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With excellent creep resistance, good high-temperature microstructural stability and good irradiation resistance, oxide dispersion strengthened (ODS) alloys are a class of important alloys that are promising for high-temperature applications. However, plagued by a nerve-wracking fact that the oxide particles tend to aggregate at grain boundary of metal matrix, their improvement effect on the mechanical properties of metal matrix tends to be limited. In this work, we employ a unique in-house synthesized oxide@W core-shell nanopowder as precursor to prepare W-based ODS alloy. After low-temperature sintering and high-energy-rate forging, high-density oxide nanoparticles are dispersed homogeneously within W grains in the prepared alloy, accompanying with the intergranular oxide particles completely disappearing. As a result, our prepared alloy achieves a great enhancement of strength and ductility at room temperature. Our strategy using core-shell powder as precursor to prepare high-performance ODS alloy has potential to be applied to other dispersion-strengthened alloy systems. Aggregation and coarsening of the second-phase oxide particles at grain boundaries have been a bottleneck for improving mechanical properties of oxide-dispersion-strengthened (ODS) alloys. Here the authors employ core-shell nanopowder precursors to achieve uniform dispersion of oxides in ODS alloys.

Excessive fibrogenic response in the liver disrupts normal hepatic anatomy and function heralding such end-stage liver diseases as hepatocellular carcinoma and cirrhosis. Sinusoidal endothelial cells contribute to myofibroblast activation and liver fibrosis by undergoing endothelial-mesenchymal transition (EndMT). The underlying mechanism remains poorly defined. Here we report that inhibition or endothelial-specific deletion of MKL1, a transcriptional modulator, attenuated liver fibrosis in mice. MKL1 inhibition or deletion suppressed EndMT induced by TGF-β. Mechanistically, MKL1 was recruited to the promoter region of TWIST1, a master regulator of EndMT, and activated TWIST1 transcription in a STAT3-dependent manner. A small-molecule STAT3 inhibitor (C188-9) alleviated EndMT in cultured cells and bile duct ligation (BDL) induced liver fibrosis in mice. Finally, direct inhibition of TWIST1 by a small-molecule compound harmine was paralleled by blockade of EndMT in cultured cells and liver fibrosis in mice. In conclusion, our data unveil a novel mechanism underlying EndMT and liver fibrosis and highlight the possibility of targeting the STAT3-MKL1-TWIST1 axis in the intervention of aberrant liver fibrogenesis.

Background Semaglutide has demonstrated potential in controlling hyperglycemia and lowering cardiovascular (CV) risk. However, its impact on arrhythmic, major CV, and renal outcomes is not well-defined. This systematic review and meta-analysis aimed to assess these effects in patients with overweight or obesity. Methods We searched the PubMed, Embase, and Cochrane databases for eligible randomized controlled trials (RCTs) reported up to January 2025. We calculated overall relative risks (RRs) with 95% confidence intervals (CIs) for these outcomes. In addition, subgroup analyses were performed based on age, treatment duration and obesity level. Results Ten RCTs involving 22,937 patients were included. Compared with the controls, semaglutide significantly reduced the risk of atrial fibrillation (AF) (RR 0.79, 95% CI 0.63–0.99), sinus node dysfunction (RR 0.43, 95% CI 0.19–1.00), acute myocardial infarction (RR 0.72, 95% CI 0.60–0.85), and angina pectoris (RR 0.77, 95% CI 0.61–0.98). Subgroup analyses revealed greater efficacy in patients over 60 years old and those treated for more than 52 weeks, especially for acute myocardial infarction, angina pectoris, and acute kidney injury. Conclusion Semaglutide reduces the risk of AF, sinus node dysfunction, acute myocardial infarction, and angina pectoris in patients with overweight or obesity. However, its effects on other arrhythmic, CV, and renal outcomes remain uncertain.

Oxide dispersion strengthened (ODS) steels with different contents of zirconium (denoted as 16Cr ODS, 16Cr-0.3Zr ODS and 16Cr-0.6Zr ODS) were fabricated to investigate the effects of Zr on strengthening mechanism of Al-alloyed 16Cr ODS steel. Electron backscatter diffraction (EBSD) results show that the mean grain size of ODS steels could be decreased by Zr addition. Transmission electron microscope (TEM) results indicate that Zr addition could increase the number density but decrease the mean diameter and inter-particle spacing of oxide particles. Furthermore, it is also found that in addition to Y-Al-O nanoparticles, Y-Zr-O oxides with finer size were observed in 16Cr-0.3Zr ODS and 16Cr-0.6Zr ODS steels. These changes in microstructure significantly increase the yield strength (YS) and ultimate tensile strength (UTS) of ODS steels through mechanisms of grain boundary strengthening and dispersion strengthening.

