At the start of the new year,Cao Xiucheng,Chairman of Henan No.2 Textile Machinery Co.,Ltd.,was on his way to visit clients when he kept receiving urgent calls from the Xinyang production base regarding order scheduli...At the start of the new year,Cao Xiucheng,Chairman of Henan No.2 Textile Machinery Co.,Ltd.,was on his way to visit clients when he kept receiving urgent calls from the Xinyang production base regarding order scheduling.It turned out that since the end of 2025,the company had successively secured bulk spindle orders from overseas clients in Bangladesh and other countries,coupled with continuous urgent requests for orders from domestic manufacturers.Faced with such a production peak right at the beginning of the year,Mr.Cao Xiucheng admitted,“It was truly unexpected.”展开更多
Objectives Therapeutic strategies for enhancing bone regeneration and combating osteoporosis remain a significant unmet medical need.This study aims to elucidate Lithospermic acid(LA)’s regulatory effects on osteobla...Objectives Therapeutic strategies for enhancing bone regeneration and combating osteoporosis remain a significant unmet medical need.This study aims to elucidate Lithospermic acid(LA)’s regulatory effects on osteoblast proliferation and differentiation,investigating its viability as a bone-healing agent.Methods This study employed various cellular and molecular biology experiments to assess the effects of LA on the viability,proliferation,cell cycle,apoptosis,differentiation,mineralization,and migration of MC3T3-E1 osteoblasts.Immunofluorescence and Western blot analyses were conducted to detect the expression of proteins related to the Wnt/β-catenin signaling pathway,investigating the regulatory mechanisms by which LA promotes osteoblast proliferation and differentiation.Additionally,Wnt inhibitor dickkopf-1(DKK-1)andβ-catenin-silenced cell models were used to further validate the role of LA in modulating this signaling pathway.Results LA significantly promoted osteoblast proliferation without apparent cytotoxicity.Flow cytometry showed that LA regulated the cell cycle by reducing G0/G1 phase arrest and promoting G2/M phase progression.Western blot results indicated that LA upregulated the expression of proteins associated with cell proliferation and enhanced osteoblast differentiation and mineralization.Immunofluorescence and Western blot analyses further confirmed that LA markedly increased the expression of Wnt andβ-catenin,facilitatingβ-catenin nuclear translocation.Treatment with the DKK-1 inhibitor significantly diminished the proliferative and differentiation-promoting effects of LA,confirming the critical role of this pathway.β-catenin knockdown experiments further substantiated its central role in LA-mediated regulation.Conclusion This study confirms that LA promotes osteoblast proliferation,differentiation,mineralization,and migration by activating the Wnt/β-catenin signaling pathway.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain ...Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.展开更多
Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus...Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.展开更多
目的运用meta分析方法系统评价补肾方剂治疗男性不育症患者精子DNA损伤(SDF)的有效性和安全性。方法从中国知网、维普、万方、PubMed、Cochrane Library、Embase、Web of Science数据库中检索补肾方剂改善SDF的随机对照试验(RCT)研究,...目的运用meta分析方法系统评价补肾方剂治疗男性不育症患者精子DNA损伤(SDF)的有效性和安全性。方法从中国知网、维普、万方、PubMed、Cochrane Library、Embase、Web of Science数据库中检索补肾方剂改善SDF的随机对照试验(RCT)研究,对文献进行方法学质量评价,运用RevMan5.3.5软件进行meta分析,并对结局指标进行GRADE质量分级。结果共纳入17项RCT研究,涉及2164例男性患者。与西医常规治疗相比,补肾方剂能够显著改善男性不育症患者DNA碎片指数(DFI)(MD=-6.50,95%CI:-7.88~-5.11,P<0.01),提高配偶妊娠率(RR=2.11,95%CI:1.12~4.00,P=0.87)、精子总活率(MD=5.56,95%CI:4.39~6.74,P<0.01)、前向运动精子百分率(MD=6.82,95%CI:5.62~8.03,P<0.01)、精子浓度(MD=6.51,95%CI:3.81~9.21,P<0.01)和正常形态精子百分率(MD=1.26,95%CI:0.45~2.06,P<0.01),且补肾方剂不会增加不良反应的发生。结论低到中等质量证据表明,与西医常规治疗相比,补肾方剂在改善男性不育症患者DFI、精液参数、配偶妊娠率等方面具有一定优势,且安全性较好。展开更多
In honeybee （Apis mellifera） colonies, queens and workers are altemative forms of the adult female honeybee that develop from genetically identical zygotes but that depend on differential nourishment. Queens and wor...In honeybee （Apis mellifera） colonies, queens and workers are altemative forms of the adult female honeybee that develop from genetically identical zygotes but that depend on differential nourishment. Queens and workers display distinct morphologies, anatomies and behavior, better known as caste differentiation. Despite some basic insights, the exact mechanism responsible for this phenomenon, especially at the molecular level, remains unclear although some progress has been achieved. In this study, we examined mRNA levels of the TOR （target of rapamycin） and Dnmt3 （DNA methyltransferase 3） genes, closely related to caste differentiation in honeybees. We also investigated mRNA expression of the S6K （similar to RPS6-p70-protein kinase） gene linked closely to organismal growth and development in queen and worker larvae （1-day and 3-day old）. Last, we investigated the methylation status of these three genes in corresponding castes. We found no difference in mRNA expression for the three genes between 1st instar queen and worker larvae; however, 3rd instar queen larvae had a higher level of TOR mRNA than worker larvae. Methylation levels of all three genes were lower in queen larvae than worker larvae but the differences were not statistically significant. These findings provide basic data for broadening our understanding of caste differentiation in female honeybees.展开更多
文摘At the start of the new year,Cao Xiucheng,Chairman of Henan No.2 Textile Machinery Co.,Ltd.,was on his way to visit clients when he kept receiving urgent calls from the Xinyang production base regarding order scheduling.It turned out that since the end of 2025,the company had successively secured bulk spindle orders from overseas clients in Bangladesh and other countries,coupled with continuous urgent requests for orders from domestic manufacturers.Faced with such a production peak right at the beginning of the year,Mr.Cao Xiucheng admitted,“It was truly unexpected.”
