This article explores the bidirectional relationship between type 2 diabetes mellitus(T2DM)and depression,focusing on their shared pathophysiological mechanisms,including immune-inflammatory responses,gut-brain axis d...This article explores the bidirectional relationship between type 2 diabetes mellitus(T2DM)and depression,focusing on their shared pathophysiological mechanisms,including immune-inflammatory responses,gut-brain axis dysregu-lation,metabolic abnormalities,and neuroendocrine modulation.Research indicates that T2DM contributes to anxiety and depression through chronic low-grade inflammation,insulin resistance,gut microbiota imbalance,and hy-peractivation of the hypothalamic-pituitary-adrenal axis.Conversely,depression may increase the risk of T2DM via lifestyle disruption,immune activation,and neurotransmitter imbalance.Additionally,metabolic pathway disturbances-such as reduced adiponectin,impaired insulin signaling,and altered amino acid me-tabolism-may influence mood regulation and cognition.The article further examines emerging therapeutic strategies targeting these shared mechanisms,including anti-inflammatory treatments,gut microbiota modulation,hypothalamic-pituitary-adrenal axis interventions,metabolic therapies(e.g.,glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors),and multidisciplinary integrative management.Emphasizing the multisystem nature of diabetes-depression comorbidity,this work highlights the importance of incorporating mental health strategies into diabetes care to optimize outcomes and enhance patient quality of life.展开更多
Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of...Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.展开更多
Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematic...Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematically invest-igates the mechanism by which curcumol ameliorates DR through regulation of the FTO/MAFG-AS1 epigenetic axis and reveals its therapeutic potential in tar-geting the retinal microenvironment via a nano-delivery system.Experimental results demonstrate that curcumol activates the demethylase activity of FTO,sta-bilizing the expression of the long non-coding RNA MAFG-AS1,thereby inhi-biting high glucose-induced retinal endothelial cell inflammation,migration,and vascular leakage.Single-cell transcriptomic analysis further uncovered the dual role of FTO in DR:On the one hand,it promotes pathological angiogenesis in endothelial cells,while on the other hand,it exerts protective effects through MAFG-AS1-mediated antioxidative and anti-inflammatory functions.Moreover,this study proposes a multidimensional epigenetic regulatory network based on histone lactylation,N6-methyladenosine modification,and DNA methylation,and verifies that curcumol delays DR progression by coordinately modulating these modifications.To overcome the limitations of conventional therapies,this study innovatively designed a macrophage membrane-coated nano-delivery system,significantly enhancing the retinal targeting and bioavailability of curcumol.Finally,the study advocates a paradigm shift from passive treatment to early prevention,proposing a three-tiered intervention strategy that integrates epigenetic biomarkers with artificial intelligence-based risk assessment.These findings not only elucidate the multi-target regulatory mechanisms of curcumol but also provide a theoretical foundation for the development of precision therapies for DR based on epigenetic remodeling and microenvironmental synergistic intervention.展开更多
BACKGROUND The association between the uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and mental health among individuals with type 2 diabetes mellitus(T2DM)has not been thoroughly investigated.AIM To exa...BACKGROUND The association between the uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and mental health among individuals with type 2 diabetes mellitus(T2DM)has not been thoroughly investigated.AIM To examine the link between UHR and symptoms of depression and anxiety in patients with T2DM.METHODS A cross-sectional analysis was carried out from March 2023 to April 2024,involving participants diagnosed with T2DM.Data on sociodemographic characteristics,clinical parameters,and UHR values were systematically gathered.The Self-Rating Depression Scale(SDS)and Self-Rating Anxiety Scale(SAS)were utilized to evaluate depressive and anxiety symptoms,respectively.To assess the relationships between UHR and SDS/SAS scores,linear regression models were employed,incorporating adjustments for potential confounding variables.Additionally,smooth curve fitting and threshold effect analyses were conducted to explore potential nonlinear relationships.RESULTS A total of 285 patients with T2DM were included.Initial univariate analysis demonstrated a significant positive correlation between elevated UHR levels and higher SDS and SAS scores.Multivariate regression