Search Results (917)

Behavioral investigation in zebrafish is essential for understanding adaptive responses, where learning represents a key process influenced by external stimuli. The applied stimulus plays a critical role in shaping such responses, therefore making physiologically relevant stimulation strategies important. Hydrodynamic stimuli represent one such modality, providing a natural and non-invasive means of activating mechanosensory responses in aquatic organisms, thereby enabling behavioral manipulation in microfluidic environments. To address this, a microfluidic assay was developed to generate controlled hydrodynamic environments by employing multiple S-shaped magnetic microactuators (SMMAs). Further, motions of these SMMAs were independently controlled to produce spatiotemporally varying vortical flow fields, enabling flow-induced transportation of zebrafish larvae. Flow dynamics were characterized by employing micro-particle image velocimetry (µPIV). Compared to the control condition, transportation time under microactuator-assisted guidance was significantly reduced, with a maximum improvement of 94.3% observed for a representative target zone. Building on this validated transport capability, training-dependent behavioral adaptation was quantified using latency under repeated hydrodynamic-training, where a reduction of 82.7% was achieved. Post-training assessment further demonstrated short-term retention of the acquired behavioral response followed by progressive extinction. These findings demonstrate that the proposed paradigm serves as a foundational behavioral assay leveraging hydrodynamic cues for studying adaptive responses in microfluidics. Full article

Rotator cuff tear (RCT) is a leading cause of shoulder pain encountered by general practitioners. Population-based screening shows that nearly half of full-thickness tears are asymptomatic, allowing many lesions to progress undetected. This narrative review summarises 105 clinical, imaging, biomechanical and rehabilitation studies published in recent years. The review follows the disorder from early tendinopathy to full-thickness tear and discusses crucial risk factors (age, diabetes, hypercholesterolaemia, overhead work). It aims to guide early primary-care management of RCT. We examine the diagnostic accuracy of classic bedside tests, including the supraspinatus weakness and external rotation lag cluster. Furthermore, we explain when ultrasound or MRI adds value and what the classic findings are. An informative overview of patient-reported outcome tools (e.g., SPADI, WOSI, Constant–Murley, ASES) could help physicians select one for follow-up. The article objectively evaluates the evidence for conservative measures—structured exercise protocols, manual therapy, oral analgesics, and corticosteroid or platelet-rich plasma injections. Moreover, we propose an evidence-based postoperative rehabilitation timeline with milestones that incorporate targeted immobilisation and progressive loading. The article presents selected clinical situations, such as the impact of type 2 diabetes on tendon biology. We explore the viability of experimental adjuncts such as extracorporeal shock-wave therapy, low-intensity pulsed ultrasound and electrical stimulation. Finally, we compare recommendations from the American Academy of Orthopaedic Surgeons and the European Society for Surgery of the Shoulder and Elbow. We highlight similarities between the recommendations (e.g., overlapping clinical examination tests), thereby facilitating their clinical application and providing a pragmatic guide for general practitioners. Our synthesis draws on orthopaedic, radiographic and rehabilitation data to reduce diagnostic delay, optimise non-specialist resource use, and improve pain and functional outcomes for the growing population affected by rotator cuff tears. Full article

The intrinsic properties of plants offer numerous opportunities for scientific and technological advancement. Considerable efforts have been directed toward developing plant-on-chip platforms to investigate cellular responses to external stimuli, including chemical, mechanical, and electrical cues. In this study, we present a fluidic platform using polydimethylsiloxane (PDMS) and a printed circuit board (PCB), integrated with electrochemical impedance spectroscopy (EIS) detection. Various experimental conditions were examined, including ionic and pH stimulation, as well as membrane dimensions, with the onion inner membrane treated as a black-box system. The measurement results are presented as Nyquist plots, and a resistance model incorporating multifactorial influences is proposed. Impedance variations in plant cells serve as a basis for electrical modulation. To explore these properties, we converted acoustic signals into electrical inputs and recorded the outputs after being modulated by onion inner epidermal cells. A transfer function analysis was subsequently performed. Our results indicate that the plant cell-on-chip (PCOC) platform holds promise for further investigations into plant cell properties. The impedance results suggest that plant cells can respond to different external stimuli, enabling modulation of the electrical properties. These findings lay the groundwork for future studies on cellular electrical characteristics and the development of preliminary bioelectrical circuits. Full article

