteoarthritis(PTOA)after ACL injury is as high as 87%,although many studies have shown that patients with ACL injury are susceptible to PTOA,but the exact mechanism is currently unknown.This may be related to biological,structural,and mechanical factors caused by the ligament injury.Previous studies have shown that elevated inflammatory mediators in the joint cavity following ACL injury can lead to chondrocytes necrosis and degradation of the cartilage matrix.These potential biochemical mediators contribute to PTOA formation,and early intervention can reduce future episodes of PTOA.In recent years,many scholars have devoted themselves to studying the potential important factors and signaling pathways involved in the formation of osteoarthritis after ACL injury,and exploring its molecular mechanism,which has led to great progress in this field.This paper mainly studies and discusses the mechanism of osteoarthritis formation after ACL injury from the biological perspective. 展开更多
关键词 Anterior cruciate ligament injury BIOLOGY osteoarthritis
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Risk of metabolic abnormalities in osteoarthritis:a new perspective to understand its pathological mechanisms 被引量:2
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作者 Guizheng Wei Ke Lu +6 位作者 Muhammad Umar Zhenglin Zhu William WLu John RSpeakman Yan Chen Liping Tong Di Chen 《Bone Research》 SCIE CAS CSCD 2023年第4期679-694,共16页
Although aging has traditionally been viewed as the most important risk factor for osteoarthritis(OA),an increasing amount of epidemiological evidence has highlighted the association between metabolic abnormalities an... Although aging has traditionally been viewed as the most important risk factor for osteoarthritis(OA),an increasing amount of epidemiological evidence has highlighted the association between metabolic abnormalities and OA,particularly in younger individuals.Metabolic abnormalities,such as obesity and typeⅡdiabetes,are strongly linked to OA,and they affect both weightbearing and non-weight-bearing joints,thus suggesting that the pathogenesis of OA is more complicated than the mechanical stress induced by overweight.This review aims to explore the recent advances in research on the relationship between metabolic abnormalities and OA risk,including the impact of abnormal glucose and lipid metabolism,the potential pathogenesis and targeted therapeutic strategies. 展开更多
关键词 METABOLISM PATHOGENESIS osteoarthritis
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Mechanisms of analgesic effect of mesenchymal stem cells in osteoarthritis pain
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作者 Fatimah Almahasneh Ejlal Abu-El-Rub Ramada R Khasawneh 《World Journal of Stem Cells》 SCIE 2023年第4期196-208,共13页
Osteoarthritis(OA)is the most common musculoskeletal disease,and it is a major cause of pain,disability and health burden.Pain is the most common and bothersome presentation of OA,but its treatment is still suboptimal... Osteoarthritis(OA)is the most common musculoskeletal disease,and it is a major cause of pain,disability and health burden.Pain is the most common and bothersome presentation of OA,but its treatment is still suboptimal,due to the short-term action of employed analgesics and their poor adverse effect profile.Due to their regenerative and anti-inflammatory properties,mesenchymal stem cells(MSCs)have been extensively investigated as a potential therapy for OA,and numerous preclinical and clinical studies found a significant improvement in joint pathology and function,pain scores and/or quality of life after administration of MSCs.Only a limited number of studies,however,addressed pain control as the primary end-point or investigated the potential mechanisms of analgesia induced by MSCs.In this paper,we review the evidence reported in literature that support the analgesic action of MSCs in OA,and we summarize the potential mechanisms of these antinociceptive effects. 展开更多
关键词 osteoarthritis PAIN INFLAMMATION Mesenchymal stem cells REGENERATION Analgesic mechanisms
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Research progress in mechanism of traditional Chinese medicine in the treatment of Knee Osteoarthritis
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作者 QIN Shu-ying SU Jing +4 位作者 WEI Cheng-yu CHEN Zhi-fen LIU Yong-li LI Liu-zhen LEI Long-ming 《Journal of Hainan Medical University》 CAS 2023年第13期71-80,共10页
