Browse Articles

Correction: Effects of DRG pulsed radiofrequency parameters on the clinical outcome for battered sensory never syndrome: a prospective, triple-blind, randomized controlled trial

Fluorescence-lifetime optical electrophysiology in contracting cardiomyocytes

Precise monitoring of cardiac electrophysiology in vitro is crucial to understanding heart function and cardiac disease. However, high-throughput, contact-free methods for directly measuring excitation–contraction coupling remain limited. Here, we introduce a paradigm for quantitative electrophysiological imaging that combines fluorescence lifetime and intensity information to capture dynamic cardiac signals with high fidelity. We show that lifetime measurements are intrinsically decoupled from motion artifacts and provide calibrated calcium concentration and membrane potential estimates across wide fields of view. Using a gated single-photon avalanche diode camera, we acquire fluorescence lifetime images at up to 200 frames per second with sufficient signal-to-noise ratio such that each frame contains meaningful lifetime information without temporal averaging. This approach yields spatially resolved maps of voltage and calcium values across contracting cardiomyocyte monolayers, revealing heterogeneous cell behaviors within individual assays and uncovering previously unreported dynamics during late-phase repolarization for real-time analysis of excitation–contraction coupling.

Design of Urban resilience model in emergency situations

In response to the current demand for urban resilience in emergency situations, we have developed an urban resilience assessment system for responding to sudden natural disasters based on housing data, infrastructure data, as well as Gross Domestic Product(GDP) and population data from 25 regions in Changchun and Hohhot. Subsequently, we conducted multidimensional consideration and analysis of the infrastructure service levels of the two cities, and based on this, designed aurora resilience in emergency situations. We have introduced three evaluation indicators: emergency response speed, resource allocation efficiency, and per capita facility density. We use Analytic Hierarchy Process (AHP) to analyze importance weights and obtain robustness of comprehensive infrastructure. Based on this, we used TOPSIS method to analyze the problems faced by two cities at different service levels and provided long-term and short-term investment strategies. Finally, we discussed the advantages and disadvantages of current urban resilience assessment models and conducted consistency and sensitivity analysis on the AHP algorithm. We found that existing models can to some extent reflect the stability and resilience of cities.

LncRNA IRAIN inhibits mantle cell lymphoma progression by inducing cell cycle arrest and apoptosis: an in vitro study

Targeting XIAP-coordinated PKC signaling resensitizes PD-1-refractory tumors for rechallenge

Despite revolutionizing oncology, PD-1/PD-L1-directed immune-checkpoint blockade (ICB) is limited by primary or acquired resistance that is routinely countered—without mechanistic clarity—by empiric rechallenge. Here, we identify substrate-based protein kinase C (PKC) activity as a prognostic biomarker in non-small cell lung cancer and a therapeutic target in anti-PD-1-refractory tumors. Pan-PKC inhibition overcomes anti-PD-1 resistance by inducing Caspase-3/GSDME-dependent immunogenic pyroptotic cell death, promoting tumor-intrinsic PD-L1 degradation via GSK3β activation, and enhancing CD8 + T cell recruitment and effector function through tumor-derived CCL4–CCR5 signaling. Mechanistically, PKC blockade destabilizes XIAP, relieving caspase inhibition, stabilizing PTEN, and suppressing Wnt/β-Catenin-ATF3 signaling to drive CCL4 expression. In resistant models, PKC inhibition synergizes more effectively with anti-CTLA-4 than with anti-PD-1/PD-L1, in association with reduced intratumoral regulatory T cells and reinforcement of CD8 + T cell effector function. These findings define the PKC–XIAP axis as a central regulator of immune resistance and provide a mechanistic rationale for PKC inhibition plus anti-CTLA-4 as a salvage strategy in ICB-refractory cancers.

