2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a stoichiometric oxidant that is frequently used in traditional organic synthesis. Recently, the rapid development of organic electrochemistry has led to new advancem...2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a stoichiometric oxidant that is frequently used in traditional organic synthesis. Recently, the rapid development of organic electrochemistry has led to new advancements in DDQ-catalyzed C—H bonds functionalization. Moreover, the challenging C—H functionalization of electron-deficient arenes has been achieved through the merger of electrochemical DDQ catalysis and photoirradiation. In addition, the synthetic utility of electrophotochemical DDQ catalysis was further demonstrated by the nucleophilic aromatic substitution (SNAr) reaction of unactivated aryl fluorides. The recent developments in electro- and electrophotochemical DDQ-catalyzed C—H/C—F func- tionalizations with attention to their strategies and mechanistic insights are summarized. It is hoped that this not only deepens the understanding of this field, but also helps relevant researchers expand the application scope of DDQ catalysis.展开更多
Listeria monocytogenes(LM)is a dangerous foodborne pathogen for humans.One emerging and validated method of indirectly assessing LM in food is detecting 3-hydroxy-2-butanone(3H2B)gas.In this study,the synthesis of 3-(...Listeria monocytogenes(LM)is a dangerous foodborne pathogen for humans.One emerging and validated method of indirectly assessing LM in food is detecting 3-hydroxy-2-butanone(3H2B)gas.In this study,the synthesis of 3-(2-aminoethylamino)propyltrimethoxysilane(AAPTMS)functionalized hierarchical hollow TiO_(2)nanospheres was achieved via precise controlling of solvothermal reaction temperature and post-grafting route.The sensors based on as-prepared materials exhibited excellent sensitivity(480 Hz@50 ppm),low detection limit(100 ppb),and outstanding selectivity.Moreover,the evaluation of LM with high sensitivity and specificity was achieved using the sensors.Such stable three-dimensional spheres,whose distinctive hierarchical and hollow nanostructure simultaneously improved both sensitivity and response/recovery speed dramatically,were spontaneously assembled by nanosheets.Meanwhile,the moderate loadings of AAPTMS significantly improved the selectivity of sensors.Then,the gas-sensing mechanism was explored by utilizing thermodynamic investigation,Gaussian 16 software,and in situ diffuse reflectance infrared transform spectroscopy,illustrating the weak chemisorption between the-NHgroup and 3H2B molecules.These portable sensors are promising for real-time assessment of LM at room temperature,which will make a magnificent contribution to food safety.展开更多
Cp_(2)TiCl_(2) as a Lewis acid precursor and nicotinic acid as a ligand have been used synergistically for the one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones.This method establishes a general strateg...Cp_(2)TiCl_(2) as a Lewis acid precursor and nicotinic acid as a ligand have been used synergistically for the one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones.This method establishes a general strategy for the functionalization and conversion of C-H bonds of 1,4-naphthoquinones into C-N bonds,providing an effective route to synthesize 2-(N-substituted amino)-1,4-naphthoquinone with high yield under mild conditions.Additionally,the synergistic catalytic mechanism was investigated by 1H NMR titration experiments and LC-MS analysis,with experimental results sufficiently and consistently supporting the proposed mechanism of the catalytic cycle.展开更多
The deposition of ultrafine single-atom nickel particles on Nb_(2)C(MXene)was successfully achieved using a wet chemistry method to synthesize Ni@Nb_(2)C composite.This study explored the effect of Ni@Nb_(2)C on the h...The deposition of ultrafine single-atom nickel particles on Nb_(2)C(MXene)was successfully achieved using a wet chemistry method to synthesize Ni@Nb_(2)C composite.This study explored the effect of Ni@Nb_(2)C on the hydrogen absorption and desorption properties of MgH_(2) through theoretical calculations and experimental investigations.Under the catalytic action of Ni@Nb2C,the initial dehydrogenation temperature of MgH_(2) was reduced by 121℃,with approximately 4.26 wt.% of H_(2) desorbed at 225℃ in 100 min.The dehydrogenation activation energy of the MgH_(2)+Ni@Nb_(2)C composite dropped to 86.7 kJ·mol^(-1),a reduction of 60.5 kJ·mol^(-1) compared to pure MgH_(2).Density functional theory calculations indicated that the incorporation of Ni@Nb_(2)C enhanced the performance of MgH_(2) performance by improving interactions among Nb_(2)C,Ni,Mg,and H atoms.In the Ni@Nb_(2)C+MgH_(2) system,the lengths of Mg-H bonds(1.91-1.99 A)were found to be longer than those observed in pure MgH_(2)(1.71 A).The dehydrogenation energy for this system(1.08 eV)was lower than that for Nb_(2)C(1.52 eV).These findings suggest that the synergistic effect of Ni and Nb2C significantly enhances the hydrogenation/dehydrogenation kinetics of MgH_(2),thereby introducing a novel approach for catalytic modification of solid hydrogen storage materials through synergistic actions.展开更多
BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly ...BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly Chinese patients with T2DM after different anti-diabetic treatments.METHODS In this longitudinal observational study,elderly patients with T2DM treated with insulin,oral antidiabetic drugs or a combination of both were enrolled to disclose their isletβ-cell function between baseline and follow-up.Isletβ-cell function was determined by the plasma Homeostasis Model forβ-cell function(HOMA-β),Cpeptide and area under the curve(AUC)based on oral glucose tolerance test.Changes inβ-cell function(decrement or increment from baseline)between different therapy groups were the outcomes.RESULTS In total,745 elderly patients(≥60 years)with T2DM[insulin monotherapy,n=105;oral anti-diabetic drugs(OAD)monotherapy,n=321;insulin plus OAD,n=319]had their baseline and follow-upβ-cell function assessed during a median observation period of 4.5 years(range,3.0-7.2 years).Overall,isletβ-cell function(HOMA-β,fasting Cpeptide,fasting insulin,AUCc-pep,AUCins,AUCc-pep/AUCglu,AUCins/AUCglu)consistently deteriorated over time regardless of the three different antidiabetic treatments.No statistical differences in decrement were observed among the three groups regarding the isletβ-cell function indices.All three groups showed an increased ratio of delayed insulin secretion response after 4.5 years of observation.CONCLUSION In Chinese elderly patients with T2DM,isletβ-cell function progressively declines regardless of insulin supplement or insulin plus OAD treatments.展开更多
Background Reproductive efficiency in goats is closely linked to the healthy development of follicles,with the proliferation of ovarian granulosa cells(GCs)playing a crucial role in this process.Sirtuin 3(SIRT3),an en...Background Reproductive efficiency in goats is closely linked to the healthy development of follicles,with the proliferation of ovarian granulosa cells(GCs)playing a crucial role in this process.Sirtuin 3(SIRT3),an enzyme that catalyzes post-translational modifications(PTMs)of proteins,is known to regulate a variety of mitochondrial metabolic pathways,thereby affecting cell fate.However,the specific effect of SIRT3 on the follicular development process remains unclear.Therefore,this study aimed to investigate the regulatory role of SIRT3 in the mitochondrial function and proliferation of goat GCs,as well as the underlying mechanisms involved.Results In this study,GCs from small follicles in goat ovaries presented increased proliferative potential and elevated SIRT3 expression levels compared with those from large follicles.In vitro,SIRT3 overexpression enhanced mitochondrial function,promoted proliferation and inhibited apoptosis in GCs.Correspondingly,the inhibition of SIRT3 led to the opposite effects.Notably,SIRT3 interacted with carnitine palmitoyl transferase 2(CPT2)and stabilized the CPT2 protein by mediating delactylation,which prolonged the half-life of CPT2 and prevented its degradation.Further investigation revealed that CPT2 overexpression enhanced fatty acidβ-oxidation and mitochondrial function in GCs.Additionally,CPT2 promoted the proliferation of GCs by increasing the protein levels ofβ-catenin and its downstream target,cyclin D1(CCND1).However,this effect was reversed by 3-TYP(a SIRT3 inhibitor).Conclusions SIRT3 stabilizes CPT2 protein expression through delactylation,thereby enhancing mitochondrial function and the proliferative capacity of GCs in goats.This study provides novel insights into the molecular mechanisms and regulatory pathways involved in mammalian follicular development.展开更多
Objective Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy(DN).This study aimed to evaluate the impact and mechanism of action of Xiaoke ...Objective Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy(DN).This study aimed to evaluate the impact and mechanism of action of Xiaoke decoction(XKD),a traditional Chinese medicine,on renal function in DN rats.Methods A rat model of DN was established,and the rats were divided into five groups(n=7 per group):normal control group(NC),DN model group(DN),low-dose XKD treatment group(DN+XKD-L,1.5 g/kg/d),high-dose XKD treatment group(DN+XKD-H,6 g/kg/d),and cyclooxygenase-2(COX-2)inhibitor(NS398)treatment group(DN+NS398,8 mg/kg/d).Medications were administered via gavage for 12 consecutive weeks,while equal