Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.

Change in Functional Status from Preoperative to One Year Postoperative in Patients Who Have Undergone Elective Open-Heart Surgery: A Repeated-Measures Study

Purpose: Although patient-related factors affect surgical outcomes, preoperative functional status is not measured by any cardiac risk score. Functional status can, however, be objectively measured using validated outcome tools such as the Late-Life Function and Disability Instrument (LLFDI). The purpose of this study was to determine 1) if there was a change over time in functional status, as measured by the LLFDI, in patients who underwent elective cardiac surgery, and if so, 2) what specific aspect(s) of functional status changed. Methods: A prospective longitudinal study of one year was conducted on elective cardiac surgery patients (n = 43) using the self-reported LLFDI, which measures Disability Frequency (frequency of participation in social tasks), Disability Limitation (ability to participate in social tasks) and Function Total (ease in performing routine activities). Higher scores indicate increased function and decreased disability. LLFDI scores were compared at three times (preoperative, six-week and one-year postoperative) using repeated measures ANOVA. Post hoc pairwise comparison was conducted for specific interactions. Results: Both Function Total and Disability Frequency significantly changed over time (p = 0.047 and p = 0.013, respectively). Specifically, patients’ function level was significantly higher one-year postoperative compared to preoperative (M difference = +3.48, SE = 1.48, p = 0.026). Likewise, Disability Frequency scores were significantly higher (i.e. more active) at one-year postoperative versus preoperative (M difference= +5.98, SE = 2.19, p = 0.033). Disability Limitation scores were not significantly different between any time points (p > 0.05). Conclusion: By one-year postoperative, patients demonstrated increased ease in their routine physical activities and were more participatory in social life tasks. Individuals who underwent elective cardiac surgery took more than six weeks to detect notable improvement in functional status, which was expected with a sternotomy approach. This study provides support for the use of the LLFDI as an effective tool to capture functional status in the cardiac population. These findings may assist cardiac patients in recovery timeline expectations.

Kill two birds with one stone:Hapatologist’s approach to metabolic dysfunction-associated steatotic liver disease and heart failure

Heart failure(HF)is a major global public health concern,and one of the less commonly known risk factors for HF development is metabolic dysfunction-associated steatotic liver disease(MASLD),as they share a similar pathophysio-logical background.In this article,we evaluated a recently published review article by Arriola-Montenegro et al.This article briefly summarizes the common pathophysiology of HF and MASLD development and evaluates the available therapeutic options to treat both conditions.Clinical practice guidelines highlight the importance of initiating and titrating guideline-directed medication therapy(GDMT)for patients with HF with reduced ejection fraction.GDMT is comprised of the four pillars currently proposed in most clinical practice guidelines,namely angiotensin-converting enzyme inhibitors(ACEIs),angiotensin receptor blockers(ARBs),angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocor-ticoid receptor antagonists,and sodium-glucose co-transporter 2 inhibitors(SGLT-2i).Given the similarity of pathophysiology and risk factors,recent studies for GDMT regarding ACEIs,ARBs,mineralocorticoid receptor antagonists,and SGLT-2i have shown beneficial effects on MASLD.Nonetheless,other medications for both conditions and novel therapies require more robust data and well-designed clinical studies to demonstrate their efficacies in both conditions.

Exercise as a modality to improve heart transplantation-related functional impairments: An article review

Heart transplantation(HT),the treatment choice of advanced heart failure pa-tients,is proven effective in increasing the survival and functional status of the recipients.However,compared to normal controls,functional status is lower in HT recipients.Exercise given in cardiac rehabilitation has been shown to improve exercise capacity as measured with peak oxygen uptake(VO2 peak)and muscle strength after completion of the program and cessation of exercise results in loss of exercise benefits.Several factors related to cardiac denervation and the use of immunosuppressive agents in HT recipients result in functional impairments including cardiovascular,pulmonary,exercise capacity,psychological,and qua-lity of life(QoL)problems.High-intensity interval training(HIIT)is the most common type of exercise used in HT recipients and given as a hospital-based program.Improvement of functional impairments was found to have occurred due to primarily musculoskeletal adaptations through improvement of muscle structure and aerobic capacity and cardiovascular adaptations.In general,exercise given after transplantation improved VO2 peak significantly and improvement was better in the HIIT group compared to moderate intensity continuous training or no-exercise groups.Improvement of QoL was ascribed to improve-ment of exercise capacity,symptoms,pulmonary function,physical capacity improve-ment,anxiety,and depression.

