Tinnitus is often initiated by damage to the peripheral auditory system, for example by acoustic overexposure. Animal studies have shown that such noise-induced tinnitus is related to increased spontaneous activity in the dorsal cochlear nucleus as well as further along the central auditory pathway. However, the role of spontaneous activity of the auditory nerve, connecting the peripheral and central auditory systems, in tinnitus emergence remains unknown. In the current study, tinnitus was induced by exposing anesthetized Mongolian gerbils of either sex to a 115-dB SPL narrowband noise. After one day of recovery, animals were behaviorally tested for gap detection deficits using a gap-prepulse inhibition of the acoustic startle reflex (GPIAS) paradigm, indicative of tinnitus. Noise-induced threshold shifts did not differ between animals with and without signs of tinnitus. Interestingly, single auditory nerve fibers recorded from animals with signs of tinnitus had significantly reduced spontaneous rates compared to both noise-exposed animals without signs of tinnitus and sham-exposed animals. Furthermore, spontaneous rate reduction was specific to fibers tuned to frequencies within the frequency bands that showed gap detection deficits. On the other hand, inter-spike interval variability and bursting behavior increased in fibers from noise-exposed compared to sham-exposed animals but did not differ with gap detection deficits. These findings suggest that tinnitus-related central hyperactivity may be initiated by reduced spontaneous rates of its innervating auditory nerve fibers. This is consistent with theoretical models explaining the central manifestation of tinnitus and offers a more detailed definition of tinnitus-related deafferentation.Significance statement Decades of previous research showed that tinnitus strongly connects to peripheral cochlear damage and to neural aberrations in the central auditory system. However, up to now, the role of the auditory nerve, connecting the peripheral to the central auditory system, in the emergence of tinnitus pathology has remained unclear. The current study showed that spontaneous activity is significantly reduced in auditory nerve fibers recorded from noise-exposed animals with behavioral signs of tinnitus shortly after the exposure. This insight helps us to understand why certain central neural correlates of tinnitus emerge. Furthermore, understanding the physiological basis of the initiation phase of tinnitus may lead to new intervention strategies to treat it.
Enhancing porosity and reducing fiber diameter significantly improves the sensitivity of nanofibers as colorimetric indicators, making them ideal for food quality monitoring. In this study, ultrathin and highly porous PCL-based nonwoven mats were developed as colorimetric indicators for detecting food spoilage, using a combination of non-solvent-induced phase separation and electrically-assisted supersonic solution blow spinning (EASBS). The nonwovens incorporated natural (curcumin and alizarin) and synthetic (bromophenol blue) pH indicators. For comparison, non-porous nanofibers were also produced via EASBS, and highly porous fibers via conventional solution blow spinning (SBS). Although the incorporation of indicators increased the fiber diameter, EASBS still resulted in finer fibers than SBS. The EASBS porous mats also exhibited the highest specific surface area, compared to SBS and EASBS non-porous specimens, contributing to their enhanced responsiveness to analytes. The EASBS nonwoven polycaprolactone/bromophenol blue specimens revealed the best performance, with the lowest limit of detection and limit of quantification for volatile amines. During storage, the values of the overall color change (ΔE) for polycaprolactone/bromophenol blue mats revealed pronounced visually perceptible color changes with ΔE increasing from 0.00 at baseline to 7.76 after 24 h and 19.21 after 72 h. Initially yellow, the mats turned green within 24 h, and the degree of greenness intensified over 72 h, consistent with spoilage parameters observed in the fish fillets (pH 8.01 and total volatile basic nitrogen of 24.73 mg/100 g). Furthermore, the nonwovens responded visibly to Escherichia coli K-12 contact within 24 h and maintained color stability over 30 days, confirming their potential as intelligent, highly-responsive indicators for food freshness monitoring.