volumes of normal saline were given to the NC and DN groups.A glucometer was used to detect changes in blood glucose(BG).Enzyme-linked immunosorbent assay(ELISA)and an automatic biochemical analyzer were employed to measure levels of insulin,serum creatinine(Scr),blood urea nitrogen(BUN),triglyceride(TG),total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL),and 24-h urine protein quantity(UP/24 h)in rats.Renal tissue sections from different treatment groups were prepared,with tissue lesions examined via periodic acid-Schiff(PAS)and hematoxylin–eosin(HE)staining.Tissue inflammation and lipid deposition were evaluated using ELISA and Oil Red O staining.Immunohistochemistry and Western blotting were used to detect changes in the expression levels of COX-2 and low-density lipoprotein receptor(LDLr)in tissues,and to clarify the regulatory mechanism of XKD on renal function in DN rats.Results XKD,particularly at the high dose(XKD-H,6 g/kg/d),significantly reduced BG,insulin levels,renal weight ratio,Scr,BUN,and UP/24 h in DN rats.DN rats showed significant renal lesions,and XKD gavage(especially XKD-H)markedly improved these pathological changes.In DN rats,XKD significantly decreased the protein expression levels of COX-2 and LDLr,downregulated the levels of inflammatory factors and lipid factors,reduced lipid deposition in renal tissues,and ameliorated structural abnormalities in glomeruli,basement membranes,and renal tubules.Conclusions XKD alleviates renal tissue damage by regulating the COX-2-mediated LDLr pathway,thereby reducing the release of inflammatory factors and lipid accumulation in DN rats and protecting renal function.Graphical Abstract XKD improves renal function in streptozotocin(STZ)-induced DN rats by regulating the COX-2-mediated LDLr pathway,reducing inflammatory factors and lipid deposition,and alleviating renal tissue damage.展开更多
BACKGROUND Increasing evidence has shown that hippocampal damage serves as a marker of early cognitive decline in patients with type 2 diabetes mellitus(T2DM);however,the association between hippocampal subregion volu...BACKGROUND Increasing evidence has shown that hippocampal damage serves as a marker of early cognitive decline in patients with type 2 diabetes mellitus(T2DM);however,the association between hippocampal subregion volume changes and cognitive decline in different dimensions remains unclear.AIM To investigate changes in hippocampal subregion volumes in patients with T2DM and their relationship with cognitive function impairment.METHODS Sixty patients with T2DM and 32 healthy controls were recruited.All participants underwent a 3.0 T magnetic resonance scan and a series of clinical assessments.Hippocampal subfield volumes were determined using FreeSurfer 7.4.1.A two-sample t-test was used to evaluate group differences.Partial correlation analysis was performed to assess the relationship between hippocampal subregion volumes and cognitive function.aP<0.05 was considered statistically significant.RESULTS Compared with controls,the volume of right hippocampus-amygdala transition area(t=-3.053,P=0.003)in patients with T2DM was significantly reduced,which was negatively correlated with the required time of the Trail Making Test(TMT)-A(r=-0.331,P=0.028)and TMT-B(r=-0.402,P=0.007)and positively correlated with the scores of Symbol Digit Modalities Test(r=0.381,P=0.011),Auditory Verbal Learning Test(AVLT)-N7(r=0.309,P=0.041),and Digital Span Test(r=0.300,P=0.048).The volume of the right molecular layer(t=-2.998,P=0.004)was also significantly reduced,which was positively associated with the scores of AVLT-N7(r=0.311,P=0.045).In addition,the left hippocampal fissure volume(t=3.617,P=0.002)was significantly increased in patients with T2DM.CONCLUSION Declines in cognitive performance,especially memory and executive function,are linked to changes in the volumes of the right hippocampus-amygdala transition area and right molecular layer in patients with T2DM.展开更多
BACKGROUND Cardiorespiratory fitness(CRF)is inversely associated with the risk of cardiovascular disease,which is related to impaired vascular function.However,its relationship with vascular function remains unknown i...BACKGROUND Cardiorespiratory fitness(CRF)is inversely associated with the risk of cardiovascular disease,which is related to impaired vascular function.However,its relationship with vascular function remains unknown in patients with type 2 diabetes.AIM To assess the relationship of CRF with vascular function in type 2 diabetes.METHODS Patients with type 2 diabetes who were aged≥18 years and underwent an incremental and symptom-limited exercise test were included.Vascular function was assessed by the construction of the vascular health index(VHI),which is defined as a composite score of ankle-brachial index,transcutaneous