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Axial compressive behavior of lithium slag and rubber concrete-filled steel tube stub columns
In order to solve the harm of industrial waste such as lithium slag and waste rubber to the environment, this paper put forward the structure of lithium slag and rubber concrete-filled steel tube (LSRuCFST) stub column, which was replaced cement and sand in concrete by lithium slag and waste rubber respectively. Through the axial compression test of 11 LSRuCFST specimens with various lithium slag replacement ratios (0, 10%, 20%, 30%) and rubber replacement ratios (0, 5%, 10%, 20%, 30%), the damage patterns and mechanical characteristics of LSRuCFST columns were studied. The experimental phenomena showed that the damage patterns of 11 specimens were similar to the ordinary concrete-filled steel tube (CFST) colunms. With 20% replacement ratio of lithium slag and 10% replacement ratio of rubber, the largest increase of bearing capacity was optimal. Then, the bearing capacities of LSRuCFST columns were investigated by domestic and international standards. Due to conservative predicted results, a modified computational formal for the LSRuCFST column bearing capacity was presented and verified by the test results of references.
Rapid inactivation of bacteria by MoS2/g-C3N4 nanohybrid structures driven by visible light
GSDMD-mediated mitochondrial dysfunction in marginal cells: A potential driver of inflammation and stria vascularis damage in CIHL
Inflammation is among the known causes of cisplatin-induced hearing loss (CIHL), but its exact pathophysiological mechanisms remain unclear. Herein, we demonstrated that pyroptosis—a recently identified inflammatory type of regulated cell death dependent on gasdermin D (GSDMD)—was activated in the cochleae of cisplatin-treated mice, causing CIHL. Meanwhile, treatment with the GSDMD inhibitor necrosulfonamide alleviated CIHL in these mice. To further examine the role of GSDMD-mediated pyroptosis in CIHL, we conducted experiments in Gsdmd- deficient mice . Gsdmd −/− mice demonstrated significantly lower cisplatin-induced cochlear damage than control mice and appeared to be invulnerable to CIHL. Furthermore, GSDMD-mediated pyroptosis in the stria vascularis (SV), but not in the hair cells (HCs), played a dominant role in CIHL. In marginal cells (MCs) of SV, cisplatin induced caspase-dependent GSDMD cleavage, and the pore-forming N-terminal of GSDMD rapidly localized to the mitochondria, leading to abnormal mitochondrial aggregation and oxidative stress. The consequent mitochondrial dysfunction in MCs might result in the severe progression of inflammation, SV damage, and HC loss. Notably, the pharmacological inhibition of pyroptosis using the FDA-approved drug disulfiram effectively alleviated the symptoms of CIHL. Collectively, these findings offer a broad avenue for inhibiting pyroptosis-induced cisplatin ototoxicity and provide valuable theoretical insights for the clinical management of CIHL.
Retraction: Control of hybrid electromagnetic bearing and elastic foil gas bearing under deep learning
A systematic review and meta-analysis of the prevalence and risk of syphilis among blood donors in Thailand
Abstract Despite rising rates of sexually transmitted infections (STIs) in Thailand, including syphilis, data on its prevalence and associated risk factors among blood donors remain scarce. This systematic review and meta-analysis aimed to estimate the prevalence of syphilis and identify the key risk factors among blood donors in Thailand to inform targeted interventions for enhanced blood safety.The study protocol was registered in PROSPERO (CRD42024560215) and conducted following PRISMA guidelines. Comprehensive searches were performed across major databases, including ProQuest, Journals@Ovid, Embase, Scopus, PubMed, and MEDLINE, to identify relevant studies. A random-effects model was used to calculate the pooled prevalence and odds ratios (ORs) for syphilis risk factors. Heterogeneity was quantified using the I² statistic, and meta-regression and subgroup analyses were employed to explore potential sources of heterogeneity. Publication bias was assessed using funnel plots and Egger’s regression test. A total of 23 studies involving 1,142,910 blood donors were included. The pooled prevalence of syphilis among blood donors in Thailand was 0.42% (95% CI 0.27–0.66%, I²: 99.3%, number of infections: 6,173), with a decreasing trend over time. Male donors were significantly more likely to have syphilis (P < 0.0001; pooled OR: 1.76; 95% CI 1.53–2.03; I²: 34.2%, 651,019 participants). First-time donors also had an elevated risk of syphilis (P = 0.02; pooled OR: 2.02; 95% CI 1.10–3.70; I²: 94.0%, 215,245 participants). Additionally, the analysis revealed a significant association between increasing age and higher syphilis risk among blood donors. The systematic review and meta-analysis indicated that syphilis prevalence among blood donors in Thailand is declining; however, male and first-time donors, as well as older age groups, remain at higher risk. To enhance blood safety, targeted interventions are needed, including refining donor screening questionnaires, expanding educational campaigns for high-risk groups, and incorporating advanced screening technologies. Strengthening and regularly updating national screening policies will ensure the effective mitigation of syphilis transmission among blood donors in Thailand.
