Search Results (331)

Background/Objectives: Sensorineural hearing loss (SNHL) is a chronic condition with no established pharmacological treatment. Recent advances in drug-based therapies offer promising opportunities to prevent or treat SNHL. This scoping review summarizes the current landscape of pharmacotherapeutics for SNHL. Methods: This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A literature search of PubMed, Google Scholar, Embase, Scopus, and Web of Science was conducted in 2024 using keywords related to SNHL and pharmacotherapeutics. A review protocol was preregistered on the Open Science Framework. A systematic search of five electronic databases identified published studies from 2004 to 2024 on pharmacological treatments for SNHL in human participants, as well as ongoing clinical trials. Interventions were categorized by mechanism of action: antioxidant therapy, steroid-based combination therapy, hematologic-based therapy, pathway modulator therapy, regenerative therapy, and gene therapy. A narrative synthesis approach was used to map key trends across treatment types, study designs, and outcomes. Results: Sixty-six records met the inclusion criteria, including 48 published studies and 18 ongoing or recently completed clinical trial records. Antioxidants, corticosteroids, hematologic agents, and pathway modulators have demonstrated potential in preventing or treating SNHL caused by cisplatin, aminoglycosides, noise-induced ototoxicity, and intraoperative cochlear implantation trauma. Emerging regenerative and gene therapies show promise as future pharmacologic treatment options. Conclusions: Pharmacologic therapies for SNHL are promising but remain constrained by small sample sizes, heterogeneous study designs, and drug delivery challenges across the blood–labyrinth barrier. Future research should prioritize multicenter randomized trials, optimized delivery strategies, and integration of precision medicine approaches. Full article

Background: mRNA vaccines, first approved in December 2020, have been used globally to prevent infectious diseases, and those for treating cancers are being developed. Safety-related labelling changes of Comirnaty and Spikevax were made in June 2025; however, concerns remain. This study assessed the potential risks associated with mRNA vaccines on the indications previously approved, utilizing Real-World Data (RWD) of Adverse Events Following Immunization (AEFIs) derived from the Vaccine Adverse Event Reporting System (VAERS) and Academic Literature Databases (ALD). Methods: A Disproportionality Analysis (DPA) was performed using the Reporting Odds Ratio (ROR) and the Bayesian Confidence Propagation Neural Network (BCPNN) algorithm on spontaneous case reports from VAERS. Statistical positive signals were cross-validated with literature case reports from ALD to provide more comprehensive medical descriptions and clearer causal assessments, and compared with safety information documented in clinical trials and on vaccine labelling. Time-to-onset, stratified, and immunization schedule analyses were conducted to characterize the safety profiles of mRNA vaccines. Results: In total, 5,040,725 spontaneous case reports and 4,387 literature case reports were analyzed. In both VAERS and ALD, new signals involving blood and lymphatic system disorders (e.g., thrombotic thrombocytopenic purpura) and ear and labyrinth disorders (e.g., deafness) were detected from Comirnaty as Designated Medical Events (DMEs), while blood and lymphatic system disorders (e.g., thrombotic thrombocytopenic purpura) from Spikevax in ALD only. No new signals were detected from other vaccines on the DMEs list. In VAERS, Serious Adverse Events (SAEs) were more common in females, while death risk was higher in males. In ALD, SAEs were more common in males for most mRNA vaccines, except Comirnaty. Medical history emerged as a key risk factor for SAEs, particularly among older adults. Conclusions: Statistically significant safety signals were detected across all mRNA vaccines based on five-year cumulative RWD, indicating the need of intensified monitoring of specific populations, including older adults and individuals with medical histories, alongside further optimization of vaccination strategies. Full article

