A major challenge involved in human-machine interfaces is developing feedback strategies that improve control and benefit patients with motor disabilities. Here, we propose, validate, and mechanistically characterize a personalized, closed-loop strategy that delivers reinforcement feedback in real time during human-machine interface control. Across five experiments involving 106 participants and two control interfaces, fewer than 20 reinforcement trials produced immediate improvements in force control and lasting retention gains. These effects were strongest when visual and/or somatosensory feedback was limited, a finding that suggests translational relevance for tasks, technologies, and pathologies with limited sensory feedback. In chronic stroke patients, real-time reinforcement likewise improved online force control under limited visual feedback, although short training did not yield retention gains. Information-theoretic analyses further revealed that reinforcement compensates for reduced feedback control when sensory feedback is sparse and promotes motor exploitation of successful actions. Overall, these findings identify real-time reinforcement as a promising strategy for enhancing human-machine interface control.
Intrinsically disordered proteins and regions (IDPs/IDRs) possess pronounced conformational heterogeneity, complicating their structural characterization. Integrating molecular dynamics (MD) simulations with experimental constraints is therefore indispensable for generating accurate conformational ensembles. A central factor limiting the accuracy of such simulations is the adequacy of force field parametrization for IDPs. In this study, we systematically characterized the intrinsically disordered headpiece (HP) domain of protein 4.1G by employing replica-exchange MD simulations alongside NMR spectroscopy and fluorescence correlation spectroscopy (FCS). Six force field/water model combinations were evaluated by benchmarking simulated ensembles against experimental NMR chemical shifts and hydrodynamic radii. Initiating simulations with a cis Ile78-Pro79 peptide bond markedly improved agreement with NMR chemical shifts. Of the tested combinations, C36IDPSFF/TIP3Pm and ff99SBdisp/TIP4P-disp showed better agreement with the available local NMR-derived descriptors. Global conformational analysis revealed distinct force field biases: ff14SB/TIP4P-D, ff99SB-ILDN/TIP3P, and ESFF1/TIP4P-D favored compact ensembles, whereas ff99SBdisp/TIP4P-disp produced the most expanded conformations. Conversion of the radius of gyration (Rg) to hydrodynamic radius (RH) yielded values approaching the experimental measurement (8.20 Å). However, this conversion proved model-dependent, complicating a definitive ranking of force field performance. These results highlight the critical impact of force field choice on both local and global properties of IDPs/IDRs and emphasize the need for integrated, multimetric validation in the computational study of disordered proteins.
Sub-inhibitory antibiotic exposure can alter biofilm architecture, but the effects on matrix mechanics remain poorly understood. Here, imipenem at half the minimum inhibitory concentration (MIC) is shown to induce viscoelastic reinforcement and physical tolerance in Pseudomonas aeruginosa (P. aeruginosa) biofilms. Ten imipenem-resistant isolates from ready-to-eat foods were cultured with and without sub-inhibitory imipenem. Treated biofilms transitioned from smooth, flat colonies to rugose, wrinkled, hyper-hydrophobic architectures, with contact angle increasing from 37.5° to 90.2°. Capillary rheometry revealed a 3.4-fold increase in apparent viscosity (185.6 vs. 54.2 mPa·s) and pronounced shear-thinning behavior. Creep-recovery tests showed lower creep compliance (0.72 vs. 1.65 Pa-1) and higher elastic recovery (48.3% vs. 17.5%), indicating a stiffer, more cross-linked matrix. Biofilm inhibitory concentrations (BIC) exceeded 128 μg/mL in all 10 imipenem-treated rugose phenotypes (range >128 μg/mL for each isolate), despite planktonic MICs of only 8-32 μg/mL. Using the Stokes-Einstein equation, the 3.4-fold viscosity increase was calculated to proportionally reduce the imipenem diffusion coefficient from 1.5 × 10-11 to 4.2 × 10-12 m2/s (71% reduction), directly limiting antibiotic flux into deep biofilm layers. Imipenem-treated biofilms required 3.6-fold higher shear stress for initial detachment and 2.7-fold higher peeling force (33.7 vs. 12.4 N/m), with failure mode shifting from adhesive to cohesive. Notably, imipenem MIC did not correlate with viscosity parameters (r = 0.24, p > 0.05), demonstrating that mechanical reinforcement operates independently of genetic resistance. These in vitro findings highlight the potential significance of matrix mechanics in biofilm persistence and provide a mechanistic explanation for reduced antimicrobial efficacy in biofilm-associated contexts. Conventional susceptibility testing fails to capture this adaptive response.