Mechanical properties and energy evolution characteristics of fissure sandstone under the interaction between water and fissures

To investigate the mechanical properties and damage evolution of fissure sandstone under the interaction between water and fissures, this study performed uniaxial compression tests on sandstone specimens with different water conditions (dry, natural, and saturated) and fissure angles (0°, 30°, 45°, 60°, and 90°). The experimental results indicate that peak strength decreased markedly with increasing water content, with reductions of 28.68%–53.99% under saturated conditions relative to dry conditions. In contrast, peak strength increased progressively with fissure angle. Crack initiation stress and crack damage stress exhibited similar trends. Based on the normalized ratios of characteristic stress, two damage evaluation indices, R c i and R c d   , were proposed to characterize the weakening effect of fissures on rock bearing capacity during the crack initiation and crack propagation stages, respectively. The energy evolution results show that the strain energy corresponding to characteristic stress decreases significantly with increasing water content and generally increases with fissure angle. In addition, this study introduced a warning coefficient λ based on the ratio of elastic strain energy to dissipated strain energy to identify precursor information associated with rock failure. The results show that λ increased with water content and varied with fissure angle in an M-shaped pattern, with significant peaks at 30° and 60°. Under saturated conditions, water exerted the strongest effect on mechanical parameters at a fissure angle of 0°, while the overall effect remained relatively small at 30°. These findings provide a valuable reference for risk assessment and disaster prevention in geotechnical engineering.

Neighborhood disorder impacts cognitive processing during navigation on a novel virtual reality paradigm

Abstract Living in neighborhoods characterized by physical and social disorder (e.g., litter, abandoned buildings, crime) is associated with poorer cognitive functioning. However, much of this work relies on decontextualized laboratory tasks, limiting insight into how everyday environmental experiences shape day-to-day cognitive functioning. Here, we introduce the Neighborhood Errand Task (NET), a novel navigation paradigm designed to approximate memory and information processing during wayfinding within disordered neighborhood contexts. Participants first learned a route through map study and guided practice, then completed navigation trials requiring choices between learned-familiar routes and novel-shortcut routes. Neighborhood disorder was experimentally manipulated via environmental cues and intermittent surprise “robbery” events. A diverse sample of U.S. adults (N = 100) completed the NET alongside self-reports of perceived neighborhood disorder and risky/impulsive behavior. Greater perceived neighborhood disorder was associated with poorer wayfinding in the learned route and shortcut trials, which may reflect differences in information processing, caution, strategy selection, or specific memory processes. Furthermore, inefficient navigation amplified the relationship between perceived neighborhood disorder and engagement in risky/impulsive behavior, suggesting that cognitive inefficiencies and environmental perceptions heighten vulnerability to behavioral dysregulation. By embedding cognition in a realistic, navigable context, the NET highlights how environmental adversity may shape adaptations relevant to survival.

Simultaneous transformations of view and place coding across reference frames in the macaque brain

Vision enables primates to remotely map their environment using eye movements rather than physical locomotion. While view-related spatial coding is prevalent in the primate hippocampus, its origin and precise relationship to standard place coding remain largely unknown. Leveraging untethered neural recording, motion capture, and wireless eye tracking, we examined view and place coding along the parietal–retrosplenial–hippocampal pathway in macaque monkeys freely exploring an open arena. We identified opposing gradients of egocentric and allocentric spatial coding across this pathway. Acting as a critical intermediate hub, the retrosplenial cortex conjunctively encoded egocentric position and allocentric gaze direction through gain modulation. Further downstream, the hippocampus exhibited both direction-dependent and direction-invariant place coding. Notably, view responses were much more prevalent than this place selectivity and were distinctly driven and modulated by shifting gaze directions. Ultimately, our findings establish that view and place coding actively coexist to varying degrees within the primate hippocampus. These results further reveal that such complex view representations emerge from the integration of distinct spatial reference frames within the retrosplenial cortex.

Correction: The structure of spontaneous speech changes in Alzheimer’s disease: Crosslingual evidence from English and Greek

A hybrid heuristic-based multi-objective strategy for optimized charging and discharging in plug-in EV energy management

Polyphosphate synthesis is essential for phosphate and ATP homeostasis during nutrient upshift

Inorganic polyphosphate (polyP) is a ubiquitous molecule found across all domains of life. Although implicated in diverse cellular processes, including phosphate storage, stress responses, and pathogenicity, loss of polyP synthesis typically causes only mild growth defects. Here, we demonstrate an essential physiological role for polyP synthesis during recovery from phosphate starvation, when cells transition from phosphate-limited to phosphate-replete conditions. Using a comprehensive transposon sequencing approach in Caulobacter crescentus , we identify genes conferring a fitness advantage during starvation for carbon, nitrogen, or phosphate and during subsequent recovery. We find that ppk1 , encoding the polyphosphate kinase responsible for polyP synthesis, is specifically required for recovery from phosphate starvation but dispensable for entry into starvation, a result confirmed with a ppk1 deletion mutant. Mutations that reduce phosphate uptake via the phosphate-specific transport system suppress the requirement for ppk1 , indicating that polyP synthesis prevents toxic accumulation of intracellular inorganic phosphate (P i ) upon refeeding. Our findings further show that buffering intracellular P i through polyP synthesis is critical for maintaining ATP homeostasis. Together, these results define a central role for polyP synthesis in regulating intracellular phosphate balance and ATP homeostasis, thereby facilitating adaptation to fluctuating nutrient conditions.