Knee osteoarthritis(KOA)is a chronic degenerative Osteoarthritis disease.The majority of patients with knee osteoarthritis were elderly patients.The disease not only greatly affects the work and life of patients but a... Knee osteoarthritis(KOA)is a chronic degenerative Osteoarthritis disease.The majority of patients with knee osteoarthritis were elderly patients.The disease not only greatly affects the work and life of patients but also brings serious burden to families and society.The traditional Chinese medicine has a long history in China,which has shown a multi-pathway and multitarget mechanism for the prevention and treatment of knee osteoarthritis.According to the properties of Chinese medicine,it was divided into four categories:drugs to promote blood circulation and remove blood stasis,drugs to clear heat,drugs to dispel wind dampness and drugs to tonify deficiency.In addition,the relevant literatures at home and abroad in recent five years were reviewed to summarize and generalize the mechanism of traditionalChinese medicine in the treatment of knee osteoarthritis,in order to provide reference for the treatment of knee osteoarthritis with traditional Chinese medicine. 展开更多
关键词 Knee osteoarthritis Chinese materia medica mechanism REVIEW
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Protective Effect and Molecular Mechanism of Shui People's Classic Prescription Jipei Dilong Ointment on Osteoarthritis in Rats
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作者 Lailai LI Baoying HUA +6 位作者 Shiyun YE Yihui CHAI Haotian WANG Jinghua RUAN Xiang PU Liyan ZHANG Sibu MA 《Medicinal Plant》 CAS 2023年第5期57-64,共8页
[Objectives]To explore the protective effect and molecular mechanism of Shui People s Classic Prescription Jipei Dilong Ointment on knee osteoarthritis in rats.[Methods]72 SPF male SD rats were divided into control gr... [Objectives]To explore the protective effect and molecular mechanism of Shui People s Classic Prescription Jipei Dilong Ointment on knee osteoarthritis in rats.[Methods]72 SPF male SD rats were divided into control group,model group,Jipei Dilong Ointment high,medium and low dose groups,and positive drug Diclofenac group,with 12 rats in each group.Except the control group,all other groups were injected with 0.2 mL of 2%papain and 0.3%L-cysteine mixture into knee joint cavity to establish osteoarthritis model,while the control group was injected with the same amount of normal saline.The Lequesne MG score was used to determine the success of the model.After successful modeling,external administration was given for 4 weeks.The histopathological changes in articular cartilage and synovium were observed by HE staining;the levels of TNF-α,IL-1βand COX-2 in serum were detected by ELISA,and the relative expression of MMP-9 and TIMP-1 mRNA in cartilage was detected by qRT-PCR;the relative expression of MMP-9,TIMP-1,TLR4,MyD88 and NF-κB in rat cartilage was detected by Western-blot.[Results]Compared with the model group,Jipei Dilong Ointment could significantly reduce the Lequesne MG score and Mankin s score of arthritic rats(P<0.01);significantly improve the pathological changes in articular cartilage and synovium,reduce tissue edema,necrosis,inflammatory cell infiltration and fibrous tissue proliferation;reduce the expression of MMP-9 mRNA(P<0.01)in different degrees and increase the expression of TIMP-1 mRNA(P<0.01);reduce the relative expression of MMP-9,TLR4,MyD88 and NF-κB protein in different degrees(P<0.01),and significantly increase the relative expression of TIMP-1 protein in cartilage(P<0.01).[Conclusions]Jipei Dilong Ointment can improve the joint injury of osteoarthritis rats,and the mechanism may be related to the regulation of TLR4/MyD88/NF-κB signaling pathway and the ratio of MMP-9/TIMP-1. 展开更多
关键词 Jipei Dilong Ointment osteoarthritis(OA) Traditional Chinese medicine application
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Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis 被引量:1
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作者 Yuhang Liu Ruihan Hao +10 位作者 Jia Lv Jie Yuan Xuelei Wang Churong Xu Ding Ma Zhouyi Duan Bingjun Zhang Liming Dai Yiyun Cheng Wei Lu Xiaoling Zhang 《Bone Research》 SCIE CAS CSCD 2024年第1期215-226,共12页
Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attem... Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA. 展开更多
关键词 osteoarthritis METABOLISM inhibited
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Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine 被引量:1
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作者 Xuyu Song Ying Liu +5 位作者 Siyi Chen Lei Zhang Huijie Zhang Xianhui Shen Hang Du Rong Sun 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第2期114-126,共13页
Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poo... Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA. 展开更多
关键词 animal models knee osteoarthritis system review traditional Chinese medicine
