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3D geometric morphometric analysis of morphological covariation in the modern human postcanine dentition
Abstract Analysis of 3D shape covariation patterns between different tooth types is rarely investigated but is important for human evolution, dental anthropology, and medicine. We explored shape covariation of the postcanine dentition (excluding third molars) within and between dental arches using geometric morphometrics. Based on micro-CT scans of 526 teeth from 136 individuals, we analyzed dentine crowns, considering enamel–dentine junction (EDJ) occlusal surface and cervical outlines. High pairwise correlations occurred within dental arches (lower P3–P4, r₁ = 0.89; upper P3–P4, r₁ = 0.81; upper M1–M2, r₁ = 0.86). Between antagonists, correlations varied from the highest in upper–lower M1 ( r = 0.90) to the lowest in upper P4–lower M1 ( r = 0.58). Unexpectedly high covariation appeared between some non-occluding teeth (lower P3–upper M2, r₁ = 0.88). Relatively high covariation also occurred between different tooth classes serving similar masticatory functions: lower P4–upper M1 (r₁ = 0.79) and upper P4–lower M1 (r₁ = 0.77). Crown height and relative proportions emerged as the main factors driving covariation within the postcanine dentition, independently from allometric effects. Overall, morphological integration is stronger within the same dental arch than between antagonistic teeth. These results provide baseline data for developmental, phylogenetic, and functional studies of the human postcanine dentition, including potential phenotype–genotype associations.
Quantum coherent Chladni-like resonance: Programming ions as matter waves for subpicosecond conduction
Achieving coherent control of ionic transport in solids, analogous to electron waveguides, remains a fundamental challenge, as ionic motion is typically limited by slow, stochastic hopping. Here, we demonstrate that a two-dimensional electrochemical cell (borophene/h-BN/graphene) possesses a collective ionic eigenmode, which, when resonantly excited by a “critical-frequency” electrical pulse (10 kHz), transforms ionic conduction from diffusive drift into a coherent, ballistic wave. Time-resolved pump–probe spectroscopy directly reveals this transition through the emergence of a strong 28 THz oscillation, a spectroscopic fingerprint of subpicosecond, wavelike motion. The entire intercalated ion ensemble moves in phase, traversing the 80 nm channel as a coherent wave packet in under 300 fs, corresponding to >1,000-fold speed enhancement over classical diffusion. Leveraging this resonant control principle, we realize an electrochemical device that can be charged in picoseconds with a laser pulse. This work demonstrates that quantum-level, Chladni-like resonance is achievable for ionic matter, establishing a universal pathway to programmable, ultrafast coherent ionic conduction. By transforming ions from disordered particles into controllable matter-waves, we unlock the field of coherent ionics for picosecond-scale energy storage and neuromorphic computing.
Compounded environmental health risks in mountain communities upstream of Bhumibol Dam, Thailand
Background Indigenous, mountain communities residing upstream of Bhumibol Dam, Thailand, rely on vulnerable natural water sources for their water supply, yet remain unaware of the associated health risks. Methods This study assessed the water quality, usage patterns, and contamination pathways across six villages upstream of Bhumibol Dam to shed light on the obstacles to sustainable water security. Samples from 38 water sources of drinking and/or non-drinking water, soil, and the edible parts of crops were subjected to analyses of physical, chemical (NO 3 -N, pH), and qualitative pesticide-related variables, alongside a 6-month assessment of a community water filter system. Results Principal component analysis identified a “at-risk group” of preferred drinking water sources all exhibiting high NO 3 -N, highly alkaline pH, and substantial pesticide contamination, which was found to likely be caused by agricultural run-off. This was reinforced by the detection of pesticide residues in all soil samples and, critically, in the below-ground edible parts of crops (taro, lemongrass, arrowroot), confirming dietary exposure in the local communities. Further compounding the risks posed by the unsafe water supply, the community water filter was found to be ineffective throughout the 6-month analysis with there being no significant difference in water quality between before and after filtration. The residents’ paradoxical preference for high-risk, still water (from sand-filtered puddles) for drinking, rather than water from flowing sources, which they used only for cooking and cleaning. Conclusion Overall, these findings reveal compounded environmental health risks emerging from the convergence of mineral-rich hydrogeology, agrochemical runoff, and vulnerable water-collection behaviours. To mitigate these threats, the study suggests that decentralized water management strategies must prioritize both the implementation of advanced filtration technologies capable of mineral and chemical removal and targeted public health education to shift community reliance away from high-risk, stagnant water sources.
