BACKGROUND Poor glycaemic control in patients with type 2 diabetes mellitus(T2DM)is often accompanied by multiple complications,including diabetic nephropathy(DN),diabetic retinopathy(DR),diabetic peripheral neuropath...BACKGROUND Poor glycaemic control in patients with type 2 diabetes mellitus(T2DM)is often accompanied by multiple complications,including diabetic nephropathy(DN),diabetic retinopathy(DR),diabetic peripheral neuropathy(DPN),and cardiac structural abnormality left ventricular hypertrophy(LVH).Early identification of high-risk populations for these complications and the implementation of intervention measures are crucial for improving patient outcomes.Serum alpha-1-microglobulin(α1-MG),a multifunctional protein synthesized by the liver and lymphocytes,has been considered a potential biomarker of diabetes-related diseases in recent years.AIM To investigate the associations of serumα1-MG with DN,DR,DPN,and LVH in T2DM patients and its predictive value.METHODS This retrospective study included 5045 T2DM patients.The study participants were stratified into quartiles according to their serumα1-MG levels.Multivariate logistic regression,restricted cubic spline,and explainable machine learning models were employed for risk assessment and feature importance evaluation.RESULTS Increasedα1-MG levels were observed in patients with DN,DR,DPN,and LVH(all P<0.001).Multivariate logistic regression revealed that each standard deviation increase inα1-MG was associated with an 84%increase in DN risk(OR:1.84,95%CI:1.62-2.10,P<0.001),a 17%increase in DR risk(OR:1.17,95%CI:1.07-1.28,P<0.001),a 14%increase in DPN risk(OR:1.14,95%CI:1.03-1.27,P=0.014),and a 28%increase in LVH risk(OR:1.28,95%CI:1.18-1.38,P<0.001).Subgroup analyses and machine learning confirmed the associations of elevatedα1-MG with these complications in T2DM patients.CONCLUSION Elevated serumα1-MG levels were independently associated with increased risks of DN,DR,DPN,and LVH in T2DM patients,suggesting its potential as a predictive biomarker.展开更多
BACKGROUND Achievement of endoscopic healing(EH)is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis.Existing biomarkers,including C-reactive protein(CRP),h...BACKGROUND Achievement of endoscopic healing(EH)is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis.Existing biomarkers,including C-reactive protein(CRP),have relatively low accuracy for predicting EH,especially in small intestinal lesions in Crohn’s disease(CD);thus,noninvasive and more accurate biomarkers are required.Leucine-rich alpha-2 glycoprotein(LRG),a 50-kD protein,is produced under inflammatory conditions and has been reported to be useful in assessing disease activity in inflammatory bowel disease.However,the usefulness of LRG in small intestinal lesions in CD remains inconclusive.AIM To determine the usefulness of LRG for EH in small bowel lesions in CD and compare it with CRP.METHODS This study included 133 consecutive patients with CD who underwent balloonassisted enteroscopy between June 2021 and March 2024 at Shiga University of Medical Science Hospital(Otsu,Japan).We retrospectively analyzed endoscopic scores in each of the ileum and colon and four markers including LRG,CRP,albumin,and Harvey-Bradshaw index(HBI).Spearman’s rank correlation coefficient and receiver operating characteristic analysis were performed.RESULTS Either active ileal or colonic lesions exhibited significant differences in LRG,CRP,albumin,and HBI compared with EH.CRP,albumin,and HBI showed a worse correlation with endoscopic activity in the ileum than that in the colon;however,LRG did not show a worse correlation(colon,r=0.5218;ileum,r=0.5602).Receiver operating characteristic analysis revealed that LRG for EH in the ileum and colon had the same cutoff values of 12.4μg/mL.Comparing the areas under the curve of LRG and CRP for predicting EH in the ileum revealed a significantly higher areas under the curve of LRG(95%confidence interval,0.017-0.194;P=0.024),whereas the two showed no significant difference in the colon.CONCLUSION LRG is a useful biomarker in assessing the endoscopic activity of CD and is more useful than CRP in the small intestine.展开更多