With the continuous increase in the operating speed of high-speed railways, the fluctuation of the contact force in pantograph-catenary systems becomes increasingly significant, posing higher requirements for current collection quality and operational reliability. Conventional passive control methods mainly rely on structural parameter optimization and lack online adaptability, which limits their effectiveness under complex operating conditions. Although the Linear Quadratic Regulator (LQR) provides good response performance and robustness, its weighting matrices are typically selected through empirical tuning, and the fixed-gain structure cannot adequately address the nonlinear and time-varying characteristics of pantograph-catenary systems. To overcome these limitations, this paper proposes an Adaptive Linear Quadratic Regulator based on the Multi-strategy Dandelion Optimization Algorithm (ALQR-MDO). First, the original Dandelion Optimization (DO) algorithm is enhanced by integrating several improvement strategies, including boundary reflection, sub-elite guidance, Gaussian-Cauchy hybrid mutation, and dynamic population adjustment, thereby improving global search capability and convergence efficiency. Second, an adaptive LQR controller based on pantograph head displacement-segmented gain scheduling is developed, in which smooth transitions of feedback gains under different operating conditions are achieved using linear interpolation. Subsequently, the weighting matrices of the ALQR controller are treated as optimization variables, and a fitness function considering both pantograph head displacement and contact force fluctuations is constructed. The optimal control parameters are obtained using the MDO algorithm. Finally, a pantograph-catenary coupled dynamic model is established and validated through simulations under different operating speeds. Additionally, control energy consumption analysis and closed-loop stability verification are conducted. Simulation results show that under 200 km/h operating conditions, the proposed ALQR-MDO method reduces the standard deviation and range of contact force as well as the standard deviation and range of pantograph head displacement by 49.72%, 41.92%, 59.69%, and 50.96%, respectively, compared with passive control. Under 300 km/h, the corresponding improvements reach 50.48%, 48.14%, 54.95%, and 48.60%. These results demonstrate that the proposed method significantly improves current collection performance while exhibiting strong adaptability to high-speed operating conditions and robust disturbance rejection capability.
The anterior component of force (ACF) is key to proximal contact loss (PCL) after implant restoration, yet its quantitative impact remains unclear. This study employed digital model analysis to indirectly assess the effects of ACF and examine its association with PCL. Following final restoration, 3D surface and buccal occlusal data were obtained from ninety first molar implant sites and mesial adjacent teeth. Occlusal force-induced changes in proximal contact gap (ΔdP) and centroid position (ΔdC) were measured using Geomagic Wrap 2021 for indirect ACF estimation. Proximal contact gaps were measured under non‑occluding conditions at baseline and 6 months to calculate the change over time (ΔD). Univariate and multivariate analyses identified PCL-related biomechanical influencing factors, and a restricted cubic spline (RCS) model was developed and validated using Cohen's Kappa. The 6-month PCL incidence was 17.78%, and ΔdP emerged as a significant biomechanical influencing factor of ΔD (P < 0.001). RCS analysis revealed that the adjacent state remains stable when ΔdP is within the range of - 13 μm to 9 μm; beyond this range, imbalance occurs. The model demonstrated good fitting capability (κ = 0.59, P = 0.003). This study achieved an indirect assessment and quantification of the effect of ACF through digital model analysis technology, and clarified its correlation with the PCL of the implant, providing new evidence and methodological references for related biomechanical research.
