Search Results (19,693)

Autoimmune diseases arise from complex interactions between genetic susceptibility, immune regulation, and tissue-specific inflammatory processes, yet most risk variants identified by genome-wide association studies occur in non-coding regions with poorly defined biological functions. This review addresses the challenge of interpreting non-coding regulatory variants in autoimmunity by synthesizing emerging analytical frameworks that integrate functional genomics, single-cell profiling, spatial transcriptomics, and multi-omics data. We describe stepwise strategies that refine statistical associations through regulatory annotation, immune cell–state resolution, and perturbational evidence, highlighting complementary approaches such as massively parallel reporter assays, transcriptome-wide association studies, and single-cell expression quantitative trait locus mapping. These methods demonstrate that many autoimmune risk variants exert context-dependent effects that emerge only in specific immune cell states, activation trajectories, or tissue microenvironments. Advances in spatial and chromatin-informed technologies further clarify how regulatory variation shapes immune circuits in diseases such as systemic lupus erythematosus and rheumatoid arthritis. Finally, we discuss how machine learning-enabled multi-omics integration supports molecular endotyping and therapeutic inference while emphasizing interpretability and reproducibility. Collectively, this review highlights a shift from static variant annotation toward dynamic, context-aware analytical frameworks that enable mechanism-informed interpretation of genetic risk in autoimmune disease. Full article

The regeneration of complex tissues demands advanced scaffolds that offer biomimetic support and tissue-specific bioactive guidance. However, the materials in clinic face big challenges with immune rejection, limited donors, and unsatisfactory inductive activity. Fortunately, cellulose-based scaffolds have risen as a leading sustainable platform, considering their natural abundance, inherent biocompatibility, and highly tunable properties. This review comprehensively presented their evolution from rational design to potential clinical application. The primary cellulose sources and key detailed engineering strategies, including chemical modification, composite formulation, and bioactive functionalization, were arranged logically. The modification of cellulose can tune the physical, chemical, and biological behavior of scaffolds, along with advanced three-dimensional printing fabrication techniques. These material advances have enabled targeted functional outcomes in preclinical models, demonstrating promise for specific applications such as wound healing and bone repair. However, their broad clinical translation is contingent upon resolving persistent challenges, including controlled biodegradation and immune compatibility, which we critically assess alongside emerging frontiers such as smart responsive systems. By bridging material innovation with clinical needs, this review may provide an integrated perspective to guide future cellulose-based scaffold design for tissue regeneration. Full article

Background and Objectives: Procalcitonin (PCT) is widely used to support the diagnosis of bacterial infection and sepsis, yet clinically relevant elevations also occur in multiple non-infectious conditions. This systematic review aimed to synthesize human evidence on non-infectious causes of elevated PCT and to summarize proposed pathophysiological mechanisms, with the goal of supporting context-based interpretation in clinical practice. Materials and Methods: A systematic search of PubMed/MEDLINE, Embase, Web of Science, and Scopus was performed from inception to 31 July 2025. Human studies published in English reporting quantitative PCT values in non-infectious contexts were eligible (observational studies, clinical trials, and case series with ≥5 patients). Results: Seventy-six unique studies were included. Evidence was organized across systemic inflammatory responses, cardiovascular pathology, nephrological disorders and renal replacement therapy, pulmonary diseases, gastrointestinal and hepatopancreatic diseases, autoimmune and rheumatologic conditions, neurologic and ophthalmologic conditions, onco-hematologic disorders, surgery, traumatology and transplanted patients. Across conditions, non-infectious PCT elevations were variable and frequently overlapped with ranges reported in bacterial infection, particularly in settings characterized by severe sterile inflammation and tissue injury (e.g., major surgery, trauma, shock, pancreatitis, and burns), as well as in selected malignancies with tumor-associated PCT production. Conclusions: Elevated PCT is not synonymous with bacterial infection. Interpretation should emphasize clinical context, timing, and serial trends rather than isolated thresholds, especially in high-acuity settings with strong non-infectious inflammatory stimuli. Standardized reporting of assays and sampling time points and condition-specific kinetic data are needed to refine diagnostic and stewardship algorithms. Full article

