The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of...The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.展开更多
State-supported programs providing loans and scholarships in exchange for service in under-served areas provide an important source of financial support for medical students while encouraging them to select careers in...State-supported programs providing loans and scholarships in exchange for service in under-served areas provide an important source of financial support for medical students while encouraging them to select careers in primary care. The purpose of this research was to seek a better understanding of these often unheralded but important state sources of support, and learn if they have continued to grow in the twenty-first century. Administrative data were obtained on state-supported programs operating in 2008 that provided financial support to students, resident or practicing physicians, physician assistants, nurse practitioners, certified nurse midwives, dentists, and licensed mental healthcare providers in exchange for service in an underserved area. The authors identified numbers, types of state-supported programs, program workforce strength, and features of state programs. In 2008, 75 state programs, operating in 37 states, collectively had 5113 program participants under contract. Loan repayment programs (n = 42, 56%) were the most common type of state-supported programs. Practitioners signed initial contracts in 2008 totaled 1173, with more non-physicians (n = 681, 58%) signing initial contracts than physicians (n = 492, 42%). Additionally, 2803 practitioners were serving in programs in 2008. Field placement was also slightly greater among non-physicians in 2008 (n = 1433, 51%) than physicians (n = 1370, 49%). State support-for-service programs remains an important source of financial assistance for those willing to make service commitments in underserved areas. Moreover, these programs continue to increase in size, even amidst the economic malaise, and provide an obligated primary care workforce in underserved areas.展开更多
Water plays an important role in many essential biological processes of membrane proteins in hydrated lipid environments.In general,the 1H polarization transfers berween water molecules and site--specific protons in p...Water plays an important role in many essential biological processes of membrane proteins in hydrated lipid environments.In general,the 1H polarization transfers berween water molecules and site--specific protons in proteins can be classified as coherent(via dipolar spin diffusion)and incoherent(via chemical exchange and nuclear Overhauser effect)transfers.Solid-state NMR is the technique of choice for studying such water-protein interactions in membrane-bound proteins/peptides through the detection of'H polarization transfers from water to the proteins.These polarization transfer mechanisms often exist simultaneously and are difficult to quantify individually.Here,we review water-protein polarization transfer techniques in solid state NMR with a focus on the recent progress for the direct detection of site-specific kinetic water-protein chemical exchange processes on the sub-millisecond time scale in membrane-bound proteins.The measurements of the pure chemical exchange ki-netics provide a unique opportunity to understand the role that water plays in the structure-function relationships of membrane bound species at the water-bilayer interface.In addi-tion,the perspective of chemical exchange saturation transfer(CEST)experiments in membrane-bound proteins/peptides is further discussed.展开更多
The high-temperature dissolution behavior of primary carbides in samples taken from GCr15 continuous-casting bloom was observed in-situ by confocal laser scanning microscopy.Equations were fitted to the dissolution ki...The high-temperature dissolution behavior of primary carbides in samples taken from GCr15 continuous-casting bloom was observed in-situ by confocal laser scanning microscopy.Equations were fitted to the dissolution kinetics of primary carbides during either heating or soaking.Dissolution of carbides proceeded in three stages(fast→slow→faster)as either temperature or holding time was increased.During the heating process and during the first and third stages of the soaking process,the original size of the carbides determined the steepness of the slope,but during the middle(“slow”)stage of the soaking process,the slope remained zero.The initial size of the carbides varied greatly,but their final dissolution temperature fell within the narrow range of 1210-1235℃,and the holding time remained within 50 min.Fractal analysis was used to study the morphological characteristics of small and medium-sized carbides during the dissolution process.According to changes in the fractal dimension before and after soaking,the carbides tended to evolve towards a more regular morphology.展开更多
Two CoⅡ-based complexes,{[Co(dps)_(2)(N_(3))_(2)]·H_(2)O}_n(1)and[Co(dps)_(2)(N_(3))_(2)]_n(2),show a 1D chain and a 3D network,respectively.The central CoⅡions in the complexes have the same coordination envir...Two CoⅡ-based complexes,{[Co(dps)_(2)(N_(3))_(2)]·H_(2)O}_n(1)and[Co(dps)_(2)(N_(3))_(2)]_n(2),show a 1D chain and a 3D network,respectively.The central CoⅡions in the complexes have the same coordination environment with the[Co(dps)_(4)(N_(3))_(2)]unit.Although the differences in crystal parameters are nearly negligible,their magnetic properties are very different.AC susceptibility data show that 1 behaves as a typical field-induced single-ion magnet(SIM)with the out-of-phase(χ_(M)”)signals,while 2 shows ac signals ofχ_(M)”without peaks even under applied dc filed within our measurement window.Far-IR magneto-spectra(FIRMS)show strong spin-phonon couplings at 0 T in 2,likely making the magnetic relaxation in 2 fast,while the couplings are negligible in 1.Small spin-phonon coupling in 1 likely leads to slower magnetic relaxation,making 1 a SIM.The difference in the properties is due to the structural rigidity of 2 in its 3D network,leading to stronger spin-phonon coupling.Combined high-field EPR(HF-EPR)and FIRMS studies give spin-Hamiltonian parameters,including D=64.0(9)cm^(-1),|E|=15.7(2)cm^(-1)for 1 and D=80.0(2)cm^(-1),|E|=19.0(1)cm^(-1)for 2.展开更多