Antibiotic resistance in Streptococcus pneumoniae remains a major clinical challenge, particularly for macrolides such as erythromycin. This resistance is commonly associated with transposons Tn2009 and Tn2010 carrying the mefA gene, which encodes a macrolide efflux protein. This study investigated the genetic characteristics of mefA from Indonesian clinical isolates and elucidated its efflux mechanism using integrated genomic analysis and molecular dynamics simulations. Whole-genome sequencing confirmed the presence of Tn2009 and Tn2010 in clinical isolates. Multiple sequence alignment showed high conservation of mefA (98-100% identity), indicating strong evolutionary stability within the species. A homology model of the mefA encoded efflux protein was constructed and used for molecular docking, revealing stable erythromycin binding within the efflux channel with multiple favorable binding poses. Molecular dynamics simulations (200 ns) demonstrated structural stability of the protein, with an average root mean square deviation of 0.174 nm. Root mean square fluctuation analysis identified localized flexibility in residues Asn195-Ser199, suggesting a functionally relevant intracellular loop involved in conformational dynamics. Despite stable interactions, erythromycin remained confined within a localized channel region and did not undergo spontaneous translocation under equilibrium conditions. Steered molecular dynamics simulations indicated that ligand transport requires external force to overcome an initial energetic barrier of 553.07 kJ/mol/nm, followed by stepwise displacement through multiple transient binding sites, consistent with a multi-site relay mechanism. Umbrella sampling further revealed a rugged free energy landscape, with a maximum potential of mean force (PMF) of ~ 45 kcal/mol near the channel exit region. The PMF profile, reconstructed using WHAM across ~ 30 windows, showed well-converged overlap and multiple intermediate minima, indicating a stable sampling of the reaction coordinate. Collectively, these findings provide structural and energetic insights into mefA mediated erythromycin resistance in S. pneumoniae. The results support a mechanism involving stable substrate binding, localized conformational flexibility, and substantial energy barriers requiring active transport, highlighting potential targets for efflux inhibition strategies.
Digital motor outcomes may surpass the sensitivity of clinician-reported outcomes in hereditary spastic paraplegia (HSP), particularly in cases of mild upper limb impairment and early disease stages. We thus validated a trial-ready quantitative motor (Q-Motor) assessment of rapid alternating limb movement tasks against clinician-reported, patient-focused, and performance outcomes in HSP. Exploratory single-center cross-sectional assessment in 41 patients with different HSP genotypes (age: 48 ± 14 years), with speeded foot tapping, diadochokinesia, and finger tapping measured by a high-resolution force transducer. Validation comprised discrimination from 48 age- and sex-matched controls; correlations to the Spastic Paraplegia Rating Scale (SPRS; mean: 18.6 ± 9.1), Friedreich Ataxia Rating Scale- Activities of Daily Living (FARS-ADL), and Nine-Hole Peg Test (9HPT); and stratification by functional stage (FARS stage: mild/moderate/severe = ambulatory/walking aid/wheelchair). Foot tapping best discriminated patients with HSP from controls (e.g., frequency: area under the curve [AUC] = 0.94-0.96), and particularly captured HSP severity and functional impairment by measures of foot elevation and cumulative tap force (across all measures: |rhoSPRS|= 0.33-0.59; |rhoADL|= 0.35-0.56). Speed measures of diadochokinesia and finger tapping captured functional impairment (|rhoADL|= 0.32-0.60) and impaired dexterity (|rho9HPT |= 0.53-0.77) in the upper limbs of patients with HSP-even in the mild stage, and with slowed finger tapping even in patients without upper limb pyramidal signs. Foot tapping measures were most sensitive in discriminating mild-stage impairment (AUC = 0.72-0.95) and predominantly changed between mild and moderate HSP, while upper limb measures of diadochokinesia and finger tapping predominantly changed from moderate to severe HSP. Q-Motor captures motor impairment in HSP, even in the upper limbs and mild disease stages, and should be further evaluated as a possible trial outcome by longitudinal validation in genotypically stratified cohorts and mapping to patient experience.