The present investigation was designed to assess how perinatal contact with the pyrethroid insecticide cyfluthrin (CY) influences cognitive performance in developing rat progeny and to clarify the contributing cellular events through examination of neuroinflammatory processes alongside pyroptotic and apoptotic pathways. An experimental framework involving CY administration during gestation was implemented using Sprague–Dawley (SD) dams, with subsequent monitoring of placental parameters and neonatal outcomes. Once offspring reached postnatal day twenty-one, their behavior was characterized via a battery consisting of the open field paradigm, novel object recognition task, and the Morris water navigation test. Hippocampal tissue architecture and fine structural details were visualized by employing hematoxylin–eosin (HE) staining and Nissl substance labeling. Protein and transcript abundances for pro-inflammatory mediators (TNF-α, IL-6), synaptic constituents (postsynaptic density protein-95, PSD-95; synaptophysin, SYP), and pyroptotic machinery components (NLRP3, GSDMD, Caspase-1) within hippocampal homogenates were quantified through immunoblotting and real-time quantitative PCR procedures, and the spatial distribution of these molecules was validated via immunohistochemical detection. Neuronal apoptosis was assessed by TUNEL staining. The results demonstrated that gestational CY exposure led to reduced placental weight and diameter, decreased blood sinus area in the labyrinth zone, lower offspring birth weight, and impaired catch-up growth. Behavioral tests revealed that CY-exposed offspring exhibited diminished spontaneous locomotor activity, impaired novel object recognition memory, and significant deficits in spatial learning and memory. Pathological analysis showed disorganized neuronal arrangement and reduced Nissl bodies in the hippocampal CA1 region. Compared to the control group, CY exposure markedly upregulated the protein expression of TNF-α and IL-6, downregulated PSD-95 and SYP, activated the NLRP3/GSDMD/Caspase-1-mediated pyroptotic pathway, and increased the expression of the apoptotic protein Caspase-3, culminating in a significant increase in hippocampal neuronal apoptosis. In conclusion, early-life exposure to cyfluthrin impairs cognitive function in offspring, an effect closely associated with the induction of hippocampal neuroinflammation and the activation of pyroptotic and apoptotic pathways. These findings provide novel toxicological evidence for a more comprehensive assessment of the potential health risks posed by CY exposure in human populations. Full article

During development, stem cells rapidly proliferate and differentiate to form the embryo and the placenta, requiring intensive increases in cellular protein synthesis and changes to the cell architecture. Chaperone proteins, including the small heat shock proteins (HSPs), are critical assistants to protein folding, preventing protein aggregation, and promoting autophagy. Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) is a stress-activated kinase that promotes fetal and placental growth. MAP3K4 directly activates p38 and JNK in trophoblast stem (TS) cells by phosphorylating MAP2K3 and MAP2K4/7, respectively. In addition, MAP3K4 promotes activation of the Akt signaling pathway by controlling Igf1r expression. TS cells differentiate to placental trophoblasts comprising the junctional zone (JZ) and labyrinth (LAB) placental layers. In this study, we demonstrate that JZ differentiation transiently increases JNK activity, whereas LAB differentiation induces sustained p38, JNK, and Akt activation. Each of these pathways is inhibited in MAP3K4 kinase-inactive (KI) LAB^KI trophoblasts. JZ and LAB differentiation also induces HSP22 and HSP27 expression and HSP27 phosphorylation; these are also reduced in TS^KI and LAB^KI cells. JZ and LAB differentiation induces GABARAP-positive autophagosomes that are deficient in KI cells. Altogether, our findings demonstrate that MAP3K4 is critical for responses during differentiation in placental trophoblasts. Full article