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Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up 被引量:2
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作者 Madhan Jeyaraman Naveen Jeyaraman +4 位作者 Tarun Jayakumar Swaminathan Ramasubramanian Rajni Ranjan Saurabh Kumar Jha Ashim Gupta 《World Journal of Orthopedics》 2024年第5期457-468,共12页
BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more rese... BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use. 展开更多
关键词 Knee osteoarthritis Adipose tissue Stromal vascular fraction Regenerative medicine Orthobiologics
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Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a 被引量:1
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作者 Fan Yang Wan-Qi Xiong +7 位作者 Chen-Zhi Li Ming-Jian Wu Xiu-Zhi Zhang Chun-Xiao Ran Zhen-Hao Li Yan Cui Bao-Yi Liu De-Wei Zhao 《World Journal of Stem Cells》 SCIE 2024年第2期191-206,共16页
BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflamm... BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA development.Early-stage treatment options primarily target symptom relief.Mesenchymal stem cells(MSCs)show promise for treatment,despite challenges.Recent research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression.This suggests exosomes(Exos)as a promising avenue for future treatment.While these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is essential.AIM To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat models.METHODS Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle suspension.The three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis.RESULTS General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control group.Additionally,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group.Imaging examination results showed that the blank control group had the fastest progression of arthritis,the normal extracellular vesicle group had a relatively slower progression,and the engineered extracellular vesicle group had the slowest progression.Gross histological observation results showed that the blank control group had the most obvious signs of arthritis,the normal extracellular vesicle group showed signs of arthritis,and the engineered extracellular vesicle group showed no significant signs of arthritis.Using the Pelletier gross score evaluation,the engineered extracellular vesicle group had the slowest progression of arthritis.Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group,and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition.Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group.Compared to the normal extracellular vesicle group,the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells.CONCLUSION Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability,thereby protecting articular cartilage,and slowing the progression of KOA. 展开更多
关键词 EXOSOMES osteoarthritis Mesenchymal stem cells MicroRNA-29a Intra-articular injection
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Failure mechanism and infrared radiation characteristic of hard siltstone induced by stratification effect 被引量:1
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作者 CHENG Yun SONG Zhanping +2 位作者 XU Zhiwei YANG Tengtian TIAN Xiaoxu 《Journal of Mountain Science》 SCIE CSCD 2024年第3期1058-1074,共17页
The deformation in sedimentary rock induced by train loads has potential threat to the safe operation of tunnels. This study investigated the influence of stratification structure on the infrared radiation and tempora... The deformation in sedimentary rock induced by train loads has potential threat to the safe operation of tunnels. This study investigated the influence of stratification structure on the infrared radiation and temporal damage mechanism of hard siltstone. The uniaxial compression tests, coupled with acoustic emission(AE) and infrared radiation temperature(IRT) were conducted on siltstones with different stratification effects. The results revealed that the stratigraphic structure significantly affects the stress-strain response and strength degradation characteristics. The mechanical parameters exhibit anisotropy characteristics, and the stratification effect exhibits a negative correlation with the cracking stress and peak stress. The failure modes caused by the stratification effect show remarkable anisotropic features, including splitting failure(Ⅰ: 0°-22.50°, Ⅱ: 90°), composite failure(45°), and shearing failure(67.50°). The AE temporal sequences demonstrate a stepwise response characteristic to the loading stress level. The AE intensity indicates that the stress sensitivity of shearing failure and composite failure is generally greater than that of splitting failure. The IRT field has