Search Results (616)

Oral cancer, the most common head and neck malignancy, has a high recurrence rate and poor prognosis largely owing to chemotherapy resistance. The adverse effects of conventional therapies have prompted investigations into safer and more effective alternative therapies. Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown potential owing to their roles in autophagy modulation and immune regulation. This study clarifies the selective efficacy of hydroxychloroquine (HCQ) and chloroquine (CQ) in oral squamous cell carcinoma models, emphasizing distinct responses in gingival (Ca9-22) and tongue (SCC-9) carcinoma cells. Non-oncogenic oral epithelial cells (GMSM-K) and oral carcinoma cell lines from the tongue (SCC-9, Cal-27) and gingiva (Ca9-22) were used. Cell viability, cytotoxicity, and colony formation were assessed via MTT, LDH, and crystal violet assays. Flow cytometry was used to measure apoptosis, autophagy, oxidative stress, mitochondrial membrane potential, and DNA damage. The transcriptomic profiles of apoptosis and autophagy-related genes were assessed by qPCR arrays. Bioinformatics analysis allowed estimation of the main gene interaction networks. Pre-screening showed that GMSM-K and Cal-27 cells were non-responsive or exhibited non-specific toxicity at high doses; therefore, subsequent analyses focused on Ca9-22 (GC) and SCC-9 (TC). HCQ significantly reduced viability and colony formation in Ca9-22 cells while moderately affecting SCC-9 cells. Autophagy inhibition was accompanied by compensatory up-regulation of autophagy-related genes, consistent with feedback activation of TFEB and FOXO3a pathways. Gene expression profiling and flow-cytometry analyses revealed cell-type-specific differences in apoptosis, mitochondrial potential, and DNA damage, suggesting HCQ’s selective anti-tumor potential in gingival carcinoma. These findings highlight HCQ as a repurposed adjuvant therapy that modulates autophagy and apoptosis to enhance chemosensitivity in oral cancer. Full article

This study compared velocity-based training (VBT) with percentage-based training (PBT) on acceleration (30-m sprint) and explosive power in high school triple jump athletes. Twelve male national-level athletes were randomized (1:1, concealed allocation; blinded assessors) to VBT (n = 6) or PBT (n = 6). Both groups completed identical lower-body resistance training three times per week for eight weeks; the VBT group additionally received real-time barbell-velocity feedback with velocity-loss (VL) based set termination (15–20%). Performance was assessed using 30-m sprint, standing long jump (SLJ), standing triple jump (STJ), and vertical jump (VJ) at pre- and post-test. Statistical analysis included baseline-adjusted ANCOVA and effect sizes (Hedges’ g). VBT improved 30-m sprint (−1.08%, d = 0.89), SLJ (+2.07%, d = 1.02), STJ (+1.64%, d = 0.63), and VJ (+6.01%, d = 1.39; all p < 0.001). PBT also improved SLJ (+1.03%, d = 0.69; p < 0.001) and showed a moderate, statistically significant within-group gain in STJ (+0.56%, d = 0.72; p = 0.001), while improvements in 30-m sprint and VJ were modest. Between-group effects favored VBT across all outcomes. These preliminary findings suggest that VBT may provide more targeted neuromuscular adaptations than PBT, particularly in explosive movements relevant to triple jump performance. However, due to the modest sample size and limited precision, the results should be interpreted with caution and confirmed in larger, adequately powered randomized trials. Nevertheless, this study offers practical insight into load prescription for youth jump athletes and represents one of the first randomized trials to directly compare VBT and PBT in this population. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a critical global health threat, with sub-Saharan Africa disproportionately affected. Antimicrobial stewardship (AMS) programs are essential in combating AMR; however, data on their implementation in resource-limited settings like Zambia remain scarce. This study assessed the post-implementation status of World Health Organization (WHO) AMS core elements in selected public hospitals in Zambia. Methods: A cross-sectional pre- and post-intervention survey was conducted in 11 public hospitals across Zambia’s 10 provinces. Baseline (pre-implementation) and 12-month follow-up (post-implementation) assessments were carried out using the WHO-adapted Periodic National and Healthcare Facility Assessment Tool. The six AMS core elements evaluated included leadership, accountability, AMS actions, education, monitoring, and feedback. Results: The average AMS program score increased from 59% at pre-implementation to 81% at post-implementation. Significant improvements were observed in education and training (+36%) and accountability (+31%). While leadership and monitoring also showed positive trends, gaps persisted in AMS actions (63%) and feedback/reporting mechanisms (68%). Drug and Therapeutics Committee (DTC) functionality improved by 23%, with 90% of facilities now holding regular DTC meetings. Implementation of AMS actions, such as ward rounds, rose from 0% to 73%. Challenges remained in clinical audit feedback, resource mobilization, and prescribing optimization. Variability across facilities highlighted differences in leadership, resources, and technical capacity. Conclusions: AMS implementation in Zambia improved substantially across key domains. However, sustained leadership, adequate financing, and continuous capacity-building are needed to address persistent gaps and ensure long-term success in mitigating AMR. Full article

Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, demanding improved biomarkers and therapeutic approaches. This review synthesizes the extensive evidence positioning the miR-200 family as a master regulator of NSCLC progression. We detail the core molecular circuitry centered on the bistable, double-negative feedback loop between miR-200 and the ZEB1/ZEB2 transcription factors, which governs epithelial–mesenchymal transition (EMT). This review connects this central mechanism to critical clinical challenges, including the development of resistance to EGFR-targeted therapies and the regulation of immune evasion through PD-L1 expression and CD8+ T cell infiltration. We evaluate the strong clinical evidence for the miR-200 family’s utility as a diagnostic, prognostic, and predictive biomarker. Finally, we explore emerging therapeutic strategies that target this network, including miRNA replacement, epigenetic reactivation, and rational combinations with immunotherapy and targeted agents. We synthesize evidence positioning the miR-200/ZEB feedback circuit as a central regulatory node in NSCLC that links EMT with therapeutic resistance and immune evasion. Beyond summarizing associations, we interpret how this circuitry could inform biomarker development and rational combinations with targeted and immune therapies. Given heterogeneous study designs and non-standardized assays, translational claims remain provisional; we outline immediate priorities for assay harmonization and biomarker-stratified trials. Full article

Soft robotic grippers have emerged as crucial tools for safe and adaptive manipulation of delicate and different objects, enabled by their compliant structures. These grippers need embedded sensing that offers proprioceptive and exteroceptive feedback in order to function consistently. Resistive sensing is unique among transduction processes since it is easy to use, scalable, and compatible with deformable materials. The three main classes of resistive sensors used in soft robotic grippers are systematically examined in this review: ionic sensors, which are emerging multimodal devices that can capture both mechanical and environmental cues; tactile sensors, which detect contact, pressure distribution, and slip; and strain sensors, which monitor deformation and actuation states. Their methods of operation, material systems, fabrication techniques, performance metrics, and integration plans are all compared in the survey. The results show that sensitivity, linearity, durability, and scalability are all trade-offs across sensor categories, with ionic sensors showing promise as a new development for multipurpose soft grippers. There is also a discussion of difficulties, including hysteresis, long-term stability, and signal processing complexity. In order to move resistive sensing from lab prototypes to reliable, practical applications in domains like healthcare, food handling, and human–robot collaboration, the review concludes that developments in hybrid material systems, additive manufacturing, and AI-enhanced signal interpretation will be crucial. Full article

Besides genomic and proteomic analyses of bulk and individual cancer cells, cancer research focuses on the mechanical analysis of cancers, such as cancer cells. Throughout the oncogenic evolution of cancer, mechanical inputs are stored as epigenetic memory, which ensures versatile coding of malignant characteristics and a quicker response to external environmental influences in comparison to solely mutation-based clonal evolutionary mechanisms. Cancer’s mechanical memory is a proposed mechanism for how complex details such as metastatic phenotypes, treatment resistance, and the interaction of cancers with their environment could be stored at multiple levels. The mechanism appears to be similar to the formation of memories in the brain and immune system like epigenetic alterations in individual cells and scattered state changes in groups of cells. Carcinogenesis could therefore be the outcome of physiological multistage feedback mechanisms triggered by specific heritable oncogenic alterations, resulting in a tumor-specific disruption of the integration of the target site/tissue into the overall organism. This review highlights and discusses the impact of the ECM on cancer cells’ mechanical memory during their metastatic spread. Additionally, it demonstrates how the emergence of a mechanical memory of cancer can give rise to new degrees of individuality within the host organism, and a connection to the cancer entity is established by discussing a connection to the metastasis cascade. The aim is to identify common mechanical memory mechanisms of different types of cancer. Finally, it is emphasized that efforts to identify the malignant potency of tumors should go way beyond sequencing approaches and include a functional diagnosis of cancer physiology and a dynamic mechanical assessment of cancer cells. Full article

