Separators play a critical role in the safety and performance of lithium-ion batteries.However,commercial polyolefin separators are limited by their poor affinity with electrolytes and low melting points.In this work,...Separators play a critical role in the safety and performance of lithium-ion batteries.However,commercial polyolefin separators are limited by their poor affinity with electrolytes and low melting points.In this work,we constructed a reinforced-concrete-like structure by homogeneously dispersing nano-Al_(2)O_(3) and cellulose on the separators to improve their stability and performance.In this reinforcedconcrete-like structure,the cellulose is a reinforcing mesh,and the nano-Al_(2)O_(3) acts as concrete to support the separator.After constructing the reinforced-concrete-like structure,the separators exhibit good stability even at 200℃(thermal shrinkage of 0.3%),enhanced tensile strain(tensile stress of 133.4 MPa and tensile strains of 62%),and better electrolyte wettability(a contact angle of 6.5°).Combining these advantages,the cells with nano-Al_(2)O_(3)@cellulose-coated separators exhibit stable cycling performance and good rate performance.Therefore,the construction of the reinforced-concretelike structure is a promising technology to promote the application of lithium-ion batteries in extreme environments.展开更多
AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment...AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)group.The cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell chamber.The EMT-related indexes and BMP-6 protein levels were detected by Western blotting.Furthermore,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression group.The EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were detected.RESULTS:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly enhanced.TGF-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in RPE.Similarly,the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced.BMP-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.展开更多
Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and function.Exactly how Wnt/β-catenin signaling is regulated in OBs remain elusive.A...Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and function.Exactly how Wnt/β-catenin signaling is regulated in OBs remain elusive.ATP6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling pathways.However,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone formation.Here we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone regions.Conditionally knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone mass.Proteomic and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not osteocytes.Additional in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not BMSCs.Further cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their degradation.Expression of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO BMSCs.Taken together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.展开更多
BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untran...BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.展开更多
BACKGROUND The role of primary-level medical pharmacists in medical institutions in China is limited;therefore,it is necessary to explore the role of pharmacists in the process of drug treatment.CASE SUMMARY A Chinese...BACKGROUND The role of primary-level medical pharmacists in medical institutions in China is limited;therefore,it is necessary to explore the role of pharmacists in the process of drug treatment.CASE SUMMARY A Chinese pharmacist participated in the complete treatment of a patient with a duodenal ulcer.The rationale for drug treatment was evaluated,and adjustments were made to the antacid and anti-infective regimen,as well as the dose and frequency of administration.Body temperature,routine blood examination,and adverse drug reactions were strictly monitored.During treatment,the pharmacist recommended anti-infective therapy with ampicillin-sulbactam,which effectively controlled the infection.Additionally,the pharmacist suggested changing famotidine to lansoprazole for acid suppression and gastroprotective treatment,combined with Chinese patent medicine such as Kangfuxin Liquid.This is the first case report of a pharmacist in primary-level medical institutions adjusting drug use for patients with duodenal ulcer and pulmonary infection.CONCLUSION A pharmacist participated in the treatment process,provided individualized medication adjustment,and achieved good clinical results.展开更多
BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main m...BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.展开更多