Ischemic stroke is a leading cause of disability worldwide, marked by profound disruption of the neurovascular unit (NVU), a dynamic grouping of neurons, astrocytes, cerebral endothelial cells (CECs), microglia, pericytes, and oligodendrocytes. While acute stroke interventions such as tissue plasminogen activator and endovascular thrombectomy address reperfusion, they fail to engage the prolonged and cell-specific processes critical for recovery. Extracellular vesicles (EVs), membrane-bound carriers of proteins, lipids, and nucleic acids, have emerged as key modulators of intercellular communication within the NVU. This review synthesizes current evidence on NVU-derived EVs as both regulators and effectors of post-stroke pathology and repair. We highlight the phase-specific roles of EVs in modulating blood–brain barrier (BBB) integrity, thrombosis, angiogenesis, neurogenesis, oligodendrogenesis, synaptic plasticity, and neuroinflammation. This review places special emphasis on how EV cargo reflects the state of their parent cells and how EV-mediated crosstalk orchestrates coordinated neurorestorative responses. We further discuss the dual nature of EVs, their therapeutic potential for stroke, and the methodological challenges impeding clinical translation, including isolation standardization, cell-specific targeting, and regulatory barriers. Thus, adherence to minimal information for studies of extracellular vesicles (MISEV) guidelines is essential to ensure rigor, reproducibility, and transparency. When combined with temporal and cellular specificity, NVU-derived EVs may represent a biomimetic platform for promoting durable recovery in stroke patients. Full article

Background/Objectives: Locally advanced midface malignant tumors require extensive resection, resulting in complex defects involving bone and multiple soft tissue structures. Reconstructing these substantial defects presents a significant challenge to restore both function and aesthetics. This study aims to compare the functional and aesthetic outcomes of chimeric free flaps versus single free flaps in midface microvascular reconstructions. Methods: This retrospective analysis included fifty consecutive patients with Type III Cordeiro defects who underwent midface reconstruction with free tissue transfer between 2020 and 2024. The cohort included fourteen patients who received prefabricated chimeric flaps and thirty-six patients who received single free flaps. Outcomes were assessed six months postoperatively using a modified University of Washington Quality of Life Questionnaire (UW-QOL), analyzing domains including speech, chewing, sensation, appearance, pain, and social activity. Statistical analysis was performed using the Mann–Whitney U test. Results: In the chimeric flap group, no major flap necrosis or complications were observed. In unadjusted comparisons, the chimeric flap group showed higher transformed UW-QOL scores in several domains. Statistically significant between-group differences were observed for opening and speech (p = 0.004), change in appearance (p = 0.022), sensation (p = 0.011), and social activity (p = 0.006). Aesthetic outcomes, assessed via patient rating of appearance, were also significantly higher in unadjusted comparisons with the chimeric flap approach. Furthermore, in Type IIIa defects, titanium mesh successfully provided reliable orbital support. Conclusions: Chimeric free flaps represent a feasible reconstructive option in selected cases of complex maxillary and midface reconstruction. Their main advantages—providing the proper amount of specific, well-vascularized tissue and offering greater mobility of components— may be associated with more favorable functional, aesthetic, and social outcomes in unadjusted comparisons compared to reconstruction using single free flaps. Full article

The endoplasmic reticulum (ER) stress response, or unfolded protein response (UPR), is crucial for cellular homeostasis and host defense. Its role in insect vectors of plant pathogens remains poorly understood. This study conducted a comprehensive molecular characterization of three core UPR genes—BiP, IRE1, and XBP1—in Diaphorina citri, the insect vector of the citrus huanglongbing pathogen Candidatus Liberibacter asiaticus (CLas). Expression profiling showed distinct developmental and tissue-specific patterns for these genes. The IRE1-mediated unconventional splicing of XBP1 mRNA was identified in D. citri and predicted across diverse insect pests. A semi-quantitative RT-PCR assay was established to detect this splicing event for monitoring ER stress. Time-course analysis of CLas-infected D. citri revealed an early activation (upregulation of BiP, IRE1, XBP1 transcripts, and increased XBP1 splicing) followed by later suppression of the UPR. Functional studies demonstrated that induction of ER stress with thapsigargin increased CLas titer. RNAi-mediated silencing showed that IRE1 silencing increased CLas proliferation, whereas XBP1 silencing reduced it. These findings provide foundational insights into the ER stress pathway in D. citri and demonstrate that the IRE1-XBP1 branch of the UPR plays a critical role in modulating CLas infection dynamics within its insect vector. Full article