This study investigated how varying concentrations of exopolysaccharide (EPS) derived from Bacillus velezensis SN-1 (B. velezensis SN-1) affect the characteristics of soy protein isolate (SPI) gels. EPS was extracted and purified, and EPS-SPI composite gels containing different EPS concentrations (0%, 0.5%, 1.0%, 1.5%, and 2.0%, w/v) were prepared. The water-holding capacity, thermal stability, rheological behavior, textural properties, microstructure, and intermolecular forces of the gels were systematically evaluated. The results demonstrated that EPS significantly enhanced moisture retention in composite gels (from 13.25% to 82.41%), improved thermal stability, and increased both storage (G') and loss (G") moduli in a concentration-dependent manner. Thus, EPS strengthened the solid-like behavior and pseudo-plastic fluid characteristics of SPI gels. Microstructural analysis revealed that EPS promoted the formation of a denser and more uniform gel network structure, reduced pore size within the gel, and increased fractal dimensions, contributing to structural reinforcement. Further analysis of molecular interactions demonstrated that gel stability was primarily maintained by hydrophobic interactions, hydrogen bonding, and disulfide bonds, with EPS acting as a cross-linking agent to enhance protein-polysaccharide interactions. Overall, this study provides a theoretical basis for the application of EPS-SPI composite gels in functional food systems, demonstrating that EPS can serve as an effective natural modifier for improving the comprehensive performance of plant protein-based gels.
It is increasingly difficult to predict all the hazards that buildings will face over their lifetime, highlighting the need to design robust structures that can tolerate unforeseen damage. Typically, robustness is pursued by providing continuity within a structural system. While this strategy performs well in expected scenarios, it increases the risk of catastrophic collapse propagation when initial damage is large. Using high-fidelity simulations, we first identified and characterised the key mechanisms responsible for continuity-enabled collapse propagation in highly continuous building structures such as those made of cast-in-place reinforced concrete. Building on this understanding, we developed: 1) a design approach that employs bespoke force-regulating fuses to interrupt continuity when it becomes detrimental, and 2) an experimental setup that allows system-level collapse propagation to be evaluated by testing only a representative part of a building. Overall, our work shows that continuity can be selectively disengaged even in intrinsically continuous structures and provides a cost-effective way of testing the next generation of solutions against unforeseen extreme events.