Design of a drive and control integrated intelligent loom control system based on the FOC algorithm
Early-stage drug discovery in a new-generation ultrahigh-throughput mass spectrometry platform
Early-stage drug discovery involves a complex set of processes that typically requires iterative exploration of a vast chemical-biological search space. Over the past few decades, these processes have been facilitated using automated experimentation in the form of high-throughput screening technologies for hit discovery via large-scale biochemical assays of candidate libraries. However, optimized generation of small-molecule candidates is still largely limited to traditional synthetic chemistry workflows, thus representing a bottleneck in the discovery endeavor. Here we describe and demonstrate the capabilities of a next-generation automated ultrahigh-throughput system based on desorption electrospray ionization (DESI) mass spectrometry (MS), which consolidates key activities of early drug discovery: i) organic reaction screening for routes to new candidates, ii) small-scale synthesis following optimized reactions, and iii) bioactivity assessment of the newly generated compounds in a direct-to-biology (i.e., product purification-free) fashion. Importantly, the first two synthetic steps leverage accelerated reactions in microdroplets for on-the-fly synthesis followed by in operando MS analysis or small-scale collection, whereas the later bioanalytical application relies on the label-free nature of MS as well as the contactless and complex-matrix-tolerant nature of DESI. Altogether, this fully automated technology, which has a combined synthetic/analytical throughput of up to ~3 Hz using (sub)nanogram sample amounts (and ca. 6 mHz at the milligram-level synthetic scale), has the potential to accelerate translational efforts via a single-platform closed-loop discovery cycle whose main aspects are illustrated herein, including the demonstration of increases in the biological activity of drug-substance analogs generated in the course of a complete DESI-based direct-to-biology campaign.
Pathways linking internalized HIV stigma to attitudes and beliefs toward ART through depression: Conditional indirect effects of food insecurity
Background Antiretroviral therapy (ART) adherence remains suboptimal in sub-Saharan Africa despite expanded access, particularly in Ghana, where structural and psychosocial stressors such as internalized HIV stigma, depression, and food insecurity interfere with sustained ART engagement. Although these factors are often studied separately, limited research has examined how they interact to influence beliefs and attitudes toward ART. Methods We conducted a cross-sectional analysis among 170 adults living with HIV in the Volta Region of Ghana. Participants completed validated measures assessing internalized HIV stigma, depressive symptoms, household food insecurity, beliefs, and attitudes towards ART. We applied mediation and moderated mediation models to test whether depression mediated the association between internalized HIV stigma and beliefs and attitudes toward ART, and whether these indirect effects varied based on food insecurity. Results Internalized HIV stigma was associated with more negative beliefs and attitudes toward ART (B = .16, SE = .02, p < .001; B = .08, SE = .02, p < .001). Depression significantly mediated these associations (B = .10, 95% CI [.06, .14]; B = .09, 95% CI [.05, .14]), and food insecurity moderated the association between internalized HIV stigma and depression (B = .36, SE = .13, p = .004). Conditional indirect effects were stronger at high (B = .11, SE = .03, 95% CI [.06, .17]) versus low (B = .06, SE = .02, 95% CI [.03, .10]) food insecurity. Conclusions These findings indicate a syndemic interaction between internalized HIV stigma, depression, and food insecurity. Addressing psychological distress alone may not improve ART adherence unless accompanied by efforts to reduce internalized stigma and improve food security. Integrating depression management, stigma reduction interventions, and food security support within HIV services may better enhance treatment engagement in Ghana and similar settings.
Cardiac Intensive Care Unit Appropriate Patient Selection and Triage: A Scientific Statement From the American Heart Association
Cardiac intensive care units are specialized, high-acuity, and resource-intensive environments for the care of critically ill patients with cardiovascular disease. Over the past 60 years, medical and interventional therapeutic advances have improved survival and reduced the risk of life-threatening arrythmias in many common cardiovascular conditions. Nonetheless, some hospitals have maintained historical cardiac intensive care admission practices, resulting in admissions of low-acuity patients who could otherwise be cared for in a telemetry-equipped hospital ward environment. These triage practices may be partially attributable to a lack of guidance from international societies on contemporary cardiac intensive care admission standards. In this scientific statement, we propose cardiac intensive care triage practice standards for common cardiovascular conditions, summarize available prediction scores, and outline priorities for future health services research in this field.