Background: Medicinal plants function as complex holobionts, with their therapeutic potential significantly shaped by the associated microbiome, particularly endophytic fungi. These symbionts engage in a sophisticated “chemical signaling” with their hosts, acting as biotic elicitors that modulate plant secondary metabolism while simultaneously responding to host cues to activate their own cryptic biosynthetic gene clusters (BGCs). This review aims to critically summarize the multi-layered mechanisms driving this metabolic crosstalk and evaluate strategies to harness this symbiotic intelligence for natural product discovery. Methods: A systematic literature survey spanning the last decade was conducted across major databases. The search specifically targeted studies investigating endophytic fungi in medicinal plants, focusing on experimental designs for BGC activation, applications of spatial metabolomics (matrix-assisted laser desorption/ionization mass spectrometry imaging, MALDI-MSI), and the structural elucidation of novel bioactive natural products through co-culture or in planta models. Results: Our analysis reveals that host-derived chemical cues, such as specific root exudates and oxylipins, act as primary triggers to awaken silent fungal BGCs. We collated numerous recently discovered bioactive metabolites—including novel polyketides, highly rearranged terpenoids, and unique alkaloids—demonstrating their potent antimicrobial and cytotoxic properties. Furthermore, a critical evaluation of spatial metabolomics studies demonstrates that metabolic exchange is highly localized at the plant–fungus interface, providing contextual insights that traditional bulk tissue extraction fails to capture. Conclusions: This review bridges the gap between ecological understanding and synthetic biology applications. We conclude that translating the mechanisms of this “chemical signaling” into biotechnological strategies offers a sustainable pathway for the bioproduction of high-value pharmaceuticals, thereby reducing reliance on the wild harvesting of medicinal plants. Full article

Winter oilseed rape achieves frost tolerance through cold acclimation, which develops naturally in autumn in response to low but non-freezing temperatures. However, ongoing climate change has led to an increasing instability in winter temperatures, with more frequent warm breaks. Such temperature fluctuations can induce deacclimation, resulting in a partial or complete loss of frost tolerance and reduced winter survival. Water management is a critical determinant of plant survival under such conditions, yet its regulation during the acclimation–deacclimation transition remains incompletely understood. This study investigated tissue-specific changes in key components of water management in winter oilseed rape subjected to non-acclimated, cold-acclimated, and deacclimated conditions. Proline accumulation, abscisic acid content in plant tissue and cell sap, and the expression of aquaporin genes BnPIP2 and BnTIP1 were analyzed in leaves, root necks, and roots. Cold acclimation induced a strong accumulation of proline and ABA, accompanied by marked downregulation of aquaporin expression in all tested tissue. Deacclimation resulted in partial reverse of proline and ABA. Aquaporins expression demonstrated tissue-specific recovery, showing increases in all tissue compared to cold-acclimated plants. Our findings demonstrate that coordinated actions of integrated water transport, osmotic adjustment, and hormonal signaling in regulating water balance and frost tolerance during winter temperature fluctuations. Full article

Purslane (Portulaca oleracea L.) is an important plant species that has been increasingly used in functional gene studies and molecular analyses. However, reference genes that exhibit stable expression across multiple tissues and stress conditions have not been systematically validated in purslane, which limits the accuracy of reverse transcription quantitative PCR (RT-qPCR) based gene expression analyses. In this study, ten candidate reference genes from six gene families (Actin, PP2A, CYP, eIF4A, Ubiquitin, and eIF5A) were selected based on transcriptome data. A combination of bioinformatic analyses and experimental validation was employed to comprehensively characterize these candidates, including their physicochemical properties, chromosomal localization, phylogenetic relationships, gene structures, and promoter cis-acting elements. Furthermore, the expression stability of the candidate genes was systematically evaluated across different tissues (seed, root, stem, leaf, and flower) and under multiple stress treatments, including salinity, temperature stress, drought, and hormone treatments. Based on conventional PCR amplification specificity, melting curve analysis, Ct value distribution, and amplification efficiency, ACT-2 and eIF5A-1 were identified as the most stably expressed reference genes under diverse experimental conditions. This study provides reliable reference gene candidates for accurate normalization of gene expression in purslane and establishes a systematic framework for reference gene selection in non-model plant species. Full article

Emphysematous cholecystitis is a rare but severe variant of acute cholecystitis characterized by gas-forming organisms within the gallbladder wall or lumen. It progresses rapidly and carries substantial mortality, making early and accurate recognition essential. Although its pathogenesis involves gallbladder wall ischemia with superimposed infection by gas-producing bacteria—most commonly Clostridium species—the clinical presentation is often nonspecific, particularly in patients with diabetes mellitus or immunosuppression. Imaging therefore serves as the cornerstone of diagnosis. Abdominal radiographs may demonstrate intraluminal or intramural gas, while ultrasound can reveal echogenic foci with reverberation artifacts, though overlying bowel gas and diagnostic mimics may limit sensitivity. Computed tomography remains the most accurate modality, precisely delineating gas within the gallbladder wall, lumen, or adjacent tissues and facilitating urgent surgical or percutaneous intervention. Magnetic resonance imaging offers complementary soft tissue characterization when computed tomography is contraindicated. This review synthesizes traditional imaging findings and emerging diagnostic innovations by critically comparing modality-specific strengths, limitations, and pitfalls. Dual-energy and photon-counting computed tomography enhance tissue contrast and gas conspicuity, while artificial intelligence-assisted image analysis enables earlier detection and expedited triage in emergency settings. By integrating evolving technologies with established radiologic principles, this article provides a forward-looking framework for improving diagnostic precision and ultimately enhancing outcomes for patients with emphysematous cholecystitis. Full article