In this article,we comment on the article by Peta et al.This study evaluates the diagnostic performance of FibroTest-Actitest,transient elastography,and the fibrosis-4 index against a histological reference.Using the ...In this article,we comment on the article by Peta et al.This study evaluates the diagnostic performance of FibroTest-Actitest,transient elastography,and the fibrosis-4 index against a histological reference.Using the Obuchowski measure,the authors demonstrate that FibroTest and vibration-controlled transient elastography outperform the fibrosis-4 index in detecting fibrosis.Additionally,Actitest offers superior estimation of inflammatory activity compared to conventional biomarkers.Assessing liver fibrosis is crucial for managing autoimmune hepatitis(AIH),yet reliance on invasive liver biopsy remains higher than in other liver diseases.This is partly due to more complex diagnostic criteria for AIH,the lack of standardized scoring for non-invasive testing,and the presence of inflammation,which can lead to falsely elevated results with non-invasive tests.A Bayesian latent class model further supports the reliability of these non-invasive tests,highlighting their potential to complement biopsy,particularly for longterm disease monitoring.These findings underscore the importance of noninvasive diagnostics in optimizing AIH management.展开更多
In this editorial,we comment on the article by Rolim et al in World Journal of Hepatology,which highlights the impacts of hepatopulmonary syndrome(HPS)related to schistosomiasis in patients with and without cirrhosis....In this editorial,we comment on the article by Rolim et al in World Journal of Hepatology,which highlights the impacts of hepatopulmonary syndrome(HPS)related to schistosomiasis in patients with and without cirrhosis.Schistosomiasis,a parasitic disease affecting millions worldwide,frequently leads to portal hypertension.Its outcomes are more devastating in cirrhosis than in non-cirrhotic portal hypertension,due to the complex interplay between cirrhosis and HPS,a severe pulmonary vascular complication.Cirrhosis distorts hepatic architecture,impairs portal blood flow,and triggers systemic vascular changes.Schistosomiasis exacerbates portal hypertension and inflammation,further injuring the liver.In non-cirrhotic portal hypertension,significant vascular resistance occurs,but preserved liver function mitigates systemic effects.In contrast,cirrhosis amplifies hypoxia,worsens pulmonary shunting,and predisposes patients to respiratory failure,infection,and death.In a retrospective study of 113 patients,Rolim et al found that cirrhosis had an impact on mortality,yet the presence of HPS did not significantly affect survival.While cirrhosis worsening outcomes are anticipated,HPS should theoretically worsen survival by impairing oxygenation.Early diagnosis,parasite control,and managing cirrhosis-related complications are critical for schistosomiasis-related liver disease.Understanding these differences underscores the importance of integrating liver health into global schistosomiasis management strategies.展开更多
Food contaminants,particularly insecticides,are important factors contributing to obesity and other adverse effects.As the most widely used diamide insecticide worldwide,chlorantraniliprole(CP)is ubiquitous in food an...Food contaminants,particularly insecticides,are important factors contributing to obesity and other adverse effects.As the most widely used diamide insecticide worldwide,chlorantraniliprole(CP)is ubiquitous in food and the environment.However,the influence of CP on obesity and the gut microbiota remains unknown.In this study,we administered CP/carboxymethyl cellulose sodium to C57BL/6J mice with a high-fat diet(HFD)via gavage for 13 weeks.The CP exposure induced significant increases in body weight gain,fat mass,serum total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C).Moreover,CP aggravated the imbalance in the gut microbiota by increasing the relative abundance of obesity-associated bacteria and reducing the relative abundance of beneficial bacteria.Based on untargeted metabolomics analysis,CP was found to be involved in the regulation of pathways including Alanine,aspartate and glutamate metabolism and Arginine and proline metabolism.Notably,CP exposure primarily induced alterations in microbial metabolites within these pathways,such as L-(+)-aspartic acid and L-glutamic acid.Additionally,individual metabolites,such as the lipid mediator(oleoyl ethanolamide),also demonstrated alterations upon CP exposure.Furthermore,Spearman correlation analysis revealed several noteworthy associations between microbial alterations,metabolite changes,and phenotypes.The results of the study demonstrate a connection between microbiota,metabolites,and the effects of CP exposure on HFD-induced obesity,elucidating the critical role of the gut microbiota and its metabolites in the toxic effects of CP.展开更多