Objective: To understand the development and current status of pediatric digestive endoscopy over the past 40 years, so as to provide strategic recommendations for the discipline's future development. Methods: A cross-sectional survey was conducted between February and March 2025 across 504 hospitals practicing pediatric endoscopy in 31 provinces, autonomous regions or municipalities. The structured questionnaire encompassed institutional and endoscopy center profiles, workforce demographics, technical capabilities, and continuing education requirements. Results: All 504 distributed questionnaires were returned valid. Pediatric endoscopy was first established in 1985 in Zhejiang Province and Beijing, with the Xizang Autonomous Region commencing services in 2023. The 5 leading provinces by center volume were Shandong (65 hospitals), Zhejiang (47 hospitals), Jiangsu (36 hospitals), Sichuan (34 hospitals) and Guangdong (29 hospitals). Geographic distribution revealed significant disparities: East China dominated with 187 centers (37.1%), North China accounted for 51 (10.1%), Southwest China accounted for 84 (16.7%), South China accounted for 65 (12.9%), Central China accounted for 41 (8.1%), Northwest China accounted for 60 (11.9%), while Northeast China accounted for merely 16 (3.2%). The workforce comprised 2 089 physicians and 1 920 nurses (physician-to-nurse ratio 1∶0.92), with general hospitals demonstrating superior staffing ratios (1∶1.06) compared to pediatric specialized and maternal-child hospitals (1∶0.51). Training predominantly relied on external fellowships (49.4%, 249/504) or combined institutional-external programs (40.9%, 206/504), supervised mainly by pediatric endoscopists (75.2%, 342/455). Diagnostic and therapeutic capabilities achieved comprehensive gastrointestinal coverage, with the five most prevalent procedures being gastroscopy (100.0%,504/504), foreign body retrieval (89.7%,452/504), colonoscopy (74.6%,376/504), polypectomy (62.5%,315/504), and hemostasis (54.0%,272/504). Conversely, advanced interventions, including endoscopic retrograde cholangiopancreatography, endoscopic retrograde appendicitis therapy and peroral endoscopic myotomy remained limited in adoption. Between 1996 and 2025, 18 practice guidelines, consensus statements and standard operating protocols were published. Conclusions: Pediatric gastrointestinal endoscopy has developed rapidly, with progress in discipline development, technical standards, talent cultivation, and consensus guideline formulation. However, challenges remain in achieving regional balance, optimizing the doctor-nurse ratio, and advancing high-level endoscopic therapeutic technologies. Future efforts should focus on refining minimally invasive technologies, integrating intelligent technologies, and achieving integrated management across the entire service chain. 目的： 了解儿童消化内镜开展40年的发展与现状，为儿童消化内镜学科的发展提供策略依据。 方法： 横断面研究。2025年2至3月通过问卷调查的方式，对我国31个省、自治区、直辖市开展儿童消化内镜的504家医院进行调研，内容涵盖医院及内镜中心基本情况、医护队伍结构与配置、内镜诊疗技术开展能力、继续教育与培训需求。 结果： 共发放问卷504份，回收有效问卷504份。调查显示1985年浙江省、北京市最早开展儿童消化内镜，西藏自治区于2023年开展。开展儿童消化内镜的单位数列前5位的地区分别为山东省（65家）、浙江省（47家）、江苏省（36家）、四川省（34家）、广东省（29家）；我国儿童消化内镜资源地域分布不均，华东地区187家（37.1%），华北地区51家（10.1%），西南地区84家（16.7%），华南地区65家（12.9%），东北地区16家（3.2%），华中地区41家（8.1%），西北地区60家（11.9%）。从业医护队伍人数为医师2 089名，护士1 920名，医护比为1∶0.92，综合医院医护比最高（1∶1.06），儿童专科医院和妇儿医院较低（均为1∶0.51）。继续教育模式以外出进修（49.4%，249/504）和“院内+外出”（40.9%，206/504）为主，带教老师主要为儿童消化内镜医师（75.2%，342/455）。我国已开展儿童消化内镜诊断和治疗各项技术，其中前5位分别是胃镜（100.0%，504/504）、异物钳取（89.7%，452/504）、肠镜（74.6%，376/504）、肠息肉切除（62.5%，315/504）、内镜下止血（54.0%，272/504），而高阶消化内镜治疗技术如内镜逆行胰胆管造影术、内镜下逆行性阑尾炎治疗术、经口内镜下肌切开术普及率较低。1996至2025年共发表儿童消化内镜相关操作常规、共识和指南18项。 结论： 儿童消化内镜发展迅速，在学科建设、技术规范、人才培养等方面取得进步，但在区域均衡发展、医护结构比例、高阶消化内镜治疗技术发展等方面仍面临挑战。未来需着力聚焦微创技术精细化、智能技术融合、全链条一体化管理。.