Impact of continuous care on cardiac function in patients with lung cancer complicated by coronary heart disease

BACKGROUND Despite sharing similar pathogenic factors,cancer and coronary heart disease(CHD)occur in comparable populations at similar ages and possess similar susceptibility factors.Consequently,it is increasingly commonplace for patients to experience the simultaneous occurrence of cancer and CHD,a trend that is steadily rising.AIM To determine the impacts of continuing care on lung cancer patients with CHD following percutaneous coronary intervention(PCI).METHODS There were 94 lung cancer patients with CHD following PCI who were randomly assigned to the intervention group(n=38)and the control group(n=41).In the intervention group,continuing care was provided,while in the control group,routine care was provided.An evaluation of cardiac and pulmonary function,medication compliance,a 6-min walk test,and patient quality of life was performed.RESULTS Differences between the two groups were significant in left ventricular ejection fraction,6-min walk test,oxygen uptake,quality of life and medication compliance(P<0.05).In comparison with the control group,the enhancement in the intervention group was more significant.The intervention group had more patients with high medication compliance than the control group,with a statistically significant difference(P<0.05).CONCLUSION After undergoing PCI,lung patients with CHD could benefit from continued care in terms of cardiac and pulmonary function,medications compliance,and quality of life.

Analysis of Cardiac Functional Status and Factors Influencing Adverse Pregnancy Outcomes in Pregnant Women with Combined Heart Disease

Objective:To investigate the cardiac function of pregnant women with complicated heart disease during pregnancy and the factors influencing the adverse pregnancy outcome.Methods:A total of 162 cases of pregnant women with complicated heart disease admitted to the Beijing Anzhen Hospital from October 2021 to December 2023 were selected to compare the occurrence of adverse pregnancy outcomes in pregnant women with complicated heart disease at different levels of cardiac function and to analyze the single and multi factors leading to adverse pregnancy outcomes in pregnant women with complicated heart disease.Results:Among 162 pregnant women with combined heart disease in pregnancy,the highest percentage of heart disease type was congenital heart disease(80/49.38%),and the lowest percentage was other(9/5.56%);the overall incidence of adverse pregnancy outcomes in pregnant women with combined heart disease in pregnancy with cardiac function grades of 3–4 cardiac function(30/68.18%)was higher than that in pregnant women with combined heart disease in cardiac function grades of 1–2(40/33.90%)(P=0.000);age,marital status,hypertension,and past history of all pregnant women were not statistically significant(P>0.05);gestational age,type of heart disease,and cardiac function grading were statistically significant(P<0.05),and these factors were all independent risk factors for adverse pregnancy resolution in pregnant women with combined heart disease(P<0.05).Conclusion:The overall incidence of adverse pregnancy outcomes was higher in pregnant women with heart disease than in those with heart disease grades 1–2,and the number of pregnancies,the type of heart disease,and heart function grades were all independent risk factors for adverse pregnancy outcomes in pregnant women with heart disease.

Effectiveness of Atorvastatin Combined with Trimetazidine in the Treatment of Coronary Heart Disease in the Elderly and Their Effect on Cardiac Function

Objective:To analyze the effect of atorvastatin combined with trimetazidine in the treatment of elderly coronary artery disease and the effect on patients’cardiac function.Methods:60 cases of elderly coronary artery disease patients were divided into 2 groups by randomization method,and all of them received conventional symptomatic treatment,while atorvastatin was added to the control group and trimetazidine was combined with atorvastatin in the observation group,and the clinical indexes were compared.Results:After treatment,the angina attack,cardiac function indexes,and inflammatory factor levels of the observation group were better than those of the control group(P<0.05),and the differences in adverse reactions between the two groups were not significant(P>0.05).Conclusion:Combined treatment of coronary heart disease in the elderly with atorvastatin and trimetazidine can positively reduce angina symptoms,improve cardiac function,and reduce inflammatory reactions,and the effect is definite.

Clinical Study on the Effect of Continuity of Care in CICU on Improving Cognitive Function and Psychological State in Patients with Heart Failure

Objective:To analyze the effect of continuity of care in the cardiac intensive care unit(CICU)on improving cognitive function and psychological state in patients with heart failure(HF).Methods:A total of 112 chronic HF patients admitted to the CICU of Xuzhou Traditional Chinese Medicine Hospital from July 2022 to August 2024 were selected and randomly divided into two groups using the red and blue ball method:a control group(n=56)and a study group(n=56).The control group received routine CICU nursing management,while the study group received routine CICU nursing combined with continuity of care management.Cognitive function(using the Montreal Cognitive Assessment,MoCA),psychological state(using the Self-Rating Depression Scale,SDS,and Self-Rating Anxiety Scale,SAS),and quality of life(using the Minnesota Living with Heart Failure Questionnaire,MLHFQ)were compared between the two groups.Results:After the intervention,the cognitive function scores of the study group were significantly higher than those of the control group(P<0.05).The SDS and SAS scores of the study group were significantly lower than those of the control group after the intervention(P<0.05).The quality of life in the study group was also significantly better than in the control group(P<0.05).Conclusion:CICU continuity of care can effectively improve cognitive function and psychological state in patients with HF,while also enhancing their quality of life.