analysis revealed that a one-unit rise in UHR was associated with a 1.13-point increase in SDS scores(95%CI:0.69-1.58)and a 0.57-point increase in SAS scores(95%CI:0.20-0.93).After controlling for confounders,UHR remained positively correlated with SDS(β=1.55,95%CI:0.57-2.53)and SAS(β=0.72,95%CI:0.35-1.09).Nonlinear analysis identified critical thresholds at UHR values of 5.02 for SDS and 4.00 for SAS,beyond which the relationships between UHR and psychological symptom scores became markedly stronger(P<0.05).CONCLUSION Higher UHR levels are significantly linked to exacerbated depressive and anxiety symptoms in patients with T2DM.These results indicate that UHR may function as a promising biomarker to identify individuals at greater risk of mental health complications within this population.展开更多
Thermomechanical Fatigue (TMF) is one of the most dangerous failure modes of high-temperature structures. The effect of coarsened and rafted microstructures on the TMF behavior of Nickel-Base Single Crystal Superalloy...Thermomechanical Fatigue (TMF) is one of the most dangerous failure modes of high-temperature structures. The effect of coarsened and rafted microstructures on the TMF behavior of Nickel-Base Single Crystal Superalloys (NBSX) was experimentally studied. TMF tests under In-Phase (IP) and Out-of-Phase (OP) paths revealed significant variations in TMF life reduction. Cyclic deformation behaviors of alloys with different microstructures were compared. The effect of microstructure on TMF damage mechanisms was unveiled from characterizations of fracture surfaces and longitudinal sections by scanning electronic microscope and optical microscope. A transition from mode-I to crystallographic fracture in the coarsened alloy during IP-TMF was observed and discussed. Due to the degraded microstructure, the dispersed distribution of crystal slips was distinguished in the coarsened and rafted alloys. The competitive or synergetic interactions among oxidation-assisted mode-I opening, casting pore-related mode-I creep and crystallographic slipping were discussed. This study underscores the complex interplay among microstructure, deformation behaviors and damage mechanisms, offering valuable insights into alloy performance under TMF conditions.展开更多
Familial androgen insensitivity syndrome (AIS), resulting from inherited mutations in the androgen receptor (AR)gene, has traditionally been examined within the framework of disorders of sex development. However, grow...Familial androgen insensitivity syndrome (AIS), resulting from inherited mutations in the androgen receptor (AR)gene, has traditionally been examined within the framework of disorders of sex development. However, growingevidence indicates that AR dysfunction also disrupts systemic metabolic homeostasis, predisposing affectedindividuals to insulin resistance and type 2 diabetes mellitus. This article synthesizes recent advances in genetics,transcriptomics, and physiology to elucidate how AR mutations drive tissue-specific metabolic reprogramming inkey organs, including pancreatic β-cells, skeletal muscle, liver, and adipose tissue. Particular attention is given to anewly identified familial AR variant (c.2117A>G;p.Asn706Ser), which not only broadens the known mutationalspectrum of AIS but also underscores the clinical importance of early metabolic risk screening in this population.We further examine how pubertal stage, hormone replacement therapy, and sex-specific signaling pathwaysinteract to influence long-term metabolic outcomes. Lastly, we propose an integrative management framework thatincorporates genetic diagnosis, endocrine surveillance, and personalized pharmacological strategies aimed atreducing the risk of type 2 diabetes mellitus and cardiometabolic complications in individuals with AIS. Distinctfrom previous AIS-centered reviews, this work integrates metabolic and endocrine perspectives into the traditionaldevelopmental paradigm, offering a more comprehensive understanding of disease risk and translational management.展开更多
The role and regulatory mechanisms of macrophage polarization in cardiac transplantation have gained significant attention.Macrophages can polarize into either the M1(pro-inflammatory)or M2(anti-inflammatory)phenotype...The role and regulatory mechanisms of macrophage polarization in cardiac transplantation have gained significant attention.Macrophages can polarize into either the M1(pro-inflammatory)or M2(anti-inflammatory)phenotype in response to environmental cues.M1 macrophages facilitate transplant rejection by releasing inflammatory mediators and activating T cells,whereas M2 macrophages support graft survival by secreting antiinflammatory factors and promoting tissue repair.Mitochondrial quality control regulation plays a crucial role in macrophage polarization,which may influence graft survival and immune responses.This review provides an overview of the current understanding of mitochondrial quality control-regulated macrophage polarization in cardiac transplantation,its effects on graft outcomes,and potential therapeutic strategies to modulate this process to enhance transplant success rates.The review was conducted by systematically analyzing recent studies and integrating findings from key research articles to synthesize a comprehensive understanding of this emerging field.展开更多