Background: Paranasal sinuses and mastoid air cells have been attributed to multiple functions—such as voice resonance, cranial lightening, and pressure regulation—yet their potential role in local thermal homeostasis remains underappreciated. The thermoregulatory hypothesis, first proposed in the mid-twentieth century, was largely abandoned after the mid-century, when anthropological findings of climate-correlated variation seemed contradictory. Hypothesis: We propose that pneumatized skull regions form a three-component craniofacial biothermal system that maintains thermal stability in the ocular vitreous and vestibular endolymph, two avascular, temperature-sensitive structures that lack intrinsic thermoregulatory capacity. This represents a novel integration that explicitly links paranasal and mastoid pneumatization into a coordinated system that protects sensory organs, distinct from previous brain-cooling hypotheses. Mechanism: The system comprises: (1) passive thermal insulation via air spaces, providing ~15-fold greater thermal resistance than bone; (2) active cold protection via mucosal heat delivery (estimated 2–5 W capacity); and (3) active heat dissipation via evaporative cooling (estimated 0.3–0.5 W capacity). This architecture provides asymmetric protection, with cold buffering exceeding heat dissipation by approximately 5- to 15-fold, consistent with thermodynamic constraints and putative evolutionary priorities. Evidence: Preliminary observations consistent with this hypothesis include the anatomical proximity of pneumatized regions to the vitreous and labyrinth, intranasal selective brain cooling studies, and clinical observations after mastoidectomy showing preserved pressure buffering but reduced vestibular thermal insulation under extreme stimulation. Climate-correlated pneumatization patterns are consistent with bidirectional thermal adaptation. Implications: We present five falsifiable predictions that can be tested with thermographic imaging, pharmacological manipulation, and computational modeling. Validation could inform surgical planning, explain postoperative thermal-sensitivity symptoms, and provide evolutionary insights into craniofacial adaptation. Full article

In the surface protection of stone and brick cultural heritage, a primary challenge is that traditional polymeric coatings are prone to photooxidative degradation under ultraviolet (UV) irradiation, and the resulting aged fragments readily block the substrate micropores, leading to a loss of “breathability”. To address the performance conflict among waterproofing, breathability, and weather resistance, this study prepared few-layer Ti₃C₂T_X MXene using a minimally intensive layer delamination (MILD) method. The poor compatibility between MXene and the fluorosilicone (FPS) resin matrix was effectively resolved through covalent modification with a silane coupling agent (KH-550). Results demonstrate that at an ultralow loading (0.5 wt%), the functionalized f-MXene is uniformly dispersed within the resin. This structure not only spontaneously constructs a hierarchical rough architecture on the surface that imparts high hydrophobicity (water contact angle of 131.6°), but its internal “labyrinth effect” also effectively blocks corrosive media. Simultaneously, the intrinsic water vapor transmission rate of the substrate is effectively maintained (with a reduction of less than 3%), and no visually perceptible color difference is generated (∆E = 1.2). Mechanically, f-MXene relies on interfacial interactions to act as a “nano-skeleton” for stress transfer, thereby increasing the uniaxial compressive strength of fragile limestone by 32.4%. Optical and spectroscopic characterizations further elucidate its anti-aging mechanism: f-MXene not only provides broadband UV shielding but also exhibits highly efficient radical scavenging activity during long-term UV aging. After 400 h of aging, the concentrations of hydroxyl and superoxide anion radicals within the system are significantly reduced, blocking the photooxidative chain reaction from the source. This work develops a composite protective material system for stone cultural heritage that simultaneously integrates high moisture permeability, minimal visual intervention, and long-term antioxidant performance. Full article

Background and Objectives: Complicated cholesteatomatous otomastoiditis includes a spectrum of inflammatory, suppurative, and destructive lesions affecting the temporal bone and surrounding critical structures, including the dura mater, labyrinth, facial nerve, sigmoid sinus, and skull base. The selection of appropriate surgical techniques and closure materials is decisive for long-term outcomes, functional preservation, and prevention of life-threatening complications. This systematic review and meta-analysis evaluates the evidence base for surgical approaches, intraoperative technologies, and autologous and synthetic closure materials used in the management of iatrogenic and disease-related fistulas in otomastoid surgery. Materials and Methods: A PRISMA 2020-compliant search was conducted across PubMed, Cochrane Library, Embase, and Scopus (2000–2024). The review was registered in PROSPERO (CRD420261370406). After the systematic screening process, 56 eligible studies involving 4218 patients were selected for inclusion. The primary outcome measures analysed were infection rates, fistula recurrence, preservation of function, and long-term integrity of the closure. Limitations include the predominance of observational studies and the absence of prospective registration prior to data extraction. Results: Autologous materials demonstrated consistently low infection rates (<10%) in contaminated operative fields and therefore remain the preferred first-line option for the reconstruction of small to moderate defects. In contrast, synthetic materials exhibited superior mechanical durability in large sterile defects, achieving closure integrity rates of 85–92% at two-year follow-up. Hybrid reconstructive constructs provided the most favourable overall outcomes, with pooled closure integrity reaching 91.6%, suggesting a synergistic advantage when combining biologic and synthetic components. Furthermore, the adjunctive use of combined microscopic–endoscopic surgical techniques was associated with a significant reduction in residual cholesteatoma rates (OR 0.56, 95% CI 0.38–0.82), supporting the growing role of endoscopic assistance in middle ear and mastoid surgery. When biologic closure strategies were appropriately selected according to defect characteristics and contamination status, functional preservation rates exceeded 90–95%, underscoring the importance of tailored reconstructive approaches. Conclusions: The durability of long-term outcomes is most strongly influenced by complete pathological clearance and by the strategic alignment of biomaterial properties with defect dimensions, contamination status, and surrounding anatomical structures. In response to these findings, an evidence-based algorithmic framework is proposed to facilitate rational intraoperative material selection. Full article