Expansion and pathogenic activation of skeletal muscle–resident macrophages in <i> mdx <sup>5cv</sup> /Ccr2 <sup>−/−</sup> </i> mice
Infiltrating macrophages contribute to muscle dystrophic changes in Duchenne muscular dystrophy (DMD). In a DMD mouse model, mdx 5cv mice, CC chemokine receptor type 2 (CCR2) deficiency diminishes Ly6C hi macrophage infiltration by blocking blood Ly6C hi inflammatory monocyte recruitment. This is accompanied by transient improvement of muscle damage, fibrosis, and regeneration. The benefit, however, is lost after the expansion of intramuscular Ly6C lo macrophages. To address the mechanisms underlying the Ly6C lo macrophage expansion, we compared mdx 5cv /Nur77 −/− and mdx 5cv /Ccr2 −/− /Nur7 −/− mice with mdx 5cv and mdx 5cv /Ccr2 −/− mice, respectively, and found no evidence to suggest Ly6C lo monocyte recruitment by dystrophic muscles. Single-cell RNA sequencing analysis and Flt3 cre /Rosa26 LSL-YFP -based lineage tracing of macrophage origins demonstrated the expansion and pathogenic activation of muscle resident macrophages in CCR2-deficient mdx 5cv mice. The expansion was associated with increased cell proliferation, which appeared induced by colony-stimulating factor-1 (CSF-1) derived from fibro/adipogenic progenitors (FAPs). Our study establishes a pathogenic role for skeletal muscle resident macrophages and supports a regulatory role of FAPs in stimulating the expansion of resident macrophages in the DMD mouse model when the inflammatory macrophage infiltration is inhibited.
Potential multiple disease progression pathways in female patients with Alzheimer’s disease inferred from transcriptome and epigenome data of the dorsolateral prefrontal cortex
Late-onset Alzheimer’s disease (AD) is a typical type of dementia for which therapeutic strategies have not yet been established. The database of the Rush Alzheimer’s Disease study by the ENCODE consortium contains transcriptome and various epigenome data. Although the Rush AD database may contain a satisfactory amount of data for women, the amount of data for men remains insufficient. Here, based on an analysis of publicly available data from female patients, this study found that AD pathology appears to be nonuniform; AD patients were divided into several groups with differential gene expression patterns, including those related to cognitive function. First, cluster analysis was performed on individuals diagnosed with “No Cognitive Impairment (NCI),” “Mild Cognitive Impairment (MCI),” and “Alzheimer’s Disease (AD)” stages in clinical trials using gene expression, and multiple substages were identified across AD progression. The epigenome data, in particular genome-wide H3k4me3 distribution data, also supported the existence of multiple AD substages. However, APOE gene polymorphisms of individuals seemed to not correlate with disease stage. An inference of adjacency networks among substages, evaluated via partition-based graph abstraction using the gene expression profiles of individuals, suggested the possibility of multiple typical disease progression pathways from NCI to different AD substages through various MCI substages. These findings could refine biomarker discovery or inform personalized therapeutic approaches.
Online high speed detection method for end face quality of cored filter rods under complex conditions
Epstein–Barr virus and the immune microenvironment in multiple sclerosis: Insights from high-dimensional brain tissue imaging
Epstein–Barr virus (EBV) is strongly implicated in the pathogenesis of multiple sclerosis (MS), yet its exact role in disease progression remains unclear. Using high-dimensional CO-detection by indexing, a technology for spatial imaging, this study examines the cellular microenvironment of MS lesions in secondary progressive MS and primary progressive MS. We analyzed immune, glial, neuronal, and endothelial cell interactions within MS lesions and normal-appearing white matter across two independent cohorts. Our findings show the enrichment of EBV markers, particularly EBNA1 and LMP1, within MS lesions. EBV-positive cells interact closely with reactive astrocytes, microglia, and neurons. Image analysis confirmed the presence of EBV-positive staining within neurons and glial cells, suggesting a direct role for EBV in neuronal and glial involvement in MS. Additionally, we observed altered immune cell interactions, including reduced associations with macrophages and memory T cells, and enhanced interactions with glial cells. Disruptions in blood–brain barrier integrity were also noted in regions of the MS brain. These results highlight EBV’s contribution to immune modulation, glial dysfunction, and neuronal damage in MS, particularly in progressive subtypes. The analysis of MS brain tissue suggests potential therapeutic targets, including antivirals and brain penetrant immune modulators, to address EBV’s impact on MS progression.