Ultra-sensitive label-free bio-detection via dielectric-modulated GOSC-SOI-TFET
Persistent trade-offs balance competition and colonization across centuries
Microbial competition drives rapid adaptation, often forcing organisms to specialize in new ecological niches. Adaptations that improve competitive ability can reduce performance in other environments creating trade-offs. Whether such trade-offs persist in nature—or are eroded as lineages adapt through compensatory changes—remains largely unknown. Here we show that a trade-off between competitive ability and host colonization has been stably maintained in natural Pseudomonas populations for centuries. Wild plant-pathogenic Pseudomonas compete using tailocins—phage-derived molecular weapons that bind to specific cell-surface receptors. Genomic surveys and functional assays reveal that the most broadly lethal tailocins remain rare—while the tailocin’s production increases competitive killing, it also compromises plant colonization. We determine that the polymorphisms behind this trade-off are not transient—historical genomes spanning two centuries show that the trade-off has been maintained for at least 10 5 to 10 6 generations. Our results demonstrate that, in natural populations, a trade-off between competition and pathogenicity is fundamental and not easily overcome.
Predicting unknown binding sites for transition-metal-based compounds in proteins
Transition-metal-based compounds are promising therapeutic agents, particularly in cancer treatment. However, predicting the binding sites of such compounds remains a major challenge. In this work, we investigate the applicability of two tools, Metal3D and Metal1D, for this purpose. Although originally trained to predict zinc ion binding sites only, both predictors correctly identify at least one of the experimentally observed binding sites for transition metal complexes in each of the apo protein structures tested. At the same time, we highlight current limitations, such as the sensitivity to side-chain conformations, and discuss possible strategies for improvement. This work provides a first step toward establishing a robust computational pipeline in which rapid and low-cost predictors are able to identify putative hotspots for transition metal binding, which can then be refined using more accurate but computationally demanding methods.
Letter by Badano et al Regarding Article, “Prognostic Value of Exercise Right Ventricular–Pulmonary Arterial Coupling in Primary Mitral Regurgitation”
Longitudinal associations between cybervictimization, generalized problematic internet use, anxiety, and depression: cross-lagged panel analysis
PANCS-spec-Binders: A system for rapidly discovering isoform- or epitope-specific binders
Proteins that bind to a target protein of interest, termed “binders”, are essential components of biological research reagents and therapeutics. Target proteins present multiple binding surfaces with varying interaction potential. “Hot spots”, or high-potential surfaces, are experimentally identified as the most probable binding sites in de novo discovery campaigns. However, hot spots and their default binding modes do not always confer the desired specificity. Related proteins or isoforms often share similar hot spots, resulting in promiscuous binding. Interaction with a hot spot may also fail to elicit the intended biological outcome. Consequently, methods that direct de novo binder discovery toward targets with defined specificity are critically needed. We recently developed phage-assisted noncontinuous selection of binders (PANCS-Binders), a selection platform with unparalleled speed and sequence-function fidelity that enables routine de novo binder discovery within days. However, because PANCS-Binders selections enrich variants based primarily on affinity, secondary screening is unlikely to identify binders to lesser hot spots because of the high likelihood of convergence. These alternative binding surfaces with weaker inherent interactions may possess desirable specificity profiles. Here, we develop PANCS-spec-Binders, which incorporates simultaneous selection and counterselection to control the specificity of enriched binders. We demonstrate PANCS-spec-Binders in two proof-of-concept applications: 1) discovery of isoform-selective binders that bind HRAS with >100-fold higher affinity than the highly related KRAS isoform, and 2) discovery of epitope-specific binders that either target or avoid the LIR interaction region of LC3B. PANCS-spec-Binders enables rapid identification of binders with defined specificity within days.