Metabolic dysfunction-associated steatohepatitis(MASH)has become a leading indication for liver transplantation.Bariatric surgery is a proven intervention for weight loss and metabolic improvement in MASH but concerns...Metabolic dysfunction-associated steatohepatitis(MASH)has become a leading indication for liver transplantation.Bariatric surgery is a proven intervention for weight loss and metabolic improvement in MASH but concerns over surgical risk in patients with advanced liver disease has expanded interest in endoscopic sleeve gastroplasty(ESG)as a less invasive alternative.This review examine the efficacy,safety,and metabolic impact of ESG vs traditional bariatric surgery(Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy)in patients with MASH,with and without cirrhosis.We analyze current evidence on weight loss outcomes,histologic and biochemical improvements in MASH,resolution of metabolic syndrome,and perioperative risks associated with these procedures.Special attention is given to the feasibility of ESG in compensated cirrhosis(Child-Pugh A/B)and the potential role of bariatric interventions in delaying or avoiding liver transplantation.As the prevalence of MASH-related cirrhosis rises,refining bariatric strategies for this high-risk population is imperative.ESG may offer a lower procedural risk profile,but current data are largely limited to small,observational studies with short-term follow-up.A tailored,multidisciplinary approach is essential to optimize weight management and liver health in MASH patients,with future studies needed to clarify the long-term efficacy and safety of ESG in MASH.展开更多
BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related deaths worldwide with an alarming rise in early-onset CRC(eoCRC)over the past several decades.Unlike late-onset CRC,the drivers behind eoC...BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related deaths worldwide with an alarming rise in early-onset CRC(eoCRC)over the past several decades.Unlike late-onset CRC,the drivers behind eoCRC remain less clear.While certain risk factors such as obesity and smoking have demonstrated a relatively strong association with eoCRC in the literature,some studies have challenged these associations,emphasizing the need for additional studies.METHODS This cross-sectional study used de-identified data from the National Health and Nutrition Examination Survey(1999-2023),including 30321 United States adults aged 18 to 49 years.Participants with missing key variables were excluded.Standardized protocols were used to collect demographic,lifestyle,anthropo-metric[body mass index(BMI),body roundness index(BRI),waist circumference(WC)],and self-reported CRC data.Logistic regression and propensity score matching assessed associations between obesity-related parameters and eoCRC.Statistical analyses were performed in R and Stata,with P<0.05 defined as significant.RESULTS Of 30321 participants,48 received a diagnosis of eoCRC.Patients with eoCRC were older(mean age 39.96 years vs 34.36 years;P<0.001)and had higher WC and BRI.None of the eoCRC patients were heavy drinkers(P=0.006).Unadjusted models demonstrated significant associations of eoCRC with BRI quartiles,as well as BMI-defined obesity,WC,and smoking.In unadjusted models,BRI remained the strongest independent predictor;those in the highest BRI quartiles had over 10-fold greater odds of eoCRC.In fully adjusted models,BRI remained significant,but BMI-and waist-based obesity were not.CONCLUSION BRI is a stronger predictor of eoCRC risk compared to other obesity indices and is a superior tool for identifying young individuals at higher risk of CRC.展开更多
Primary biliary cholangitis(PBC)is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction,leading to fibrosis,cirrhosis,and eventual liver failure.Over the past two decades,s...Primary biliary cholangitis(PBC)is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction,leading to fibrosis,cirrhosis,and eventual liver failure.Over the past two decades,significant advancements have paved the way for novel therapeutic strategies.Ursodeoxycholic acid(UDCA)has been the cornerstone of PBC management,improving survival and delaying disease progression in most patients.However,up to 40%of patients demonstrate an inadequate response to UDCA,necessitating additional treatment options.Obeticholic acid(OCA),a farnesoid X receptor agonist,has emerged as a second-line therapy,showing efficacy in reducing alkaline phosphatase levels and improving liver biochemistry.Beyond UDCA and OCA,a new wave of therapeutic agents are reshaping the PBC landscape.These include fibrates,peroxisome proliferator-activated receptor agonists and novel immunomodulatory drugs aimed at reducing autoimmune-mediated liver injury.Bile acid transport inhibitors,anti-fibrotic agents,and gut microbiome-targeted therapies are also under investigation,offering hope for personalized treatment approaches.This review highlights the evolution of PBC therapy,emphasizing the unmet needs of patients with refractory disease and the potential of emerging therapies to improve outcomes.As the therapeutic landscape continues to expand,optimizing treatment strategies through precision medicine holds the promise of transforming the management of PBC.展开更多