The annual generation of waste cotton textiles is substantial, yet the recycling rate remains limited. Waste cotton textiles represent an abundant cellulose-rich resource for high-value recycling, yet their excessively high degree of polymerization (DP) limits direct dissolution and subsequent regeneration into cellulose fibers. This study employs a hydrated choline chloride/lactic acid/water deep eutectic solvent to convert waste cotton textiles into high-purity dissolving pulp through targeted depolymerization. By tuning the water content to 30%, the DP of waste cotton pulp was controllably reduced from 2409 to the range of 500-700, while preserving chemical composition and crystalline structure. The resulting dissolving pulp exhibits an α-cellulose content of 98.80%, a whiteness of 85.80%, an iron content of 17.01 ppm, and a pulp yield of 88.01%. Moreover, the DES achieved a recovery rate of 80.80%. The dissolving pulp was successfully processed into regenerated cellulose fibers using wet-spinning, giving fibers with a breaking strength of 1.27 cN·dtex-1 and an elongation at break of 13.63%. This work establishes a novel solvent-mediated strategy for the sustainable valorization of waste cotton fabrics into high-quality regenerated cellulose products, providing an energy-efficient and environmentally benign pathway for the high-value recycling of cellulose-rich textile waste.
Nitride ceramics with high thermal conductivity can effectively dissipate localized heat and prevent hotspot formation in advanced electronics. However, their intrinsic brittleness and limited deformability render them susceptible to structural damage under multiaxial mechanical loading, disrupting the continuity of heat transfer pathways and compromising long-term device reliability. Here, a multiscale structural optimization strategy based on organic-inorganic hybrid chains is proposed to produce high-strength, flexible, yet highly thermally conductive nitride ceramic nanofibers. This achievement arises from an optimized grain structure with high crystallinity at the microscopic scale, coupled with a continuous, defect-minimized fibrous architecture at the mesoscale, collectively striking an optimal balance between stress transfer and phonon scattering to achieve rapid stress dissipation and efficient heat transport. Building on this feature, the nitride ceramic nanofibers exhibit excellent flexibility and a mechanical strength of up to 528.3 MPa despite possessing high crystallinity, a characteristic that typically leads to brittleness. Meanwhile, large-area, free-standing aligned fiber membranes fabricated via electrospinning achieve a high thermal conductivity of 16.58 W m- 1 K- 1 and structural stability during bending. This work offers new opportunities for high-performance fibrous materials in next-generation electronic systems.
Recent transcriptomic and microneurography studies have refined our understanding of human C-fiber diversity and function. This review summarizes knowledge of human C-low-threshold mechanoreceptors (C-LTMRs) and C-nociceptors, with emphasis on their molecular, physiological, and pathological roles in pain signaling and modulation, and discusses how these insights may inform therapeutic strategies targeting C-fibers. Human single-cell transcriptomic studies have identified multiple distinct C-fiber populations with both conserved and human-specific features. Integration with microneurography has begun linking these molecular identities to functional phenotypes. Recent findings indicate that human C-LTMRs are polymodal afferents, responding to gentle touch as well as innocuous cooling and warming stimuli, whereas C-mechanoresponsive (CM) and C-mechanoinsensitive (CMi) nociceptors can develop features of peripheral sensitization under pathological conditions. Transcriptomic studies further reveal that molecular targets, such as transient receptor potential vanilloid 1, are shared across functionally distinct C-fiber classes, suggesting that analgesic therapies may act across broader and more functionally diverse C-fiber populations than traditionally appreciated. Human C-fibers are highly heterogeneous and contribute to pain signaling through diverse and context-dependent mechanisms. Integration of transcriptomics with microneurography provides a framework for linking molecular identity with physiological function in humans and may facilitate the development of selective approaches for targeting pain-relevant afferent populations.
Electrospun silk fibroin nanofibers (SFNFs) combine exceptional biocompatibility, tunable mechanical properties, and a native extracellular matrix (ECM)-mimetic architecture, making them compelling scaffolds for tissue engineering. Despite rapid progress, current research often pursues isolated material enhancements, lacking a cohesive strategy that aligns scaffold design with the complex biophysical and biochemical microenvironments of targeted tissues. To bridge this gap, this review presents a "design-application coupling" framework that systematically integrates SFNF composition, processing, and surface modifications with tissue-specific regenerative demands. Rather than exhaustively detailing basic manufacturing, we concisely distill advanced electrospinning modalities and targeted functionalization strategies─such as inorganic reinforcement and immunomodulation─that dictate mechanical robustness and bioactivity. Crucially, we map these engineered properties directly to their emerging clinical applications, comprehensively analyzing SFNF performance in the regeneration of bone, skeletal muscle, cardiovascular, neural, and skin tissues. Finally, we discuss critical challenges to clinical translation, including scalability and regulatory standardization, and propose future directions toward smart, bioresponsive materials. This framework provides a systematic pathway from bench-side innovation to bedside application, guiding the next generation of SFNF-based regenerative scaffolds.