Macrophage-dependent inflammatory response is considered a pivotal biological process that contributes to a host of diseases when aberrantly activated. The underlying epigenetic mechanism is not completely understood. We report here that MKL1 was both sufficient and necessary for p65-dependent pro-inflammatory transcriptional program in immortalized macrophages, in primary human and mouse macrophages, and in an animal model of systemic inflammation (endotoxic shock). Extensive chromatin immunoprecipitation (ChIP) profiling and ChIP-seq analyses revealed that MKL1 deficiency erased key histone modifications synonymous with transactivation on p65 target promoters. Specifically, MKL1 defined histone H3K4 trimethylation landscape for NF-κB dependent transcription. MKL1 recruited an H3K4 trimethyltransferase SET1 to the promoter regions of p65 target genes. There, our work has identified a novel modifier of p65-dependent pro-inflammatory transcription, which may serve as potential therapeutic targets in treating inflammation related diseases.

Plastic pollution has become a global concern, and research has shown that carbon emissions during the lifecycle of plastics are rapidly consuming global carbon credits. This study focuses on the effective assessment of carbon emissions from polyvinyl chloride (PVC) plastics using a life cycle assessment (LCA) method during the production and recycling stages. The greenhouse gas emission potential is evaluated using 1kg PVC plastic as a functional unit. Research has shown that the total carbon emissions during the production stage of PVC plastic are 7.83kg CO 2-eq . The carbon emissions during the production stage of hydrochloric acid, acetylene, electricity, and water vapor are 2.340 kg CO 2-eq , 4.900 kg CO 2-eq , 0.117 kg CO 2-eq , and 0.468 kg CO 2-eq , respectively. During the recycling phase, the carbon emissions from the power consumption zone are 0.184 kg CO 2-eq , followed by 0.156 kg CO 2-eq from natural gas. Research has shown that fossil materials contribute the largest carbon emissions during the production stage of PVC plastics. Therefore, how to effectively reduce the use of fossil fuels or seek alternative raw materials can effectively reduce carbon emissions.

Background The efficacy of antenatal corticosteroids (ACS) in late-preterm birth remains uncertain, with benefits of repeated courses not well established. The aim of this study was to assess real-world effectiveness of antenatal dexamethasone in late-preterm births and identify optimal dosing, timing, and beneficiary subgroups. Methods This retrospective cohort study utilized data from all deliveries occurring between January 1, 2018, and June 30, 2025 at a Chinese tertiary center. 3,703 individuals with singleton or multiple gestations who delivered during the late preterm period were included. The primary outcome was the incidence of neonatal respiratory distress syndrome (RDS, defined as requiring clinical signs, radiography, ≥ 24-hour persistence, and respiratory support or oxygen). The association between antenatal dexamethasone exposure and pregnancy outcomes was evaluated using propensity score matching (PSM) to balance baseline characteristics, and multivariate logistic regression to adjust for potential confounders. Results Of 3,703 eligible late-preterm births, 1,279 (34.5%; mean [standard deviation] maternal age, 30.6 [4.0] years) were exposed to ACS. After PSM ( n  = 820 per group), ACS showed no significant association with neonatal RDS [OR (odds ratio) 0.97; 95% CI (confidence interval): 0.70–1.35; P  = 0.867] but was associated with an increased risk of neonatal hypoglycemia (OR 1.49; 95% CI: 1.17–1.91; P  = 0.011). Administration of a complete course 36 h to 7 days before delivery was associated with a reduced risk of RDS (OR 0.44; 95% CI: 0.24–0.80; P  = 0.008). Repeated courses were also associated with reduced RDS risk (OR 0.40; 95% CI: 0.18–0.90; P  = 0.026) but with an increased risk of hypoglycemia (OR 2.93; 95% CI: 1.56–5.49; P  = 0.001). In singletons, treatment prevented 24 RDS cases per 1000 but resulted in 26 additional chorioamnionitis and 110 hypoglycemia cases. No benefit was observed in twins. The relative excess risk due to interaction test was − 1.08 (95% CI: -3.91, 0.23), suggesting a potential non-significant antagonistic interaction between ACS and twin pregnancy. Conclusions Among late-preterm births, ACS exposure was associated with a reduction in neonatal RDS for singleton pregnancies when administered in optimally timed or repeated courses; however, it was also associated with an increased risk of neonatal hypoglycemia. In twin pregnancies delivering late-preterm, no significant respiratory benefit was observed. These findings highlight that both treatment timing and pregnancy type are critical considerations when administering ACS.