Skin aging is a major consideration regarding cosmetic skin care. The cosmetic field is seeking new active ingredients able to slow down the appearance of signs of age. Some lichens and more specifically the genus Cetraria s. str. presents an interest as a source of active molecules because it is already being used in traditional and modern medicines. To better evaluate the potential of C. islandica as anti-aging skin care, we investigated some key aspects to protect skin from external aggression and to avoid skin alteration, which would exacerbate signs of age. Among them, our results reveal (i) antioxidant capacities; (ii) anti-inflammatory properties on human keratinocytes once stimulated, as shown by a decrease in IL-6, IL-8, CXCL9, CXCL10, and CCL5; (iii) a downregulation of MT1-MMP, which corresponds to decreased tissue remodeling; and (iv) an inhibition of human tyrosinase, which could correct the appearance over time of age-related skin spots. Altogether, these results highlight the potential use of C. islandica in anti-aging skin care. Full article

The increasing demand for broadband and self-powered optoelectronic devices has stimulated the development of two-dimensional (2D) material-based photodetectors. Here, we construct a self-powered photodetector based on a MoSe₂/SnS₂ van der Waals (vdW) heterostructure. The unique combination of MoSe₂ and SnS₂ provides complementary light absorption and a type-II band alignment, which generates an interfacial built-in electric field to facilitate photogenerated carrier separation and transport, enabling efficient self-powered operation without external bias. The device exhibits a broad spectral photoresponse from ultraviolet (UV) to infrared (IR) wavelengths (350–1050 nm). Under zero bias, the photodetector achieves a responsivity of 0.6 mA/W and a rapid response time of 5.8/6.1 ms (rise/fall) under 405 nm illumination, demonstrating effective self-driven photoresponse. With an applied reverse bias of −2 V, the device further reaches a responsivity of 161 mA/W and a detectivity of 8.6 × 10¹⁰ Jones under 405 nm illumination. In addition, the device exhibits a low dark current of 5 pA and a high on/off ratio of 1180. These results demonstrate the potential of the MoSe₂/SnS₂ vdW heterostructure for broadband and self-powered optoelectronic applications. Full article

Background/Objectives: Spinal cord epidural stimulation (scES) holds significant potential for restoring autonomic function after chronic spinal cord injury (SCI). A significant and often debilitating sequela of SCI is neurogenic lower urinary tract dysfunction, characterized by loss of voluntary bladder control, which adversely impacts patients’ dignity, urological health, and overall quality of life. In a pilot study of three individuals with SCI, an epidural electrode array was implanted between L2 and sacral segments to modulate lower urinary tract function for efficient emptying. Methods: Three participants with chronic thoracic clinically complete SCI were implanted with an epidural stimulator over the lumbosacral spinal cord. Array placement was confirmed using intraoperative and postoperative spatiotemporal mapping of known motor neuron pools following published protocols. In a controlled laboratory mapping, bladder storage and voiding neural networks were targeted during filling cystometry by interactively optimizing lower urinary tract stimulation parameters (electrode configuration, frequency, intensity, and pulse width). Efficacy was assessed during six-hour laboratory sessions of natural bladder filling, followed by approximately four months of daily at-home use. Results: Pre-implant cystometry revealed poor voiding efficiency and absent bladder sensation. Following bladder scES mapping and home training, one of the three participants regained direct bladder sensation, exceeded the 90% clinical threshold for efficient voiding, and continues to use scES for bladder management instead of intermittent catheterization, with no urinary tract infections reported since completion of training (February 2022). The inability of two participants to attain high voiding efficiency may be due to suboptimal adherence to prescribed bladder training protocols in one case and the presence of an elevated bladder neck in the other. All three participants reported off-target improvements in bowel and sexual functions. Conclusions: The present novel pilot study provides the first evidence supporting the potential use of epidural stimulation for bladder management and the importance of activity-based recovery training for durable performance. Full article

This paper presents a compact, low-power RC-less 4-ray Amplitude-Shift Keying (ASK) demodulator designed for high-density implantable devices. The proposed system addresses the challenges of wireless telemetry in high-density implantable systems, including high-speed data transfer and energy efficiency. In this paper, Schmitt trigger-based digital envelope detector (DED) enables flexible adaptation to various external influences through externally adjustable threshold levels. The system demodulates four types of data signals simultaneously, achieving high data rates while operating within a single frequency band using inductively coupled coils. Fabricated using the DB HiTeK 180 nm BCDMOS process, we tested the system in a benchtop wireless power transmission environment, demonstrating stable and accurate performance. The results indicate the system’s potential for application in implantable medical devices, particularly in scenarios requiring high-density stimulation. Full article