Existing multiplexed salivary diagnostics struggle to achieve a delicate balance between high sensitivity, low cost, and portability. This balance is essential for practical at-home diabetes monitoring. To address this challenge, we developed an integrated smartphone-based 3D paper sensor for multiplexed salivary metabolic monitoring featuring in situ-formed supraparticle zinc-coordination assemblies (SP-ZnCA) on wax-printed microzones. This design combines ratiometric fluorescence-using a DABSA probe with large Stokes shift and a multi-enzyme cascade (glucose oxidase, uricase, and cholesterol oxidase-horseradish peroxidase) for simultaneous quantification of salivary glucose, uric acid, and cholesterol with ultra-low detection limits (0.83-1.67 μM). We developed a custom modular micro fluorescence analysis device (μ-FAD) equipped with a 254 nm UV-LED, a 3D-printed dark chamber, and smartphone-based imaging. Through an optimized coaxial optical pathway, the μ-FAD enables rapid on-site testing within 8 min. Remarkably, the system reduces equipment costs to just 1/200 of those of conventional fluorometers. Clinical validation using 18 human saliva samples demonstrated high accuracy (R2 > 0.97) relative to ELISA, at a mere $0.05 per test. By harmonizing material innovation, enzymatic signal amplification, and accessible diagnostics, our work successfully resolves the sensitivity-cost-portability trade-off and offers a scalable, affordable platform for decentralized diabetes management.
Considering the tensile and elongational forces involved in natural silk spinning, silk fiber production resembles drawing processes in conventional fiber manufacturing. Understanding how protein sequence and "drawing" conditions govern molecular structure and mechanical properties is essential for the rational design of silk materials. Here, we employ a coarse-grained molecular dynamics model to simulate the self-assembly of spidroin-mimetic chains with varying β-sheet-forming (hard) segment contents under different spinning strains and times. The simulations reveal distinct degrees of macromolecular alignment and β-sheet nanocrystal formation. Uniaxial tensile simulations show that spinning strain, rather than time, predominantly dictates mechanical performance through its impact on nanoscale structure. The results show that spidroin-like macromolecules with low hard segment content are the best candidates for achieving simultaneous strengthening and toughening through increased spinning strain. These findings establish design guidelines for optimizing silk performance through the coordinated control of sequence architecture and spinning conditions.
Arundo donax L. is a promising lignocellulosic biomass source for sustainable cellulose fiber production. However, pulping and spinning processes often rely on environmentally harmful solvents. Herein, A full-process deep eutectic solvent (DES) strategy is reported for efficient cellulose isolation from Arundo donax L. and direct fabrication of regenerated cellulose fibers. The approach combines acidic DES pretreatment with alkaline DES dissolution, significantly improving processing efficiency. The cellulose pulp achieves approximately 85% α-cellulose content while maintaining favorable specific surface area. The DES can be recovered at above 90% for cyclic reuse. Regenerated cellulose fibers (RCF) underwent crystal transition from cellulose I to cellulose II, displaying uniform morphology and enhanced thermal stability. Mechanical testing reveals a breaking strength of 121.5 MPa and elongation of 6.6%. These results demonstrate that this integrated DES approach offers a green and recyclable route for converting non-wood biomass into regenerated cellulose fibers.