oxygen pressure,pulse wave velocity,and carotid intima-media thickness.Impaired vascular function is defined as a VHI of<8 points.Linear and logistic regression analyses were used to assess the associations.RESULTS We included 343 patients with type 2 diabetes.CRF was positively correlated with VHI(β=0.10,P=0.047),particularly with ankle-brachial index and pulse wave velocity.The odds ratio(OR)of impaired vascular function was 0.44[95%confidence interval(CI):0.20-0.96]for the highest vs the lowest CRF category.For each one metabolic equivalent increase in CRF,the OR of impaired vascular function was 0.73(95%CI:0.57-0.93).CONCLUSION Higher CRF was associated with better vascular function and lower odds of impaired vascular function in patients with type 2 diabetes.展开更多
BACKGROUND Increased blood urea nitrogen(BUN)levels have been demonstrated to be associated with broader metabolic disturbances and the incidence of type 2 diabetes(T2D),potentially playing a role in the development o...BACKGROUND Increased blood urea nitrogen(BUN)levels have been demonstrated to be associated with broader metabolic disturbances and the incidence of type 2 diabetes(T2D),potentially playing a role in the development of diabetic complications,including diabetic peripheral neuropathy.AIM To examine the relationship between BUN levels and peripheral nerve function in patients with T2D.METHODS This observational study involved the systematic recruitment of 585 patients with T2D for whom BUN levels and estimated glomerular filtration rate were measured.Electromyography was used to assess peripheral motor and sensory nerve function in all patients,and overall composite Z-scores were subsequently calculated for nerve latency,amplitude,and conduction velocity(NCV)across the median,ulnar,common peroneal,posterior tibial,superficial peroneal,and sural nerves.RESULTS Across the quartiles of BUN levels,the overall composite Z-score for latency(F=38.996,P for trend<0.001)showed a significant increasing trend,whereas the overall composite Z-scores for amplitude(F=50.972,P for trend<0.001)and NCV(F=30.636,P for trend<0.001)exhibited a significant decreasing trend.Moreover,the BUN levels were closely correlated with the latency,amplitude,and NCV of each peripheral nerve.Furthermore,multivariate linear regression analysis revealed that elevated BUN levels were linked to a higher overall composite Z-score for latency(β=0.166,t=3.864,P<0.001)and lower overall composite Z-scores for amplitude(β=-0.184,t=-4.577,P<0.001)and NCV(β=-0.117,t=-2.787,P=0.006)independent of the estimated glomerular filtration rate and other clinical covariates.Additionally,when the analysis was restricted to sensory or motor nerves,elevated BUN levels remained associated with sensory or motor peripheral nerve dysfunction.CONCLUSION Increased BUN levels were independently associated with compromised peripheral nerve function in patients with T2D.展开更多
Diabetic cardiomyopathy(DCM)is a major cause of heart failure in diabetic patients.It progresses asymptomatically prior to the onset of severe cardiac symptoms[1];therefore,elucidating the underlying mechanisms of DCM...Diabetic cardiomyopathy(DCM)is a major cause of heart failure in diabetic patients.It progresses asymptomatically prior to the onset of severe cardiac symptoms[1];therefore,elucidating the underlying mechanisms of DCM is critical to providing early treatment options.This commentary elaborates on the findings of Jiang et al.[2],who investigated the role of adipokine hormone,Adipsin,as a cardioprotective factor in DCM.We provide an exposition and alternative treatment considerations,like Fisetin,and discuss the potential of investigating other cellular targets implicated in cardiac dysfunction,like the interleukin-1 receptor-associated kinaselike 2(Irak2)protein[3]and protein kinase R[4].展开更多
文摘2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a stoichiometric oxidant that is frequently used in traditional organic synthesis. Recently, the rapid development of organic electrochemistry has led to new advancements in DDQ-catalyzed C—H bonds functionalization. Moreover, the challenging C—H functionalization of electron-deficient arenes has been achieved through the merger of electrochemical DDQ catalysis and photoirradiation. In addition, the synthetic utility of electrophotochemical DDQ catalysis was further demonstrated by the nucleophilic aromatic substitution (SNAr) reaction of unactivated aryl fluorides. The recent developments in electro- and electrophotochemical DDQ-catalyzed C—H/C—F func- tionalizations with attention to their strategies and mechanistic insights are summarized. It is hoped that this not only deepens the understanding of this field, but also helps relevant researchers expand the application scope of DDQ catalysis.