Senescence-related molecular nodes linking hepatic stress with immune dysregulation in metabolic dysfunction-associated steatotic liver disease (MASLD) remain poorly defined. This study aimed to identify and experimentally validate a senescence-related gene (SRG) signature associated with immune dysregulation in MASLD. Four transcriptomic datasets (127 controls, 127 MASLD) were integrated as the discovery cohort. Candidate SRGs were identified through differential expression analysis, weighted gene co-expression network analysis, and three machine learning algorithms. Immune infiltration was assessed using CIBERSORT, and a three-gene signature was evaluated in internal and external cohorts. Potential GADD45G-associated compounds were predicted by molecular docking. Experimental validation was performed in high-fat diet (HFD)-induced obese mice and palmitic acid (PA)-stimulated bone marrow-derived macrophages (BMDMs). Single-cell RNA sequencing analysis of GSE300744 was further performed to evaluate GADD45G distribution in hepatic cell populations. SOCS1, SOCS2, and GADD45G were identified as core SRGs. Their expression was reduced in MASLD liver tissues and correlated with histological features and immune alterations. The three-gene signature showed favorable classification performance in validation cohorts. In HFD mice, GADD45G expression was decreased at both mRNA and protein levels, with reduced immunoreactivity in F4/80-positive hepatic macrophages. Single-cell analysis further supported macrophage-associated expression of Gadd45g. In PA-stimulated BMDMs, reduced GADD45G protein expression was partially restored by camptothecin and myristicin treatment. Overall, SOCS1, SOCS2, and GADD45G represent a candidate senescence-related immune signature associated with MASLD. The macrophage-associated reduction in GADD45G and its modulation in vitro provide preliminary evidence for a potential role of GADD45G in MASLD-associated immune dysregulation. Full article

As an industry policy commonly adopted by governments worldwide, the digital industry cluster policy facilitates data resource accessibility. Whether this policy can also promote enterprise collaborative innovation, especially facilitating strong alliances among enterprises with high breakthrough innovation capabilities, is the key to cultivate internationally competitive advantages. To address this question, this paper takes China’s digital industry cluster policy as a quasi-natural experiment and employs the staggered difference-in-differences model to analyze the impact of digital industry clusters on enterprise collaborative innovation. This study finds that digital industry cluster policy drives an increase in the number of scientific, technological, and legal intermediaries, improves the level of judicial protection, and thus optimizes the external environment for enterprise collaborative innovation. Meanwhile, the policy promotes the deepening of enterprise division of labor, strengthens specialized agglomeration, and improves the allocation efficiency of data and labor factors, thereby stimulating the internal demand of enterprise collaborative innovation. Further analysis reveals that the policy does not facilitate strong–strong enterprise partnerships; instead, it promotes weak–weak and strong–weak enterprise partnerships. The academic contributions of this research are twofold: first, it investigates the impact of improved enterprise conditions on collaborative innovation from the perspective of enterprises’ own factor allocation capabilities; second, it examines the cooperative characteristics of enterprises with distinct breakthrough innovation capabilities, which expands the research scope of cooperative innovation characteristics. Full article

Electrical cues are essential regulators of tissue repair processes such as wound healing, nerve regeneration, and bone remodeling. Implantable electrical stimulation systems have therefore attracted increasing interest; however, conventional devices typically rely on external power supplies or batteries, leading to limitations including bulky system integration, finite lifetime, mechanical mismatch, and elevated risks of infection and revision surgery. Herein, we propose a conceptual classification of implantable electrical stimulation materials based on their relationship with electric charges, categorizing them into charge-storing materials, charge-conducting materials, and charge-generating materials. Among these, charge-generating materials represent an emerging class capable of autonomously converting endogenous mechanical, chemical, thermal, or optical energy into electrical signals, enabling self-powered and self-sustained electrical stimulation without external energy input. This review systematically summarizes the underlying mechanisms, material design strategies, and recent advances of representative charge-generating systems, including piezoelectric, triboelectric, and electrochemical materials. Their applications in tissue repair are critically discussed, highlighting unique advantages in device miniaturization, long-term operation, and intelligent responsiveness. Finally, current challenges and future perspectives are outlined to guide the development of next-generation self-powered bioelectronic therapies. Full article

The innovation-driven transformation of carbon-intensive industries is central to global climate governance and sustainable industrial specialization. Integrating Global Value Chain (GVC) embedding, external environmental dynamics, and industrial innovation, this study utilizes micro-to-macro extracted panel data from China’s carbon-intensive industries from 2007 to 2023 to construct a double debiased machine learning (DDML) model. We identify a robust innovation-promoting effect driven by both GVC participation and the GVC Domestic Content Ratio (DCR). Employing a causal mediation framework, we reveal that GVC embedding indirectly drives innovation by reshaping four functional dimensions: upgrading intermediate export quality, stimulating technology market activity, internalizing climate policy uncertainty, and aligning environmental violation disclosure. Furthermore, structural heterogeneity tests demonstrate that mature resource-based cities and backward-linked industries benefit substantially from learning-by-doing effects. In contrast, forward-linked industries and non-mature cities face an elevated risk of a positioning paradox and comparative advantage lock-in. This study provides rigorous empirical evidence for advancing SDG 9 in developing economies seeking to reconcile deeper global economic integration with carbon neutrality objectives. Full article