Cardiovascular diseases remain a leading cause of mortality worldwide. Small-diameter vascular grafts (SDVGs) continue to face critical clinical challenges, including acute thrombosis, intimal hyperplasia, and insufficient endothelialization. Inspired by the hierarchical structure of skeletal muscle, in which myofibrils assemble into muscle fibers and then into functional tissue, we developed a novel tissue-engineered vascular graft (TEVG) based on a muscle-mimetic composite yarn. Using friction spinning technology, we fabricated a core-sheath composite yarn with a poly(ethylene terephthalate) (PET) filament as the artificial myofibril core to provide durable mechanical support, and poly(glycolic acid) (PGA) staple fibers as the sheath component to replicate the extracellular matrix (ECM) topology of muscle fibers, thereby enhancing bioactivity. The knitted tubular scaffold was implanted subcutaneously in rabbits for in vivo tissue induction, followed by decellularization, yielding an extracellular matrix-rich and biocompatible graft. This "yarn mimicking muscle, fabric transforming into vessel" strategy achieved staged vascular regeneration. In a canine carotid artery replacement model, the TEVG maintained 100% patency at one month, with histological evidence of endothelialization (CD31+), smooth muscle regeneration (α-SMA+), and collagen deposition. This bioinspired approach demonstrates short-term feasibility for small-diameter vascular regeneration in a canine model, providing a promising platform for long-term studies and clinical translation.
DNA technology has enabled the creation of molecular structures with endless creativity and exceptional fidelity. These structures, including DNA origami, are on the order of tens to hundreds of nanometers in size and have previously been shown to influence solid-forming reactions like silica, calcium carbonate, and calcium phosphate mineralization related to bone and enamel formation, providing new promise for biomedical applications. In this work, we expand the dimensions of DNA technology to produce micron-sized (0.01-100 μm2) DNA origami arrays. These arrays are controllable in their assembly and enhance the mineralization of calcium phosphate within the footprint of the array. Structures that resemble sheets, webs, and fibers have been mineralized. TEM and AFM imaging has identified a range of mineral morphologies including small (10-50 nm) amorphous clusters, dense layers of mineral, and mineral forming along the length of origami fibers. This range of morphologies shows the versatility of this array design. Mineralized materials with specific micron dimensions, such as these, could prove useful in future bone repair applications.
Plasma membrane repair is critical for tissue integrity, especially for elongated contractile muscle cells. Genetically-mediated defects in plasma membrane resealing produce persistent leak, leading to a disordered extracellular matrix. Loss of the membrane repair protein dysferlin slows sarcolemmal resealing and promotes excess leak. Annexin A6 is also implicated in sarcolemmal repair, forming repair caps at the site of membrane disruption. On its own, deletion of the gene for annexin A6, Anxa6, had little effect on muscle health. In contrast, combined loss of dysferlin and annexin A6 (DysfA6) generated muscle fibers with profoundly defective membrane leak. Strikingly, Anxa6 deletion in the context of loss of dystrophin (mdxA6) did not exacerbate muscle defects. The persistent membrane leak in DysfA6 muscle resulted in marked macrophage infiltration with disordered macrophage polarization. Injured muscle fibers were targets of macrophage efferocytosis. Loss of Anxa6 was associated with increased expression of annexins A1 and A2, both of which were heavily deposited into the extracellular matrix. In vitro, macrophages exposed to annexins A1 and A2 increased Csf1 expression, consistent with a model where excess leak results in annexins A1 and A2 in the extracellular matrix, where this protein composition influences macrophage proliferation and efferocytosis.