Introduction: Major depressive disorder (MDD) is a mental disorder with a high prevalence rate and a high recurrence rate. Therefore, identifying and intervening in the core symptoms of MDD patients is of great significance. Anhedonia is manifested as an individual losing interest in activities or experiencing a significant decrease in the sense of pleasure, which is one of the two core symptoms of MDD. Episodic Future Thinking (EFT) training refers to the process of stimulating individuals’ hope for positive future scenarios and encouraging them to take purposeful actions, which may have an effect in alleviating anhedonia. However, the perception of anhedonia of MDD patients among Chinese healthcare professionals is still unclear, and there has been no exploration of the views of healthcare professionals regarding the implementation of EFT training for MDD patients led by psychiatric nurses in a clinical setting. Aim: This study aimed to understand the attention paid by Chinese healthcare professionals to the symptom of anhedonia in patients with MDD, as well as their previous coping strategies. This study further explored the views of healthcare professionals regarding the implementation of EFT training for MDD patients led by psychiatric nurses with a psychological therapist certificate in China, as well as suggestions for future implementation. Methods: This qualitative descriptive study adopted a phenomenological approach. Using purposive sampling, 15 healthcare professionals (psychiatrists, psychiatric nurses and psychological counselors) were recruited from the psychiatry department of a public tertiary hospital in Wuhan, Hubei Province, China. Using the NVivo 12 Plus software, the semi-structured interviews and analyses were conducted by applying Colaizzi’s seven-step phenomenological method. Rigor was ensured through checks of credibility, dependability, and confirmability during data collection and analysis. Results: A thematic analysis revealed that, while psychia-trists and psychological counselors viewed anhedonia as a significant treatment target, nurses were more focused on immediate patient safety concerns. Participants recognized the potential of EFT training to alleviate anhedonia but identified several implementation challenges, including patient resistance, cognitive limitations, and the need for tailored interventions. Conclusions: The research results indicated that psychiatric nurses had relatively poor ability to identify anhedonia. Therefore, it is necessary to enhance the awareness of psychiatric nurses regarding the clinical significance of anhedonia, and incorporate knowledge related to anhedonia into routine nursing training. It is suggested that communication and collaboration among psychiatrists, psychiatric nurses and psychological counselors should be strengthened, and an assessment and feedback process for the lack of anhedonia in patients with MDD should be established, so as to assist these patients in achieving faster psychological recovery. Given the sufficient staffing conditions in the field of psychiatry nursing in China, the design concept and curriculum of EFT training for psychiatry nurses with a psychological therapist certificate should be promoted. Encourage psychiatry nurses with a psychological therapist certificate to conduct offline and online group EFT training intervention forms for MDD patients in the hospital wards during their hospitalization periods, as well as after discharge at home. Full article

The intricate connections between plants and the microbial populations that surround them are crucial for plant development and resilience, but little is known about the evolutionary processes influencing these partnerships. Less is known about how pathogenic and beneficial microbes coevolve with their plant hosts over ecological and evolutionary timeframes, despite the fact that several studies identify rhizosphere and endophytic microbes that support nutrient acquisition, disease resistance, and stress tolerance. Using molecular, ecological, and evolutionary investigations from soil, rhizosphere, and endosphere habitats, this review summarizes current findings on microbial coevolution in plant–microbe systems. We look at the endosymbiotic processes that underlie the development of organelles, the mechanisms of mutualism and antagonism, and the eco-evolutionary feedbacks that affect plant health and agricultural output. The inadequate comprehension of intraspecific microbial diversity, the application of laboratory coevolution experiments to field settings, and the long-term effects of climate change on the evolutionary dynamics of plants and microbiomes are some of the major knowledge gaps. When pathogenic and beneficial microbes apply selective pressures to one another and their common host, coevolution takes place. This results in mutual genetic and physiological adaptations, such as modifications to host immunity, microbial virulence, or competitive tactics, which influence the way the two types interact over time. We conclude that understanding plants as holobiont-integrated units of hosts and their microbiomes offers fresh chances to develop microbiome-based approaches to sustainable agriculture, such as coevolutionary breeding programs, precision biofertilizers, and resilient cropping systems. Full article