基金supported by the National Natural Science Foundation of China(No.32272399)the Shanghai Natural Science Foundation(No.21ZR1427500).
文摘Listeria monocytogenes(LM)is a dangerous foodborne pathogen for humans.One emerging and validated method of indirectly assessing LM in food is detecting 3-hydroxy-2-butanone(3H2B)gas.In this study,the synthesis of 3-(2-aminoethylamino)propyltrimethoxysilane(AAPTMS)functionalized hierarchical hollow TiO_(2)nanospheres was achieved via precise controlling of solvothermal reaction temperature and post-grafting route.The sensors based on as-prepared materials exhibited excellent sensitivity(480 Hz@50 ppm),low detection limit(100 ppb),and outstanding selectivity.Moreover,the evaluation of LM with high sensitivity and specificity was achieved using the sensors.Such stable three-dimensional spheres,whose distinctive hierarchical and hollow nanostructure simultaneously improved both sensitivity and response/recovery speed dramatically,were spontaneously assembled by nanosheets.Meanwhile,the moderate loadings of AAPTMS significantly improved the selectivity of sensors.Then,the gas-sensing mechanism was explored by utilizing thermodynamic investigation,Gaussian 16 software,and in situ diffuse reflectance infrared transform spectroscopy,illustrating the weak chemisorption between the-NHgroup and 3H2B molecules.These portable sensors are promising for real-time assessment of LM at room temperature,which will make a magnificent contribution to food safety.
基金2024 Special Talent Introduction Projects of Key R&D Program of Ningxia Hui Autonomous Region(2024BEH04049)the 2024 Guyuan City Innovation-Driven Achievement Transformation Project(2024BGTYF01-47)2025 Ningxia Natural Science Foundation Program(2025AAC030624).
文摘Cp_(2)TiCl_(2) as a Lewis acid precursor and nicotinic acid as a ligand have been used synergistically for the one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones.This method establishes a general strategy for the functionalization and conversion of C-H bonds of 1,4-naphthoquinones into C-N bonds,providing an effective route to synthesize 2-(N-substituted amino)-1,4-naphthoquinone with high yield under mild conditions.Additionally,the synergistic catalytic mechanism was investigated by 1H NMR titration experiments and LC-MS analysis,with experimental results sufficiently and consistently supporting the proposed mechanism of the catalytic cycle.
基金financially supported by the National Natural Science Foundation of China under Grant numbers 22379030,52001079 and 52261038the Guangxi Key Laboratory of Green Manufacturing for Ecological Aluminum Industry(GXGMEA2024)the Nanning Excellent Young Talents Cultivation Project for Scientific and Technological Innovation and Entrepreneurship(RC20220102).
文摘The deposition of ultrafine single-atom nickel particles on Nb_(2)C(MXene)was successfully achieved using a wet chemistry method to synthesize Ni@Nb_(2)C composite.This study explored the effect of Ni@Nb_(2)C on the hydrogen absorption and desorption properties of MgH_(2) through theoretical calculations and experimental investigations.Under the catalytic action of Ni@Nb2C,the initial dehydrogenation temperature of MgH_(2) was reduced by 121℃,with approximately 4.26 wt.% of H_(2) desorbed at 225℃ in 100 min.The dehydrogenation activation energy of the MgH_(2)+Ni@Nb_(2)C composite dropped to 86.7 kJ·mol^(-1),a reduction of 60.5 kJ·mol^(-1) compared to pure MgH_(2).Density functional theory calculations indicated that the incorporation of Ni@Nb_(2)C enhanced the performance of MgH_(2) performance by improving interactions among Nb_(2)C,Ni,Mg,and H atoms.In the Ni@Nb_(2)C+MgH_(2) system,the lengths of Mg-H bonds(1.91-1.99 A)were found to be longer than those observed in pure MgH_(2)(1.71 A).The dehydrogenation energy for this system(1.08 eV)was lower than that for Nb_(2)C(1.52 eV).These findings suggest that the synergistic effect of Ni and Nb2C significantly enhances the hydrogenation/dehydrogenation kinetics of MgH_(2),thereby introducing a novel approach for catalytic modification of solid hydrogen storage materials through synergistic actions.