An evidence-based guidance framework for neural network system diagrams
Accurate communication of research is essential. We present the first evidence-based framework for formatting neural network architecture diagrams within scholarly publications. Neural networks are a prevalent and important machine learning component, and their application is leading to significant scientific progress in many domains. Diagrams are key to their communication, appearing in almost all papers describing novel systems. However, there are currently no established, evidenced-based conventions describing how they should be presented. We study the use of neural network system diagrams through interviews, card sorting, and qualitative feedback structured around ecologically-derived example diagrams. We find that diagrams in scholarly publications can be difficult to interpret due to ambiguity and variance in their presentation, and that there is a high diversity of usage, perception and preference in both the creation and interpretation of diagrams. We examine the results in the context of existing design, information visualisation, and user experience guidelines and use this foundation to derive a framework for formatting diagrams, which is evaluated through an experimental study, and a comprehensive “corpus-based” approach examining properties of published diagrams in top neural network venues. The studies demonstrate that 1) both the usability and utility of the framework are high and 2) papers containing diagrams that conform to the guidelines receive more citations than those containing diagrams that violate them.
Anticancer drugs targeting topoisomerase II for antifungal treatment
Abstract Fungal topoisomerase II (TopoII) has been identified as essential for viability. Thus, our research aimed to investigate the potential of fungal TopoII as a novel target for antifungal chemotherapy. We conducted studies on eleventh antitumor compounds targeting human topoisomerase II, either approved by the U.S. Food and Drug Administration (FDA) or currently under clinical trials to evaluate their potential for use in other therapeutic applications. While most of the compounds we analyzed are potent inhibitors of yeast TopoII, only a few exhibited antifungal activity. Idarubicin emerged as the most potent compound effectively inhibiting the growth of five reference fungal strains as well as clinical Candida glabrata fluconazole-resistant cells. Antifungal activity of this compound corresponded with its very high yeast TopoII inhibitory effectiveness. Additionally, idarubicin ability to be effectively accumulated into fungal cells is crucial for yeast TopoII targeting. Idarubicin, epirubicin, and bisantrene appeared to be even more effective inhibitors of yeast enzyme than its human counterpart. In fungal cells idarubicin exhibited a multifaceted mechanisms of action, including nuclear DNA fragmentation, disruption of mitochondrial network architecture and mitochondrial DNA aggregation as well as oxidative stress induction. Our results indicate that fungal topoisomerase II targeting is worth considering in antifungal treatment and the reported drugs may serve as a starting point for the reinnovation of a new molecule.
A unified neural representation model for spatial and conceptual computations
The hippocampus and entorhinal cortex encode spaces by spatially local and hexagonal grid activity patterns (place cells and grid cells), respectively. In addition, the same brain regions also implicate neural representations for nonspatial, semantic concepts (concept cells). These observations suggest that neurocomputational mechanisms for spatial knowledge and semantic concepts are related in the brain. However, the exact relationship remains to be understood. Here, we show a mathematical correspondence between a value function for goal-directed spatial navigation and an information measure for word embedding models in natural language processing. Based on this relationship, we integrate spatial and semantic computations into a neural representation model called “disentangled successor information” (DSI). DSI generates biologically plausible neural representations: spatial representations like place cells and grid cells, and concept-specific word representations which resemble concept cells. Furthermore, with DSI representations, we can perform inferences of spatial contexts and words by a common computational framework based on simple arithmetic operations. This computation can be biologically interpreted by partial modulations of cell assemblies of nongrid cells and concept cells. Our model offers a theoretical connection of spatial and semantic computations and suggests possible computational roles of hippocampal and entorhinal neural representations.
Correction: Perceptions of primary health care professionals from Brazil about the food and nutrition monitoring system
Publisher Correction: Novel application of sinh cosh optimizer for robust controller design in hybrid photovoltaic-thermal power systems
Structural mechanisms underlying the modulation of CXCR4 by diverse small-molecule antagonists
CXCR4 (CXC chemokine receptor type 4), a member of the G protein–coupled receptor superfamily, plays a role in cell migration and functions as a coreceptor for HIV entry. Molecular therapeutics targeting CXCR4 have been under intensive investigation. To date, only two small-molecule antagonist drugs targeting CXCR4, plerixafor (AMD3100) and mavorixafor (AMD070), have been approved. Here, we present the high-resolution structures of CXCR4 complexed with AMD3100 and AMD070, as well as a small-molecule antagonist HF51116 that has very different chemical structure and binding mechanism from AMD3100 and AMD070. The interactions between these antagonists and the receptor are analyzed in details, and the mechanisms of antagonism are elucidated. Both the major and minor subpockets on CXCR4 are found to be involved in binding of these small-molecule antagonists. The distinct conformations of Trp94 2.60 observed in these structures highlight the plasticity of the binding pocket on CXCR4, offering valuable insights into the exploration and refinement of therapeutic strategies targeting this chemokine receptor.