Background:Skin,being a vital organ that regulates physiological responses in the human body,is prone to injury from external environmental factors.Healing full-thickness skin defects becomes especially challenging wh...Background:Skin,being a vital organ that regulates physiological responses in the human body,is prone to injury from external environmental factors.Healing full-thickness skin defects becomes especially challenging when infections and vascular injuries are involved.Traditional wound dressings with single functions,such as antibacterial or angiogenic properties,fall short in achieving rapid wound healing.To address this,there is a need to develop wound dressing materials that possess both effective antibacterial and angiogenic properties.Methods:In this study,we utilized electrospinning technology to fabricate hyaluronic acid-cellulose acetate fibrous membrane dressings,incorporating poly(ionic liquid)as an antibacterial polymer and deferoxamine as an angiogenic agent.Results:The resulting fibrous membrane dressing contained poly(ionic liquid)and deferoxamin showcased a microporous structure,drug-releasing capabilities,and excellent air permeability.It not only demonstrated highly effective antibacterial properties but also exhibited remarkable angiogenesis,thereby promoting the healing of full-thickness skin defect wounds in both in vitro and in vivo assays.Conclusion:These findings highlight the immense potential of this wound dressing material for future clinical applications.展开更多
Severe polysulfide shuttling and sluggish sulfur redox kinetics significantly decrease sulfur utilization and cycling stability in lithium-sulfur batteries(LSBs).Herein,we develop a hollow CoO/CoP-Box core-shell heter...Severe polysulfide shuttling and sluggish sulfur redox kinetics significantly decrease sulfur utilization and cycling stability in lithium-sulfur batteries(LSBs).Herein,we develop a hollow CoO/CoP-Box core-shell heterostructure as a model and multifunctional catalyst modified on separators to induce interfacial charge modulation and expose more active sites for promoting the adsorption and catalytic conversion ability of sulfur species.Theoretical and experimental findings verify that the in-situ formed core-shell hetero-interface induces the formation of P-Co-O binding and charge redistribution to activate surface O active sites for binding lithium polysulfides(LiPSs)via strong Li-O bonding,thus strongly adsorbing with Li PSs.Meanwhile,the strong Li-O bonding weakens the competing Li-S bonding in LiPSs or Li2S adsorbed on CoO/CoP-Box surface,plus the hollow heterostructure provides abundant active sites and fast electron/Li+transfer,so reducing Li2S nucleation/dissolution activation energy.As expected,LSBs with CoO/CoP-Box modified separator and traditional sulfur/carbon black cathode display a large initial capacity of 1240 mA h g^(-1)and a long cycling stability with 300 cycles(~60.1%capacity retention)at 0.5C.Impressively,the thick sulfur cathode(sulfur loading:5.2 mg cm^(-2))displays a high initial areal capacity of 6.9 mA h cm^(-2).This work verifies a deep mechanism understanding and an effective strategy to induce interfacial charge modulation and enhance active sites for designing efficient dual-directional Li-S catalysts via engineering hollow core-shell hetero-structure.展开更多
Structural damage is significantly influenced by the various parameters of a close-in explosion.To establish a close-in blast loading model for cylindrical charges according to these parameters,a series of field exper...Structural damage is significantly influenced by the various parameters of a close-in explosion.To establish a close-in blast loading model for cylindrical charges according to these parameters,a series of field experiments and a systematic numerical analysis were conducted.A high-fidelity finite element model developed using AUTODYN was first validated using blast data collected from field tests conducted in this and previous studies.A quantitative analysis was then performed to determine the influence of the charge shape,aspect ratio(length to diameter),orientation,and detonation configuration on the characteristics and distributions of the blast loading(incident peak overpressure and impulse)according to scaled distance.The results revealed that the secondary peak overpressure generated by a cylindrical charge was mainly distributed along the axial direction and was smaller than the overpressure generated by an equivalent spherical charge.The effects of charge shape on the blast loading at 45°and 67.5°in the axial plane could be neglected at scaled distances greater than 2 m/kg^(1/3);the effect of aspect ratios greater than 2 on the peak overpressure in the 90°(radial)direction could be neglected at all scaled distances;and double-end detonation increased the radial blast loading by up to 60%compared to singleend detonation.Finally,an empirical cylindrical charge blast loading model was developed considering the influences of charge aspect ratio,orientation,and detonation configuration.The results obtained in this study can serve as a reference for the design of blast tests using cylindrical charges and aid engineers in the design of blast-resistant structures.展开更多