Ménière’s disease is a complex disorder of the inner ear, characterized by recurrent episodes of vertigo, progressive hearing loss, tinnitus, and aural fullness. The pathophysiology of this condition is dominated by endolymphatic hydrops, reflecting imbalances in fluid regulation and pressure within the membranous labyrinth, which impair cellular function and the transmission of vestibular and auditory signals. Although genetic predisposition provides a susceptible background, recent studies emphasize that non-genetic factors act as critical triggers of clinical events, determining both the onset of symptoms and the modulation of their severity. These factors directly influence pathophysiology by disrupting endolymphatic homeostasis and altering the intracellular and tissue dynamics of the membranous labyrinth, thereby contributing to the phenotypic variability observed among patients. The key to this process lies in the synergistic interaction between genetic predisposition and external or contextual influences, which determines the threshold at which the compensatory mechanisms of the inner ear fail, triggering the characteristic episodes. Understanding this interdependence, as well as the underlying disease mechanisms, provides essential insights for the identification of preventive and therapeutic strategies aimed not only at symptom control but also at modulating the factors that influence susceptibility to endolymphatic imbalance. Full article

Ototoxicity is traditionally viewed as a local cochlear adverse effect of indispensable therapies such as cisplatin and aminoglycosides. However, emerging evidence suggests that cochlear vulnerability is shaped by systemic physiology, including inflammatory tone, vascular barrier integrity, and metabolic state. In this Review, we propose a Gut–Mito–Ear axis in which gut ecosystem function influences circulating mediator modules that converge on two cochlear mediator nodes: blood–labyrinth barrier (BLB) gating and mitochondrial stress tolerance. We synthesize evidence showing that gut perturbation can alter cochlear outcomes in vivo, that at least one microbiota-derived metabolite signal can directly protect hearing in experimental settings, and that BLB dysfunction and inflammatory trafficking are mechanistically relevant to cisplatin- and aminoglycoside-induced injury. We further organize the literature using an evidence-weighted framework that distinguishes direct cochlear causality from mechanistic plausibility and explicitly retains negative studies as boundary-setting evidence. Finally, we outline a translational roadmap in which microbiome-targeted prevention is pursued through mediator-anchored, non-interference-aware strategies and evaluated across linked state variables spanning exposure context, gut function, defined mediator modules, BLB gating, mitochondrial stress tolerance, and auditory phenotype. The Gut–Mito–Ear axis is not considered an established mechanism. We present it as a falsifiable systems-biology model that organizes the current evidence. Within this model, we define the minimum and ideal standards for A-tier causal evidence, explicit criteria for interpreting boundary-setting negative (A−) studies, and a set of testable predictions for causal validation. Full article