The study by Ohno et al provides valuable insights into the role of leucine-rich alpha-2-glycoprotein(LRG)as a potential biomarker for identifying small bowel lesions in Crohn's disease(CD).However,several methodo...The study by Ohno et al provides valuable insights into the role of leucine-rich alpha-2-glycoprotein(LRG)as a potential biomarker for identifying small bowel lesions in Crohn's disease(CD).However,several methodological challenges hinder its immediate use in clinical practice.Notably,the current research was retrospective,lacks comparative studies with fecal calprotectin,and did not provide long-term predictive data.Further prospective studies are needed to improve the applicability of LRG.Moreover,integrating LRG with additional biomarkers and employing artificial intelligence techniques may improve its effectiveness in disease monitoring.Future research should address interobserver variability,assess LRG's cost-effectiveness,and standardize endoscopic healing definitions to ensure broader applicability.Advancing these areas is vital for establishing LRG's role in precision medicine strategies for the management of CD.展开更多
Ternary blending as one of the most successful strategies has achieved continuous performance breakthroughs in organic solar cells(OSCs)over the past few years.Here,a small molecule featuring a dithieno[3,2-f:2′,3′-...Ternary blending as one of the most successful strategies has achieved continuous performance breakthroughs in organic solar cells(OSCs)over the past few years.Here,a small molecule featuring a dithieno[3,2-f:2′,3′-h]phthalimide derivative as the intermediate unit,named DTP-C8-R,is designed and utilized as the third component to construct ternary OSCs(TOSCs).The increased molecular packing of L8-BO as well as the charge transfer excitons between PM6 and DTP-C8-R lead to a very low nonradiative energy loss of 0.179 eV and a high open-circuit voltage(V_(OC))of 0.910 V in the TOSCs based on the PM6:L8-BO host blend.Moreover,the DTP-C8-R:PM6:L8-BO film(0.05:0.95:1.2,w/w)possesses better fibrous nanophase separation and the enhancedπ-πstacking ordering of the acceptors with a larger crystal coherence length compared with the PM6:L8-BO blend film,so the TOSCs present more efficient exciton dissociation,longer carrier lifetime,faster carrier transport and less charge recombination.It boosts the power conversion efficiency to 19.22%with a short-circuit current density of 27.10 mA cm^(-2).This work demonstrates that the small molecule based on a dithieno[3,2-f:2′,3′-h]phthalimide derivative as the minor component is an executable strategy to achieve high-performance TOSCs with high V_(OC).展开更多
Hydroxylation of inert benzene through the activation of the C_(sp2)-H bond is a representative reaction about the transformation of C-H bonds to C-O bonds,which has far-reaching guiding significance but remains a cha...Hydroxylation of inert benzene through the activation of the C_(sp2)-H bond is a representative reaction about the transformation of C-H bonds to C-O bonds,which has far-reaching guiding significance but remains a challenging scientific problem.To overcome this problem,a series of VOx-Ga_(2)O_(3)/SiO_(2)-Al_(2)O_(3)were prepared to achieve an efficient and economical hydroxylation path of benzene to phenol.The results showed that the phenol yield was 72.89%(selectivity>98.1%)under the optimum conditions.The reason is that the C-H bond in the benzene ring is activated by heterolysis over a VOx-Ga_(2)O_(3)/SiO_(2)-Al_(2)O_(3)catalyst.Meanwhile,the introduction of aluminum(Al)and gallium(Ga)made a qualitative change in the catalyst,enhancing the electron motion and spin motion of vanadium species,resulting in the increase of V4^(+)/V5^(+)ratio.In addition,the catalyst can provide an optimal acidic environment and a threedimensional cross-linked surface structure that facilitates product diffusion.展开更多