BACKGROUND Immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy but are associated with immune-related adverse events,including ICIs hepatitis.Mycophenolate mofetil(MMF)is often used as a second-line i...BACKGROUND Immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy but are associated with immune-related adverse events,including ICIs hepatitis.Mycophenolate mofetil(MMF)is often used as a second-line immunosuppressive agent for steroid-refractory cases.However,there is no standardized approach to MMF tapering,leading to uncertainties regarding relapse risk,optimal tapering strategies,and long-term outcomes.AIM To evaluate current evidence on MMF tapering in ICI hepatitis,focusing on strategies,clinical outcomes,and the risk of hepatitis recurrence.Additionally,we explore the feasibility of reintroducing ICI therapy after immunosuppression withdrawal.METHODS A comprehensive literature search was conducted in PubMed,EMBASE,and clinical trial registries to identify studies reporting MMF use and tapering strategies in ICI hepatitis.We extracted data from manuscripts including patient characteristics,MMF dosing regimens,tapering duration,relapse rates,and oncologic outcomes.Risk factors for recurrence and successful tapering were analyzed.RESULTS There was significant heterogeneity in the duration of MMF taper,which ranged from 4 weeks to greater than 6 months.The tapering schedules presented were individualized based on the severity of liver injury,patient response to treatment,and risk factors for relapse.We summarize current tapering approaches,including rapid vs slow withdrawal,predictors of successful tapering,and alternative immunosuppressive strategies.The impact of MMF duration on liver recovery,relapse risk,and cancer prognosis will be discussed.Evidence on ICI rechallenge post-taper will also be reviewed.CONCLUSION While MMF is effective in managing ICI hepatitis,tapering remains a clinical challenge with potential risks of hepatitis flare and disease progression.Standardized tapering protocols are needed to optimize immunosuppression while preserving anticancer efficacy.Future studies should focus on biomarker-driven tapering strategies and prospective trials to establish best practices.展开更多
A thyroid storm(TS)or thyrotoxic crisis is an infrequent,life-threatening endocrinological emergency due to the worsening of the hyperthyroid state.Thyroid hormones(THs)influence almost all the body cells and tissues&...A thyroid storm(TS)or thyrotoxic crisis is an infrequent,life-threatening endocrinological emergency due to the worsening of the hyperthyroid state.Thyroid hormones(THs)influence almost all the body cells and tissues'differentiation,growth,and energy metabolism.Consequently,excess THs are expected to lead to profound organ function,regulation,and hemodynamic changes.In addition to their roles in metabolism and thermoregulation,THs play critical role in maintaining cardiovascular homeostasis through both genomic and non-genomic mechanisms.Receptors for THs are expressed in myocardial and vascular endothelial tissues,allowing fluctuations in circulating hormone levels to directly influence cardiovascular function.Excess TS induces a hyper-dynamic cardiovascular state,characterized by increased ventricular contractility and improved systolic and diastolic performance.The chronotropic and inotropic properties of THs result in dysregulation of blood pressure,heart rate,contractility,cardiac output,and systemic vascular resistance.This could lead to serious consequences such as cardiomyopathy,heart failure,and life-threatening arrhythmia,ultimately contributing to cardiocirculatory collapse and cardiac death.The management of TS necessitates a systematic approach that emphasizes the significance of resuscitation and identification of the underlying causes.It is crucial to prioritize assessing cardiac function in patients with TS.This review explores the clinical impact of TS on the heart and its clinical repercussions,emphasizing the intricate molecular and pathophysiological mechanisms and the interplay between TS and key cardiovascular parameters.This review summarizes the current knowledge of pathophysiology,pharmacological and mechanical interventions,ranging from beta-blocker use to the surgical approach.展开更多
This editorial comment is on the article by Xu et al.It offers an in-depth analysis of liver function assessment tools and their prognostic roles in non-malignant liver diseases,with a focus on the albumin-bilirubin(A...This editorial comment is on the article by Xu et al.It offers an in-depth analysis of liver function assessment tools and their prognostic roles in non-malignant liver diseases,with a focus on the albumin-bilirubin(ALBI)score.ALBI’s components,grading system,and clinical relevance across various liver conditions are reviewed and compared with traditional models such as the Child-Pugh and model for end-stage liver disease scores.We included recent studies evaluating ALBI’s role in estimating liver function,suggesting it may help differentiate patients who appear similar under other staging systems,and assist in guiding clinical decisions.Although ALBI is primarily used as an indicator of hepatic reservoir in hepatocellular carcinoma,it has been demonstrated a positive correlation with overall survival,tumor recurrence,and post-hepatectomy liver failure in patients undergoing potentially curative treatments such as liver resection,liver transplantation,and local ablation.Moreover,several studies suggest that ALBI can also predict survival outcomes,treatment-related toxicity,and liver-related complications in patients receiving trans-arterial chemoembolization,radioembolization,external-beam radiotherapy,or systemic therapies.Its growing use in nonmalignant liver diseases,including primary biliary cholangitis,cirrhosis,acute and chronic liver failure,and viral hepatitis highlights the need for large,prospective studies.Further studies are warranted to validate the integration of ALBI into routine clinical practice and to clarify its role in guiding prognosis and treatment planning.展开更多
文摘The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.