spatiotemporal migration and progressive dissimilation with stress loading and its dissimilation degree increases under higher stress levels. The stronger the stratification effect, the greater the dissimilation degree of the IRT field. The abnormal characteristic points of average infrared radiation temperature(AIRT) variance at local stress drop and peak stress can be used as early and late precursors to identify fracture instability. Theoretical analysis shows that the competitive relationship between compaction strengthening and fracturing damage intensifies the dissimilation of the infrared thermal field for an increasing stress level. The present study provides a theoretical reference for disaster warnings in hard sedimentary rock mass. 展开更多
关键词 Hard siltstone Failure mechanism Stratification effect Infrared radiation characteristic Temporal-damage mechanism DISSIMILATION
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Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics 被引量:2
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作者 Qian-Yun Guo Jia-Qi Yang +1 位作者 Xun-Xun Feng Yu-Jie Zhou 《Military Medical Research》 SCIE CAS CSCD 2024年第1期80-97,共18页
Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public hea... Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury. 展开更多
关键词 Heart regeneration Cardiac disease THERAPEUTICS Signaling mechanisms
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The underlying mechanism of variety–water–nitrogen–stubble damage interactions on yield formation in ratoon rice with low stubble height under mechanized harvesting 被引量:2
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作者 Jingnan Zou Ziqin Pang +11 位作者 Zhou Li Chunlin Guo Hongmei Lin Zheng Li Hongfei Chen Jinwen Huang Ting Chen Hailong Xu Bin Qin Puleng Letuma Weiwei Lin Wenxiong Lin 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2024年第3期806-823,共18页
Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary ... Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019.The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status.Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvesting, the timely application of nitrogen fertilizer is fundamental,coupled with moderate field drying for root-vigor preservation and tiller promotion before and after the mechanical harvesting of the main crop. 展开更多
关键词 mechanized harvesting ratoon rice rice stubble yield attributes
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Drug resistance mechanisms in cancers:Execution of prosurvival strategies 被引量:1
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作者 Pavan Kumar Dhanyamraju 《Journal of Biomedical Research》 CAS CSCD 2024年第2期95-121,共27页
One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon o... One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions. 展开更多
关键词 cancer drug resistance mechanismS MICRORNAS treatment strategies
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To explore the mechanism of Yigong San anti-gastric cancer and immune regulation 被引量:1
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作者 Dou-Dou Lu Ling Yuan +8 位作者 Zhao-Zhao Wang Jian-Jun Zhao Yu-Hua Du Na Ning Guo-Qing Chen Shi-Cong Huang Yi Yang Zhe Zhang Yi Nan 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第5期1965-1994,共30页
BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate ... BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation. 展开更多
关键词 Gastric cancer Yigong San mechanism IMMUNE
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Deep Insight of Design,Mechanism,and Cancer Theranostic Strategy of Nanozymes 被引量:1
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作者 Lu Yang Shuming Dong +6 位作者 Shili Gai Dan Yang He Ding Lili Feng Guixin Yang Ziaur Rehman Piaoping Yang 《Nano-Micro Letters》 SCIE EI CAS CSCD 2024年第2期165-217,共53页
Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction... Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction conditions,good stability,and suitable for large-scale production.Recently,with the cross fusion of nanomedicine and nanocatalysis,nanozyme-based theranostic strategies attract great attention,since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects.Thus,various nanozymes have been developed and used for tumor therapy.In this review,more than 270 research articles are discussed systematically to present progress in the past five years.First,the discovery and development of nanozymes are summarized.Second,classification and catalytic mechanism of nanozymes are discussed.Third,activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory,machine learning,biomimetic and chemical design.Then,synergistic theranostic strategy of nanozymes are introduced.Finally,current challenges and future prospects of nanozymes used for tumor theranostic are outlined,including selectivity,biosafety,repeatability and stability,in-depth catalytic mechanism,predicting and evaluating activities. 展开更多