Mediating function of heart failure in the causal relationship between diastolic blood pressure and hypertensive renal disease with renal failure:a mediated Mendelian randomization study

Objective:To study the causality relationship between diastolic blood pressure(DBP)and hypertensive renal disease with renal failure(HRDRF)and the mediating role of hear t failure(HF)in the causality relationship by network Mendelian randomization(MR).Methods:Genome-wide analysis of DBP,HRDRF,and HF was downloaded from the public database(Genome-Wide Analysis Study[GWAS])and was used to analyze the results and to conduct mediated MR analysis.Results:Analysis showed that DBP was positively correlated with HRDRF(OR=1.0002,95%CI:1.0001–1.0003,P=1.8076e-05)and DBP was positively correlated with HF(OR=1.0295,95%CI:1.0221–1.0370,P=2.5292e-15).HF and HRDRF had a positive causal effect(OR=1.0001,95%CI:1.0000–1.0001,P=0.0152).Mediation analysis showed that the contribution ratio of HF to the combined effect of DBP and HRDRF was 24.69%.Conclusions:DBP can increase the risk of renal disease with renal failure,and HF may play an impor tant role in mediating this causal relationship.

Lyophilized recombinant human brain natriuretic peptide for chronic heart failure:Effects on cardiac function and inflammation

BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative treatments.Recombinant human brain natriuretic peptide(BNP)has emerged as a potential therapy,with evidence suggesting that it can improve cardiac function and reduce inflammation in patients with CHF.However,further research is required to determine the efficacy and safety of lyophilized recombinant human BNP in CHF patients and its impact on microinflammatory status.This study aimed to investigate the effects of lyophilized recombinant human BNP therapy on CHF patients’cardiac function and microinflammatory status.AIM To investigate the effects of freeze-dried recombinant human BNP therapy on cardiac function and microinflammatory status in patients with CHF.METHODS In total,102 CHF patients admitted to our hospital from January 2021 to January 2022 were randomly assigned to control and observation groups(n=51 patients/group).The control patients were treated with standard HF therapy for 3 d,whereas the observational patients were injected with the recombinant human BNP for 3 d.Clinical efficacy,inflammatory factor levels,myocardial damage,cardiac function before and after the treatment,and adverse reactions during treatment were compared between the two groups.RESULTS The overall clinical efficacy was higher in the observation group than in the control group.Compared with baseline,serum hypersensitive C-reactive protein,N-terminal proBNP,and troponin I level,and physical,emotional,social,and economic scores were lower in both groups after treatment,with greater reductions in levels and scores noted in the observation group than in the control group.The overall incidence of adverse reactions in the observation group was not significantly different compared with that in the control group(P>0.05).CONCLUSION Freeze-dried recombinant human BNP therapy can improve heart function and enhance microinflammatory status,thereby improving overall quality of life without any obvious side effects.This therapy is safe and reliable.

Skeletal muscle atrophy,regeneration,and dysfunction in heart failure:Impact of exercise training

This review highlights some established and some more contemporary mechanisms responsible for heart failure(HF)-induced skeletal muscle wasting and weakness.We first describe the effects of HF on the relationship between protein synthesis and degradation rates,which determine muscle mass,the involvement of the satellite cells for continual muscle regeneration,and changes in myofiber calcium homeostasis linked to contractile dysfunction.We then highlight key mechanistic effects of both aerobic and resistance exercise training on skeletal muscle in HF and outline its application as a beneficial treatment.Overall,HF causes multiple impairments related to autophagy,anabolic-catabolic signaling,satellite cell proliferation,and calcium homeostasis,which together promote fiber atrophy,contractile dysfunction,and impaired regeneration.Although both wasting and weakness are partly rescued by aerobic and resistance exercise training in HF,the effects of satellite cell dynamics remain poorly explored.