文摘State-supported programs providing loans and scholarships in exchange for service in under-served areas provide an important source of financial support for medical students while encouraging them to select careers in primary care. The purpose of this research was to seek a better understanding of these often unheralded but important state sources of support, and learn if they have continued to grow in the twenty-first century. Administrative data were obtained on state-supported programs operating in 2008 that provided financial support to students, resident or practicing physicians, physician assistants, nurse practitioners, certified nurse midwives, dentists, and licensed mental healthcare providers in exchange for service in an underserved area. The authors identified numbers, types of state-supported programs, program workforce strength, and features of state programs. In 2008, 75 state programs, operating in 37 states, collectively had 5113 program participants under contract. Loan repayment programs (n = 42, 56%) were the most common type of state-supported programs. Practitioners signed initial contracts in 2008 totaled 1173, with more non-physicians (n = 681, 58%) signing initial contracts than physicians (n = 492, 42%). Additionally, 2803 practitioners were serving in programs in 2008. Field placement was also slightly greater among non-physicians in 2008 (n = 1433, 51%) than physicians (n = 1370, 49%). State support-for-service programs remains an important source of financial assistance for those willing to make service commitments in underserved areas. Moreover, these programs continue to increase in size, even amidst the economic malaise, and provide an obligated primary care workforce in underserved areas.
基金This work was supported by NIH Grants AI023007 and GM122698All NMR experiments were carried out at the National High Magnetic Field lab(NHMFL)supported by the NSF Cooperative Agreement DMR-1644779 and the State of Florida.
文摘Water plays an important role in many essential biological processes of membrane proteins in hydrated lipid environments.In general,the 1H polarization transfers berween water molecules and site--specific protons in proteins can be classified as coherent(via dipolar spin diffusion)and incoherent(via chemical exchange and nuclear Overhauser effect)transfers.Solid-state NMR is the technique of choice for studying such water-protein interactions in membrane-bound proteins/peptides through the detection of'H polarization transfers from water to the proteins.These polarization transfer mechanisms often exist simultaneously and are difficult to quantify individually.Here,we review water-protein polarization transfer techniques in solid state NMR with a focus on the recent progress for the direct detection of site-specific kinetic water-protein chemical exchange processes on the sub-millisecond time scale in membrane-bound proteins.The measurements of the pure chemical exchange ki-netics provide a unique opportunity to understand the role that water plays in the structure-function relationships of membrane bound species at the water-bilayer interface.In addi-tion,the perspective of chemical exchange saturation transfer(CEST)experiments in membrane-bound proteins/peptides is further discussed.
基金supported by Independent Research Project of State Key Laboratory of Advanced Special Steel,Shanghai Key Laboratory of Advanced Ferrometallurgy,Shanghai University(SKLASS-2023-Z13)the Science and Technology Commission of Shanghai Municipality(No.19DZ2270200)+1 种基金A portion of the work was performed at US National High Magnetic Field Laboratory,which is supported by the National Science Foundation(Cooperative Agreement No.DMR-1157490 and DMR-1644779)the State of Florida.Thanks also to Mary Tyler for editing.
文摘The high-temperature dissolution behavior of primary carbides in samples taken from GCr15 continuous-casting bloom was observed in-situ by confocal laser scanning microscopy.Equations were fitted to the dissolution kinetics of primary carbides during either heating or soaking.Dissolution of carbides proceeded in three stages(fast→slow→faster)as either temperature or holding time was increased.During the heating process and during the first and third stages of the soaking process,the original size of the carbides determined the steepness of the slope,but during the middle(“slow”)stage of the soaking process,the slope remained zero.The initial size of the carbides varied greatly,but their final dissolution temperature fell within the narrow range of 1210-1235℃,and the holding time remained within 50 min.Fractal analysis was used to study the morphological characteristics of small and medium-sized carbides during the dissolution process.According to changes in the fractal dimension before and after soaking,the carbides tended to evolve towards a more regular morphology.