BACKGROUND Intracranial aneurysms(IAs)pose significant health risks,attributable to their potential for sudden rupture,which can result in severe outcomes such as stroke and death.Despite extensive research,the variab...BACKGROUND Intracranial aneurysms(IAs)pose significant health risks,attributable to their potential for sudden rupture,which can result in severe outcomes such as stroke and death.Despite extensive research,the variability of aneurysm behavior,with some remaining stable for years while others rupture unexpectedly,remains poorly understood.AIM To employ bibliometric analysis to map the research landscape concerning risk factors associated with IAs rupture.METHODS A systematic literature review of publications from 2004 to 2023 was conducted,analyzing 3804 documents from the Web of Science Core Collection database,with a focus on full-text articles and reviews in English.The analysis encompassed citation and co-citation networks,keyword bursts,and temporal trends to delineate the evolution of research themes and collaboration patterns.Advanced software tools,CiteSpace and VOSviewer,were utilized for comprehensive data visualization and trend analysis.RESULTS Analysis uncovered a total of 3804 publications on IA rupture risk factors between 2006 and 2023.Research interest surged after 2013,peaking in 2023.The United States led with 28.97%of publications,garnering 37706 citations.Notable United States-China collaborations were observed.Capital Medical University produced 184 publications,while Utrecht University boasted a citation average of 69.62 per publication.“World Neurosurgery”published the most papers,contrasting with“Stroke”,the most cited journal.The PHASES score from“Lancet Neurology”emerged as a vital rupture risk prediction tool.Early research favored endovascular therapy,transitioning to magnetic resonance imaging and flow diverters.CONCLUSION This study assesses global IA research trends and highlights crucial gaps,guiding future investigations to improve preventive and therapeutic approaches.展开更多
Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome ...Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.展开更多
Dear Editor, The current flu epidemic caused by influenza A H1N1 （A/H1N1） virus, which first appeared in Mexico emerged as a communicable human disease in late March and rapidly spread throughout the world in April ...Dear Editor, The current flu epidemic caused by influenza A H1N1 （A/H1N1） virus, which first appeared in Mexico emerged as a communicable human disease in late March and rapidly spread throughout the world in April 2009. Due to the rapid transport systems in modern times, the epidemic affected about 121 countries in less than 4 months （http：//www.who.int/csr/don/2009_07_16/en/）.展开更多
Yttrium tantalate(YTaO_(4))is the next generation of higher service temperature thermal barrier coatings(TBCs)materials due to its smaller volume effect in phase change,lower thermal conductivity and unique ferroelast...Yttrium tantalate(YTaO_(4))is the next generation of higher service temperature thermal barrier coatings(TBCs)materials due to its smaller volume effect in phase change,lower thermal conductivity and unique ferroelastic domain structure.However,the low fracture toughness limits its application.We first characterized the diffraction patterns of variants,and two variants(M_(1)and M_(2))observed in transmission electron microscopy(TEM)results were determined from four possible variants by mechanical derivation.The role of Zr^(4+)doping in ferroelastic toughening was explained in detail.With the increase of Zr^(4+)doping concentration,the monoclinic angle β and the domain rotation angleαdecrease,respectively.The spontaneous strain component and the principal strain in the main space also have a similar decreasing trend.The decrease of the ferroelastic domain inversion energy barrier is beneficial to the improvement of fracture toughness.Combining the results of Vickers indentation,we found that Zr^(4+)could be enriched at the domain boundary to inhibit the generation of cracks.An appropriate amount of Zr^(4+)is conducive to the improvement of fracture toughness,and the excessive Zr^(4+)will reduce the fracture toughness due to the generation of by-product t-ZrO_(2).So,the optimal composition is Y_(0.44)Ta_(0.44)Zr_(0.12)O_(2) and the best fracture toughness(2.9–3.8MPa m^(1/2))is equivalent to the commercial 8YSZ.This result will promote the application of a new generation of TBCs.展开更多