Diallyl trisulfide (DATS) protects against apoptosis during myocardial ischemia-reperfusion (MI/R) injury in diabetic state, although the underlying mechanisms remain poorly defined. Previously, we and others demonstrated that silent information regulator 1 (SIRT1) activation inhibited oxidative stress and endoplasmic reticulum (ER) stress during MI/R injury. We hypothesize that DATS reduces diabetic MI/R injury by activating SIRT1 signaling. Streptozotocin (STZ)-induced type 1 diabetic rats were subjected to MI/R surgery with or without perioperative administration of DATS (40 mg/kg). We found that DATS treatment markedly improved left ventricular systolic pressure and the first derivative of left ventricular pressure, reduced myocardial infarct size as well as serum creatine kinase and lactate dehydrogenase activities. Furthermore, the myocardial apoptosis was also suppressed by DATS as evidenced by reduced apoptotic index and cleaved caspase-3 expression. However, these effects were abolished by EX527 (the inhibitor of SIRT1 signaling, 5 mg/kg). We further found that DATS effectively upregulated SIRT1 expression and its nuclear distribution. Additionally, PERK/eIF2α/ATF4/CHOP-mediated ER stress-induced apoptosis was suppressed by DATS treatment. Moreover, DATS significantly activated Nrf-2/HO-1 antioxidant signaling pathway, thus reducing Nox-2/4 expressions. However, the ameliorative effects of DATS on oxidative stress and ER stress-mediated myocardial apoptosis were inhibited by EX527 administration. Taken together, these data suggest that perioperative DATS treatment effectively ameliorates MI/R injury in type 1 diabetic setting by enhancing cardiac SIRT1 signaling. SIRT1 activation not only upregulated Nrf-2/HO-1-mediated antioxidant signaling pathway but also suppressed PERK/eIF2α/ATF4/CHOP-mediated ER stress level, thus reducing myocardial apoptosis and eventually preserving cardiac function.

Mesenchymal stem cells (MSCs) show protective effects on ischemia/reperfusion- (I/R-) induced endothelial cell (EC) injury and vascular damage. Stem cell-released exosomes (EXs) could modulate target cell functions by delivering their cargos, and exert therapeutic effects as their mother cells. miR-126 is an important regulator of EC functions and angiogenesis. In this study, we determined whether EXs released from MSC-EXs provided beneficial effects on hypoxia/reoxygenation- (H/R-) injured ECs by transferring miR-126. MSCs were transfected with a miR-126 mimic or miR-126 short hairpin RNA to obtain miR-126-overexpressing MSC-EXs (MSC-EXsmiR-126) and miR-126 knockdown MSC-EXs (MSC-EXsSimiR-126). For functional studies, H/R-injured ECs were coincubated with various MSC-EXs. The viability, migration, tube formation ability, and apoptosis of ECs were measured. miR-126 and proangiogenic/growth factor (VEGF, EGF, PDGF, and bFGF) expressions were detected by qRT-PCR. Akt, p-Akt, p-eNOS, and cleaved caspase-3 expressions were examined by western blot. The PI3K inhibitor (LY294002) was used in pathway analysis. We found that overexpression/knockdown of miR-126 increased/decreased the proliferation of MSCs, as well as miR-126 expression in their derived MSC-EXs. MSC-EXsmiR-126 were more effective in promoting proliferation, migration, and tube formation ability of H/R-injured ECs than MSC-EXs. These effects were associated with the increase in p-Akt/Akt and p-eNOS, which could be abolished by LY294002. Besides, MSC-EXsmiR-126 were more effective than MSC-EXs in reducing the apoptosis of ECs, coupled with the decrease in cleaved caspase-3. Moreover, compared to MSC-EXs, MSC-EXsmiR-126 significantly upregulated the level of VEGF, EGF, PDGF, and bFGF in H/R-injured ECs. Downregulation of miR-126 in MSC-EXs inhibited these effects of MSC-EXs. The results suggest that MSC-EXs could enhance the survival and angiogenic function of H/R-injured ECs via delivering miR-126 to ECs and subsequently activate the PI3K/Akt/eNOS pathway, decrease cleaved caspase-3 expression, and increase angiogenic and growth factors.

Two oxide-dispersion-strengthened (ODS) steels with different compositions (14Cr-ODS and 14Cr-Zr-ODS) were investigated to reveal the influences of microalloying element addition on the microstructure and to clarify the refining mechanism of precipitated particles. TEM and HRTEM results indicated that precipitated particles in the Zr-containing ODS steel had finer sizes and dispersed more homogeneously within the grains. It was found that rhombohedral Y4Zr3O12 particles with complex lattice structures were formed and could pin the migration of the grain boundaries during heat treatment due to their high thermal stability. In addition, the Zr-containing ODS steel exhibited a finer and more uniform grain morphology. Tensile tests showed that microalloying element addition could significantly improve the comprehensive mechanical properties of 14Cr ODS steels at room temperature.