Factors influencing the adoption of sustainable rice farming practices in Khyber Pakhtunkhwa, Pakistan
Rice is a major staple crop and an important source of income for rural households in Pakistan. Its production in Khyber Pakhtunkhwa (KPK) is challenged by rising input costs, climate variability, and limited institutional support, which undermine productivity and long-term sustainability. Sustainable farming practices (SFPs) offer opportunities to improve resource efficiency and farm profitability. This study identifies the key factors that influence the adoption of SFPs among rice farmers in KPK and evaluates their economic impacts. Primary data were collected from 283 rice-growing households in Khyber Pakhtunkhwa, Pakistan, between 18 th January 2025 and 27 th April 2025 using multistage random sampling. Adoption patterns of practices such as crop rotation and intercropping, reduced chemical use, natural fertilizers, and water-saving methods were examined using descriptive statistics, chi-square testing, cost–benefit analysis, logistic regression, propensity score matching, structural equation modeling, and a decision-tree model. Results show that 56.2 percent of farmers adopted at least one sustainable practice. Education, farm size, access to credit and subsidies, market proximity, and participation in training significantly increased the likelihood of adoption. Adopters achieved higher yields (about 430 kg/ha more) and greater profitability than non-adopters (P < 0.01). Cost–benefit analysis confirmed stronger benefit-cost ratios for sustainable systems. Propensity score matching further supported positive effects on profitability, yield, and household income. The findings highlight the economic viability of SFPs in smallholder rice systems. Wider adoption will require expanded farmer training, improved access to concessional credit and subsidies, and stronger extension support. Promoting these practices can raise farm incomes, improve resource use, and support climate-resilient rice production in KPK, Pakistan.
Prevalence and Burden of Cardiac Amyloidosis in a Population-Based Autopsy Cohort
Design, analysis, and experimental research on installation robot for hanging column
Abstract To address the challenges of labor-intensive operations, high safety risks, and low operational efficiency in the installation of hanging columns within tunnels, we propose a robotics-based mechanized and automated solution. First, integrated operational equipment is designed to perform hoisting, gripping, lifting, and installation. Next, the robot linkage coordinate system is established via the modified D–H parameter method to obtain a forward kinematic model and simulate the workspace. To improve the accuracy of solving the inverse kinematic solution, a hybrid approach combining algebraic methods and genetic algorithms is proposed, and the optimal inverse solution is selected on the basis of the shortest path. Furthermore, to avoid impact and vibration while achieving optimal efficiency, a time-optimal trajectory based on seventh-degree polynomial interpolation is presented. Finally, experiments validation was conducted. The results show that the robot’s workspace fully covers the required operational range. The proposed method achieves high accuracy, with orientation accuracy better than 10 −6 and position accuracy better than 10 × 10 −3 . The motion of the joint is smooth and shock-free. The experiments confirm the equipment’s capability to efficiently complete installation tasks, verifying the feasibility of the proposed solution. The research results provide a theoretical foundation for equipment design and offer important references for subsequent improvements.
Impacts of future sea level change on Greenland from community knowledge, coastal mapping, and glacial isostatic adjustment models
Making predictions of global change relevant to individual communities is a critical challenge, especially where local impacts diverge from global predictions. While sea level is rising globally, in Greenland, sea level is predicted to fall over the coming century due to land rebound and sea surface lowering, consequences of glacial isostatic adjustment from both past and future ice loss. Here we present results of a US and Greenland scientific partnership, working with the community of Aasiaat, West Greenland, to identify the impacts of future sea level change where sea level is projected to fall 0.41 to 0.93 m by 2100 CE. Through collaboratively designed, conducted, and interpreted multibeam bathymetry surveys combined with targeted glacial isostatic adjustment models, we identify areas that will be most impacted by sea level fall. We identify two shallow channels where disruption to navigation and nutrient cycles will occur when water level falls beneath critical depth thresholds. To make these predictions useful we established communication pathways to share findings effectively across a broad array of interest groups by engaging with community members, government officials, and students. This multipronged approach of collaboratively designed observations, locally targeted impact modeling and integrated formal and informal communication can be expanded to coastal communities facing environmental challenges around the world.