基金supported by the National Key Research and Development Program of China(No.2021YFA1600304)Joint Fund for Regional Innovation and Development(No.U20A2073)+4 种基金National Natural Science Foundation of China(Nos.22373048,21973038,61904119 and 22105089)Jiangxi Provincial Key Laboratory of Functional Molecular Materials Chemistry(No.20212BCD42018)US National Science Foundation(NSF,No.CHE-2055499)the Interdisciplinary program of Wuhan National High Magnetic Field Center(No.WHMFC202133)the support of the NSF Research Traineeship Program(No.DGE-2152168)。
文摘Two CoⅡ-based complexes,{[Co(dps)_(2)(N_(3))_(2)]·H_(2)O}_n(1)and[Co(dps)_(2)(N_(3))_(2)]_n(2),show a 1D chain and a 3D network,respectively.The central CoⅡions in the complexes have the same coordination environment with the[Co(dps)_(4)(N_(3))_(2)]unit.Although the differences in crystal parameters are nearly negligible,their magnetic properties are very different.AC susceptibility data show that 1 behaves as a typical field-induced single-ion magnet(SIM)with the out-of-phase(χ_(M)”)signals,while 2 shows ac signals ofχ_(M)”without peaks even under applied dc filed within our measurement window.Far-IR magneto-spectra(FIRMS)show strong spin-phonon couplings at 0 T in 2,likely making the magnetic relaxation in 2 fast,while the couplings are negligible in 1.Small spin-phonon coupling in 1 likely leads to slower magnetic relaxation,making 1 a SIM.The difference in the properties is due to the structural rigidity of 2 in its 3D network,leading to stronger spin-phonon coupling.Combined high-field EPR(HF-EPR)and FIRMS studies give spin-Hamiltonian parameters,including D=64.0(9)cm^(-1),|E|=15.7(2)cm^(-1)for 1 and D=80.0(2)cm^(-1),|E|=19.0(1)cm^(-1)for 2.
文摘In this article,we comment on the article by Peta et al.This study evaluates the diagnostic performance of FibroTest-Actitest,transient elastography,and the fibrosis-4 index against a histological reference.Using the Obuchowski measure,the authors demonstrate that FibroTest and vibration-controlled transient elastography outperform the fibrosis-4 index in detecting fibrosis.Additionally,Actitest offers superior estimation of inflammatory activity compared to conventional biomarkers.Assessing liver fibrosis is crucial for managing autoimmune hepatitis(AIH),yet reliance on invasive liver biopsy remains higher than in other liver diseases.This is partly due to more complex diagnostic criteria for AIH,the lack of standardized scoring for non-invasive testing,and the presence of inflammation,which can lead to falsely elevated results with non-invasive tests.A Bayesian latent class model further supports the reliability of these non-invasive tests,highlighting their potential to complement biopsy,particularly for longterm disease monitoring.These findings underscore the importance of noninvasive diagnostics in optimizing AIH management.
文摘In this editorial,we comment on the article by Rolim et al in World Journal of Hepatology,which highlights the impacts of hepatopulmonary syndrome(HPS)related to schistosomiasis in patients with and without cirrhosis.Schistosomiasis,a parasitic disease affecting millions worldwide,frequently leads to portal hypertension.Its outcomes are more devastating in cirrhosis than in non-cirrhotic portal hypertension,due to the complex interplay between cirrhosis and HPS,a severe pulmonary vascular complication.Cirrhosis distorts hepatic architecture,impairs portal blood flow,and triggers systemic vascular changes.Schistosomiasis exacerbates portal hypertension and inflammation,further injuring the liver.In non-cirrhotic portal hypertension,significant vascular resistance occurs,but preserved liver function mitigates systemic effects.In contrast,cirrhosis amplifies hypoxia,worsens pulmonary shunting,and predisposes patients to respiratory failure,infection,and death.In a retrospective study of 113 patients,Rolim et al found that cirrhosis had an impact on mortality,yet the presence of HPS did not significantly affect survival.While cirrhosis worsening outcomes are anticipated,HPS should theoretically worsen survival by impairing oxygenation.Early diagnosis,parasite control,and managing cirrhosis-related complications are critical for schistosomiasis-related liver disease.Understanding these differences underscores the importance of integrating liver health into global schistosomiasis management strategies.