Training deep neural networks(DNNs)requires a significant amount of time and resources to obtain acceptable results,which severely limits its deployment in resource-limited platforms.This paper proposes DarkFPGA,a nov...Training deep neural networks(DNNs)requires a significant amount of time and resources to obtain acceptable results,which severely limits its deployment in resource-limited platforms.This paper proposes DarkFPGA,a novel customizable framework to efficiently accelerate the entire DNN training on a single FPGA platform.First,we explore batch-level parallelism to enable efficient FPGA-based DNN training.Second,we devise a novel hardware architecture optimised by a batch-oriented data pattern and tiling techniques to effectively exploit parallelism.Moreover,an analytical model is developed to determine the optimal design parameters for the DarkFPGA accelerator with respect to a specific network specification and FPGA resource constraints.Our results show that the accelerator is able to perform about 10 times faster than CPU training and about a third of the energy consumption than GPU training using 8-bit integers for training VGG-like networks on the CIFAR dataset for the Maxeler MAX5 platform.展开更多
BACKGROUND Gastric hepatoid adenocarcinoma(GHA)is a rare and aggressive cancer that is characterized by foci with features of both hepatocellular differentiation and adenomatous differentiation.However,there is curren...BACKGROUND Gastric hepatoid adenocarcinoma(GHA)is a rare and aggressive cancer that is characterized by foci with features of both hepatocellular differentiation and adenomatous differentiation.However,there is currently no standard treatment for this disease,which has a poor prognosis.CASE SUMMARY A 72-year-old male with a body mass index of 20.9 was diagnosed with GHA with perigastric lymph node and liver metastasis.He underwent first-line chemotherapy but that failed.Pembrolizumab and bevacizumab with chemotherapy were used in the second-line treatment.The progression-free survival and overall survival were 14 mo and 16 mo,respectively,after treatment.In addition,the main adverse reaction was tolerable.The patient did not die of tumor progression.CONCLUSION The combination of pembrolizumab and bevacizumab with chemotherapy is an effective and safe regimen for GHA and may be recommended as a new choice for GHA treatment.Further studies should evaluate this treatment in a larger cohort or a randomized controlled trial.展开更多
The Yangla Copper Ore Field in Northwest Yunnan Province, China, is a large region of deposits dominated by copper-bearing skarns whose origin remains debatable despite numerous studies over the past two decades. We h...The Yangla Copper Ore Field in Northwest Yunnan Province, China, is a large region of deposits dominated by copper-bearing skarns whose origin remains debatable despite numerous studies over the past two decades. We have investigated the geological and geochemical characteristics of the skarns using field and microscopic observations combined with chemical analyses. The results show that the skarns fall into two categories. The first category is metamorphic skarn, which constitute the majority （〉90%） of skarns in the deposit and is characterized by stratiform occurrences conformable to Devonian host strata, anhydrous mineral assemblages such as diopside＋hedenbergite＋quartz, widespread banded structure, fine-grainsize （〈200 μm） and preserved tuff-like textures. Whole-rock major element compositions, REE and trace-element compositions resemble those of the country rock slates or schists. The skarn layers occur at variable distances （0-2 000 m） from Indosinian plutonic bodies. Fracture-filling veins and/or alteration halos are scarce or absent in or near the skarn layers. This category of skarn probably formed by isochemical contact metamorphism of fine calcareous clastic sediments or impure carbonate rocks during emplacement of the plutonic bodies with no significant material migration by hydrothermal fluids involved during the process, in which case metallic enrichment of the skarn layers was present in the protolith of the skarn. The second category is metasomatic skarn with relatively coarse-grained textures （200-〉1 000 μm） and volatile-reach assemblages such as diopside＋tremolite＋scapolite at or near the igneous contact zones, which constitutes only a minor pro-portion of ore compared with metamorphic skarn. Taking into consideration diverse existing opinions about the genetic type of the deposit, we suggest that the geological and whole-rock geochemical characteristics of the skarus are consistent with a metamorphosed and metasomatized SEDEX （sedimentary exhalative deposit） type rather than a hydrothermal metasomatic skarn type.展开更多
基金Supported by the Quzhou Science and Technology Plan Project funded by the Quzhou Municipal Science and Technology Bureau,No.2022K67,No.2022K69,and No.2024K076.