The newly released nomenclature of metabolic dysfunction-associated steatotic liver disease(MASLD)in the 2023 European Association for the Study of the Liver Congress has raised great clinical concerns.This marks the ...The newly released nomenclature of metabolic dysfunction-associated steatotic liver disease(MASLD)in the 2023 European Association for the Study of the Liver Congress has raised great clinical concerns.This marks the second instance of significant renaming of non-alcoholic fatty liver disease since the introduction of metabolic dysfunction-associated fatty liver disease(MAFLD)in 2020.The nomenclature and definitions of MASLD and MAFLD exhibit significant disparities as well as substantial consensus.The disparities regarding the framework of nomenclature,the definitions,the clinical management,and the impact on the clinical outcomes between MASLD and MAFLD were comprehensively compared in this editorial.Additionally,the consensus reached by the MASLD and MAFLD definitions also emphasizes positive diagnosis rather than negative diagnosis within the framework of establishing a diagnostic approach.Furthermore,they acknowledged the pivotal role of metabolic dysfunction in the pathogenesis of MAFLD or MASLD and the positive role of increasing the awareness of the disease in public.Fortunately,the non-invasive tests remains effective in the MASLD and MAFLD era.Elucidating these disparities would contribute to a more comprehensive comprehension of the nature of steatotic liver disease and enhance clinical practice.Thus,more efforts are required to reach more consensus about these important topics.展开更多
目的 检索、总结宫颈癌患者术后性健康教育有关的最佳证据,为更好地对临床宫颈癌患者提供性健康和功能障碍方面的宣教奠定基础。方法 以“6S”金字塔为模型,使用计算机检索BMJ Best Practice、Up To Date、国际指南协作网、美国国立指...目的 检索、总结宫颈癌患者术后性健康教育有关的最佳证据,为更好地对临床宫颈癌患者提供性健康和功能障碍方面的宣教奠定基础。方法 以“6S”金字塔为模型,使用计算机检索BMJ Best Practice、Up To Date、国际指南协作网、美国国立指南库、英国国家临床医学研究所指南库、苏格兰学院间指南网等关于宫颈癌患者性健康教育相关的指南(检索时限为建库至2022年9月20日),并检索了性专业网站及肿瘤相关网站。根据纳入标准遴选文献,由2名研究者背对背对纳入文献进行质量评价和证据提取。结果 本研究最终共纳入5篇指南,形成的证据包括5个方面(分别为评估问询、相关症状、性心理、阴道扩张和用药指导)共20条证据。结论 宫颈癌患者术后性健康教育的最佳证据总结,有助于指导医护人员以更科学的方式对宫颈癌患者进行健康宣教,从而改善患者的生活质量和心理幸福感。展开更多
基金funding from the Natural Science Foundation of China(22278150,22075086,22138005,and 22141001)the Guangdong Basic and Applied Basic Research Foundation(2022A1515010980,2023A1515010046)the Fundamental Research Funds for the Central Universities(2022ZYGXZR101).
文摘Separators play a critical role in the safety and performance of lithium-ion batteries.However,commercial polyolefin separators are limited by their poor affinity with electrolytes and low melting points.In this work,we constructed a reinforced-concrete-like structure by homogeneously dispersing nano-Al_(2)O_(3) and cellulose on the separators to improve their stability and performance.In this reinforcedconcrete-like structure,the cellulose is a reinforcing mesh,and the nano-Al_(2)O_(3) acts as concrete to support the separator.After constructing the reinforced-concrete-like structure,the separators exhibit good stability even at 200℃(thermal shrinkage of 0.3%),enhanced tensile strain(tensile stress of 133.4 MPa and tensile strains of 62%),and better electrolyte wettability(a contact angle of 6.5°).Combining these advantages,the cells with nano-Al_(2)O_(3)@cellulose-coated separators exhibit stable cycling performance and good rate performance.Therefore,the construction of the reinforced-concretelike structure is a promising technology to promote the application of lithium-ion batteries in extreme environments.
基金Supported by the Key Research&Development Program of Shaanxi Province(No.2022SF-311,No.2024SFYBXM-328,No.2024SF-YBXM-325)the Natural Science Basic Research Program of Shaanxi Province,China(No.2021JQ-385).
文摘AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)group.The cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell chamber.The EMT-related indexes and BMP-6 protein levels were detected by Western blotting.Furthermore,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression group.The EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were detected.RESULTS:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly enhanced.TGF-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in RPE.Similarly,the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced.BMP-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.
基金supported in part by grants from the National Institutes of Health(AG045781,AG051510,and AG066526)(to WCX).
文摘Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and function.Exactly how Wnt/β-catenin signaling is regulated in OBs remain elusive.ATP6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling pathways.However,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone formation.Here we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone regions.Conditionally knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone mass.Proteomic and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not osteocytes.Additional in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not BMSCs.Further cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their degradation.Expression of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO BMSCs.Taken together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.
