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Growing evidences have confirmed the effect of Sacubitril/Valsartan (SV) on antihypertension and cardiac protection in general population. However, there was no prospective study about the effect and safety of SV on resistant hypertension and myocardial work in hemodialysis patients. In this single‐center, prospective, before‐after study, enrolled patients were endured with resistant hypertension for more than 6 months. Participants were initially instructed to take SV 50 mg twice daily, and the dosage was gradually increased up to 100 mg twice daily. The primary outcomes were blood pressure (BP) control, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), myocardial work (MW), fatigue and life quality. In addition, the adverse events were also recorded in this cohort. A total of 18 patients (34–64 years old) was finally enrolled and completed in this study. The SV‐based regimen provided significantly mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (‐20.7/‐8.3 mm Hg), respectively. The cardiac remodeling parameters were partially improved. Compared to the baseline, NT‐proBNP was significantly reduced at week 4 (8119.50 [3710.75, 29300] pg/ml to 7216.50 [4124.75, 17455.00] pg/ml, p = .046), which was much lower at week 12 (3130.50 [2244.50, 9565.70] pg/ml, p = .037). Global MW index was higher at week 12 compared to the baseline (p = .026). MW efficiency was also improved accordingly compared to the baseline, even though the statistical difference was not significant (p = .226). Life quality and fatigue were improved at week 12 compared to the baseline (all p = .000). There was no serious adverse events were observed. SV safely and effectively controlled resistant hypertension and improved MW as well as life quality in hemodialysis patients.

Thermal dynamics in cylindrical Li-ion batteries, governed by electrochemical heat generation, are critical to performance and safety in high-power applications such as electric vehicles and grid storage. Building on our previous work, which introduced and validated both single-layer and multi-layer models, this study focuses exclusively on experimentally validating the multi-layer formulation under a broader range of ambient temperatures. The proposed multi-layer model captures temperature evolution across all internal components, including the electrolyte, electrodes, current collectors, and casing, accurately resolving spatial heat accumulation. Experimental validation is conducted across four temperatures (21 C, 0 C, 40 C, and − 10 C), demonstrating strong agreement and highlighting the model’s robustness. These results offer actionable insights into internal thermal behavior and may support the design of advanced thermal management strategies, contributing to the development of safer and more efficient Li-ion batteries for next-generation energy storage systems.

In answer to the growing demands for temperature-related engineering applications in marine geotechnical engineering, this article explores the effect of temperature on the drained shear behavior of calcareous sand. Sixteen drained triaxial shear tests were therefore performed on calcareous sand under various temperatures, and in addition, a further eight were carried out on Fujian standard quartz sand by way of comparison. The results showed that an increase in temperature aggravated the particle breakage of calcareous sand in shear. Increasing the temperature improved the strength and dilatancy of quartz sand but weakened them in calcareous sand. This aggravation of particle breakage at high temperature seems to be one of the main reasons behind the decrease in the strength and dilatancy of calcareous sand. Increasing the temperature led to a decrease in the peak-state friction angle φps, the maximum dilatancy angle ψps, the critical-state friction angle φcs and the critical-state void ratio of calcareous sand. A stress-dilatancy equation for the impairment of the stress-dilatancy behavior caused by increasing the temperature was proposed for calcareous sand, and an empirical model for estimating φcs was then put forward. An increase in the temperature caused the increase in relative particle breakage Br of calcareous sand. φps and ψmax decreased with Br as a negative correlation power function. Additionally, the effect of particle breakage on φcs had a correlation with the stress state. This study may be helpful in reducing the deterioration of structural stability in projects with an inadequate design due to the lack of a full understanding of the effect of temperature on calcareous sand.

Background Chronic obstructive pulmonary disease (COPD) complicated by atrial fibrillation (AF) in ICU patients is associated with higher risks of adverse outcomes. The red cell distribution width to albumin ratio (RAR), may predict mortality in critical illness, yet its link to 28-day mortality in ICU patients with COPD and AF remains unclear. Methods This retrospective cohort study analyzed 693 ICU patients with COPD and AF from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, grouped by RAR tertiles. The primary endpoint was 28-day mortality, with secondary endpoints including 90-day, 365-day, and ICU mortality. Multivariate cox models estimated hazard ratios (HRs) for mortality, while restricted cubic spline regression assessed the linearity of the RAR-mortality relationship. Kaplan-Meier curves compared survival across tertiles, and subgroup analyses explored RAR’s impact across age, gender, race, and comorbidities. Results Our study included 693 ICU patients with both COPD and AF, with an average age of 74.9 years. The 28-day mortality was 30.7%. Patients in the highest RAR tertile had significantly worse 28-day survival ( p  < 0.0001). Higher RAR was linearly associated with increased 28-day mortality ( p for non-linearity > 0.05), with each 1-unit increase in RAR linked to an 18% rise in mortality risk (95% CI: 1.08–1.29). Sensitivity analyses confirmed RAR’s relevance for 90-day, 365-day, and ICU mortality. Conclusions RAR is independently associated with 28-day mortality in COPD patients with AF. Elevated RAR levels correlate with higher 28-day mortality rates in this population. Clinical trial number Not applicable.