基金Medical Ethics Committee of the Nanxishan Hospital of Guangxi Zhuang Autonomous Region(Approval No.NXSYY-2024-209).
文摘BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly Chinese patients with T2DM after different anti-diabetic treatments.METHODS In this longitudinal observational study,elderly patients with T2DM treated with insulin,oral antidiabetic drugs or a combination of both were enrolled to disclose their isletβ-cell function between baseline and follow-up.Isletβ-cell function was determined by the plasma Homeostasis Model forβ-cell function(HOMA-β),Cpeptide and area under the curve(AUC)based on oral glucose tolerance test.Changes inβ-cell function(decrement or increment from baseline)between different therapy groups were the outcomes.RESULTS In total,745 elderly patients(≥60 years)with T2DM[insulin monotherapy,n=105;oral anti-diabetic drugs(OAD)monotherapy,n=321;insulin plus OAD,n=319]had their baseline and follow-upβ-cell function assessed during a median observation period of 4.5 years(range,3.0-7.2 years).Overall,isletβ-cell function(HOMA-β,fasting Cpeptide,fasting insulin,AUCc-pep,AUCins,AUCc-pep/AUCglu,AUCins/AUCglu)consistently deteriorated over time regardless of the three different antidiabetic treatments.No statistical differences in decrement were observed among the three groups regarding the isletβ-cell function indices.All three groups showed an increased ratio of delayed insulin secretion response after 4.5 years of observation.CONCLUSION In Chinese elderly patients with T2DM,isletβ-cell function progressively declines regardless of insulin supplement or insulin plus OAD treatments.
基金supported by the National Key Research and Development Program of China(2022YFD1300202)the Technology Innovation and Application Development Special Project of Chongqing(cstc2021jscx-gksbX0008).
文摘Background Reproductive efficiency in goats is closely linked to the healthy development of follicles,with the proliferation of ovarian granulosa cells(GCs)playing a crucial role in this process.Sirtuin 3(SIRT3),an enzyme that catalyzes post-translational modifications(PTMs)of proteins,is known to regulate a variety of mitochondrial metabolic pathways,thereby affecting cell fate.However,the specific effect of SIRT3 on the follicular development process remains unclear.Therefore,this study aimed to investigate the regulatory role of SIRT3 in the mitochondrial function and proliferation of goat GCs,as well as the underlying mechanisms involved.Results In this study,GCs from small follicles in goat ovaries presented increased proliferative potential and elevated SIRT3 expression levels compared with those from large follicles.In vitro,SIRT3 overexpression enhanced mitochondrial function,promoted proliferation and inhibited apoptosis in GCs.Correspondingly,the inhibition of SIRT3 led to the opposite effects.Notably,SIRT3 interacted with carnitine palmitoyl transferase 2(CPT2)and stabilized the CPT2 protein by mediating delactylation,which prolonged the half-life of CPT2 and prevented its degradation.Further investigation revealed that CPT2 overexpression enhanced fatty acidβ-oxidation and mitochondrial function in GCs.Additionally,CPT2 promoted the proliferation of GCs by increasing the protein levels ofβ-catenin and its downstream target,cyclin D1(CCND1).However,this effect was reversed by 3-TYP(a SIRT3 inhibitor).Conclusions SIRT3 stabilizes CPT2 protein expression through delactylation,thereby enhancing mitochondrial function and the proliferative capacity of GCs in goats.This study provides novel insights into the molecular mechanisms and regulatory pathways involved in mammalian follicular development.
基金supported by the Budget Project of Shanghai University of Traditional Chinese Medicine(18LK058).