文摘This article explores the bidirectional relationship between type 2 diabetes mellitus(T2DM)and depression,focusing on their shared pathophysiological mechanisms,including immune-inflammatory responses,gut-brain axis dysregu-lation,metabolic abnormalities,and neuroendocrine modulation.Research indicates that T2DM contributes to anxiety and depression through chronic low-grade inflammation,insulin resistance,gut microbiota imbalance,and hy-peractivation of the hypothalamic-pituitary-adrenal axis.Conversely,depression may increase the risk of T2DM via lifestyle disruption,immune activation,and neurotransmitter imbalance.Additionally,metabolic pathway disturbances-such as reduced adiponectin,impaired insulin signaling,and altered amino acid me-tabolism-may influence mood regulation and cognition.The article further examines emerging therapeutic strategies targeting these shared mechanisms,including anti-inflammatory treatments,gut microbiota modulation,hypothalamic-pituitary-adrenal axis interventions,metabolic therapies(e.g.,glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors),and multidisciplinary integrative management.Emphasizing the multisystem nature of diabetes-depression comorbidity,this work highlights the importance of incorporating mental health strategies into diabetes care to optimize outcomes and enhance patient quality of life.
基金Supported by Clinical Medical Research Fund of the Zhejiang Medical Association,No.2025ZYC-Z32Henan Provincial Key Research and Development Program,No.231111311000+1 种基金Henan Provincial Science and Technology Research Project,No.232102310411Clinical Medical Research Fund of the Zhejiang Medical Association,2024ZYC-Z30.
文摘Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.
基金Supported by Quzhou Science and Technology Plan Project,No.2024K076.
文摘Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematically invest-igates the mechanism by which curcumol ameliorates DR through regulation of the FTO/MAFG-AS1 epigenetic axis and reveals its therapeutic potential in tar-geting the retinal microenvironment via a nano-delivery system.Experimental results demonstrate that curcumol activates the demethylase activity of FTO,sta-bilizing the expression of the long non-coding RNA MAFG-AS1,thereby inhi-biting high glucose-induced retinal endothelial cell inflammation,migration,and vascular leakage.Single-cell transcriptomic analysis further uncovered the dual role of FTO in DR:On the one hand,it promotes pathological angiogenesis in endothelial cells,while on the other hand,it exerts protective effects through MAFG-AS1-mediated antioxidative and anti-inflammatory functions.Moreover,this study proposes a multidimensional epigenetic regulatory network based on histone lactylation,N6-methyladenosine modification,and DNA methylation,and verifies that curcumol delays DR progression by coordinately modulating these modifications.To overcome the limitations of conventional therapies,this study innovatively designed a macrophage membrane-coated nano-delivery system,significantly enhancing the retinal targeting and bioavailability of curcumol.Finally,the study advocates a paradigm shift from passive treatment to early prevention,proposing a three-tiered intervention strategy that integrates epigenetic biomarkers with artificial intelligence-based risk assessment.These findings not only elucidate the multi-target regulatory mechanisms of curcumol but also provide a theoretical foundation for the development of precision therapies for DR based on epigenetic remodeling and microenvironmental synergistic intervention.
基金Supported by Science and Technology Program of Quzhou,China,No.2022K67Zhejiang Medical Association Clinical Research Fund Project,No.2024ZYC-A526and the Research Project of Quzhou People’s Hospital,No.KYQD2024-006.