Identification and diagnostic potential of pyroptosis-related genes in endometriosis: A novel bioinformatics analysis and validation
Background Endometriosis (EMs) is a chronic inflammatory disease characterized by ectopic endometrial growth. This study aimed to identify and analyze potential signatures of pyroptosis-related genes in EMs. Methods We conducted a comprehensive bioinformatics analysis using transcriptomic datasets from the GEO database to identify pyroptosis-related differentially expressed genes (PRDEGs) in endometriosis. Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), Weighted Gene Co-expression Network Analysis (WGCNA), and Protein-Protein Interaction (PPI) network construction were applied to explore the functional relevance of PRDEGs. A candidate gene signature was constructed using Least Absolute Shrinkage and Selection Operator (LASSO) regression based on pyroptosis scores, and its predictive performance was evaluated in an independent dataset. The expression of key PRDEGs was validated by RT-qPCR in eutopic and ectopic endometrial tissue samples from patients (n = 10 each). Results Based on the pyroptosis score, endometriosis samples were divided into high- and low-score groups, with a significant difference in score distribution between the two groups. This score was primarily used to characterize the pyroptosis-related stratification features within the samples. Further screening of differentially expressed genes identified five candidate diagnostic-related genes ( KIF13B, BAG6, MYO5A, HEATR2, and AK055981 ). The model constructed using these genes showed moderate discriminatory ability in an independent dataset. RT-qPCR results confirmed differential expression of KIF13B, BAG6, MYO5A, and HEATR2 between ectopic and normal endometrial tissues, and several IL-17 pathway‑related genes exhibited consistent trends. Conclusions This study suggests a potential role for pyroptosis in endometriosis and identifies a candidate gene signature. These findings may provide new clues for understanding inflammation- and cell death-related mechanisms in endometriosis and serve as a reference for future studies conducted in larger cohorts and under more rigorous validation frameworks.
<i>Mir147</i> Limits the Contribution of Non-Foamy Macrophages to Atherosclerosis
BACKGROUND: Hypercholesterolemia and a high-fat diet promote 2 macrophage subtypes involved in atherosclerosis by inducing lipid droplet accumulation in foamy macrophages (FMs) and triggering inflammatory activation in non-foamy macrophages (NFMs). MicroRNAs are key regulators of macrophage subtypes in atherosclerosis; for instance, miR-10a-5p limits lipid droplet formation, while miR-155-5p enhances inflammation. miR-147-3p is upregulated by inflammatory stimuli in macrophages and in atherosclerotic lesions, suggesting a potential role in NFMs. METHODS: The role of miR-147-3p in macrophages, with or without enhanced green fluorescent protein expression, in atherosclerosis was examined in Apoe –/– (apolipoprotein E-deficient) mice with a myeloid cell-specific knockout of the microRNA 147 ( Mir147 ) gene. Using live-plaque 4D confocal imaging, we assessed lipid droplets, caspase-3 activation, phagocytosis of apoptotic DNA, cholesterol crystal (CC) formation, mitochondrial function, macrophage migration, and tubular membrane extension formation. Green fluorescent protein-tAgo2 (tagged Argonaute 2) immunoprecipitation combined with prime RNA sequencing was performed using atherosclerotic aortas from Apoe –/– mice that expressed tAgo2 in myeloid cells. The effect of the galectin-3 inhibitor GB1107 was studied using 4D live-plaque imaging. RESULTS: Unlike FMs, NFMs are primarily located in the plaque core and show higher miR-147-3p levels in both mouse and human atherosclerosis. Knocking out Mir147 in myeloid cells increases atherosclerosis, with enhanced CC formation and apoptotic DNA accumulation in necrotic cores. Removing Mir147 reduces mitochondrial activity and elevates caspase-3 activity in NFMs, but not in FMs, and lowers the spare respiratory capacity of plaque macrophages. Moreover, deleting Mir147 impairs NFM uptake of apoptotic DNA, increases extracellular apoptotic DNA, and promotes CC formation. Additionally, Mir147 deficiency in NFMs induces caspase-3 activation in endothelial cells, facilitating the transendothelial extension of FM projections. The Lgals3 transcript, encoding galectin-3, was reduced in the tAgo2 immunoprecipitate after Mir147 knockout. A miR-147-3p binding site in the Lgals3 3’-UTR was functionally confirmed. GB1107 treatment reversed the Mir147 knockout effect in macrophages. CONCLUSIONS: miR-147-3p reduces atherosclerosis by suppressing the harmful effects of NFMs on endothelial cells and by enhancing their clearance of apoptotic DNA through targeting galectin-3. Increasing miR-147-3p levels might thus slow the expansion of the necrotic core and reduce atherothrombosis caused by NFM-induced endothelial damage.