The COVID-19 pandemic had a catastrophic impact on human life and business globally. Susceptible occupations and individuals need to be specially identified, and the risk needs to be assessed for better protection of workers and the sustainability of a business. This study aims to assess workplace risk based on U.S. Occupational Safety and Health Administration (OSHA)-confirmed work-related COVID-19 infection cases. A total of 3,799 workplace COVID-19 infection reports investigated and published by OSHA between 2020 and 2024 were collected and analyzed, and 4,615 infected employees were identified from these reports, which included 64.5% fatalities and 29.7% hospitalized injuries. Analysis of OSHA reports shows that certain industries had a higher risk of COVID-19 exposure and infection, particularly health care and social assistance, public administration, and manufacturing. These industries often require direct and close contact with other people, or working in a confined environment. For example, the Health Care and Social Assistance (North American Industry Classification System Code (NAICS, #62) accounted for 49% of OSHA investigations. Compared with the whole civilian population, civilian labor force has a higher risk (average +24%) of COVID-19 deaths across all age groups assessed (25-34, 35-44, 45-54, and 55-64), and male civilian labor force had 15% higher chance of COVID-19 deaths than the female group. The higher mortality risk among workers implies that additional occupational control measures need to be established and implemented.
Conventional musculoskeletal spine models often rely on deterministic kinematic constraints to estimate spinopelvic kinematics and kinetics, which can produce unrealistic intervertebral motions and loading patterns. Incorporating intervertebral stiffness in kinematic evaluations would improve physiological accuracy, particularly during lifting tasks where spinal loading is critical. We developed a stiffness-dependent kinematics estimation workflow that integrates nonlinear intervertebral stiffness within an optimal control formulation, enabling spinal motion to emerge from mechanical behaviour rather than prescribed kinematic constraints in full body musculoskeletal models. Eleven healthy participants performed trunk flexion, lateral bending, and axial rotation tasks, with and without lifting a load. Predicted kinematics and compressive forces were compared against a conventional constraints-driven approach. A single-subject dataset with biplanar radiography provided ground-truth validation of vertebral motions. The stiffness-dependent method generated smoother, more physiologically plausible motion distributions and consistently reduced lumbar compressive loading. Vertebral orientation and position errors were lower than with the constraints-driven approach, and compressive forces aligned with literature ranges. Nonlinear stiffness modelling yields more evenly distributed spinal kinematics and reduced lumbar loading, providing a physiologically grounded framework for spine biomechanics and injury prevention research.
Arterial pulsation is used to differentiate arteries from veins on ultrasound imaging. However, the mechanism by which the arterial pulsation amplitude changes when an ultrasound probe compresses the artery has not been reported. Here, we aimed to investigate whether this mechanism resembles the oscillometric maximum amplitude algorithm. An automatic blood pressure cuff was placed on the upper left arm of 7 healthy participants (four men and 3 women; aged 27-46 years). An ultrasound probe attached to a force sensor was gradually applied to the distal brachial artery using an automated test stand until the lumen of the artery was completely occluded. Probe pressure and arterial pulsation data were recorded and analyzed during compression. Sequential ultrasound images and probe pressure measurements were obtained over time under 2 conditions: without cuff occlusion and with the cuff inflated above the systolic blood pressure. Without cuff inflation, ultrasonography-detected arterial pulsations and probe pressure oscillations were perfectly synchronized. The timing of the maximum amplitude occurrences in both signals coincided. Conversely, when pulsatile flow was stopped by cuff inflation above the systolic pressure, neither arterial pulsation nor probe pressure oscillations were observed. Pulsatile oscillations in the probe pressure persisted after local arterial occlusion by the probe. The mechanism underlying arterial pulsation generation under probe compression can be explained by the transmural pressure-volume relationship of the artery, in which pulsatile flow and reduced transmural pressure cause changes in arterial volume and produce observed probe pressure oscillations. These findings link ultrasound imaging and oscillometric blood pressure principles, providing a unique perspective for noninvasive arterial hemodynamic assessment.