文摘BACKGROUND The association between the uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and mental health among individuals with type 2 diabetes mellitus(T2DM)has not been thoroughly investigated.AIM To examine the link between UHR and symptoms of depression and anxiety in patients with T2DM.METHODS A cross-sectional analysis was carried out from March 2023 to April 2024,involving participants diagnosed with T2DM.Data on sociodemographic characteristics,clinical parameters,and UHR values were systematically gathered.The Self-Rating Depression Scale(SDS)and Self-Rating Anxiety Scale(SAS)were utilized to evaluate depressive and anxiety symptoms,respectively.To assess the relationships between UHR and SDS/SAS scores,linear regression models were employed,incorporating adjustments for potential confounding variables.Additionally,smooth curve fitting and threshold effect analyses were conducted to explore potential nonlinear relationships.RESULTS A total of 285 patients with T2DM were included.Initial univariate analysis demonstrated a significant positive correlation between elevated UHR levels and higher SDS and SAS scores.Multivariate regression analysis revealed that a one-unit rise in UHR was associated with a 1.13-point increase in SDS scores(95%CI:0.69-1.58)and a 0.57-point increase in SAS scores(95%CI:0.20-0.93).After controlling for confounders,UHR remained positively correlated with SDS(β=1.55,95%CI:0.57-2.53)and SAS(β=0.72,95%CI:0.35-1.09).Nonlinear analysis identified critical thresholds at UHR values of 5.02 for SDS and 4.00 for SAS,beyond which the relationships between UHR and psychological symptom scores became markedly stronger(P<0.05).CONCLUSION Higher UHR levels are significantly linked to exacerbated depressive and anxiety symptoms in patients with T2DM.These results indicate that UHR may function as a promising biomarker to identify individuals at greater risk of mental health complications within this population.
基金financed by the National Natural Science Foundation of China(Nos.12402071,92160204)the China Postdoctoral Science Foundation(No.2024M751635)+1 种基金the Postdoctoral Fellowship Program of CPSF,China(No.GZB20240365)the National Science and Technology Major Projects of China(No.J2019-IV-0011-0079).
文摘Thermomechanical Fatigue (TMF) is one of the most dangerous failure modes of high-temperature structures. The effect of coarsened and rafted microstructures on the TMF behavior of Nickel-Base Single Crystal Superalloys (NBSX) was experimentally studied. TMF tests under In-Phase (IP) and Out-of-Phase (OP) paths revealed significant variations in TMF life reduction. Cyclic deformation behaviors of alloys with different microstructures were compared. The effect of microstructure on TMF damage mechanisms was unveiled from characterizations of fracture surfaces and longitudinal sections by scanning electronic microscope and optical microscope. A transition from mode-I to crystallographic fracture in the coarsened alloy during IP-TMF was observed and discussed. Due to the degraded microstructure, the dispersed distribution of crystal slips was distinguished in the coarsened and rafted alloys. The competitive or synergetic interactions among oxidation-assisted mode-I opening, casting pore-related mode-I creep and crystallographic slipping were discussed. This study underscores the complex interplay among microstructure, deformation behaviors and damage mechanisms, offering valuable insights into alloy performance under TMF conditions.
基金Supported by the Quzhou Science and Technology Plan Project,No.2022K69.
文摘Familial androgen insensitivity syndrome (AIS), resulting from inherited mutations in the androgen receptor (AR)gene, has traditionally been examined within the framework of disorders of sex development. However, growingevidence indicates that AR dysfunction also disrupts systemic metabolic homeostasis, predisposing affectedindividuals to insulin resistance and type 2 diabetes mellitus. This article synthesizes recent advances in genetics,transcriptomics, and physiology to elucidate how AR mutations drive tissue-specific metabolic reprogramming inkey organs, including pancreatic β-cells, skeletal muscle, liver, and adipose tissue. Particular attention is given to anewly identified familial AR variant (c.2117A>G;p.Asn706Ser), which not only broadens the known mutationalspectrum of AIS but also underscores the clinical importance of early metabolic risk screening in this population.We further examine how pubertal stage, hormone replacement therapy, and sex-specific signaling pathwaysinteract to influence long-term metabolic outcomes. Lastly, we propose an integrative management framework thatincorporates genetic diagnosis, endocrine surveillance, and personalized pharmacological strategies aimed atreducing the risk of type 2 diabetes mellitus and cardiometabolic complications in individuals with AIS. Distinctfrom previous AIS-centered reviews, this work integrates metabolic and endocrine perspectives into the traditionaldevelopmental paradigm, offering a more comprehensive understanding of disease risk and translational management.
基金supported by Guangxi Natural Science Foundation(2023GXNSFAA026128).