基于SHERPA和HEART的老年人车载信息系统界面设计研究

目的改善老年驾驶员对车载信息系统界面的使用体验。方法提出基于SHERPA(系统人为错误减少与预测方法)和HEART(人误评估与减少技术)的老年人车载信息系统界面设计研究方法。首先,成立焦点小组对评估界面进行SHERPA定性分析,绘制车载信息系统界面层次任务分析图,通过错误分类表定义错误类型;其次,运用HEART定量分析错误类型,设定差错诱发条件,确定各条件的影响评估比例,从而计算人误概率;最后,在此基础上,分析差错诱发条件,归纳差错发生原因,根据差错纠正措施进行设计改良,对改良界面进行结果验证。结论该方法可以有效发现与老年人车载信息系统界面显著相关的差错诱发条件,既可帮助设计师找到交互设计改良的重点,也可减少老年驾驶员对车载信息系统界面的误操作情况。

A Study on Enhancing Pancreatic Islet Function in Type 2 Diabetes and Coronary Heart Disease Patients with Liraglutide and Metformin Combination Therapy

Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 diabetes and coronary heart disease admitted from February 2022 to August 2023 were selected as research subjects.They were randomly assigned to either control or treatment groups,with 30 patients in each.The control group received metformin alone,while the treatment group received liraglutide in combination with metformin.Various indicators,including blood sugar levels,pancreatic islet function,and cardiac function between the two groups were compared.Results:The results of FPG,2hPG,HbA1c,HOMA-IR,NT-proBNP,and LVEDD in the treatment group were lower than those in the control group,whereas the values of FINS,HOMA-β,E/A,and LVEF in the treatment group were higher than those in the control group(P<0.05).Conclusion:The use of liraglutide in combination with metformin significantly benefits patients with type 2 diabetes and coronary heart disease.It leads to improved pancreatic islet function,better blood sugar control,and enhanced cardiac function.This combination therapy is recommended for clinical adoption.

Correlation between the Six-Minute Walk Test and Subjective Functional Class in Patients with Heart Failure

Introduction: The Six-Minute Walk Test (6MWT) is an inexpensive method to objectively evaluate physical capacity or limitation and stratify prognosis in patients with Heart Failure (HF). Since the clinical perception of symptoms may be adapted or compromised, regular evaluation from medical interviews often fails to determine functional classification. This study aimed to assess the correlation between New York Heart Association Functional Class (NYHA-FC) and the distance walked in the 6MWT. Methods: We conducted a cross-sectional observational study that included patients with HF with reduced ejection fraction followed up at an outpatient service of a teaching hospital, from August 2018 to April 2019. Patients in NYHA-FC I, II, or III were included. We compared NYHA-FC subjectively obtained during the consultation with the 6MWT performed after medical consultation, and the correlation between these two parameters was assessed. Results: The study included 70 patients with HF, 41 (58.6%) of whom were female. The mean age was 61.2 ± 12.7 years. The most prevalent etiologies were dilated idiopathic cardiomyopathy (35.7%) followed by ischemic cardiomyopathy (25.7%). The mean ejection fraction was 34.1% ± 9.8%. The average distance walked in the 6MWT by NYHA-FC I patients was 437.8 ± 95.8 meters, NYHA-FC II 360.1 ± 96.4, and NYHA-FC III 248.4 ± 98.3. Functional class measured by the 6MWT was different than that estimated by NYHA-FC in 34 patients (48.6%), 23 (32.9%) for a higher functional class and 11 (15.7%) for a lower one (p = 0.07). Pearson’s correlation coefficient between NYHA-FC and the 6MWT was -0.55. Conclusion: There was a moderate correlation between the subjective NYHA-FC and the 6MWT. The 6MWT revealed a different classification from NYHA-FC in almost half of the patients. Among those who presented discrepancies between methods, 6MWT reclassification towards a higher functional class was more common.

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

Effect of continuous nursing on treatment compliance and side effect management of coronary heart disease

BACKGROUND There are relatively few studies on continuing care of coronary heart disease(CHD),and its research value needs to be further clarified.AIM To investigate the effect of continuous nursing on treatment compliance and side effect management in patients with CHD.METHODS This is a retrospective study with patients from January 2021 to 2023.The study was divided into two groups with 30 participants in each group.Self-rating anxiety scale(SAS)and Self-rating depression scale(SDS)were used to assess patients'anxiety and depression,and medical coping questionnaire was used to assess patients'coping styles.The pelvic floor dysfunction questionnaire(PFDI-20)was used to assess the status of pelvic floor function,including bladder symptoms,intestinal symptoms,and pelvic symptoms.RESULTS SAS score decreased from 57.33±3.01before treatment to 41.33±3.42 after treatment,SDS score decreased from 50.40±1.45 to 39.47±1.57.The decrease of these two indexes was statistically significant(P<0.05).PFDI-20 scores decreased from the mean 16.83±1.72 before treatment to 10.47±1.3the mean after treatment,which was statistically significant(P<0.05).CONCLUSION The results of this study indicate that pioneering research in continuous care of CHD has a positive impact on improving patients'treatment compliance,reducing anxiety and depression levels,and improving coping styles and pelvic floor functional status.