Drip irrigation system performance is largely governed by emitter hydraulic characteristics. This study systematically compares the hydraulic performance of a novel cylindrical asteroid-shaped channel emitter against a conventional toothed labyrinth design. Standardized specimens were produced using precision molds and integrated into drip tapes at 300 mm spacing. To comprehensively analyze flow behavior, pressure–discharge relationships, flow indices, and internal flow fields, a combination of physical experiments and CFD simulations was employed. Experimental results showed that across 20–200 kPa, the cylindrical asteroid-shaped emitter delivered flow rates 24–28% higher than the labyrinth type while maintaining a lower flow index, demonstrating enhanced hydraulic stability. Flow field analysis at 100 kPa revealed that the divergent asteroid geometry generates more intense and sustained turbulent kinetic energy throughout the channel units, resulting in superior energy dissipation. The cylindrical asteroid-shaped unit achieved a pressure drop of 17.5 kPa, exceeding the 15.3 kPa observed in the labyrinth channel, with outlet velocities of 1.6 m/s versus 1.76 m/s. Additionally, the flow pattern promotes comprehensive wall scouring through large-scale vortices, indicating improved resistance to clogging. These findings validate the design superiority of the cylindrical asteroid-shaped emitter and offer a theoretical reference for developing high-uniformity, water-saving irrigation devices. Full article

In water-scarce regions such as Xinjiang, China, agricultural development is constrained not only by limited water resources but also by a strong reliance on water-saving irrigation technologies. Drip irrigation is a key measure for improving irrigation efficiency and promoting the sustainable development of water-saving agriculture. However, defects arising during the manufacture of labyrinth Drip emitters—the core components of drip irrigation systems—can undermine system reliability, leading to channel blockage and non-uniform irrigation. To tackle this issue, a defect detection approach is developed by integrating Digital Twin technology with an enhanced YOLOv8 model for online inspection of labyrinth Drip emitters on drip irrigation tape production lines. In parallel, a self-built dataset covering six defect categories is established. Supported by the DT framework, the standard YOLOv8 network is refined to strengthen its capability in identifying complex micro-defects. Specifically, DySnakeConv is introduced to better represent the curved and slender characteristics of labyrinth channels; DySample is incorporated to improve the reconstruction and representation of fine-grained details; an Efficient Multi-Scale Attention module is adopted to capture richer contextual information while suppressing background noise; and Inner-SIoU is applied to optimize the bounding-box regression process. Experimental results show that the model achieves 89.6% precision, 90.9% recall, and 93.9% mAP50. Compared with the baseline YOLOv8, precision, recall, and mAP50 are improved by 7.3, 3.9, and 3.3 percentage points, respectively. Under the same training conditions, the proposed model outperforms YOLOv10 and YOLOv11 in accuracy-related metrics. Specifically, compared with YOLOv11, precision, recall, and mAP50 are improved by 4.8, 5.0, and 2.6 percentage points, respectively; compared with YOLOv10, they are improved by 10.0, 7.7, and 7.3 percentage points, respectively. Meanwhile, the model maintains a lightweight size of 3.7 M parameters and a real-time inference speed of 150.2 FPS, demonstrating a favorable accuracy–efficiency trade-off. By extending manufacturing-level quality control to agricultural applications, the approach helps ensure uniform irrigation and improve water-use efficiency, providing practical technical support for precision agriculture in arid regions. Full article

Mountain Social–Ecological Systems (MtSES) are global assets, providing essential ecosystem services to nearly half of humanity, yet they are disproportionately vulnerable to global change, experiencing “polytraps” of depopulation, poverty, and environmental degradation. Despite the inherent human dimension in sustainability, the social pillar remains conceptually chaotic, forming a highly fragmented “publication labyrinth”, and is often neglected in favor of more easily quantifiable environmental and economic metrics. These oversights leave mountain communities in a precarious state, underscoring an urgent need for robust, context-specific assessment tools. This paper addresses this critical gap by employing a two-step methodology: first, a literature review identifies prevailing social sustainability issues in mountain contexts; second, a comparative analysis evaluates prominent frameworks and indicator-based tools against these themes, using Ostrom’s multi-tier Social–Ecological Systems (SES) framework as the theoretical lens. Our findings reveal a persistent environmental bias in MtSES research and highlight the necessity for frameworks that integrate local knowledge, address power imbalances, and support bottom-up governance. A tool is proposed with indicators specifically for mountainous contexts. This study contributes to theory by offering a structured approach to unpack the elusive “social” in SES and to practice by providing a model and tool for developing actionable, context-sensitive social sustainability assessments, thereby fostering resilience and equitable development in vulnerable mountain regions. Ultimately, by operationalizing these social dimensions, this research provides a direct roadmap for achieving key United Nations Sustainable Development Goals in marginalized high-altitude contexts, particularly focusing on No Poverty (SDG 1), Good Health and Well-being (SDG 3), Reduced Inequalities (SDG 10), Sustainable Communities (SDG 11), and Peace, Justice, and Strong Institutions (SDG 16). Full article