Can heat stress affect the psychophysiological responses and locomotor demands of young soccer players during small-sided soccer games?

The study compared the effects of three different heat stress conditions on the psycho-physiological responses and locomotor demands of young players in different small-sided soccer games (SSGs). Sixteen soccer players (age: 16.5 ± 0.5 years) performed 2-a-side and 4-a-side SSGs under three environmental heat stress conditions: low environmental heat (LEH) ≤ 23.9°C, moderate environmental heat (MEH) 24.0–27.9°C, and high environmental heat (HEH) 28.0–32.9°C. Players’ heart rate (HR) responses and total distance covered (TDC) were continuously monitored for all SSGs; the rating of perceived exertion (RPE) and visual analog scale (VAS) were used after each bout. Tympanic temperature (TT) was recorded daily before and after the SSGs. The results demonstrated that for both 2-a-side and 4-a-side SSGs, significant main effects of temperature were observed for HR, %HR max , RPE, and VAS responses (all p < 0.05), indicating progressively increased cardiovascular strain and perceptual load under higher heat stress conditions. In contrast, no significant main effects of temperature were found for TDC and TT responses in either game format. Interaction analyses revealed significant temperature × bout effects for most psychophysiological variables in both SSG formats, including HR, %HR max , RPE, and VAS responses (all p < 0.05), suggesting that responses to heat stress varied across repeated bouts. However, no significant interaction effects were observed for TDC or TT in the 4-a-side SSGs, while only limited interaction effects emerged for TDC in the 2-a-side SSGs format. Overall, the findings indicate that heat stress substantially amplifies cardiovascular and perceptual responses during SSGs, with effects modulated by game format and bout structure. In contrast, TDC and TT appear less sensitive to these conditions. Coaches may use this evidence to manage players’ internal and external load and optimize their team’s performance across various heat-stress conditions.

Control strategy for offshore wind power HVDC transmission system based on series-connected DRU-MMC topology

A conserved mechanism for stabilization of viral innate immune antagonists via interaction with Elongin BC

Interferon regulator factor 3 (IRF3) inhibition is a shared strategy of many virally encoded proteins to effectively block the induction of interferon signaling. Although rotavirus nonstructural protein 1 (NSP1) is known to target IRF3 for proteasomal degradation, the exact molecular mechanism remains unclear. Here, we found that rotavirus NSP1 contains a BC box motif that mediates interaction with the Elongin BC complex. Either siRNA knockdown or CRISPR knockout of TCEB2 , which encodes Elongin B, substantially prevented IRF3 degradation by NSP1. Recombinant rotaviruses that encode NSP1 with BC box mutations failed to degrade IRF3, induced elevated interferon responses, and were attenuated in interferon-competent cells in vitro and in vivo. NSP1 protein was significantly less stable in infected cells in the absence of Elongin B. Importantly, Elongin BC was required for the stability of additional BC box-containing viral antagonists, including pestiviral N proteases and human adenovirus E4orf6, indicating that Elongin BC functions not only as an adaptor for host protein degradation but also as a broadly exploited stabilizing factor for viral innate immune antagonists. This knowledge of virus co-opting of the host ubiquitin ligase machinery may instruct the development of broad-spectrum antiviral therapeutics.