文摘The role and regulatory mechanisms of macrophage polarization in cardiac transplantation have gained significant attention.Macrophages can polarize into either the M1(pro-inflammatory)or M2(anti-inflammatory)phenotype in response to environmental cues.M1 macrophages facilitate transplant rejection by releasing inflammatory mediators and activating T cells,whereas M2 macrophages support graft survival by secreting antiinflammatory factors and promoting tissue repair.Mitochondrial quality control regulation plays a crucial role in macrophage polarization,which may influence graft survival and immune responses.This review provides an overview of the current understanding of mitochondrial quality control-regulated macrophage polarization in cardiac transplantation,its effects on graft outcomes,and potential therapeutic strategies to modulate this process to enhance transplant success rates.The review was conducted by systematically analyzing recent studies and integrating findings from key research articles to synthesize a comprehensive understanding of this emerging field.
基金Guangdong Provincial Medical Science and Technology Research Fund Project,No.A2024525.
文摘BACKGROUND Intracranial aneurysms(IAs)pose significant health risks,attributable to their potential for sudden rupture,which can result in severe outcomes such as stroke and death.Despite extensive research,the variability of aneurysm behavior,with some remaining stable for years while others rupture unexpectedly,remains poorly understood.AIM To employ bibliometric analysis to map the research landscape concerning risk factors associated with IAs rupture.METHODS A systematic literature review of publications from 2004 to 2023 was conducted,analyzing 3804 documents from the Web of Science Core Collection database,with a focus on full-text articles and reviews in English.The analysis encompassed citation and co-citation networks,keyword bursts,and temporal trends to delineate the evolution of research themes and collaboration patterns.Advanced software tools,CiteSpace and VOSviewer,were utilized for comprehensive data visualization and trend analysis.RESULTS Analysis uncovered a total of 3804 publications on IA rupture risk factors between 2006 and 2023.Research interest surged after 2013,peaking in 2023.The United States led with 28.97%of publications,garnering 37706 citations.Notable United States-China collaborations were observed.Capital Medical University produced 184 publications,while Utrecht University boasted a citation average of 69.62 per publication.“World Neurosurgery”published the most papers,contrasting with“Stroke”,the most cited journal.The PHASES score from“Lancet Neurology”emerged as a vital rupture risk prediction tool.Early research favored endovascular therapy,transitioning to magnetic resonance imaging and flow diverters.CONCLUSION This study assesses global IA research trends and highlights crucial gaps,guiding future investigations to improve preventive and therapeutic approaches.
基金supported by the Natural Science Foundation of China(Grant Nos.:22225702 and 32322048)the National Key R&D Program of China(Grant No.:2020YFE0202200)+8 种基金the Shanghai Academic/Technology Research Leader Program,China(Grant No.:22XD1420900)Guangdong High-level New R&D Institute,China(Grant No.:2019B090904008)Guangdong High-level Innovative Research Institute,China(Grant No.:2021B0909050003)the Shanghai Rising-Star Program,China(Grant No.:22QA1411100)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.:2021276)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology,China(Grant No.:2022QNRC001)the open fund of State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,China(Grant No.:KF-202201)We also thank the support of the Innovative Research Team of High-Level Local Universities in Shanghai,China(Grant No.:SHSMU-ZDCX20212700)Sanofi scholarship program.
文摘Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.
文摘Dear Editor, The current flu epidemic caused by influenza A H1N1 （A/H1N1） virus, which first appeared in Mexico emerged as a communicable human disease in late March and rapidly spread throughout the world in April 2009. Due to the rapid transport systems in modern times, the epidemic affected about 121 countries in less than 4 months （http：//www.who.int/csr/don/2009_07_16/en/）.
基金the National Natural Science Foundation of China(Nos.11890684 and 52102142)the Foundation for Innovative Research Groups of Hunan Province(No.2020JJ1005)。
文摘Yttrium tantalate(YTaO_(4))is the next generation of higher service temperature thermal barrier coatings(TBCs)materials due to its smaller volume effect in phase change,lower thermal conductivity and unique ferroelastic domain structure.However,the low fracture toughness limits its application.We first characterized the diffraction patterns of variants,and two variants(M_(1)and M_(2))observed in transmission electron microscopy(TEM)results were determined from four possible variants by mechanical derivation.The role of Zr^(4+)doping in ferroelastic toughening was explained in detail.With the increase of Zr^(4+)doping concentration,the monoclinic angle β and the domain rotation angleαdecrease,respectively.The spontaneous strain component and the principal strain in the main space also have a similar decreasing trend.The decrease of the ferroelastic domain inversion energy barrier is beneficial to the improvement of fracture toughness.Combining the results of Vickers indentation,we found that Zr^(4+)could be enriched at the domain boundary to inhibit the generation of cracks.An appropriate amount of Zr^(4+)is conducive to the improvement of fracture toughness,and the excessive Zr^(4+)will reduce the fracture toughness due to the generation of by-product t-ZrO_(2).So,the optimal composition is Y_(0.44)Ta_(0.44)Zr_(0.12)O_(2) and the best fracture toughness(2.9–3.8MPa m^(1/2))is equivalent to the commercial 8YSZ.This result will promote the application of a new generation of TBCs.