Background: Autopsy pathology remains the reference standard for determining the cause of death, reconstructing disease and injury mechanisms, ensuring diagnostic quality, and supporting medical education and forensic investigations. However, declining autopsy rates, workforce shortages, biosafety concerns, increasing diagnostic complexity, and the rapid evolution of digital technologies have stimulated the development of complementary investigative approaches. This review critically examines whether artificial intelligence (AI) and emerging technologies are driving a genuine paradigm shift toward digitally integrated death investigation. Methods: A structured narrative review informed by a systematic literature search was conducted in PubMed/MEDLINE, Embase, Scopus, and Web of Science, covering publications from January 2000 through June 2026. Evidence addressing postmortem imaging, virtopsy, digital pathology, computational pathology, molecular autopsy, robotics, artificial intelligence, machine learning, and emerging omics technologies was critically appraised. Owing to the methodological heterogeneity of the available literature, findings were synthesized qualitatively according to technological maturity, forensic applicability, validation status, and implementation readiness. Results: The reviewed evidence demonstrates substantial progress in postmortem computed tomography, postmortem CT angiography, postmortem magnetic resonance imaging, whole-slide imaging, molecular autopsy, robotic-assisted postmortem procedures, three-dimensional reconstruction, and AI-assisted forensic analysis. These technologies enhance trauma evaluation, vascular imaging, ballistic reconstruction, digital documentation, remote consultation, diagnostic reproducibility, and multimodal integration of forensic evidence. Nevertheless, the level of evidence varies considerably across technological domains. Postmortem imaging represents the most mature and extensively validated technology, whereas most AI applications remain supported predominantly by retrospective proof-of-concept studies with limited multicenter external validation. Current systematic evidence further indicates that AI should presently be regarded as an assistive technology that augments expert forensic interpretation rather than replacing conventional autopsy or autonomous medicolegal decision-making. Conclusions: Contemporary autopsy pathology is evolving toward a hybrid model of digitally integrated death investigation in which conventional autopsy, imaging, digital pathology, molecular diagnostics, robotics, and AI function as complementary components of a unified forensic workflow. Current evidence supports a conceptual paradigm shift characterized by transformation of evidence acquisition, preservation, interpretation, and integration, while reaffirming that conventional autopsy remains the indispensable biological reference standard for the development, validation, and medicolegal interpretation of all emerging technologies. Future implementation should prioritize multicenter validation, standardized forensic datasets, explainable AI, digital chain-of-custody procedures, and robust regulatory governance to ensure safe and scientifically reliable integration into forensic practice. Full article

Background: Low-load resistance exercise with blood flow restriction (BFR) may increase neuromuscular stimulation while reducing external load. This pilot study examined the acute effects of unilateral knee extension at 20% one-repetition maximum (1RM) with BFR at 80% estimated arterial occlusion pressure (AOP), compared with the same protocol without BFR, on vastus lateralis surface electromyographic (sEMG) activity in healthy young adults. Methods: Twenty participants were randomized to receive BFR on either the dominant (n = 10) or non-dominant limb (n = 10); the contralateral limb completed the non-BFR condition. Both conditions were performed in randomized order during one session, separated by 10 min. Each limb completed 75 repetitions (30-15-15-15) at 20% of its limb-specific 1RM. The prespecified primary outcome was normalized RMS amplitude across 12 protocol windows, analyzed using a linear mixed model. Results: Normalized RMS amplitude was higher under BFR (between-condition difference, 21.12%MVIC; 95% CI, 14.54 to 27.71; p < 0.001). Exploratory analyses showed higher global mean and peak RMS under BFR, whereas within-protocol RMS change and temporal slope did not differ. The post-exercise percentage reduction in MVIC-derived RMS amplitude was smaller under BFR (−0.6 ± 14.1% vs. −15.4 ± 12.3%; p = 0.002). Significant secondary findings remained significant after Holm adjustment. No adverse events were spontaneously reported or observed immediately. Conclusions: Under this acute laboratory protocol, individualized BFR was associated with higher vastus lateralis sEMG amplitude than unrestricted exercise. MVIC-derived findings were exploratory and should not be interpreted as evidence of preserved strength or reduced neuromuscular fatigue. Larger studies, including clinical populations, are required. Full article