Early-onset muscle weakness (MW) syndrome is a genetic disorder in Holstein cattle, that was first described in the US in 2022 and is caused by a recessively inherited variant in the CACNA1S gene. This report documents the first confirmed case of MW in Holstein cattle in Europe. A 17-day-old female Swiss Holstein calf was presented for progressive, non-ambulatory weakness and inability to stand up without assistance. Clinical examination revealed generalized muscle atrophy and tremors, a wide-based stance, and inability to acquire the quadrupedal stance without assistance. Hematologic and biochemical analyses were unremarkable, except for mild monocytopenia and reduced plasma creatinine. Histopathological analysis of semitendinosus and semimembranosus muscles revealed pronounced fiber size variability, rounded hypertrophic fibers, small fibers with central nuclei, mild mononuclear infiltration, and increased connective tissue, findings consistent with chronic myopathic change. Pedigree analysis revealed that the affected calf was inbred and could be traced back to two known US MW carriers suggesting recessive inheritance. Genetic testing of the case confirmed homozygosity for CACNA1S, whereas both parents were heterozygous. The estimate of the frequency of this defect allele in the Swiss Holstein population is 0,56 %and 1,07 % in Swiss Fleckvieh. MW should be considered as a differential diagnosis in young calves of these two breeds presenting with signs of recumbency and weakness and should be tested accordingly using genetic diagnostics. Das Early-onset Muscle Weakness Syndrom (MW) ist eine 2022 erstmalig in den USA beschriebene genetische Erkrankung bei Holstein-Rindern, die durch eine rezessiv vererbte Variante im CACNA1S-Gen verursacht wird. Dieser Bericht dokumentiert den ersten bestätigten MW-Fall beim Holstein-Rind in Europa. Ein 17 Tage altes weibliches Schweizer Holstein-Kalb wurde wegen fortschreitender Schwäche und der Unfähigkeit, ohne Hilfe aufzustehen, vorgestellt. Bei der klinischen Untersuchung wurden eine generalisierte Muskelatrophie und ein Tremor, eine breite Standhaltung sowie die Unfähigkeit, ohne Hilfe eine stehende Haltung einzunehmen, festgestellt. Die hämatologischen und biochemischen Untersuchungen waren unauffällig, mit Ausnahme einer leichten Monozytopenie und eines reduzierten Plasmakreatininspiegels. Die histopathologische Untersuchung der Muskeln Mm. semitendinosus und semimembranosus zeigte eine ausgeprägte Variabilität der Fasergrösse, abgerundete, hypertrophe Fasern, kleine Fasern mit zentralen Kernen, eine leichte mononukleäre Infiltration sowie vermehrtes Bindegewebe. Diese Befunde, stimmen mit einer chronischen myopathischen Veränderung überein. Gemäss der Stammbaumanalyse war das betroffene Kalb ingezüchtet und konnte auf zwei bekannte US-amerikanische MW-Anlageträger zurückgeführt werden, was auf eine rezessive Vererbung hindeutete. Die genetische Untersuchung bestätigte die CACNA1S-Homozygotie beim Fall und eine Heterozygotie der beiden Elternteile. Die Frequenz dieses Defektallels liegt in der Schweizer Holstein-Population bei 0,56 % und 1,07 % beim Swiss Fleckvieh. MW sollte als Differentialdiagnose bei jungen Kälbern dieser beiden Rassen, die Festliegen und Schwächeerscheinungen zeigen, in Betracht gezogen und entsprechend mittels genetischer Diagnostik getestet werden. Le syndrome de faiblesse musculaire précoce (MW) est une maladie génétique chez les bovins Holstein, décrite pour la première fois aux États-Unis en 2022 et causée par une variante du gène CACNA1S transmise selon un mode récessif. Ce rapport documente le premier cas confirmé de MW chez un bovin Holstein en Europe. Une génisse Holstein suisse âgée de 17 jours a été présentée pour une faiblesse progressive entraînant une incapacité à marcher et à se lever sans aide. L’examen clinique a révélé une atrophie musculaire généralisée, des tremblements, une base de sustentation élargie et une incapacité à se lever sans aide. Les analyses hématologiques et biochimiques étaient normales, à l’exception d’une légère monocytopénie et d’une créatinine plasmatique réduite. L’analyse histopathologique des muscles semi-tendineux et semi-membraneux a révélé une variabilité prononcée de la taille des fibres, des fibres hypertrophiques arrondies, de petites fibres à noyaux centraux, une légère infiltration mononucléaire et une augmentation du tissu conjonctif, résultats compatibles avec une altération myopathique chronique. L’analyse généalogique a révélé que la génisse atteinte était consanguine et pouvait être reliée à deux porteurs américains de la MW, ce qui suggère une transmission récessive. Le test génétique de ce cas a confirmé l’homozygotie pour le gène CACNA1S, alors que les deux parents étaient hétérozygotes. Une estimation de la fréquence de cet allèle défectueux dans la population