The mechanisms of manual therapy: A living review of systematic, narrative, and scoping reviews
Introduction Treatment mechanisms are the underlying process or pathway through which a treatment influences the body. This includes molecular, cellular and physiological processes or pathways contributing to treatment effect. Manual therapy (MT) evokes complex mechanistic responses across body systems, interacting with the individual patient and context to promote a treatment response. Challenges arise as mechanistic studies are spread across multiple professions, settings and populations. The purpose of this review is to summarize treatment mechanisms that have been reported to occur with MT application. Methods Four electronic databases were searched (Medline, CINAHL, Cochrane Library, and PEDro) for reviews investigating mechanistic responses which occur during/post application of MT. This review was registered a priori with PROSPERO (CRD42023444839). Methodological quality (AMSTAR-2) and risk of bias (ROBIS) were assessed for systematic and scoping reviews. Data were synthesized by mechanistic domain. Results Sixty-two reviews were included. Systematic reviews (n = 35), narrative reviews (n = 24), and scoping reviews (n = 4) of asymptomatic (n = 37), symptomatic (n = 43), non-specified human subjects (n = 7) and animals (n = 7) were included. Reviews of moderate quality supported neurovascular, neurological, and neurotransmitter/neuropeptide changes. Reviews of low quality supported neuroimmunce, neuromuscular, and neuroendocrine changes. Reviews of critically low quality support biomechanical changes. Conclusions Findings support critically low to moderate quality evidence of complex multisystem mechanistic responses occurring with the application of MT. Results support peripheral, segmental spinal, and supraspinal mechanisms occurring with the application of MT, which can be measured directly or indirectly. The clinical value of these findings has not been well established. While MT has proven to be an effective intervention to treat conditions such as pain, the current body of literature leaves uncertainty as to ‘why’ MT interventions work, and future research should look to better define which mechanisms (or combinations of mechanisms) are mediators of clinical response.
Therapeutic path of Brazilians with spinal cord injury until rehabilitation
A mechanistic basis for genetic assimilation in natural fly populations
Genetic assimilation is a process by which a trait originally driven by the environment becomes independent of the initial cue and is expressed constitutively in a population. More than seven decades have passed since Waddington’s pioneering demonstration of the acquisition of morphological traits through genetic assimilation, but the underlying mechanism remains unknown. Here, we address this gap by performing combined genomic analyses of Waddington’s genetic assimilation experiments using the ectopic veins (EV) phenocopy in Drosophila as a model. Our study reveals the assimilation of EV in both outbred and inbred fly natural populations, despite their limited genetic diversity. We identified key changes in the expression of developmental genes and pinpointed selected alleles involved in EV assimilation. The assimilation of EV is mainly driven by the selection of regulatory alleles already present in the ancestral populations, including the downregulation of the receptor tyrosine kinase gene Cad96Ca by the insertion of a transposable element in its 3′ untranslated region. The genetic variation at this locus in the inbred population is maintained by a large chromosomal inversion. In outbred populations, the evolution of EV results from a polygenic response shaped by the selective environment. Our results support a model in which selection for multiple preexisting alleles in the ancestral population, rather than stress-induced genetic or epigenetic variation, drives the evolution of EV in natural fly populations.
Utility of a patient similarity-based digital tool for risk communication to patients with type 2 diabetes mellitus: perspectives from primary care physicians in ambulatory care
Background Inaccurate risk perceptions of diabetes complications are responsible for the inertia among patients to engage in protective health behaviours. One potential approach to changing risk perceptions is to use social comparison of their diabetes to other people of similar clinicodemographic profiles. Objectives This study examined the perspectives of primary care physicians (PCPs) in ambulatory care on the utility of a patient similarity-based digital tool for risk communication to patients with type 2 diabetes mellitus (T2DM). Methods A qualitative study design using direct observation and in-depth interviews was conducted on 11 PCP participants. Participants had at least 6 months of clinical experience in ambulatory primary care. Participants went through three hypothetical case scenarios using the digital tool under direct observation and shared their perspectives on its utility during an in-depth interview. Data were coded and analysed using thematic analysis. Results PCPs perceived the digital tool to be useful in educating patients with newly diagnosed or uncontrolled T2DM and to motivate them to achieve better glycated haemoglobin (HBA1c) levels. Patients who do not practise social comparison would refrain from HBA1c comparison and prefer to know the absolute state of their diabetes. PCPs were also concerned about patients’ potential for false reassurance or negative reactions instead of correctly understanding the risk message intended for them. Conclusion The patient similarity-based digital tool requires further work to support PCPs in risk communication to patients with T2DM. Usage should be targeted at patient subgroups with newly diagnosed or uncontrolled T2DM and who practise social comparison. Strategies to maximise benefit include identifying patients who practise social comparison and training PCPs to be adept at framing and communicating risk information in a person-centric manner to mitigate the possibility of false reassurance or negative reactions from their patients.