文摘Training deep neural networks(DNNs)requires a significant amount of time and resources to obtain acceptable results,which severely limits its deployment in resource-limited platforms.This paper proposes DarkFPGA,a novel customizable framework to efficiently accelerate the entire DNN training on a single FPGA platform.First,we explore batch-level parallelism to enable efficient FPGA-based DNN training.Second,we devise a novel hardware architecture optimised by a batch-oriented data pattern and tiling techniques to effectively exploit parallelism.Moreover,an analytical model is developed to determine the optimal design parameters for the DarkFPGA accelerator with respect to a specific network specification and FPGA resource constraints.Our results show that the accelerator is able to perform about 10 times faster than CPU training and about a third of the energy consumption than GPU training using 8-bit integers for training VGG-like networks on the CIFAR dataset for the Maxeler MAX5 platform.
文摘BACKGROUND Gastric hepatoid adenocarcinoma(GHA)is a rare and aggressive cancer that is characterized by foci with features of both hepatocellular differentiation and adenomatous differentiation.However,there is currently no standard treatment for this disease,which has a poor prognosis.CASE SUMMARY A 72-year-old male with a body mass index of 20.9 was diagnosed with GHA with perigastric lymph node and liver metastasis.He underwent first-line chemotherapy but that failed.Pembrolizumab and bevacizumab with chemotherapy were used in the second-line treatment.The progression-free survival and overall survival were 14 mo and 16 mo,respectively,after treatment.In addition,the main adverse reaction was tolerable.The patient did not die of tumor progression.CONCLUSION The combination of pembrolizumab and bevacizumab with chemotherapy is an effective and safe regimen for GHA and may be recommended as a new choice for GHA treatment.Further studies should evaluate this treatment in a larger cohort or a randomized controlled trial.
基金financially supported by the China Geological Survey(No.12120113079400)
文摘The Yangla Copper Ore Field in Northwest Yunnan Province, China, is a large region of deposits dominated by copper-bearing skarns whose origin remains debatable despite numerous studies over the past two decades. We have investigated the geological and geochemical characteristics of the skarns using field and microscopic observations combined with chemical analyses. The results show that the skarns fall into two categories. The first category is metamorphic skarn, which constitute the majority （〉90%） of skarns in the deposit and is characterized by stratiform occurrences conformable to Devonian host strata, anhydrous mineral assemblages such as diopside＋hedenbergite＋quartz, widespread banded structure, fine-grainsize （〈200 μm） and preserved tuff-like textures. Whole-rock major element compositions, REE and trace-element compositions resemble those of the country rock slates or schists. The skarn layers occur at variable distances （0-2 000 m） from Indosinian plutonic bodies. Fracture-filling veins and/or alteration halos are scarce or absent in or near the skarn layers. This category of skarn probably formed by isochemical contact metamorphism of fine calcareous clastic sediments or impure carbonate rocks during emplacement of the plutonic bodies with no significant material migration by hydrothermal fluids involved during the process, in which case metallic enrichment of the skarn layers was present in the protolith of the skarn. The second category is metasomatic skarn with relatively coarse-grained textures （200-〉1 000 μm） and volatile-reach assemblages such as diopside＋tremolite＋scapolite at or near the igneous contact zones, which constitutes only a minor pro-portion of ore compared with metamorphic skarn. Taking into consideration diverse existing opinions about the genetic type of the deposit, we suggest that the geological and whole-rock geochemical characteristics of the skarus are consistent with a metamorphosed and metasomatized SEDEX （sedimentary exhalative deposit） type rather than a hydrothermal metasomatic skarn type.