关键词 Nanozymes Classification Prediction and design Catalytic mechanism Tumor theranostics
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Instability mechanism of mining roadway passing through fault at different angles in kilometre-deep mine and control measures of roof cutting and NPR cables 被引量:2
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作者 SUN Xiaoming WANG Jian +6 位作者 ZHAO Wenchao MING Jiang ZHANG Yong LI Zhihu MIAO Chengyu GUO Zhibiao HE Manchao 《Journal of Mountain Science》 SCIE CSCD 2024年第1期236-251,共16页
The angle α between the fault strike and the axial direction of the roadway produces different damage characteristics. In this paper, the research methodology includes theoretical analyses, numerical simulations and ... The angle α between the fault strike and the axial direction of the roadway produces different damage characteristics. In this paper, the research methodology includes theoretical analyses, numerical simulations and field experiments in the context of the Daqiang coal mine located in Shenyang, China. The stability control countermeasure of "pre-splitting cutting roof + NPR anchor cable"(PSCR-NPR) is simultaneously proposed. According to the different deformation characteristics of the roadway, the faults are innovatively classified into three types, with α of type I being 0°-30°, α of type II being 30°-60°, and α of type III being 60°-90°. The full-cycle stress evolution paths during mining roadway traverses across different types of faults are investigated by numerical simulation. Different pinch angles α lead to high stress concentration areas at different locations in the surrounding rock. The non-uniform stress field formed in the shallow surrounding rock is an important reason for the instability of the roadway. The pre-cracked cut top shifted the high stress region to the deep rock mass and formed a low stress region in the shallow rock mass. The high prestressing NPR anchor cable transforms the non-uniform stress field of the shallow surrounding rock into a uniform stress field. PSCR-NPR is applied in the fault-through roadway of Daqiang mine. The low stress area of the surrounding rock was enlarged by 3-7 times, and the cumulative convergence was reduced by 45%-50%. It provides a reference for the stability control of the deep fault-through mining roadway. 展开更多
关键词 Kilometre-deep mine Fault Mining roadway Failure mechanism Pre-splitting cutting roof High pre-stress NPR anchor cable
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Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation 被引量:2
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作者 Fuhuan Yuan Yu Fu +8 位作者 Liang Ma Hankun Zhu Yong Yu Xin Feng Yi Sun Hongjie Dai Xin Liu Zhengfang Liu Yuhao Zhang 《Food Science and Human Wellness》 SCIE CSCD 2024年第3期1485-1493,共9页
This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instan... This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were investigated.The structural characterization revealed that RBCP successfully chelated with calcium ions.Furthermore,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two peptides.Overall,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides. 展开更多
关键词 Rabbit bone Collagen peptide Peptide-calcium chelate Chelation mechanism Liquid chromatography-tandem mass(LC-MS/MS)
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Molecular Mechanism and Molecular Design of Lubricating Oil Antioxidants 被引量:1
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作者 Su Shuo Long Jun +2 位作者 Duan Qinghua Zhou Han Zhao Yi 《China Petroleum Processing & Petrochemical Technology》 SCIE CAS CSCD 2024年第2期135-145,共11页
To overcome the limitations of traditional experimental“trial and error”methods in lubricant additive design,a new molecular design method based on molecular structure parameters is established here.The molecular me... To overcome the limitations of traditional experimental“trial and error”methods in lubricant additive design,a new molecular design method based on molecular structure parameters is established here.The molecular mechanism of the antioxidant reaction of hindered phenol,diphenylamine,and alkyl sulfide are studied via molecular simulations.Calculation results show that the strong electron-donating ability and high hydrogen-donating activity of the antioxidant molecule and the low hydrogen-abstracting activity of free radicals formed after dehydrogenation are the internal molecular causes of the shielding of