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Cracking from a fine equiaxed zone (FQZ), often just tens of microns across, plagues the welding of 7000 series aluminum alloys. Using a multiscale correlative methodology, from the millimeter scale to the nanoscale, we shed light on the strengthening mechanisms and the resulting intergranular failure at the FQZ. We show that intergranular AlCuMg phases give rise to cracking by micro-void nucleation and subsequent link-up due to the plastic incompatibility between the hard phases and soft (low precipitate density) grain interiors in the FQZ. To mitigate this, we propose a hybrid welding strategy exploiting laser beam oscillation and a pulsed magnetic field. This achieves a wavy and interrupted FQZ along with a higher precipitate density, thereby considerably increasing tensile strength over conventionally hybrid welded butt joints, and even friction stir welds. Fusion welding of 7000 series aluminum alloy is plagued by cracking from a fine equiaxed zone (FQZ). Here, the authors quantify key softening mechanisms, show the damage accumulation sequence, and propose a hybrid laser/arc welding strategy to mitigate the FQZ and increase weld strength and toughness.

Adaptive resistance limits durable benefit from immune checkpoint blockade (ICB) in the majority of cancer patients, yet the transcriptomic dynamics of the broader checkpoint landscape during treatment remain poorly characterized across tumor types. Here we present CheckDyn, a multi-cohort computational framework that profiles paired pre- and post-treatment transcriptomes to quantify treatment-induced changes across 38 immune checkpoint and exhaustion-associated genes and to predict adaptive resistance. We integrated publicly available RNA-seq and scRNA-seq data from 64 paired tumor samples spanning melanoma, basal cell carcinoma, and non-small-cell lung cancer (GSE91061, GSE120575, GSE123813, GSE176021), applying pseudo-bulk aggregation, Z-score batch correction, and Stouffer meta-analysis for cross-cohort harmonization. Paired Wilcoxon signed-rank testing and linear mixed-effects meta-analysis identified LAG3 (log FC = 0.596, padj = 0.015), PDCD1 (log FC = 0.810, padj = 0.003), TOX2 (log FC = 0.605, padj = 0.003), CD274 (log FC = 0.402, padj = 0.015), and IDO1 (log FC = 0.381, padj = 0.026) as consistently upregulated post-treatment across cohorts. Co-expression network analysis revealed extensive rewiring, with ENTPD1 (ΔDegree = +0.297) emerging as the largest hub-degree shift, suggesting a shift toward metabolic immune suppression. Temporal trajectory modeling showed that all 38 checkpoint genes followed linear upregulation trajectories, with PDCD1 and LAG3 carrying the steepest slopes. An ensemble classifier combining logistic regression and random forest on pre-to-post expression deltas achieved an area under the receiver operating characteristic curve (AUC) of 0.812 (95% CI: 0.694-0.930; 5-fold cross-validated AUC = 0.806) for adaptive resistance prediction across n = 59 patients with available response annotations. These findings establish a consistent transcriptional signature of compensatory checkpoint upregulation during ICB therapy and provide a data-driven framework for early identification of adaptive resistance that warrants external prospective validation.

Endothelial dysfunction is a critical and initiating factor ofthe vascular complications of diabetes. Inflammation plays an important role in endothelial dysfunction regulated by epigenetic modifications. N6-methyladenosine (m6A) is one ofthe most prevalent epigenetic modifications in eukaryotic cells. In this research, we identified an m6A demethylase, fat mass and obesity-associated protein (FTO), as an essential epitranscriptomic regulator in diabetes-induced vascular endothelial dysfunction. We showed that enhanced FTO reduced the global level of m6A in hyperglycemia. FTO knockdown in endothelial cells (ECs) resulted in less inflammation and compromised ability of migration and tube formation. Compared with EC Ftofl,fl diabetic mice, EC-specific Fto-deficient (EC Fto&,&) diabetic mice displayed less retinal vascular leakage and acellular capillary formation. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with RNA-Seq indicated that Tnipl served as a downstream target of FTO. Luciferase activity assays and RNA pull-down demonstrated that FTO repressed TNIP1 mRNA expression by erasing its m6A methylation. In addition, TNIP1 depletion activated NF-кВ and other inflammatory factors, which aggravated retinal vascular leakage and acellular capillary formation, while sustained expression of Tnipl by intravitreal injection of adeno-associated virus alleviated endothelial impairments. These findings suggest that the FTO-TNIP1-NF-kB network provides potential targets to treat diabetic vascular complications.