文摘Objective Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy(DN).This study aimed to evaluate the impact and mechanism of action of Xiaoke decoction(XKD),a traditional Chinese medicine,on renal function in DN rats.Methods A rat model of DN was established,and the rats were divided into five groups(n=7 per group):normal control group(NC),DN model group(DN),low-dose XKD treatment group(DN+XKD-L,1.5 g/kg/d),high-dose XKD treatment group(DN+XKD-H,6 g/kg/d),and cyclooxygenase-2(COX-2)inhibitor(NS398)treatment group(DN+NS398,8 mg/kg/d).Medications were administered via gavage for 12 consecutive weeks,while equal volumes of normal saline were given to the NC and DN groups.A glucometer was used to detect changes in blood glucose(BG).Enzyme-linked immunosorbent assay(ELISA)and an automatic biochemical analyzer were employed to measure levels of insulin,serum creatinine(Scr),blood urea nitrogen(BUN),triglyceride(TG),total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL),and 24-h urine protein quantity(UP/24 h)in rats.Renal tissue sections from different treatment groups were prepared,with tissue lesions examined via periodic acid-Schiff(PAS)and hematoxylin–eosin(HE)staining.Tissue inflammation and lipid deposition were evaluated using ELISA and Oil Red O staining.Immunohistochemistry and Western blotting were used to detect changes in the expression levels of COX-2 and low-density lipoprotein receptor(LDLr)in tissues,and to clarify the regulatory mechanism of XKD on renal function in DN rats.Results XKD,particularly at the high dose(XKD-H,6 g/kg/d),significantly reduced BG,insulin levels,renal weight ratio,Scr,BUN,and UP/24 h in DN rats.DN rats showed significant renal lesions,and XKD gavage(especially XKD-H)markedly improved these pathological changes.In DN rats,XKD significantly decreased the protein expression levels of COX-2 and LDLr,downregulated the levels of inflammatory factors and lipid factors,reduced lipid deposition in renal tissues,and ameliorated structural abnormalities in glomeruli,basement membranes,and renal tubules.Conclusions XKD alleviates renal tissue damage by regulating the COX-2-mediated LDLr pathway,thereby reducing the release of inflammatory factors and lipid accumulation in DN rats and protecting renal function.Graphical Abstract XKD improves renal function in streptozotocin(STZ)-induced DN rats by regulating the COX-2-mediated LDLr pathway,reducing inflammatory factors and lipid deposition,and alleviating renal tissue damage.
基金Supported by the Bethune Charitable Foundation,No.Z04JKM2022E035the Liyang City's 2023 Annual research and development Plan Follows Nanjing Project,No.LC2024001.
文摘BACKGROUND Increasing evidence has shown that hippocampal damage serves as a marker of early cognitive decline in patients with type 2 diabetes mellitus(T2DM);however,the association between hippocampal subregion volume changes and cognitive decline in different dimensions remains unclear.AIM To investigate changes in hippocampal subregion volumes in patients with T2DM and their relationship with cognitive function impairment.METHODS Sixty patients with T2DM and 32 healthy controls were recruited.All participants underwent a 3.0 T magnetic resonance scan and a series of clinical assessments.Hippocampal subfield volumes were determined using FreeSurfer 7.4.1.A two-sample t-test was used to evaluate group differences.Partial correlation analysis was performed to assess the relationship between hippocampal subregion volumes and cognitive function.aP<0.05 was considered statistically significant.RESULTS Compared with controls,the volume of right hippocampus-amygdala transition area(t=-3.053,P=0.003)in patients with T2DM was significantly reduced,which was negatively correlated with the required time of the Trail Making Test(TMT)-A(r=-0.331,P=0.028)and TMT-B(r=-0.402,P=0.007)and positively correlated with the scores of Symbol Digit Modalities Test(r=0.381,P=0.011),Auditory Verbal Learning Test(AVLT)-N7(r=0.309,P=0.041),and Digital Span Test(r=0.300,P=0.048).The volume of the right molecular layer(t=-2.998,P=0.004)was also significantly reduced,which was positively associated with the scores of AVLT-N7(r=0.311,P=0.045).In addition,the left hippocampal fissure volume(t=3.617,P=0.002)was significantly increased in patients with T2DM.CONCLUSION Declines in cognitive performance,especially memory and executive function,are linked to changes in the volumes of the right hippocampus-amygdala transition area and right molecular layer in patients with T2DM.