基金funded by Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(2023ZL128)Zhejiang Province Medical and Health Science and Technology Project(2022504276)Hangzhou Municipal Health and Family Planning Science and Technology Program General Project(A20210086).
文摘Objectives Therapeutic strategies for enhancing bone regeneration and combating osteoporosis remain a significant unmet medical need.This study aims to elucidate Lithospermic acid(LA)’s regulatory effects on osteoblast proliferation and differentiation,investigating its viability as a bone-healing agent.Methods This study employed various cellular and molecular biology experiments to assess the effects of LA on the viability,proliferation,cell cycle,apoptosis,differentiation,mineralization,and migration of MC3T3-E1 osteoblasts.Immunofluorescence and Western blot analyses were conducted to detect the expression of proteins related to the Wnt/β-catenin signaling pathway,investigating the regulatory mechanisms by which LA promotes osteoblast proliferation and differentiation.Additionally,Wnt inhibitor dickkopf-1(DKK-1)andβ-catenin-silenced cell models were used to further validate the role of LA in modulating this signaling pathway.Results LA significantly promoted osteoblast proliferation without apparent cytotoxicity.Flow cytometry showed that LA regulated the cell cycle by reducing G0/G1 phase arrest and promoting G2/M phase progression.Western blot results indicated that LA upregulated the expression of proteins associated with cell proliferation and enhanced osteoblast differentiation and mineralization.Immunofluorescence and Western blot analyses further confirmed that LA markedly increased the expression of Wnt andβ-catenin,facilitatingβ-catenin nuclear translocation.Treatment with the DKK-1 inhibitor significantly diminished the proliferative and differentiation-promoting effects of LA,confirming the critical role of this pathway.β-catenin knockdown experiments further substantiated its central role in LA-mediated regulation.Conclusion This study confirms that LA promotes osteoblast proliferation,differentiation,mineralization,and migration by activating the Wnt/β-catenin signaling pathway.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
文摘Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.
基金supported by the Natural Science Foundation of Hubei Province of China(Grant No.2023AFB671)the National Natural Science Foundation of China(Grant Nos.82360177 and 82560182)+1 种基金the Key Project of Jiangxi Provincial Natural Science Foundation(Grant No.20224ACB206011)“Xuncheng Talents”Project in Jiujiang City,Jiangxi Province(Grant No.JJXC2023071).
文摘Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.
文摘目的运用meta分析方法系统评价补肾方剂治疗男性不育症患者精子DNA损伤(SDF)的有效性和安全性。方法从中国知网、维普、万方、PubMed、Cochrane Library、Embase、Web of Science数据库中检索补肾方剂改善SDF的随机对照试验(RCT)研究,对文献进行方法学质量评价,运用RevMan5.3.5软件进行meta分析,并对结局指标进行GRADE质量分级。结果共纳入17项RCT研究,涉及2164例男性患者。与西医常规治疗相比,补肾方剂能够显著改善男性不育症患者DNA碎片指数(DFI)(MD=-6.50,95%CI:-7.88~-5.11,P<0.01),提高配偶妊娠率(RR=2.11,95%CI:1.12~4.00,P=0.87)、精子总活率(MD=5.56,95%CI:4.39~6.74,P<0.01)、前向运动精子百分率(MD=6.82,95%CI:5.62~8.03,P<0.01)、精子浓度(MD=6.51,95%CI:3.81~9.21,P<0.01)和正常形态精子百分率(MD=1.26,95%CI:0.45~2.06,P<0.01),且补肾方剂不会增加不良反应的发生。结论低到中等质量证据表明,与西医常规治疗相比,补肾方剂在改善男性不育症患者DFI、精液参数、配偶妊娠率等方面具有一定优势,且安全性较好。
基金supported by the Yunnan Government(2009CI119)Modern Agricultural Industry Technology System(Honeybee)(CARS-45-kxj14)
文摘In honeybee （Apis mellifera） colonies, queens and workers are altemative forms of the adult female honeybee that develop from genetically identical zygotes but that depend on differential nourishment. Queens and workers display distinct morphologies, anatomies and behavior, better known as caste differentiation. Despite some basic insights, the exact mechanism responsible for this phenomenon, especially at the molecular level, remains unclear although some progress has been achieved. In this study, we examined mRNA levels of the TOR （target of rapamycin） and Dnmt3 （DNA methyltransferase 3） genes, closely related to caste differentiation in honeybees. We also investigated mRNA expression of the S6K （similar to RPS6-p70-protein kinase） gene linked closely to organismal growth and development in queen and worker larvae （1-day and 3-day old）. Last, we investigated the methylation status of these three genes in corresponding castes. We found no difference in mRNA expression for the three genes between 1st instar queen and worker larvae; however, 3rd instar queen larvae had a higher level of TOR mRNA than worker larvae. Methylation levels of all three genes were lower in queen larvae than worker larvae but the differences were not statistically significant. These findings provide basic data for broadening our understanding of caste differentiation in female honeybees.