CVB3 is a single positive-strand enterovirus, and a common pathogen in myocarditis etiology. Although a number of antiviral candidates are under development, specific targeted therapy is not available for CVB3. Ferroptosis is a new type of regulatory cell death discovered in recent years. In this study, our team provided the first evidence that ferroptosis existed in CVB3 infection in vivo and in vitro by iron overload, and massive accumulation of lipid peroxides. Mechanistically, we construct a classical model of HeLa cells following a time-course infection (6, 12, 24, 36, 48 h) with CVB3 (MOI = 10). We demonstrated that the TFRC gene plays an important role in promoting ferroptosis in CVB3 infection and downregulation of TFRC attenuated the ferroptosis. Interestingly, we observed that TFRC was nuclear translocation induced by the CVB3, which was predominantly localized in the cell membrane, but redistributed to the nucleus during CVB3 infection. Moreover, we found that the transcription factor Sp1 was an essential factor that could bind to the TFRC promoter and upregulate the TFRC transcription. Collectively, these results suggest that the Sp1/TFRC/Fe axis may provide a new target for the development of therapies against CVB3 infection.

While existing literature has compared the methodological strengths and limitations of randomized controlled trials (RCTs) and real‐world data (RWD) in general medical research, two critical gaps remain unaddressed: (1) no prior communication papers have specifically examined this comparison in the context of maternity care where unique ethical and practical considerations exist, and (2) no studies have systematically compared cost‐effectiveness analyses derived from RCTs versus RWD approaches—a crucial dimension for value‐based maternity care decisions. This article examines how both approaches can strengthen the evidence base and support the delivery of value‐based maternity care. We argue that neither RCTs nor RWD should be regarded as inherently superior in guiding decision‐making. Each study design offers valuable insights, and their findings must be critically appraised in light of methodological rigor, context, and relevance, particularly when their results diverge.

Huanglongbing (HLB), a disease that's ubiquitous worldwide, wreaks havoc on the citrus industry. The primary culprit of HLB is the gram-negative bacterium Liberibacter asiaticus (CLas) that infects the phloem, but its damaging mechanism is yet to be fully understood. In this study, a multitude of tools including weighted correlation network analysis (WGCNA), protein-protein interaction (PPI) network analysis and gene expression profiling are employed to unravel the intricacies of its pathogenesis. The investigation pinpoints various central genes, such as the ethylene-responsive transcription factor 9 ( ) and thioredoxin reductase 1 ( ), that are associated with CLas invasion and resultant disturbances in numerous biological operations. Additionally, the study uncovers a range of responses through the detection of differential expressed genes (DEGs) across different experiments. The discovery of core DEGs leads to the identification of pivotal genes such as the sieve element occlusion ( ) and the wall-associated receptor kinase-like 15 ( ). PPI network analysis highlights potential vital proteins, while GO and KEGG pathway enrichment analysis illustrate a significant impact on multiple defensive and metabolic pathways. Gene set enrichment analysis (GSEA) indicates significant alterations in biological processes such as leaf senescence and response to biotic stimuli. This all-encompassing approach extends valuable understanding into the pathogenesis of CLas, potentially aiding future research and therapeutic strategies for HLB.

Background Healing of MRSA (methicillin-resistant Staphylococcus aureus) infected deep burn wounds (MIDBW) in diabetic patients remains an obstacle but is a cutting-edge research problem in clinical science. Surgical debridement and continuous antibiotic use remain the primary clinical treatment for MIDBW. However, suboptimal pharmacokinetics and high doses of antibiotics often cause serious side effects such as fatal complications of drug-resistant bacterial infections. MRSA, which causes wound infection, is currently a bacterium of concern in diabetic wound healing. In more severe cases, it can even lead to amputation of the patient's limb. The development of bioactive nanomaterials that can promote infected wound healing is significant. Results The present work proposed a strategy of using EGCG (Epigallocatechin gallate) modified black phosphorus quantum dots (BPQDs) as therapeutic nanoplatforms for MIDBW to achieve the synergistic functions of NIR (near-infrared)-response, ROS-generation, sterilization, and promoting wound healing. The electron spin resonance results revealed that EGCG-BPQDs@H had a more vital photocatalytic ability to produce singlet oxygen than BPQDs@H. The inhibition results indicated an effective bactericidal rate of 88.6% against MRSA. Molecular biology analysis demonstrated that EGCG-BPQDs significantly upregulated CD31 nearly fourfold and basic fibroblast growth factor (bFGF) nearly twofold, which were beneficial for promoting the proliferation of vascular endothelial cells and skin epidermal cells. Under NIR irradiation, EGCG-BPQDs hydrogel (EGCG-BPQDs@H) treated MIDBW area could rapidly raise temperature up to 55 °C for sterilization. The MIBDW closure rate of rats after 21 days of treatment was 92.4%, much better than that of 61.1% of the control group. The engineered EGCG-BPQDs@H were found to promote MIDBW healing by triggering the PI3K/AKT and ERK1/2 signaling pathways, which could enhance cell proliferation and differentiation. In addition, intravenous circulation experiment showed good biocompatibility of EGCG-BPQDs@H. No significant damage to major organs was observed in rats. Conclusions The obtained results demonstrated that EGCG-BPQDs@H achieved the synergistic functions of photocatalytic property, photothermal effects and promoted wound healing, and are promising multifunctional nanoplatforms for MIDBW healing in diabetics. Graphical Abstract