Understanding the workload in military primary care is essential to inform policy making, resource allocation and training for the general practitioners of tomorrow. Due to well-recognised limitations with coding in primary care and additional barriers within UK Armed Forces (UKAF) Defence Primary Healthcare (DPHC), the understanding of reasons for visit (RFV) is difficult to ascertain from a top-down perspective. A multicentre, cross-sectional study to describe the frequency of patient RFV over a 2 week period in general practices across the DPHC network was undertaken. RFV was documented using the International Classification of Diseases 11 (ICD-11) tier one codes, with specific conditions highlighted based on published literature and Defence needs. 18 medical centres, representing all DPHC regions and 26% of the Defence population, were included. A total of 6693 RFV were recorded, which differed from the published literature for primary care in developed countries, cementing the function of DPHC as an occupationally focused service with musculoskeletal injuries and mental health presentations being most common. DPHC can better understand the RFV across its service and intelligently target service delivery, pathway development and managed clinical networks based on this study, which differs from some previous evidence.This study also is a proof of concept for a network of researchers, collaborating with a Defence-wide perspective, allowing grassroots data collection outside of overburdened centralised systems and developing interest and engagement in research, audit and collaboration among our clinicians.
Processing bodies (P-bodies) are cytoplasmic granules that regulate mRNA storage, repression, and decay, yet how their internal organization supports selective mRNA regulation remains poorly understood. Here, we show that the conserved LSm protein Trailer Hitch (Tral) is a key organizer of P-body architecture and function in Drosophila melanogaster nurse cells. Using quantitative confocal imaging, super-resolution microscopy, and chemical perturbation of intermolecular interactions, we demonstrate that Tral coordinates the incorporation and spatial organization of the core P-body proteins Me31B and Cup. Loss of Tral alters their partitioning into P-bodies, promotes demixing into distinct subdomains, and shifts condensates toward a less dynamic, structurally heterogeneous state. These organizational changes have functional consequences for mRNA storage: Tral depletion selectively releases maternal mRNA bicoid, while nanos mRNA remains P-body associated and stable. We further identify twinstar mRNA, encoding the actin regulator Cofilin, as a Tral-dependent P-body client whose localization and organization within P-bodies requires Tral:RNA interactions and electrostatic forces. Reduced twinstar mRNA levels in the absence of Tral are associated with decreased nuclear G-actin and altered transcription of me31B and cup, revealing a potential feedback mechanism that links cytoplasmic P-body organization to nuclear gene expression. Together, these findings establish Tral as a central regulator of P-body architecture that couples condensate organization to selective mRNA regulation and transcriptional homeostasis in D. melanogaster nurse cells.
Fast ion transport across nanofluidics, driven by salinity gradients, has drawn ever-increasing attention, due to its huge potential in osmotic energy generators. Previous studies have reported a concentration polarization (CP) effect over highly conductive nanofluidics surfaces, where the rate of ion dissipation surpasses ion accumulation. The phenomenon results in low cation/anion transmembrane selectivity, especially for large-scale nanofluidics, thereby limiting the energy conversion efficiency. Here, we propose a strategy of cation-π and electrostatics interplay to design ultraselective polymeric nanofluidics with great immunity to CP, using two polyanions with carbazole and sulfonic moieties. Experimental results show an anomalous CP effect that is contrary to ion dissipation-dominated salinity gradient decline in typical nanofluidics. Through simulations, we reveal an "adsorption-to-transport" mechanism, relying on cation accumulation driven by strong cation-π forces. On the two sides of nanofluidics, the interphase salinity gradients are increased to weaken cation dissipation and promote cation/anion transmembrane selectivity. Applied to osmotic power generators, a record single-cell voltage output and ultrahigh energy conversion efficiency are provided for over 72 days. This work provides inspiring insights into the role of supramolecular effects on ultraselective nanofluidic systems.