Recent advances in bladder cancer immunotherapy have shown promise, particularly in addressing limitations of the current gold standard, Bacillus Calmette-Guérin (BCG). Novel combinations, such as sasanlimab (a PD-1 monoclonal antibody) with BCG, have improved event-free survival in high-risk non-muscle-invasive bladder cancer (NMIBC). Intravesical anti-PD-1/PD-L1 agents like pembrolizumab and nadofaragene firadenovec have demonstrated efficacy and safety in BCG-unresponsive NMIBC, leading to regulatory approval. Additionally, BCG combined with immunostimulatory protein complexes (e.g., N-803) achieved high complete response rates while preserving quality of life. For muscle-invasive bladder cancer (MIBC) patients ineligible for cisplatin, neoadjuvant immunotherapy trials are exploring anti-PD-1/PD-L1 monotherapy or combinations with anti-CTLA-4 antibodies. The Pandore trial highlights the role of mucosal immunity in predicting response to systemic immune checkpoint inhibitors. Promising results have also been observed with intravesical oncolytic immunotherapy combined with systemic anti-PD-1 therapy in cisplatin-ineligible MIBC. These advancements underscore the potential of intravesical and systemic immunotherapies to improve bladder cancer outcomes and warrant further investigation.

Hydrogen energy from solar water-splitting is known as an ideal method with which to address the energy crisis and global environmental pollution. Herein, the first-principles calculations are carried out to study the photocatalytic water-splitting performance of single-layer GaInSe3 under biaxial strains from −2% to +2%. Calculations reveal that single-layer GaInSe3 under various biaxial strains has electronic bandgaps ranging from 1.11 to 1.28 eV under biaxial strain from −2% to +2%, as well as a completely separated valence band maximum and conduction band minimum. Meanwhile, the appropriate band edges for water-splitting and visible optical absorption up to ~3 × 105 cm−1 are obtained under biaxial strains from −2% to 0%. More impressively, the solar conversion efficiency of single-layer GaInSe3 under biaxial strains from −2% to 0% reaches over 30%. The OER of unstrained single-layer GaInSe3 can proceed without co-catalysts. These demonstrate that single-layer GaInSe3 is a viable material for solar water-splitting.

Liver fibrosis is a major cause of liver failure, but treatment remains ineffective. In the present study, we investigated the mechanisms and anti-hepatofibrotic activities of asiatic acid (AA) in a rat model of liver fibrosis induced by carbon tetrachloride (CCl(4)) and in vitro in TGF-beta1-stimulated rat hepatic stellate cell line (HSC-T6). Treatment with AA significantly attenuated CCl(4)-induced liver fibrosis and functional impairment in a dosage-dependent manner, including blockade of the activation of HSC as determined by inhibiting de novo alpha smooth muscle actin (a-SMA) and collagen matrix expression, and an increase in ALT and AST (all p<0.01). The hepatoprotective effects of AA on fibrosis were associated with upregulation of hepatic Smad7, an inhibitor of TGF-beta signaling, thereby blocking upregulation of TGF-beta1 and CTGF and the activation of TGF-beta/Smad signaling. The anti-fibrosis activity and mechanisms of AA were further detected in vitro in HSC-T6. Addition of AA significantly induced Smad7 expression by HSC-T6 cells, thereby inhibiting TGF-beta1-induced Smad2/3 activation, myofibroblast transformation, and collagen matrix expression in a dosage-dependent manner. In contrast, knockdown of Smad7 in HSC-T6 cells prevented AA-induced inhibition of HSC-T6 cell activation and fibrosis in response to TGF-beta1, revealing an essential role for Smad7 in AA-induced anti-fibrotic activities during liver fibrosis in vivo and in vitro. In conclusion, AA may be a novel therapeutic agent for liver fibrosis. Induction of Smad7-dependent inhibition of TGF-beta/Smad-mediated fibrogenesis may be a central mechanism by which AA protects liver from injury.

The composition of waste-activated sludge (WAS) is complex, containing a large amount of harmful substances, which pose a threat to the environment and human health. The reduction and resource utilization of sludge has become a development demand in sludge treatment and disposal. Based on the technical bottlenecks in the practical application of direct anaerobic digestion technology, this study adopted two different thermal and thermal–alkali hydrolysis technologies to pretreat sludge. A pilot-scale experiment was conducted to investigate the experimental conditions, parameters, and effects of two hydrolysis technologies. This study showed that the optimal hydrolysis temperature was 70 °C, the hydrolysis effect and pH can reach equilibrium with the hydrolysis retention time was 4–8 h, and the optimal alkali concentration range was 0.0125–0.015 kg NaOH/kg dry-sludge. Thermal–alkali combination treatment greatly improved the performance of methane production, the addition of NaOH increased methane yield by 31.2% than that of 70 °C thermal hydrolysis. The average energy consumption is 75 kWh/m3 80% water-content sludge during the experiment. This study provides a better pretreatment strategy for exploring efficient anaerobic digestion treatment technologies suitable for southern characteristic sewage sludge.

Lobeline is an alkaloid derived from the leaves of an Indian tobacco plant (Lobelia inflata), which has been prepared by chemical synthesis. It is classified as a partial nicotinic agonist and has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. The presence of both cis and trans isomers in lobeline is well known, and many studies on the relationship between the structure and pharmacological activity of lobeline and its analogs have been reported. However, it is a remarkable fact that no studies have reported the differences in pharmacological activities between the two isomers. In this article, we found that different degrees of isomerization of lobeline injection have significant differences in respiratory excitatory effects in pentobarbital sodium anesthetized rats. Compared with cis-lobeline injections, the respiratory excitatory effect was significantly reduced by 50.2% after administration of injections which contained 36.9% trans-lobeline. The study on the influencing factors of isomerization between two isomers shown that this isomerization was a one-way isomerism and only converted from cis to trans, where temperature was the catalytic factor and pH was the key factor. This study reports a new discovery. Despite the widespread use of ventilators, first-aid medicines such as nikethamide and lobeline has retired to second line, but as a nonselective antagonist with high affinity for a4b2 and a3b2 nicotinic acetylcholine receptors (nAChRs). In recent years, lobeline has shown great promise as a therapeutic drug for mental addiction and nervous system disorders, such as depression, Alzheimer disease and Parkinson disease. Therefore, we suggest that the differences between two isomers should be concerned in subsequent research papers and applications.