The determination of the weights of decision makers (DMs) is an important problem in multi-attribute group decision making. Many approaches have been presented to determine DMs' weights. However, the computed weight vectors of DMs are usually assumed to be constant in existing studies, and this may cause irrationalities in the decision results. Therefore, this article proposes a novel method to determine DMs' weights based on variable weights theory in which the evaluation information is described as intuitionistic fuzzy sets (IFSs). First, DMs provide their assessment with IFSs, and the intuitionistic fuzzy weighted averaging (IFWA) operator is applied to obtain weighted decision matrix based on the prior given DMs' and attributes' weights. Second, the DMs' weights are obtained based on variable weights theory, and an alternative decision can be computed. Finally, the converted value of the achieved IFS of each alternative is calculated, and the best appropriate alternative is acquired. Two illustrative examples and the comparisons with exsiting approaches are also used to reflect the effectiveness of the proposed approach.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. It is characterised by the following: amyloid-β (Aβ) deposition, tau hyperphosphorylation, neuroinflammation and oxidative stress. Unfortunately, there is no curative treatment available. Recently, natural products have attracted growing interest as potential therapeutic agents for AD, thanks to their multi-target actions and favourable safety profiles. This review highlights recent advances in the use of various natural compounds, including flavonoids, phenolic compounds, saponins, terpenoids, alkaloids and coumarins, with a particular focus on how they modulate the mitogen-activated protein kinase (MAPK) signaling pathway. Representative agents such as myricetin, nobiletin, resveratrol, gallic acid, paeoniflorin, ganoderic acid A, huperzine A, triptolide, berberine, crocin, and ginsenosides have been shown to regulate MAPK subpathways (ERK, JNK, p38), thereby attenuating oxidative stress, neuroinflammation, synaptic dysfunction, and neuronal apoptosis. Preclinical studies suggest that these compounds improve cognitive function and ameliorate AD-related pathology, thereby supporting the idea that MAPK signaling is a critical therapeutic target. Nevertheless, current evidence is limited by short-term animal experiments, insufficient toxicological evaluations, and challenges related to bioavailability and blood–brain barrier penetration. Future studies should emphasize long-term efficacy, safety assessments, optimized drug delivery systems, and high-quality clinical trials. Overall, natural products represent a valuable source for AD drug discovery, and targeting MAPK signaling offers promising opportunities for novel therapeutic development.

Background At present, “Belt and Road” (“B&R”) member states (accounting for about 61.78% of the world’s population) face different types of cancer threats to varying degrees. We analyzed the incidence and mortality and risk factors of cancer in the member countries of the “B&R” to explore the basis of health and medical cooperation between countries and provide a foundation for formulating cancer prevention and control policies for building a healthy \"B&R.\" Methods Data were derived from the Global Cancer Observatory and Cancer Country Profiles in 2020. Incidence and mortality were age-standardized rates (ASRs). Population attributable fractions (PAFs) was applied to measure risk factors of cancers in the “B&R” countries. The mortality­to­incidence ratio (MIR) was calculated by dividing the mortality rate by the incidence rate. Results A total of 26 cancers were included in the study. Lung, breast, colorectal, stomach, liver, prostate, cervical, esophageal, thyroid, and uterine cancers were the most common and highest in age-standardized mortality in the “B&R” countries. For men, Hungary had the highest cancer age-standardized incidence and mortality (ASR, 289.3 per 100,000 and ASR, 235.7 per 100,000, respectively), followed by Latvia (ASR, 288.6 per 100,000 and ASR, 196.5 per 100,000, respectively). In females, the highest incidence rates were estimated in Greece (ASR, 238.7 per 100,000), and the highest mortality rate was Brunei (ASR, 192.3 per 100,000). All countries were in the middle or high HDI range, with about half (46.88%) of countries achieving high HDI, mostly in Central and Eastern Europe (13 countries) and West Asia (10 countries). The United Arab Emirates had the highest MIR in male and female (1.59 vs 2.19). Tobacco products, infectious factors, and ultraviolet rays were the three main cancer risk factors in the “B&R” countries. Conclusion The overall burden of cancer in the countries along the “B&R” remains substantial, while the corresponding cancer prevention and control policies need to be improved. Strengthening health cooperation among member countries will contribute to a joint response to the risks and challenges posed by cancer.