Long-term operation of drip emitters under sediment-laden water conditions readily induces particle deposition and clogging, leading to discharge reduction and deterioration of irrigation uniformity. To clarify the temporal evolution and spatial distribution of clogging and to support structure-oriented anti-clogging improvement, three integrated drip tape emitters with different labyrinth-channel geometries were tested at sediment concentrations of 1, 2, and 3 g·L⁻¹ under a constant pressure of 100 kPa. The average relative discharge ratio (Dra) and Christiansen’s uniformity coefficient (CU) were continuously monitored, and cross-sectional observation and numerical simulation were combined to identify dominant deposition hotspot regions within the labyrinth channel. The results showed that increasing sediment concentration significantly accelerated clogging development and shortened operating lifetime. At 1 g·L⁻¹, the times required for the three emitter types to reach the clogging criterion of Dra < 75% were 120, 81, and 107 h, respectively, whereas at 3 g·L⁻¹ these values decreased to 39, 42, and 39 h. CU continuously declined with operating time and, in some treatments, responded earlier than Dra to system deterioration. Sediment deposition was mainly concentrated in the inlet section and bend regions, indicating that these locations were the dominant hotspots for clogging initiation and propagation. These findings demonstrate that clogging in drip emitters is jointly regulated by sediment load and labyrinth-channel geometry, and that hotspot-based structural optimization provides an effective basis for improving anti-clogging performance under sediment-laden water conditions. Full article

The runner of a pump turbine features a relatively flat structural configuration. The clearance cavities formed between the upper crown, lower band, and surrounding stationary components play a critical role in its dynamic behavior and operational stability. Consequently, a detailed modal analysis of the runner is essential to ensure safe and stable operation. In this study, an acoustic–structure coupling method is adopted to investigate the wet modal characteristics of the pump-turbine runner, explicitly accounting for the added mass effect induced by the fluid in the external flow passages. By systematically varying the geometric parameters of the upper crown clearance cavity, the influence of seal clearance dimensions on the runner’s modal characteristics is examined. The results demonstrate that the radial clearance and the axial height of the seal cavity are the most influential parameters, reducing natural frequencies by up to 15.85% and 16.93%, respectively. The pitch of the seal teeth shows a secondary yet notable effect, inducing a frequency variation of 13.73%. In contrast, local labyrinth seal parameters, such as the number of teeth and tooth width, have a comparatively limited effect. This study provides practical guidance for vibration risk prediction, anti-resonance design, and operational stability assessment of high-head, large-capacity turbine runners by revealing the quantitative relationship between geometric parameters and modal frequencies. Full article

This qualitative study examines the organizational structures shaping the experience of 18 women assistant heads working at K-12 independent, co-educational, day schools serving students of 700 students or more. Specifically, we were interested in better understanding the disproportionate representation of women in the assistant headship and whether, and to what degree, this may be a function of the role. We wondered if gendered structural elements shaping the role and specifically feminization (e.g., gendered expectations, role elasticity, diminished professional autonomy, and compensation structures that devalue care work) may hamper these women’s overall success and well-being. We found that the structures shaping their role did appear to be feminized, such that while many participants felt a sense of purpose in their work, the expansive and seemingly endless nature of their responsibilities; the emotional labor the role necessitated; the limited guidance, autonomy, and feedback they received; and their frequent perception that their efforts were under-compensated contributed to diminished well-being. The implications of this study include the need for training in, and implementation of, best practices for evaluation, mentorship, and mitigating gender bias and discrimination in all aspects of school operations. Full article