Native amino-directed palladium-catalyzed C(sp^(3))-H activation/functionalization has been developed for modification ofα-amino acids and peptides.Herein a palladium(Ⅱ)-catalyzed C(sp^(2))-H arylation ofα-amino-β...Native amino-directed palladium-catalyzed C(sp^(3))-H activation/functionalization has been developed for modification ofα-amino acids and peptides.Herein a palladium(Ⅱ)-catalyzed C(sp^(2))-H arylation ofα-amino-β-aryl esters has been disclosed,using the native amino as the directing group.A variety of chiralα-amino-β-aryl esters can be functionalized to give the corresponding ortho-substituted mono-and di-arylated products.展开更多
Introduction:Dexamethasone(Dex)caused impaired osteoblast differentiation and oxidative stress(OS)in bone marrow mesenchymal stem cells(BMSCs).This work sought to elucidate the precise molecular pathway through which ...Introduction:Dexamethasone(Dex)caused impaired osteoblast differentiation and oxidative stress(OS)in bone marrow mesenchymal stem cells(BMSCs).This work sought to elucidate the precise molecular pathway through which Dex influences osteogenic differentiation(OD)and OS in BMSCs.Methods:The expression of Runt-related transcription factor 1(RUNX1)and alpha-2 macroglobulin(A2M)was assessed in Dex-treated BMSCs using qRTPCR and Western Blot.Following the functional rescue experiments,cell proliferation was determined by MTT assay,reactive oxygen species(ROS)expression by DCFH-DA fluorescent probe,lactate dehydrogenase(LDH),superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(Gpx)expression by kits,OD by alkaline phosphatase(ALP)staining and activity quantification,and the expression of OD-related proteins RUNX2,collagen type 1 alpha 1(COL1A1),and osteocalcin(OCN)by qRT-PCR and Western Blot.The binding of RUNX1 to A2M was initially analyzed through Jaspar website and subsequently verified by dual-luciferase reporter and ChIP assays.Results:Dextreated BMSCs had low RUNX1 and A2M expression.Dex treatment apparently elevated ROS and LDH levels,diminished cell proliferation rate and SOD,CAT,and Gpx expression,lightened intensity of ALP staining,and declined calcified nodules,ALP activity,and RUNX2,COL1A1,and OCN expression in BMSCs,which was counterweighed by RUNX1 or A2M overexpression.RUNX1 positively targeted A2M.A2M knockdown effectively nullified the ameliorative effects of RUNX1 overexpression on impaired OD and OS injury in Dex-induced BMSCs.Conclusions:Overexpression of RUNX1 attenuated Dex-induced impaired OD and OS injury in BMSCs by promoting A2M transcription.展开更多
文摘BACKGROUND Poor glycaemic control in patients with type 2 diabetes mellitus(T2DM)is often accompanied by multiple complications,including diabetic nephropathy(DN),diabetic retinopathy(DR),diabetic peripheral neuropathy(DPN),and cardiac structural abnormality left ventricular hypertrophy(LVH).Early identification of high-risk populations for these complications and the implementation of intervention measures are crucial for improving patient outcomes.Serum alpha-1-microglobulin(α1-MG),a multifunctional protein synthesized by the liver and lymphocytes,has been considered a potential biomarker of diabetes-related diseases in recent years.AIM To investigate the associations of serumα1-MG with DN,DR,DPN,and LVH in T2DM patients and its predictive value.METHODS This retrospective study included 5045 T2DM patients.The study participants were stratified into quartiles according to their serumα1-MG levels.Multivariate logistic regression,restricted cubic spline,and explainable machine learning models were employed for risk assessment and feature importance evaluation.RESULTS Increasedα1-MG levels were observed in patients with DN,DR,DPN,and LVH(all P<0.001).Multivariate logistic regression revealed that each standard deviation increase inα1-MG was associated with an 84%increase in DN risk(OR:1.84,95%CI:1.62-2.10,P<0.001),a 17%increase in DR risk(OR:1.17,95%CI:1.07-1.28,P<0.001),a 14%increase in DPN risk(OR:1.14,95%CI:1.03-1.27,P=0.014),and a 28%increase in LVH risk(OR:1.28,95%CI:1.18-1.38,P<0.001).Subgroup analyses and machine learning confirmed the associations of elevatedα1-MG with these complications in T2DM patients.CONCLUSION Elevated serumα1-MG levels were independently associated with increased risks of DN,DR,DPN,and LVH in T2DM patients,suggesting its potential as a predictive biomarker.
基金Supported by the Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science,and Technology of Japan,No.21K15947 and No.23K07435.