基金Supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2024ZD0523303the Funding for Pairing Support to Jiangsu High-Level Hospitals-Zhongda Hospital,No.ZDLYG19the Key Research and Development Program in Jiangsu Province,No.BE2022828.
文摘BACKGROUND Cardiorespiratory fitness(CRF)is inversely associated with the risk of cardiovascular disease,which is related to impaired vascular function.However,its relationship with vascular function remains unknown in patients with type 2 diabetes.AIM To assess the relationship of CRF with vascular function in type 2 diabetes.METHODS Patients with type 2 diabetes who were aged≥18 years and underwent an incremental and symptom-limited exercise test were included.Vascular function was assessed by the construction of the vascular health index(VHI),which is defined as a composite score of ankle-brachial index,transcutaneous oxygen pressure,pulse wave velocity,and carotid intima-media thickness.Impaired vascular function is defined as a VHI of<8 points.Linear and logistic regression analyses were used to assess the associations.RESULTS We included 343 patients with type 2 diabetes.CRF was positively correlated with VHI(β=0.10,P=0.047),particularly with ankle-brachial index and pulse wave velocity.The odds ratio(OR)of impaired vascular function was 0.44[95%confidence interval(CI):0.20-0.96]for the highest vs the lowest CRF category.For each one metabolic equivalent increase in CRF,the OR of impaired vascular function was 0.73(95%CI:0.57-0.93).CONCLUSION Higher CRF was associated with better vascular function and lower odds of impaired vascular function in patients with type 2 diabetes.
基金Supported by the Social Development Projects of Nantong,No.MS12019019,No.HS2022004 and No.MS2023083the Medical Research Project of the Jiangsu Health Commission,No.Z2022058the National Natural Science Foundation of China,No.32101027。
文摘BACKGROUND Increased blood urea nitrogen(BUN)levels have been demonstrated to be associated with broader metabolic disturbances and the incidence of type 2 diabetes(T2D),potentially playing a role in the development of diabetic complications,including diabetic peripheral neuropathy.AIM To examine the relationship between BUN levels and peripheral nerve function in patients with T2D.METHODS This observational study involved the systematic recruitment of 585 patients with T2D for whom BUN levels and estimated glomerular filtration rate were measured.Electromyography was used to assess peripheral motor and sensory nerve function in all patients,and overall composite Z-scores were subsequently calculated for nerve latency,amplitude,and conduction velocity(NCV)across the median,ulnar,common peroneal,posterior tibial,superficial peroneal,and sural nerves.RESULTS Across the quartiles of BUN levels,the overall composite Z-score for latency(F=38.996,P for trend<0.001)showed a significant increasing trend,whereas the overall composite Z-scores for amplitude(F=50.972,P for trend<0.001)and NCV(F=30.636,P for trend<0.001)exhibited a significant decreasing trend.Moreover,the BUN levels were closely correlated with the latency,amplitude,and NCV of each peripheral nerve.Furthermore,multivariate linear regression analysis revealed that elevated BUN levels were linked to a higher overall composite Z-score for latency(β=0.166,t=3.864,P<0.001)and lower overall composite Z-scores for amplitude(β=-0.184,t=-4.577,P<0.001)and NCV(β=-0.117,t=-2.787,P=0.006)independent of the estimated glomerular filtration rate and other clinical covariates.Additionally,when the analysis was restricted to sensory or motor nerves,elevated BUN levels remained associated with sensory or motor peripheral nerve dysfunction.CONCLUSION Increased BUN levels were independently associated with compromised peripheral nerve function in patients with T2D.
基金supported by the Office of Naval Research Grant(N00014-22-1-2184)。
文摘Diabetic cardiomyopathy(DCM)is a major cause of heart failure in diabetic patients.It progresses asymptomatically prior to the onset of severe cardiac symptoms[1];therefore,elucidating the underlying mechanisms of DCM is critical to providing early treatment options.This commentary elaborates on the findings of Jiang et al.[2],who investigated the role of adipokine hormone,Adipsin,as a cardioprotective factor in DCM.We provide an exposition and alternative treatment considerations,like Fisetin,and discuss the potential of investigating other cellular targets implicated in cardiac dysfunction,like the interleukin-1 receptor-associated kinaselike 2(Irak2)protein[3]and protein kinase R[4].