An Assessment of Cardiovascular Functional Capacity of a Group of Chronic Heart Failure Patients Using the 6-Minute Walk Test in a Cameroonian Urban Setting

Background: Chronic heart failure is a public health problem worldwide. It has a high mortality rate and is accompanied by a decreased functional capacity and alteration of the quality of life. Objective: This study aimed to assess the cardiovascular functional capacity of a group of patients suffering from heart failure using the 6-minute walk test (6 MWT). Methods: This was a cross-sectional study carried out in the cardiology unit of Douala’s general hospital for 4 months. We included all eligible patients aged 18 years or more who had stable chronic heart failure and gave informed consent. Those who had an acute coronary syndrome (≤1 month), tachycardia (HR ≥ 120 bpm), high blood pressure (SBP ≥ 180 mmHg and/or DBP ≥ 100 mmHg) and reduced mobility due to orthopaedic reasons were excluded. A 6 MWT was done according to the American Thoracic Society guidelines. The 6 MWT result was considered poor for - 450 m and good for >450 m. Results: We recruited a total of 81 patients (61.7% women) with a mean age of 65.9 ± 10.6 years. The most frequent risk factor for heart failure was high blood pressure (77.8%), alcohol consumption(69.1%) and a sedentary lifestyle (53.1%). The left ventricular ejection fraction was mostly preserved (42.0%) or mildly altered (46.9). The 6 MWT results were poor in 55.6% of cases, average in 19.8% of cases and good in only 24.7% of cases. More than half (59.3%) of the participants perceived the effort as being difficult. The cardiovascular functional capacity was significantly associated with age, heart failure stage and physical activity (p Conclusion: Most patients suffering from chronic stable heart failure in the general hospital of Douala have poor cardiovascular functional capacity.

Combining stochastic density functional theory with deep potential molecular dynamics to study warm dense matter

In traditional finite-temperature Kohn–Sham density functional theory(KSDFT),the partial occupation of a large number of high-energy KS eigenstates restricts the use of first-principles molecular dynamics methods at extremely high temperatures.However,stochastic density functional theory(SDFT)can overcome this limitation.Recently,SDFT and the related mixed stochastic–deterministic density functional theory,based on a plane-wave basis set,have been implemented in the first-principles electronic structure software ABACUS[Q.Liu and M.Chen,Phys.Rev.B 106,125132(2022)].In this study,we combine SDFT with the Born–Oppenheimer molecular dynamics method to investigate systems with temperatures ranging from a few tens of eV to 1000 eV.Importantly,we train machine-learning-based interatomic models using the SDFT data and employ these deep potential models to simulate large-scale systems with long trajectories.Subsequently,we compute and analyze the structural properties,dynamic properties,and transport coefficients of warm dense matter.

Tailoring MXene Thickness and Functionalization for Enhanced Room‑Temperature Trace NO_(2) Sensing

In this study,precise control over the thickness and termination of Ti3C2TX MXene flakes is achieved to enhance their electrical properties,environmental stability,and gas-sensing performance.Utilizing a hybrid method involving high-pressure processing,stirring,and immiscible solutions,sub-100 nm MXene flake thickness is achieved within the MXene film on the Si-wafer.Functionalization control is achieved by defunctionalizing MXene at 650℃ under vacuum and H2 gas in a CVD furnace,followed by refunctionalization with iodine and bromine vaporization from a bubbler attached to the CVD.Notably,the introduction of iodine,which has a larger atomic size,lower electronegativity,reduce shielding effect,and lower hydrophilicity(contact angle:99°),profoundly affecting MXene.It improves the surface area(36.2 cm^(2) g^(-1)),oxidation stability in aqueous/ambient environments(21 days/80 days),and film conductivity(749 S m^(-1)).Additionally,it significantly enhances the gas-sensing performance,including the sensitivity(0.1119Ωppm^(-1)),response(0.2% and 23%to 50 ppb and 200 ppm NO_(2)),and response/recovery times(90/100 s).The reduced shielding effect of the–I-terminals and the metallic characteristics of MXene enhance the selectivity of I-MXene toward NO2.This approach paves the way for the development of stable and high-performance gas-sensing two-dimensional materials with promising prospects for future studies.

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.