Holstein suisse se monte à 0,56 % et à 1,07% chez Swiss Fleckvieh. La MW doit être envisagée comme diagnostic différentiel chez les jeunes veaux de ces deux races présentant des signes de décubitus et de faiblesse et doit faire l’objet d’un dépistage génétique en conséquence. La sindrome da debolezza muscolare a esordio precoce (Muscle Weakness, MW) è una malattia genetica dei bovini Holstein, descritta per la prima volta negli Stati Uniti nel 2022, causata da una variante a trasmissione recessiva del gene CACNA1S. Questo lavoro documenta il primo caso confermato di MW in un bovino Holstein in Europa. Un vitello femmina Holstein svizzero di 17 giorni è stato presentato per debolezza progressiva e l’incapacità di alzarsi senza assistenza. L’esame clinico ha evidenziato atrofia muscolare generalizzata e tremori, una postura a base allargata e l’incapacità di assumere la stazione quadrupedale senza aiuto. Gli esami ematologici e biochimici non hanno mostrato anomalie significative, ad eccezione di una lieve monocitopenia e di una riduzione della concentrazione plasmatica di creatinina. L’esame istopatologico dei muscoli semitendinoso e semimembranoso ha evidenziato una marcata variabilità delle dimensioni delle fibre muscolari, fibre arrotondate e ipertrofiche, piccole fibre con nuclei centrali, una lieve infiltrazione mononucleare e un aumento del tessuto connettivo. Questi reperti sono compatibili con alterazioni miopatiche croniche. L’analisi genealogica ha mostrato che il vitello affetto era consanguineo e che la sua ascendenza poteva essere ricondotta a due portatori statunitensi della variante MW, suggerendo una modalità di trasmissione recessiva. L’analisi genetica ha confermato l’omozigosi per la variante del gene CACNA1S nel vitello affetto e l’eterozigosi in entrambi i genitori. La frequenza di questo allele deleterio nella popolazione Holstein svizzera è pari allo 0,56 % e all’1,07% nella razza Swiss Fleckvieh. La MW dovrebbe essere considerata una diagnosi differenziale nei vitelli che presentano decubito persistente e segni di debolezza muscolare e dovrebbe essere confermata mediante appropriati test genetici.
Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital malformation. We report a case involving a 20-month-old girl who presented with a congenital midline philtral mass. Histopathological examination revealed mature striated muscle fibers interspersed with adipose tissue and prominent adnexal structures, including sebaceous glands originating from hair follicles. The lesion's prominent folliculosebaceous components initially suggested folliculosebaceous cystic hamartoma (FSCH). However, the presence of striated muscle hyperplasia, midline location, congenital onset, and the absence of characteristic cleft formation confirmed the diagnosis of RMH. The patient underwent complete surgical excision and was recurrence-free after 5 years of follow-up. This case highlights the importance of considering RMH in the differential diagnosis of congenital midline facial lesions, including those with adnexal components.
Microplastic contamination has become a widespread environmental issue, prompting extensive research into its potential health and ecological impacts. This study investigates the occurrence, characteristics, and seasonal dynamics of microplastics in the drinking water supply system of Khorramabad, Iran, and evaluates associated exposure risks. Water samples were collected from 55 strategic locations-including wells, springs, and inlets/outlets of treatment plants-across the city's distribution network during the wet (April, May) and dry (August, September) seasons of 2023. Microplastics were detected and quantified using density separation techniques, with µ-Raman spectroscopy employed to determine their polymer composition. The results revealed an average microplastic concentration of 2.06 MPs/L, with white fibers ranging from 250 to 5000 μm being the most prevalent morphology. The dominant polymer types identified included polyethylene (PE), polypropylene (PP), and polystyrene (PS). Seasonal analysis revealed a statistically significant increase in microplastic abundance during the wet seasons (P < 0.001), indicating that rainfall is a primary factor driving groundwater contamination. Spatial variability across sampling points was not statistically significant (P = 0.25). Based on the risk assessment, the drinking water in Khorramabad was classified as low-risk. However, despite the minimal risk posed by these polymers, their potential health impacts should not be overlooked. This study highlights the need for improved monitoring, optimized treatment processes, and public awareness campaigns to mitigate microplastic pollution in urban water systems. This study is notably the first to investigate microplastics in drinking water within the western region of the country.