文摘BACKGROUND Achievement of endoscopic healing(EH)is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis.Existing biomarkers,including C-reactive protein(CRP),have relatively low accuracy for predicting EH,especially in small intestinal lesions in Crohn’s disease(CD);thus,noninvasive and more accurate biomarkers are required.Leucine-rich alpha-2 glycoprotein(LRG),a 50-kD protein,is produced under inflammatory conditions and has been reported to be useful in assessing disease activity in inflammatory bowel disease.However,the usefulness of LRG in small intestinal lesions in CD remains inconclusive.AIM To determine the usefulness of LRG for EH in small bowel lesions in CD and compare it with CRP.METHODS This study included 133 consecutive patients with CD who underwent balloonassisted enteroscopy between June 2021 and March 2024 at Shiga University of Medical Science Hospital(Otsu,Japan).We retrospectively analyzed endoscopic scores in each of the ileum and colon and four markers including LRG,CRP,albumin,and Harvey-Bradshaw index(HBI).Spearman’s rank correlation coefficient and receiver operating characteristic analysis were performed.RESULTS Either active ileal or colonic lesions exhibited significant differences in LRG,CRP,albumin,and HBI compared with EH.CRP,albumin,and HBI showed a worse correlation with endoscopic activity in the ileum than that in the colon;however,LRG did not show a worse correlation(colon,r=0.5218;ileum,r=0.5602).Receiver operating characteristic analysis revealed that LRG for EH in the ileum and colon had the same cutoff values of 12.4μg/mL.Comparing the areas under the curve of LRG and CRP for predicting EH in the ileum revealed a significantly higher areas under the curve of LRG(95%confidence interval,0.017-0.194;P=0.024),whereas the two showed no significant difference in the colon.CONCLUSION LRG is a useful biomarker in assessing the endoscopic activity of CD and is more useful than CRP in the small intestine.
文摘The study by Ohno et al provides valuable insights into the role of leucine-rich alpha-2-glycoprotein(LRG)as a potential biomarker for identifying small bowel lesions in Crohn's disease(CD).However,several methodological challenges hinder its immediate use in clinical practice.Notably,the current research was retrospective,lacks comparative studies with fecal calprotectin,and did not provide long-term predictive data.Further prospective studies are needed to improve the applicability of LRG.Moreover,integrating LRG with additional biomarkers and employing artificial intelligence techniques may improve its effectiveness in disease monitoring.Future research should address interobserver variability,assess LRG's cost-effectiveness,and standardize endoscopic healing definitions to ensure broader applicability.Advancing these areas is vital for establishing LRG's role in precision medicine strategies for the management of CD.
基金financially supported by the National Natural Science Foundation of China(51873177,52303252)the Natural Science Foundation of Hunan Province(2024JJ4039)+1 种基金the Advanced Photoelectricity and Supramolecular Functional Materials of the Ministry of Education(IRT-17R90)the Hunan 2011 Collaborative Innovation Centre of Chemical Engineering&Technology with Environmental Benignity and Effective Resource Utilization。
文摘Ternary blending as one of the most successful strategies has achieved continuous performance breakthroughs in organic solar cells(OSCs)over the past few years.Here,a small molecule featuring a dithieno[3,2-f:2′,3′-h]phthalimide derivative as the intermediate unit,named DTP-C8-R,is designed and utilized as the third component to construct ternary OSCs(TOSCs).The increased molecular packing of L8-BO as well as the charge transfer excitons between PM6 and DTP-C8-R lead to a very low nonradiative energy loss of 0.179 eV and a high open-circuit voltage(V_(OC))of 0.910 V in the TOSCs based on the PM6:L8-BO host blend.Moreover,the DTP-C8-R:PM6:L8-BO film(0.05:0.95:1.2,w/w)possesses better fibrous nanophase separation and the enhancedπ-πstacking ordering of the acceptors with a larger crystal coherence length compared with the PM6:L8-BO blend film,so the TOSCs present more efficient exciton dissociation,longer carrier lifetime,faster carrier transport and less charge recombination.It boosts the power conversion efficiency to 19.22%with a short-circuit current density of 27.10 mA cm^(-2).This work demonstrates that the small molecule based on a dithieno[3,2-f:2′,3′-h]phthalimide derivative as the minor component is an executable strategy to achieve high-performance TOSCs with high V_(OC).