phenol and diphenylamine from scavenging peroxy free radicals,and the strong electron-donating ability is the internal molecular cause of the high activity of thioether in decomposing alkyl hydrogen peroxide.Based on this antioxidant molecular mechanism,a molecular design rule of antioxidant is proposed,namely“high EHOMO,large Q(S),low bond dissociation energy BDE(O—H)and BDE(N—H)”.Two new antioxidants,PAS-I and PAS-II,are designed and prepared by chemical bonding of hindered phenol,diphenylamine,and sulfur atoms.Experimental results show that these antioxidants both have excellent antioxidant effects in lubricating oil,and that PAS-II is the superior antioxidant,consistent with theoretical predictions. 展开更多
关键词 lubricating oil ANTIOXIDANT molecular mechanism molecular design antioxidant performance
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Recent research progress in the mechanism and suppression of fusion welding-induced liquation cracking of nickel based superalloys 被引量:1
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作者 Zongli Yi Jiguo Shan +2 位作者 Yue Zhao Zhenlin Zhang Aiping Wu 《International Journal of Minerals,Metallurgy and Materials》 SCIE EI CAS CSCD 2024年第5期1072-1088,共17页
Nickel-based superalloys are extensively used in the crucial hot-section components of industrial gas turbines,aeronautics,and astronautics because of their excellent mechanical properties and corrosion resistance at ... Nickel-based superalloys are extensively used in the crucial hot-section components of industrial gas turbines,aeronautics,and astronautics because of their excellent mechanical properties and corrosion resistance at high temperatures.Fusion welding serves as an effective means for joining and repairing these alloys;however,fusion welding-induced liquation cracking has been a challenging issue.This paper comprehensively reviewed recent liquation cracking,discussing the formation mechanisms,cracking criteria,and remedies.In recent investigations,regulating material composition,changing the preweld heat treatment of the base metal,optimizing the welding process parameters,and applying auxiliary control methods are effective strategies for mitigating cracks.To promote the application of nickel-based superalloys,further research on the combination impact of multiple elements on cracking prevention and specific quantitative criteria for liquation cracking is necessary. 展开更多
关键词 nickel-based superalloy fusion welding liquation cracking cracking mechanism cracking suppression
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Preliminary discussion on the ignition mechanism of exploding foil initiators igniting boron potassium nitrate 被引量:1
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作者 Haotian Jian Guoqiang Zheng +4 位作者 Lejian Chen Zheng Ning Guofu Yin Peng Zhu Ruiqi Shen 《Defence Technology(防务技术)》 SCIE EI CAS CSCD 2024年第2期222-231,共10页
Exploding foil initiator(EFI)is a kind of advanced device for initiating explosives,but its function is unstable when it comes to directly igniting pyrotechnics.To solve the problem,this research aims to reveal the ig... Exploding foil initiator(EFI)is a kind of advanced device for initiating explosives,but its function is unstable when it comes to directly igniting pyrotechnics.To solve the problem,this research aims to reveal the ignition mechanism of EFIs directly igniting pyrotechnics.An oscilloscope,a photon Doppler velocimetry,and a plasma spectrum measurement system were employed to obtain information of electric characteristics,impact pressure,and plasma temperature.The results of the electric characteristics and the impact pressure were inconsistent with ignition results.The only thing that the ignition success tests had in common was that their plasma all had a relatively long period of high-temperature duration(HTD).It eventually concludes that the ignition mechanism in this research is the microconvection heat transfer rather than the shock initiation,which differs from that of exploding foil initiators detonating explosives.Furthermore,the methods for evaluating the ignition success of semiconductor bridge initiators are not entirely applicable to the tests mentioned in this paper.The HTD is the critical parameter for judging the ignition success,and it is influenced by two factors:the late time discharge and the energy of the electric explosion.The longer time of the late time discharge and the more energy of the electric explosion,the easier it is to expand the HTD,which improves the probability of the ignition success. 展开更多
关键词 Exploding foil initiator PDV Plasma spectrum Ignition mechanism Boron potassium nitrate
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