SPI1 is a hub gene associated with intracranial aneurysms (IA) and is highly expressed in IA tissues. However, its functional role in IA formation remains unclear. This study aimed to investigate the effect of SPI1 on IA development and its underlying mechanisms. An in vitro IA cell model was established using Platelet-Derived Growth Factor BB (PDGF-BB)-induced vascular smooth muscle cells (VSMCs). SPI1 expression was silenced via sh-SPI1 plasmids to assess its effects on VSMC phenotypic switching and the Wnt pathway. The binding of SPI1 to the Wnt5a promoter was verified by chromatin immunoprecipitation (ChIP) assays. Furthermore, to investigate whether SPI1 influences the contractile-to-synthetic phenotypic transition of VSMCs via the Wnt pathway, the cells were treated with the Wnt5a inhibitor Box5. The in vivo effects of SPI1 knockdown were assessed using an IA mouse model. Compared with the control group, PDGF-BB treatment increased the expression of SPI1, synthetic phenotype markers (MMP3/9), and Wnt pathway-related proteins (β-catenin and c-Myc), while reducing the expression of contractile markers (α-SMA and SM22α) and Wnt5a. Silencing of SPI1 reversed these changes. ChIP assays further confirmed that SPI1 could bind directly to the Wnt5a promoter. Moreover, treatment with the Wnt5a inhibitor Box5 reversed the SPI1 knockdown-induced changes in Wnt5a, β-catenin, and c-Myc in VSMCs. In vivo, SPI1 knockdown alleviated vascular wall thickening in the cerebral artery ring of IA mice, improved the loss of elastic fibers, and suppressed inflammatory responses. In addition, SPI1 knockdown promoted Wnt5a expression while restoring the expression of β-catenin, c-Myc, and phenotypic markers toward control levels. This study suggests that SPI1 promotes intracranial aneurysm formation by inhibiting Wnt5a transcription, thereby promoting activation of the canonical Wnt/β-catenin pathway and driving VSMC phenotypic switching toward a synthetic phenotype. In vivo, SPI1 knockdown alleviated vascular wall injury and inflammation. These findings indicate that the SPI1/Wnt5a signaling axis may represent a potential therapeutic target for intracranial aneurysms.
Dentin hypersensitivity is a common oral condition characterized by sharp pain triggered by exposed dentin in response to external stimuli, reflecting complex interactions between dentin structure, fluid dynamics, and neural responses, although its underlying biological mechanisms remain incompletely understood. Among the proposed mechanisms of dentinal nociception, the odontoblast transducer theory suggests that odontoblasts act as sensory cells capable of detecting stimuli and activating adjacent pulpal nerve fibers. This study aimed to characterize the scientific landscape of the odontoblast transducer theory through bibliometric and altmetric analyses. A bibliometric review was conducted using the Web of Science Core Collection and Scopus, without restrictions on publication year, language, or study design. Publication trends, citation metrics, journals, authorship, institutions, countries, keywords, and study designs were analyzed using VOSviewer and MapChart. A total of 65 studies were included, accumulating 1986 citations. Scientific output peaked in 2015, with Japan identified as the leading contributor. Altmetric data were retrieved from Dimensions to assess online visibility and dissemination. The highest Altmetric Attention Score reached 827, indicating substantial online dissemination of studies addressing molecular mechanisms. Most studies were in vitro and focused on molecular and cellular mechanisms, particularly transient receptor potential channels and ATP-mediated signaling. Research on the odontoblast transducer theory is concentrated in specific research groups and primarily addresses molecular mechanisms, highlighting the need for translational and clinically oriented investigations.
Meat quality is a critical determinant of the economic value in the broiler industry, with its foundational characteristics established during early post-hatch development. Skeletal muscles comprise a complex mixture of myofiber types, whose initial distribution and molecular signatures set the stage for post-mortem meat quality. However, the early regulatory landscapes governing these myofiber compositions remain to be fully elucidated. In this study, we employed high-resolution single-nucleus RNA sequencing (snRNA-seq) to characterize the transcriptomic divergence between broiler breast muscle (BM) and leg muscle (LM) at the neonatal stage (Day 1). Our panoramic atlas of muscle-resident cells revealed that neonatal LM already possesses a significantly higher proportion of oxidative fibers (Type I and Type IIA) and an enriched population of preadipocytes/adipocytes compared to BM. Functional enrichment analysis identified a prominent upregulation of the adipocytokine signaling pathway in D1 LM, suggesting an early molecular framework for the flavor and juiciness characteristics typically associated with leg meat. Furthermore, GSEA and KEGG analyses revealed a correlation between elevated FOS expression and apoptosis signatures in Type IIA and IIB myonuclei within LM, suggesting its potential involvement in shaping early myofiber type proportions. Additionally, PRKAG2 was identified as a candidate regulator linked to intramuscular lipid and fatty acid biosynthetic pathways. Our analysis indicated a regulatory link between the transcription factor EGR1 and its putative target PRKAG2, which coincides with initial lipid droplet accumulation in intramuscular adipocytes. Collectively, these findings provide a high-resolution genetic blueprint of early-postnatal muscle fiber characteristics and lipid deposition, offering novel developmental insights that may inform molecular breeding strategies aimed at predetermining the nutritional and sensory potential of broiler meat.