Background: Primary care overload, limited access to physicians, and rising antimicrobial resistance highlight the role of pharmacists in managing minor ailments such as sore throats. We evaluated pharmacy-based counseling in Poland supported by point-of-care testing and symptomatic therapy. Methods: Multicenter, prospective observational study across 23 community pharmacies. Adults (≥18 years) with sore throat underwent group A streptococcus (GAS) rapid antigen testing. Patients with a positive test result were referred to physicians, while others received pharmacist counseling and ketoprofen throat spray. Standardized questionnaires captured symptom severity, perceived effectiveness, onset/duration, convenience, adherence, and patient-reported outcomes. Results: 142 patients were included. Among ketoprofen users, 98.4% reported improvement, and 75% rated relief ≥8/10. Compared with prior remedies, 88.3% judged ketoprofen more effective, and 86.7% reported faster onset. The spray was convenient for 91.4% of participants; no overdosing occurred. Qualitative feedback emphasized rapid relief, easier swallowing/speaking, and return to daily activities without physician consultation. Conclusions: Polish community pharmacy practice, an integrated sore throat pathway combining point-of-care RADT with structured pharmacist counseling and symptomatic treatment, was feasible, acceptable, and without notable safety concerns. As a pilot, these practice-based findings warrant larger comparative and economic studies to confirm clinical effects and assess potential impact on antibiotic use. Full article

Assessment practices are central to higher education, particularly critical in theory-based programs, where they facilitate the development of conceptual understanding and higher-order cognitive skills. They also support Saudi Arabia’s Vision 2030 agenda, which aims to drive educational innovation. This narrative review examines assessment practices in theory-based programs at a Saudi public university, identifies discrepancies with learning objectives, and proposes potential solutions. A narrative review synthesised peer-reviewed literature (2015–2025) from Scopus, Web of Science, ERIC, and Google Scholar, focusing on traditional and alternative assessments, barriers, progress, and comparisons with international standards. The review found that traditional summative methods (quizzes, final exams) still dominate and emphasise memorisation, limiting the development of higher-order skills. Emerging techniques, such as projects, portfolios, oral presentations, and peer assessment, are gaining traction but face institutional constraints and resistance from faculty. Digital adoption is growing: 63% of students are satisfied with learning management system tools, and 75% find online materials easy to understand; yet, advanced analytics and AI-based assessments are rare. A comparative analysis reveals that international standards favour formative feedback, adaptive technologies, and holistic competencies. The misalignment between current practices and Vision 2030 highlights the need to broaden assessment portfolios, integrate technology, and provide faculty training. Saudi theory-based programs must transition from memory-oriented evaluations to student-centred, evidence-based assessments that foster critical thinking and real-world application. Adopt diverse assessments (projects, portfolios, peer reviews), invest in digital analytics and adaptive learning, align assessments with learning outcomes and Vision 2030 competencies, and implement ongoing faculty development. The study offers practical pathways for reform and highlights strategic opportunities for achieving Saudi Arabia’s national learning outcomes. Full article

A broad-temperature-range wavelength tracking system employing a thermistor monitoring circuit and a tunable optical filter is proposed and experimentally demonstrated. In this scheme, a thermistor monitoring circuit is utilized to acquire the real-time resistance values of a distributed feedback laser diode (DFB-LD). When the mapping relationship curve among thermistor resistance, temperature, and center wavelength of the DFB-LD is established, the drive voltage of the narrowband tunable optical filter is dynamically adjusted to regulate its filter window. Therefore, wavelength tracking is achieved by matching the filter window and the center wavelength of the DFB-LD. The experimental results show that the proposed system can achieve adaptive wavelength tracking within the operation band of 1539.4 nm to 1548.6 nm across a temperature range from −40 °C to 60 °C. The wavelength detection resolution and the minimum step of wavelength control are better than 0.79 pm and 0.1 nm, respectively. By exploiting the conversion characteristics between the thermistor and the center wavelength of the DFB-LD, this approach transforms laser wavelength detection into a low-cost, real-time electrical measurement, significantly enhancing transmission stability and reliability of laser sources in complex thermal environments. Full article

As wind power penetration continues to increase, the sub-synchronous control interaction (SSCI) problem caused by the interaction between doubly fed induction generators (DFIGs) and series-compensated transmission lines has become increasingly prominent, posing a serious threat to power system stability. To address this problem, this research proposes a centralized sub-synchronous oscillation damping controller (CSODC) for wind farms. First, a DFIG impedance model was constructed based on multi-operating-point impedance scanning and a Taylor series expansion, achieving impedance prediction with an error of less than 2% under various power conditions. Subsequently, a CSODC comprising a sub-synchronous damping calculator (SSDC) and a power electronic converter is designed. By optimizing feedback signals, phase shift angles, gain parameters, and filter parameters, dynamic adjustment of controllable impedance in the sub-synchronous frequency band is achieved. Frequency-domain impedance analysis demonstrates that the CSODC significantly enhances the system’s equivalent resistance, reversing it from negative to positive at the resonance frequency point. Time-domain simulations validated the CSODC’s effectiveness in scenarios involving series capacitor switching and wind speed disturbances, demonstrating rapid sub-synchronous current decay. The results confirm that the proposed strategy effectively suppresses sub-synchronous oscillations across multiple scenarios, offering an economical and efficient solution to stability challenges in high-penetration renewable energy grids. Full article