基金Supported by General Program of National Natural Science Foundation of China,No.81770197Scientific and Technological Research Major Program of Chongqing Municipal Education Commission,No.KJZD-M202312802+1 种基金Chongqing Natural Science Foundation of China,No.CSTB2022NSCQ-MSX0190,No.CSTB2022NSCQ-MSX0176,and No.cstc2020jcyj-msxmX0051Xinqiao Young Postdoc Talent Incubation Program,No.2022YQB098.
文摘BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.
文摘BACKGROUND The role of primary-level medical pharmacists in medical institutions in China is limited;therefore,it is necessary to explore the role of pharmacists in the process of drug treatment.CASE SUMMARY A Chinese pharmacist participated in the complete treatment of a patient with a duodenal ulcer.The rationale for drug treatment was evaluated,and adjustments were made to the antacid and anti-infective regimen,as well as the dose and frequency of administration.Body temperature,routine blood examination,and adverse drug reactions were strictly monitored.During treatment,the pharmacist recommended anti-infective therapy with ampicillin-sulbactam,which effectively controlled the infection.Additionally,the pharmacist suggested changing famotidine to lansoprazole for acid suppression and gastroprotective treatment,combined with Chinese patent medicine such as Kangfuxin Liquid.This is the first case report of a pharmacist in primary-level medical institutions adjusting drug use for patients with duodenal ulcer and pulmonary infection.CONCLUSION A pharmacist participated in the treatment process,provided individualized medication adjustment,and achieved good clinical results.
基金Supported by National Natural Science Foundation of China,No.82270845。
文摘BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.
基金support from National Natural Science Foundation of China(Grant No 52105295)the Natural Science Foundation of Jiangsu Province(Grant No BK20210082)+3 种基金Natural Science of Foundation of the Jiangsu Higher Education Institutions of China(Grant No 21KJB460003)Basic Research Project of Changzhou Medical Center of Nanjing Medical University(CMCB202314),Qinghai Province Health System Guidance Plan Project(2022-wjzdx-106 and 2023-wjzdx-104)Top Talent of Changzhou“The 14th Five-Year Plan”High-Level Health Talents Training Project(2022CZBJ059 and 2022CZBJ061)Nursing research project of the Second People's Hospital of Changzhou(2022HZD002).
文摘Background:Skin,being a vital organ that regulates physiological responses in the human body,is prone to injury from external environmental factors.Healing full-thickness skin defects becomes especially challenging when infections and vascular injuries are involved.Traditional wound dressings with single functions,such as antibacterial or angiogenic properties,fall short in achieving rapid wound healing.To address this,there is a need to develop wound dressing materials that possess both effective antibacterial and angiogenic properties.Methods:In this study,we utilized electrospinning technology to fabricate hyaluronic acid-cellulose acetate fibrous membrane dressings,incorporating poly(ionic liquid)as an antibacterial polymer and deferoxamine as an angiogenic agent.Results:The resulting fibrous membrane dressing contained poly(ionic liquid)and deferoxamin showcased a microporous structure,drug-releasing capabilities,and excellent air permeability.It not only demonstrated highly effective antibacterial properties but also exhibited remarkable angiogenesis,thereby promoting the healing of full-thickness skin defect wounds in both in vitro and in vivo assays.Conclusion:These findings highlight the immense potential of this wound dressing material for future clinical applications.
基金supported by the National Natural Science Foundation of China(51972066)the Natural Science Foundation of Guangdong Province of China(2021A1515011718)the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2017。
文摘Severe polysulfide shuttling and sluggish sulfur redox kinetics significantly decrease sulfur utilization and cycling stability in lithium-sulfur batteries(LSBs).Herein,we develop a hollow CoO/CoP-Box core-shell heterostructure as a model and multifunctional catalyst modified on separators to induce interfacial charge modulation and expose more active sites for promoting the adsorption and catalytic conversion ability of sulfur species.Theoretical and experimental findings verify that the in-situ formed core-shell hetero-interface induces the formation of P-Co-O binding and charge redistribution to activate surface O active sites for binding lithium polysulfides(LiPSs)via strong Li-O bonding,thus strongly adsorbing with Li PSs.Meanwhile,the strong Li-O bonding weakens the competing Li-S bonding in LiPSs or Li2S adsorbed on CoO/CoP-Box surface,plus the hollow heterostructure provides abundant active sites and fast electron/Li+transfer,so reducing Li2S nucleation/dissolution activation energy.As expected,LSBs with CoO/CoP-Box modified separator and traditional sulfur/carbon black cathode display a large initial capacity of 1240 mA h g^(-1)and a long cycling stability with 300 cycles(~60.1%capacity retention)at 0.5C.Impressively,the thick sulfur cathode(sulfur loading:5.2 mg cm^(-2))displays a high initial areal capacity of 6.9 mA h cm^(-2).This work verifies a deep mechanism understanding and an effective strategy to induce interfacial charge modulation and enhance active sites for designing efficient dual-directional Li-S catalysts via engineering hollow core-shell hetero-structure.