Background: Thyroid function tests are frequently requested, but manufacturer reference intervals often lack age- or sex-based stratification. This study established indirect reference intervals for thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) in a large adult population. We evaluated unsupervised algorithms and conventional partitioning to identify subgroups, compared multiple limit estimation methods, and assessed the diagnostic performance of the derived intervals against an independent, clinically defined external validation cohort. Methods: Data from 37,255 adults (age ≥ 18) collected between 2022 and 2024 were analyzed; a reference population of 5870 individuals was established following standardized exclusion criteria. Age-based subgroups were identified through hierarchical clustering with the Elbow method, and variable importance was assessed using Random Forest analysis. Reference intervals were calculated using non-parametric, Bhattacharya, refineR, and reflimR algorithms, applied to three population frameworks: (1) the total population without stratification, (2) subgroups derived from hierarchical clustering and (3) subgroups defined by the conventional Harris–Boyd partitioning method. Diagnostic performance was subsequently evaluated in an independent external cohort (National Health and Nutrition Examination Survey [NHANES]; N = 2297) for all estimated reference intervals. Three classification scenarios were assessed: TSH-only, fT4-only, and combined TSH + fT4, with sensitivity, specificity, Youden index, and decision curve analysis performed for each. Results: Random Forest analysis identified age as the dominant variable influencing TSH, fT4 and fT3 distributions (mean decrease in accuracy: TSH 41.62, fT4 44.18, fT3 43.7), while sex showed the lowest impact. Clustering yielded six age-based subgroups for analytes. Harris–Boyd partitioning yielded six age-based subgroups for TSH, two sex-based subgroups for fT4, and six combined age-and-sex subgroups for fT3. TSH limits were broadly concordant across all three approaches (six-subgroup partitioning: 0.36–0.68 to 4.75–5.67 mIU/L). For fT4, conventional (sex-based) and clustering (age-based) partitioning produced similar ranges (11.33–20.08 pmol/L), except reflimR’s notably lower limit (10.90 pmol/L). For fT3, conventional (age + sex) and clustering (age-only) partitioning showed comparable ranges (3.36–7.03 pmol/L), with clustering revealing a clearer age-related decline in the oldest group. Diagnostic performance varied markedly by analyte. TSH-only classification achieved positive discrimination across all 13 methods (Youden index: 0.173–0.239). In contrast, fT4-only and combined TSH + fT4 classifications performed at or below chance for most methods, with 75% of the cohort falling outside fT4 reference intervals, indicating an inter-platform harmonization issue rather than a partitioning failure. Decision curve analysis confirmed TSH-only classification’s superiority, exceeding universal testing from pt ≈ 0.20 onward across all methods. Conclusions: Age-stratified reference intervals combined with limit estimation showed potential diagnostic advantages over manufacturer and non-stratified intervals; however, an independent external validation using a clinically defined outcome indicated that this advantage was not consistently reproduced and was dependent on the clinical decision threshold considered. These results suggest that age stratification and algorithm choice merit further clinically adjudicated validation before broad clinical adoption, and that unsupervised clustering offers a practical, objective alternative to manual subgrouping for laboratories pursuing this approach. Full article

The round window membrane (RWM) presents a major barrier to local drug delivery into the inner ear. Although magnetically guided superparamagnetic iron oxide nanoparticles (SPIONs) have shown promise for enhancing transport across the RWM, the effectiveness of magnetic-field-driven delivery decreases rapidly with distance from the magnet, limiting clinical applicability. In this study, PEGylated SPIONs were investigated as externally actuated carriers for enhanced transport across membrane barriers using magnetic, photothermal, ultrasonic, and vibrational stimulation. Nanoparticle transport was evaluated using a custom dual-chamber benchtop platform containing porcine small intestinal submucosa (SIS) membranes as a model transport barrier. Transport studies demonstrated that magnetic-field-assisted delivery significantly increased magnetic nanoparticle (MNP) transport rates relative to passive diffusion; however, transport enhancement decreased sharply with increasing magnet-to-membrane distance. To overcome this limitation, alternative external actuation strategies were explored. Laser-induced photothermal heating, ultrasonication, and mechanical vibration all significantly enhanced MNP transport, even in the absence of magnetic fields. Among the conditions examined, combined magnetic and photothermal stimulation produced the highest transport rates, indicating synergistic enhancement. These results show that MNP transport can be effectively enhanced through magnetic, thermal, and mechanical mechanisms. The findings establish a multimodal transport-engineering framework for improving drug delivery across the RWM and suggest clinically translatable alternatives to magnetic-field-only approaches for inner-ear therapy. Full article