基金the Support Program for Hongliu Young Teachers of Lanzhou University of Technology(02/062214)Young Talent Innovation Project of Lanzhou(2023-QN-103)Major science and technology projects of Gansu Province(22ZD6GA013).
文摘Hydroxylation of inert benzene through the activation of the C_(sp2)-H bond is a representative reaction about the transformation of C-H bonds to C-O bonds,which has far-reaching guiding significance but remains a challenging scientific problem.To overcome this problem,a series of VOx-Ga_(2)O_(3)/SiO_(2)-Al_(2)O_(3)were prepared to achieve an efficient and economical hydroxylation path of benzene to phenol.The results showed that the phenol yield was 72.89%(selectivity>98.1%)under the optimum conditions.The reason is that the C-H bond in the benzene ring is activated by heterolysis over a VOx-Ga_(2)O_(3)/SiO_(2)-Al_(2)O_(3)catalyst.Meanwhile,the introduction of aluminum(Al)and gallium(Ga)made a qualitative change in the catalyst,enhancing the electron motion and spin motion of vanadium species,resulting in the increase of V4^(+)/V5^(+)ratio.In addition,the catalyst can provide an optimal acidic environment and a threedimensional cross-linked surface structure that facilitates product diffusion.
基金supported by the National Key Research and Development Program of China(No.2018YFA0704502)the National Natural Science Foundation of China(Nos.21871261,21931011)Fujian Science&Technology Innovation Laboratory for Optoelectronic Information of China(No.2021ZZ105).
文摘Native amino-directed palladium-catalyzed C(sp^(3))-H activation/functionalization has been developed for modification ofα-amino acids and peptides.Herein a palladium(Ⅱ)-catalyzed C(sp^(2))-H arylation ofα-amino-β-aryl esters has been disclosed,using the native amino as the directing group.A variety of chiralα-amino-β-aryl esters can be functionalized to give the corresponding ortho-substituted mono-and di-arylated products.
基金the Natural Science Foundation of Fujian Province(No.2023J011558)the Innovation of Science and Technology of Fujian Province(No.2021Y9098)Fujian Provincial Finance Project(No.BPB-2022FSH).
文摘Introduction:Dexamethasone(Dex)caused impaired osteoblast differentiation and oxidative stress(OS)in bone marrow mesenchymal stem cells(BMSCs).This work sought to elucidate the precise molecular pathway through which Dex influences osteogenic differentiation(OD)and OS in BMSCs.Methods:The expression of Runt-related transcription factor 1(RUNX1)and alpha-2 macroglobulin(A2M)was assessed in Dex-treated BMSCs using qRTPCR and Western Blot.Following the functional rescue experiments,cell proliferation was determined by MTT assay,reactive oxygen species(ROS)expression by DCFH-DA fluorescent probe,lactate dehydrogenase(LDH),superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(Gpx)expression by kits,OD by alkaline phosphatase(ALP)staining and activity quantification,and the expression of OD-related proteins RUNX2,collagen type 1 alpha 1(COL1A1),and osteocalcin(OCN)by qRT-PCR and Western Blot.The binding of RUNX1 to A2M was initially analyzed through Jaspar website and subsequently verified by dual-luciferase reporter and ChIP assays.Results:Dextreated BMSCs had low RUNX1 and A2M expression.Dex treatment apparently elevated ROS and LDH levels,diminished cell proliferation rate and SOD,CAT,and Gpx expression,lightened intensity of ALP staining,and declined calcified nodules,ALP activity,and RUNX2,COL1A1,and OCN expression in BMSCs,which was counterweighed by RUNX1 or A2M overexpression.RUNX1 positively targeted A2M.A2M knockdown effectively nullified the ameliorative effects of RUNX1 overexpression on impaired OD and OS injury in Dex-induced BMSCs.Conclusions:Overexpression of RUNX1 attenuated Dex-induced impaired OD and OS injury in BMSCs by promoting A2M transcription.