基金supported by the National Natural Science Foundation of China[No.51978166]。
文摘Structural damage is significantly influenced by the various parameters of a close-in explosion.To establish a close-in blast loading model for cylindrical charges according to these parameters,a series of field experiments and a systematic numerical analysis were conducted.A high-fidelity finite element model developed using AUTODYN was first validated using blast data collected from field tests conducted in this and previous studies.A quantitative analysis was then performed to determine the influence of the charge shape,aspect ratio(length to diameter),orientation,and detonation configuration on the characteristics and distributions of the blast loading(incident peak overpressure and impulse)according to scaled distance.The results revealed that the secondary peak overpressure generated by a cylindrical charge was mainly distributed along the axial direction and was smaller than the overpressure generated by an equivalent spherical charge.The effects of charge shape on the blast loading at 45°and 67.5°in the axial plane could be neglected at scaled distances greater than 2 m/kg^(1/3);the effect of aspect ratios greater than 2 on the peak overpressure in the 90°(radial)direction could be neglected at all scaled distances;and double-end detonation increased the radial blast loading by up to 60%compared to singleend detonation.Finally,an empirical cylindrical charge blast loading model was developed considering the influences of charge aspect ratio,orientation,and detonation configuration.The results obtained in this study can serve as a reference for the design of blast tests using cylindrical charges and aid engineers in the design of blast-resistant structures.
文摘The newly released nomenclature of metabolic dysfunction-associated steatotic liver disease(MASLD)in the 2023 European Association for the Study of the Liver Congress has raised great clinical concerns.This marks the second instance of significant renaming of non-alcoholic fatty liver disease since the introduction of metabolic dysfunction-associated fatty liver disease(MAFLD)in 2020.The nomenclature and definitions of MASLD and MAFLD exhibit significant disparities as well as substantial consensus.The disparities regarding the framework of nomenclature,the definitions,the clinical management,and the impact on the clinical outcomes between MASLD and MAFLD were comprehensively compared in this editorial.Additionally,the consensus reached by the MASLD and MAFLD definitions also emphasizes positive diagnosis rather than negative diagnosis within the framework of establishing a diagnostic approach.Furthermore,they acknowledged the pivotal role of metabolic dysfunction in the pathogenesis of MAFLD or MASLD and the positive role of increasing the awareness of the disease in public.Fortunately,the non-invasive tests remains effective in the MASLD and MAFLD era.Elucidating these disparities would contribute to a more comprehensive comprehension of the nature of steatotic liver disease and enhance clinical practice.Thus,more efforts are required to reach more consensus about these important topics.
文摘目的 检索、总结宫颈癌患者术后性健康教育有关的最佳证据,为更好地对临床宫颈癌患者提供性健康和功能障碍方面的宣教奠定基础。方法 以“6S”金字塔为模型,使用计算机检索BMJ Best Practice、Up To Date、国际指南协作网、美国国立指南库、英国国家临床医学研究所指南库、苏格兰学院间指南网等关于宫颈癌患者性健康教育相关的指南(检索时限为建库至2022年9月20日),并检索了性专业网站及肿瘤相关网站。根据纳入标准遴选文献,由2名研究者背对背对纳入文献进行质量评价和证据提取。结果 本研究最终共纳入5篇指南,形成的证据包括5个方面(分别为评估问询、相关症状、性心理、阴道扩张和用药指导)共20条证据。结论 宫颈癌患者术后性健康教育的最佳证据总结,有助于指导医护人员以更科学的方式对宫颈癌患者进行健康宣教,从而改善患者的生活质量和心理幸福感。