Background/Objectives: Antibiotic use for respiratory tract infections is often suboptimal and does not follow clinical guidelines. Inappropriate antibiotic use is a driver for antimicrobial resistance. Our aims were to identify antimicrobial prescribing guidelines used to aid decision-making, describe perceptions on guideline compliance, and explore barriers and enablers to optimal antimicrobial use in hospitalised patients with respiratory tract infections. Methods: Qualitative semi-structured interviews were conducted with antimicrobial stewardship pharmacists (n = 10) and respiratory (n = 5) and infectious diseases (n = 2) specialists from hospitals in New South Wales, Australia. Interviews were recorded, transcribed verbatim, and coded thematically. Results: Participants primarily used an online evidence-based national consensus guideline to inform antibiotic choices. These guidelines were perceived to be useful and simple to access but did not contain all relevant information and were deemed too verbose to be practical. Pharmacists and physicians had different perceptions on guideline compliance. Barriers to guideline compliance and optimal antibiotic use included inadequate diagnostics and staffing, patient treatment pressure, and lack of knowledge and ownership of the impact of prescribing decisions. A positive working relationship with the antimicrobial stewardship team, prescribing feedback, and increasing the availability of data and decision support tools were reported as enablers. Conclusions: National prescribing guidelines are available to guide decisions but adherence to their recommendations was variable. Insufficient access to useful diagnostics, resourcing, and knowledge may negatively impact antimicrobial prescribing. Education, feedback, and tools and data to aid decision-making may improve optimal antimicrobial use. Focusing on incorporating these enablers into future prescribing interventions will be vital for antimicrobial stewardship practices. Full article

Autoimmune diseases are chronic inflammatory conditions characterized by the breakdown of immune tolerance to self-antigens. While genetic and environmental factors play key roles, growing evidence highlights chronic stress as a significant contributor to immune dysregulation through its impact on the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis, primarily via cortisol secretion, serves as the major neuroendocrine mediator of stress responses, influencing both immune regulation and systemic homeostasis. This review synthesizes current literature on HPA axis physiology, the mechanisms of cortisol signaling, and the maladaptive effects of chronic stress. Emphasis is placed on clinical and experimental findings linking HPA dysfunction to immune imbalance and autoimmunity, as well as organ-specific consequences across neuroimmune, endocrine, cardiovascular, gastrointestinal, integumentary, and musculoskeletal systems. Chronic stress leads to impaired HPA axis feedback, glucocorticoid receptor resistance, and paradoxical cortisol dysregulation, fostering a pro-inflammatory state. This dysregulation promotes cytokine imbalance, weakens protective immune mechanisms, and shifts the immune response toward autoimmunity. Evidence from both human and animal studies associates persistent HPA dysfunction with diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. HPA axis dysregulation under chronic stress constitutes a critical mechanistic link between psychological stress and autoimmune disease. Understanding these pathways provides opportunities for therapeutic interventions, including stress management, lifestyle modification, and neuroendocrine-targeted treatments. Future research should focus on multi-omics and longitudinal approaches to clarify the reversibility of HPA alterations and identify resilience factors. Full article

We present a hybrid partial differential equation-agent-based model (PDE-ABM). In our framework, tumor cells secrete tumor angiogenic factor (TAF), while endothelial cells chemotactically migrate and branch in response. Reaction–diffusion PDEs for TAF, oxygen, and cytotoxic drug are coupled to discrete stochastic dynamics of tumor cells and endothelial tip cells, ensuring multiscale integration. Motivated by observed perfusion heterogeneity in tumors and its pharmacokinetic consequences, we conduct a linear stability analysis for a reduced endothelial–TAF reaction–diffusion subsystem and derive an explicit finite-domain threshold for Turing instability. We demonstrate that bidirectional coupling, where endothelial cells both chemotactically migrate along TAF gradients and secrete TAF, is necessary and sufficient to generate spatially periodic vascular clusters and inter-cluster hypoxic regions. These emergent patterns produce heterogeneous drug penetration and resistant niches. Our results identify TAF clearance, chemotactic sensitivity, and endothelial motility as effective levers to homogenize perfusion. The model is two-dimensional and employs simplified kinetics, and we outline necessary extensions to three dimensions and saturable kinetics required for quantitative calibration. The study links reaction–diffusion mechanisms with clinical principles and suggests actionable strategies to mitigate resistance by targeting endothelial–TAF feedback. Full article