Innovative molecular solar thermal (MOST) energy storage systems based on the [4 + 4] photodimerization and exothermic thermal retro-cycloaddition of substituted anthracenes have been developed by the Han group. We present new experimental results and comprehensive computational investigations elucidating the mechanisms underlying these MOST systems. Density functional theory (DFT) and spin-flip time-dependent DFT (SF-TDDFT) calculations are employed to examine the photochemical [4 + 4] dimerization and the stepwise diradical thermal retro-cycloaddition responsible for heat release. The onset temperature for retro-cycloaddition is found to relate to the computed activation barrier. A linear relationship between the calculated reaction exothermicity and the experimental activation temperature provides a principle that is useful for the design of anthracene-based MOST energy storage systems. QM/MM calculations on reactions in the crystalline state reveal how crystal forces influence the mechanism and rate of a solid-state retro-cycloaddition. The quantitative relationships among these energetic quantities lead to new designs of promising MOST molecules.
Regulatory inspections act as a primary mechanism ensuring workplaces are safe for workers. While the effectiveness of inspections conducted by the Occupational Safety and Health Administration (OSHA) has been the subject of numerous academic publications, there is no research observing a fairly foundational question regarding OSHA inspections, that being the degree to which their parameters affect rates of violations or injurious accidents uncovered. Functionally, inspections may be programmed (e.g., pre-planned in the traditional routine of activities conducted by OSHA) or unprogrammed (e.g., reacting to an incident or external force. Not pre-planned in the same manner). Along with differences in inspections, workplaces also have variations that may affect the rates of violations or injurious accidents, namely the type of industry or the state context in which they function. This paper aims to look at rates of violations and injurious accidents for programmed/unprogrammed inspections and, generally,within all industries and states. Further, the current work observes the way these rates change over the course of 40 years. Results indicate that inspection characteristics significantly impact violation and accident rates in two clear ways. Generally, unprogrammed inspections result in more violations, but this trend is shifting towards programmed inspections. Unprogrammed inspections reveal higher injurious accident rates, as expected. Future research implications are outlined.
In 2015, the Republic of Korea Armed Forces implemented a telemedicine pilot program that included teleophthalmology services provided through booths in remote and medically underserved military units linked to the Medical Emergency Operation Center. This study aimed to evaluate the epidemiology, distribution, and injury patterns of eye diseases managed using this military telemedicine program. Teleophthalmology consultations conducted between January 1, 2016, and December 31, 2023 were retrospectively reviewed. Diagnoses, causes of trauma, seasonal distributions, and evacuation trends were analyzed. Among the 47,701 telemedicine patients, 3,167 were ophthalmology patients. The most common diagnoses were hordeolum/chalazion (39.3%) and viral conjunctivitis (20.3%). Ocular trauma and injury occurred in 384 cases, most of which were caused by task-related activities (47.1%), particularly welding and exposure to metal fragments. Seasonal variation was significant, with the highest trauma incidence observed in summer (P = 0.014). Evacuation was required in 19.4% of ophthalmology patients and 49.9% of trauma and injury cases. This was the first long-term analysis of a military teleophthalmology program in South Korea. The study findings demonstrate the effectiveness of telemedicine in remote military environments, and underscore the need for protective equipment and task-specific safety training. Further development of remote diagnostic tools and targeted preventive strategies is warranted to reduce injury-related evacuations and to support combat readiness.
Human mesenchymal stem cells (hMSCs) undergo progressive functional decline during long-term ex vivo expansion, which limits their therapeutic potential. However, the contribution of intercellular adhesion to this process remains unclear. By comparing hMSCs at different passage stages, we found that replicative senescence is accompanied by impaired collective motility homeostasis in near-confluent monolayers, diminished traction forces and altered monolayer stress distribution, concomitant with upregulated N-cadherin expression. Notably, N-cadherin knockdown or pharmacological blockade of its homophilic binding using ADH-1 restored migratory dynamics, enhanced traction generation and alleviated senescence-associated phenotypes. These findings identify N-cadherin as a crucial regulator of replicative senescence and highlight intercellular adhesion as a potential target for delaying senescence during ex vivo stem cell expansion.