基金supported by national natural science foundation of China(32001794)awarded to Dr.Ye Peng。
文摘Food contaminants,particularly insecticides,are important factors contributing to obesity and other adverse effects.As the most widely used diamide insecticide worldwide,chlorantraniliprole(CP)is ubiquitous in food and the environment.However,the influence of CP on obesity and the gut microbiota remains unknown.In this study,we administered CP/carboxymethyl cellulose sodium to C57BL/6J mice with a high-fat diet(HFD)via gavage for 13 weeks.The CP exposure induced significant increases in body weight gain,fat mass,serum total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C).Moreover,CP aggravated the imbalance in the gut microbiota by increasing the relative abundance of obesity-associated bacteria and reducing the relative abundance of beneficial bacteria.Based on untargeted metabolomics analysis,CP was found to be involved in the regulation of pathways including Alanine,aspartate and glutamate metabolism and Arginine and proline metabolism.Notably,CP exposure primarily induced alterations in microbial metabolites within these pathways,such as L-(+)-aspartic acid and L-glutamic acid.Additionally,individual metabolites,such as the lipid mediator(oleoyl ethanolamide),also demonstrated alterations upon CP exposure.Furthermore,Spearman correlation analysis revealed several noteworthy associations between microbial alterations,metabolite changes,and phenotypes.The results of the study demonstrate a connection between microbiota,metabolites,and the effects of CP exposure on HFD-induced obesity,elucidating the critical role of the gut microbiota and its metabolites in the toxic effects of CP.
文摘Metabolic dysfunction-associated steatohepatitis(MASH)has become a leading indication for liver transplantation.Bariatric surgery is a proven intervention for weight loss and metabolic improvement in MASH but concerns over surgical risk in patients with advanced liver disease has expanded interest in endoscopic sleeve gastroplasty(ESG)as a less invasive alternative.This review examine the efficacy,safety,and metabolic impact of ESG vs traditional bariatric surgery(Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy)in patients with MASH,with and without cirrhosis.We analyze current evidence on weight loss outcomes,histologic and biochemical improvements in MASH,resolution of metabolic syndrome,and perioperative risks associated with these procedures.Special attention is given to the feasibility of ESG in compensated cirrhosis(Child-Pugh A/B)and the potential role of bariatric interventions in delaying or avoiding liver transplantation.As the prevalence of MASH-related cirrhosis rises,refining bariatric strategies for this high-risk population is imperative.ESG may offer a lower procedural risk profile,but current data are largely limited to small,observational studies with short-term follow-up.A tailored,multidisciplinary approach is essential to optimize weight management and liver health in MASH patients,with future studies needed to clarify the long-term efficacy and safety of ESG in MASH.
文摘BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related deaths worldwide with an alarming rise in early-onset CRC(eoCRC)over the past several decades.Unlike late-onset CRC,the drivers behind eoCRC remain less clear.While certain risk factors such as obesity and smoking have demonstrated a relatively strong association with eoCRC in the literature,some studies have challenged these associations,emphasizing the need for additional studies.METHODS This cross-sectional study used de-identified data from the National Health and Nutrition Examination Survey(1999-2023),including 30321 United States adults aged 18 to 49 years.Participants with missing key variables were excluded.Standardized protocols were used to collect demographic,lifestyle,anthropo-metric[body mass index(BMI),body roundness index(BRI),waist circumference(WC)],and self-reported CRC data.Logistic regression and propensity score matching assessed associations between obesity-related parameters and eoCRC.Statistical analyses were performed in R and Stata,with P<0.05 defined as significant.RESULTS Of 30321 participants,48 received a diagnosis of eoCRC.Patients with eoCRC were older(mean age 39.96 years vs 34.36 years;P<0.001)and had higher WC and BRI.None of the eoCRC patients were heavy drinkers(P=0.006).Unadjusted models demonstrated significant associations of eoCRC with BRI quartiles,as well as BMI-defined obesity,WC,and smoking.In unadjusted models,BRI remained the strongest independent predictor;those in the highest BRI quartiles had over 10-fold greater odds of eoCRC.In fully adjusted models,BRI remained significant,but BMI-and waist-based obesity were not.CONCLUSION BRI is a stronger predictor of eoCRC risk compared to other obesity indices and is a superior tool for identifying young individuals at higher risk of CRC.
文摘Primary biliary cholangitis(PBC)is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction,leading to fibrosis,cirrhosis,and eventual liver failure.Over the past two decades,significant advancements have paved the way for novel therapeutic strategies.Ursodeoxycholic acid(UDCA)has been the cornerstone of PBC management,improving survival and delaying disease progression in most patients.However,up to 40%of patients demonstrate an inadequate response to UDCA,necessitating additional treatment options.Obeticholic acid(OCA),a farnesoid X receptor agonist,has emerged as a second-line therapy,showing efficacy in reducing alkaline phosphatase levels and improving liver biochemistry.Beyond UDCA and OCA,a new wave of therapeutic agents are reshaping the PBC landscape.These include fibrates,peroxisome proliferator-activated receptor agonists and novel immunomodulatory drugs aimed at reducing autoimmune-mediated liver injury.Bile acid transport inhibitors,anti-fibrotic agents,and gut microbiome-targeted therapies are also under investigation,offering hope for personalized treatment approaches.This review highlights the evolution of PBC therapy,emphasizing the unmet needs of patients with refractory disease and the potential of emerging therapies to improve outcomes.As the therapeutic landscape continues to expand,optimizing treatment strategies through precision medicine holds the promise of transforming the management of PBC.