Biomedical engineer density per hospital bed: A medical device quality indicator for Mexican Healthcare System

Background The measurement of health indicators that enable the estimation of a system’s capacity to provide adequate patient care constitutes a highly relevant factor in the evaluation of healthcare systems. Traditionally, these indicators include variables such as physician density, nursing staff, and other human resources; however, a critical component that often receives less attention is the capacity of healthcare institutions to sustain high-quality infrastructure and medical technology, which are essential to ensuring the continuity, safety, and efficiency of healthcare services. In this context, an important complementary metric would be the density of biomedical engineers within hospital settings, as these professionals are required to design, evaluate, regulate, acquire, maintain, and manage medical technologies and healthcare infrastructure. Current WHO metrics measure biomedical engineer density per 10,000 inhabitants, not reflecting their direct relationship with medical devices and hospital infrastructure. Objective To develop a novel biomedical engineer density indicator per hospital beds ( ρBEhb ) that relates workforce capacity to medical devices rather than general population, and to evaluate its applicability within the Mexican healthcare system. Methods The ρBEhb calculates the ratio between biomedical engineers providing professional services (internal or mixed staff) and available hospital beds for a given year. The methodological framework follows PAHO/WHO ‘Health Indicators’ guidelines. Data from the Mexican healthcare system (2017–2022) were analyzed alongside international benchmarks. Results The Mexican healthcare system showed generally positive ρBEhb trends from 2017 to 2022, with a −0.53% decrease (2017−2018) and a notable 14.41% increase (2020−2021) coinciding with the SARS-CoV-2 pandemic. While Mexico's absolute number of biomedical engineers is comparable to the USA, ρBEhb analysis reveals a dual structural deficit — insufficient hospital beds and inadequate biomedical engineering workforce — when adjusted for population size and international standards. Conclusions The ρBEhb indicator exposes Mexico's dual deficit in hospital beds and biomedical engineers relative to population needs. This metric provides a more relevant measure for assessing medical device management capacity and healthcare quality than traditional population-based indicators.

Predicting gene essentiality and drug response from preclinical perturbation screens with layered ensemble of autoencoders and predictors

Extended sequence context shapes mutational bias in <i>Escherichia coli</i>

Understanding how sequence context influences the likelihood of mutation at a given genomic locus is critical for deciphering evolutionary processes. It is well established that the immediately adjacent bases influence mutation rates, but the role of more distal bases remains poorly understood. Here, we analyze over 100,000 mutations from 32 Escherichia coli mutation accumulation experiments, encompassing strains with varying DNA proofreading and mismatch repair capabilities. By quantifying the frequency of each nucleotide up to 6 bp around mutation sites, we reveal complex mutational biases that extend beyond the immediately adjacent bases and are unique to each type of base pair substitution. Furthermore, which sequence contexts contribute most to mutational bias depends on what repair mechanisms are active and which strand serves as the leading versus lagging template during replication. Mononucleotide runs are prominent mutational hotspots–we systematically characterize which types of runs are the most mutagenic, including a previously undescribed hotspot for G:C→C:G transversions that can increase their frequency by up to four orders of magnitude. Remarkably, extending our analysis to 1,000 bp from mutation sites reveals that sequence context can influence mutational bias over unexpectedly long distances. These findings expose the intricate interactions between extended sequence context and DNA repair systems that shape spontaneous mutagenesis, and shed light on the mechanistic origins and evolutionary consequences of mutational signatures.

Correction: Evolving threats: Leveraging C. elegans to decode the virulence profiles of highly related environmental Salmonella Newport isolates

High blood glucose and shoulder pain in middle-aged and older Chinese adults: a secondary analysis of the China health and retirement longitudinal study (CHARLS)

DNA-intercalating antiphage molecules trigger abortive infection through mutual destruction and synergize with bacterial immunity

Bacteria deploy diverse antiphage defense systems, including small bioactive molecules providing protection at the multicellular level. DNA-intercalating anthracyclines, such as daunorubicin, exhibit broad antiphage activity, but the underlying mechanism has remained elusive. Here, we systematically screened the Escherichia coli BASEL phage collection to elucidate the mode of action of DNA-intercalating antiphage molecules. We identified taxonomically distinct clusters of susceptible viral groups and show that for the Tequintavirus Bas33 ( Markadamsvirinae ), daunorubicin blocks infection after first-step transfer. In the presence of daunorubicin, continued expression of pre-early genes leads to abortive infection via “mutual destruction,” where both phage and host succumb. Analogous abortive-infection phenotypes occur across taxonomically diverse phages exposed to chemically distinct DNA-intercalating molecules. Notably, we show that daunorubicin synergizes with downstream nucleic acid-targeting defenses underscoring context-dependent outcomes. Together, these findings reveal how chemical defense contributes to the multilayered antiviral immunity and highlight the intricate interplay between mechanistic inhibition and infection outcome.