This in-vitro study compared cemental and periodontal ligament changes in fluorosed and non-fluorosed teeth using Scanning Electron Microscopy. Sixty premolar teeth (30 fluorosed and 30 non-fluorosed) extracted for orthodontic indications were retrieved from the Department of Oral and Maxillofacial Surgery, Mamata Dental College, Khammam, Telangana. Teeth were sectioned transverse to the cemento-enamel junction to separate crown and root portions. scanning electron microscopy photomicrographs of root specimens were analyzed for hypermineralized surfaces, mineralized debris, resorption bays/cavitation, calculus-related debris, fiber insertion areas, and mineralization of connective tissue fibers. Results revealed a higher percentage of resorption bays, calculus and calculus-related debris, and globular mineralized debris in fluorosed teeth compared to non-fluorosed counterparts. Additionally, partial and initial mineralization of connective tissue fibers was more prevalent in fluorosed teeth. These findings suggest that dental fluorosis induces distinct structural alterations at the cemental and periodontal ligament level, even in periodontally healthy teeth. This study concludes that fluorosis causes definite cemental and periodontal ligament changes on the root surface, which may have implications for periodontal health and clinical management of fluorosed dentition.
To identify factors associated with White matter hyperintensities burden in adults with focal epilepsy. We conducted a retrospective review of 60 patients with focal epilepsy treated at the Second Affiliated Hospital of Xinjiang Medical University between October 2024 and October 2025. Patients were selected according to predefined inclusion and exclusion criteria. All patients underwent 17-h scalp video electroencephalography and 3 T brain magnetic resonance imaging (3D T1 and 3D FLAIR sequences, 1.0-mm slices). Clinical features were documented from caregiver-reported symptoms, video recordings, seizure frequency and duration during the preceding two months, and medical history. Seizure type and epilepsy classification were determined in a multidisciplinary conference in accordance with the 2017 International League Against Epilepsy guidelines. White matter hyperintensities (WMH) in the frontal, temporal, parietal, and occipital lobes and the periventricular region were scored using the modified Scheltens scale, and a total WMH score was calculated. Non-parametric tests were used to compare regional WMH scores. The total WMH score was categorized into four levels: 0 (score ≤1), 1 (score >1-5), 2 (score >5-10), and 3 (score ≥10). Univariate and multivariate ordinal logistic regression analyses were performed to identify risk factors associated with WMH burden. White matter hyperintensities were observed in 71.7% of patients. Lesions were predominantly located in the subcortical U-fibers and deep white matter, with fewer in the white matter adjacent to the cortex and in the corpus callosum. Frontal lobe WMH scores were significantly higher than temporal and occipital scores (P < 0.05). Most WMH were smaller than 3 mm in diameter(58%), whereas larger lesions were uncommon(42%). In multivariate analysis, age (OR = 1.60, 95% CI 1.01-1.10), seizure duration (OR = 1.06, 95% CI 1.13-2.24), and the presence of interictal epileptiform discharges (OR = 5.83, 95% CI 1.71-19.87) were independently associated with greater WMH burden. After adjustment for age, seizure duration, interictal epileptiform discharges, and a seizure frequency exceeding once per day were identified as independent risk factors for WMH burden. WMH are common in adults with focal epilepsy, and the frontal lobe is the most frequently affected region. Age, interictal epileptiform discharges, and seizure duration are independent risk factors for greater WMH burden. WMH may serve as an imaging marker for clinical seizure severity.