文摘BACKGROUND Immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy but are associated with immune-related adverse events,including ICIs hepatitis.Mycophenolate mofetil(MMF)is often used as a second-line immunosuppressive agent for steroid-refractory cases.However,there is no standardized approach to MMF tapering,leading to uncertainties regarding relapse risk,optimal tapering strategies,and long-term outcomes.AIM To evaluate current evidence on MMF tapering in ICI hepatitis,focusing on strategies,clinical outcomes,and the risk of hepatitis recurrence.Additionally,we explore the feasibility of reintroducing ICI therapy after immunosuppression withdrawal.METHODS A comprehensive literature search was conducted in PubMed,EMBASE,and clinical trial registries to identify studies reporting MMF use and tapering strategies in ICI hepatitis.We extracted data from manuscripts including patient characteristics,MMF dosing regimens,tapering duration,relapse rates,and oncologic outcomes.Risk factors for recurrence and successful tapering were analyzed.RESULTS There was significant heterogeneity in the duration of MMF taper,which ranged from 4 weeks to greater than 6 months.The tapering schedules presented were individualized based on the severity of liver injury,patient response to treatment,and risk factors for relapse.We summarize current tapering approaches,including rapid vs slow withdrawal,predictors of successful tapering,and alternative immunosuppressive strategies.The impact of MMF duration on liver recovery,relapse risk,and cancer prognosis will be discussed.Evidence on ICI rechallenge post-taper will also be reviewed.CONCLUSION While MMF is effective in managing ICI hepatitis,tapering remains a clinical challenge with potential risks of hepatitis flare and disease progression.Standardized tapering protocols are needed to optimize immunosuppression while preserving anticancer efficacy.Future studies should focus on biomarker-driven tapering strategies and prospective trials to establish best practices.
文摘A thyroid storm(TS)or thyrotoxic crisis is an infrequent,life-threatening endocrinological emergency due to the worsening of the hyperthyroid state.Thyroid hormones(THs)influence almost all the body cells and tissues'differentiation,growth,and energy metabolism.Consequently,excess THs are expected to lead to profound organ function,regulation,and hemodynamic changes.In addition to their roles in metabolism and thermoregulation,THs play critical role in maintaining cardiovascular homeostasis through both genomic and non-genomic mechanisms.Receptors for THs are expressed in myocardial and vascular endothelial tissues,allowing fluctuations in circulating hormone levels to directly influence cardiovascular function.Excess TS induces a hyper-dynamic cardiovascular state,characterized by increased ventricular contractility and improved systolic and diastolic performance.The chronotropic and inotropic properties of THs result in dysregulation of blood pressure,heart rate,contractility,cardiac output,and systemic vascular resistance.This could lead to serious consequences such as cardiomyopathy,heart failure,and life-threatening arrhythmia,ultimately contributing to cardiocirculatory collapse and cardiac death.The management of TS necessitates a systematic approach that emphasizes the significance of resuscitation and identification of the underlying causes.It is crucial to prioritize assessing cardiac function in patients with TS.This review explores the clinical impact of TS on the heart and its clinical repercussions,emphasizing the intricate molecular and pathophysiological mechanisms and the interplay between TS and key cardiovascular parameters.This review summarizes the current knowledge of pathophysiology,pharmacological and mechanical interventions,ranging from beta-blocker use to the surgical approach.
文摘This editorial comment is on the article by Xu et al.It offers an in-depth analysis of liver function assessment tools and their prognostic roles in non-malignant liver diseases,with a focus on the albumin-bilirubin(ALBI)score.ALBI’s components,grading system,and clinical relevance across various liver conditions are reviewed and compared with traditional models such as the Child-Pugh and model for end-stage liver disease scores.We included recent studies evaluating ALBI’s role in estimating liver function,suggesting it may help differentiate patients who appear similar under other staging systems,and assist in guiding clinical decisions.Although ALBI is primarily used as an indicator of hepatic reservoir in hepatocellular carcinoma,it has been demonstrated a positive correlation with overall survival,tumor recurrence,and post-hepatectomy liver failure in patients undergoing potentially curative treatments such as liver resection,liver transplantation,and local ablation.Moreover,several studies suggest that ALBI can also predict survival outcomes,treatment-related toxicity,and liver-related complications in patients receiving trans-arterial chemoembolization,radioembolization,external-beam radiotherapy,or systemic therapies.Its growing use in nonmalignant liver diseases,including primary biliary cholangitis,cirrhosis,acute and chronic liver failure,and viral hepatitis highlights the need for large,prospective studies.Further studies are warranted to validate the integration of ALBI into routine clinical practice and to clarify its role in guiding prognosis and treatment planning.