The coelomic cavity of sea turtles is affected by congenital, developmental, traumatic, infectious, and organ- or system-specific disorders, making accurate anatomical knowledge essential for veterinary practice. This study presents an open-access, interactive two-dimensional (2D) anatomical atlas of the coelomic cavity of the loggerhead sea turtle (Caretta caretta), developed using images obtained from osteology, gross anatomical dissections, computed tomography (CT), and magnetic resonance imaging (MRI). The atlas comprises six osteology images, sixteen anatomical dissection images, eight transverse CT images acquired using bone and soft-tissue windows, six three-dimensional (3D) volume-rendered CT images, and fourteen MRI images (four transverse, five dorsal, and five sagittal), all provided in PNG format. Relevant anatomical structures were segmented and colour-coded for each figure using manual layer-based segmentation software. The Unity 3D platform was employed for image visualisation and assessment, supporting the development of interactive two-dimensional content. This atlas serves as a useful interactive tool for anatomical learning and clinical reference for professionals and students engaged in the conservation of loggerhead sea turtles. Full article

Background: The necessity of a pre-therapeutic biopsy for soft tissue tumors is assessed differently depending on imaging. We examined the concordance of histopathological and radiological imaging-based diagnoses of soft tissue tumors in a monocentric, multidisciplinary sarcoma board. Methods: From October 2022 to December 2024, we prospectively included 184 patients presenting with preoperative imaging but without prior histology who are presented at the multidisciplinary sarcoma board of the University Hospital of Erlangen. We evaluated tumor dignity (benign/malignant) and most probable tumor subtype based on cross-sectional imaging assisted by the demographic and anatomic characteristics of individual cases. This assessment was then compared with the final pathological results. Results: We classified 75 tumors as benign and 109 tumors as malignant. Of the 75 patients with a suspected benign tumor, 66 (88%) had a benign diagnosis confirmed by pathological assessment, while two (2.7%) had a malignant tumor and seven (9.3%) an intermediate biology tumor. Of the 109 patients with suspected malignant tumors, 69 (63.3%) had a malignant pathology, while 30 (27.5%) had a benign pathology, and 10 (9.2%) an intermediate tumor. Matching the multidisciplinary sarcoma board’s assessment with the pathological results revealed significant sensitivity and a negative predictive value for malignant tumors, as well as a significant positive predictive value and specificity for benign tumors. Conclusions: The study shows that, despite the high degree of predictability at an experienced sarcoma center, imaging cannot completely replace biopsies and caution should be exercised when deciding against a biopsy. It is emphasized that the decision not to perform a biopsy can only be made in cases where lipomatous tumors appear benign in imaging procedures, and only in an experienced center. Full article

Periodontitis is a multifactorial inflammatory disease characterized by dysbiotic microbial communities and progressive destruction of the supporting periodontal tissues, ultimately leading to alveolar bone loss. Achieving predictable periodontal regeneration remains a major clinical challenge because of the complex interplay between inflammation, microbial burden, and tissue remodeling. In this context, hyaluronic acid (HA), a naturally occurring component of the extracellular matrix (ECM), has gained increasing attention as a bioactive adjunct in periodontal therapy. This narrative review aims to describe current evidence regarding the biological properties, molecular mechanisms, and clinical applications of HA in periodontal therapy, with a particular focus on its immunomodulatory, antimicrobial, and regenerative potential. Available data indicate that HA exerts molecular weight–dependent effects, ranging from anti-inflammatory and extracellular matrix–stabilizing actions to osteogenic and immunostimulatory responses. Clinically, HA has been investigated as an adjunct in both nonsurgical and surgical periodontal therapies, as well as in minimally invasive regenerative approaches, as it has favorable effects on inflammation control, soft tissue healing, and clinical attachment gain. Recent advances in materials science have further expanded the role of HA through the development of engineered hydrogels and hybrid delivery systems incorporating nanoparticles, bioactive glass, growth factors, or antimicrobial agents, which have demonstrated promising osteogenic and antibacterial outcomes in preclinical models. However, the interpretation of existing evidence is limited by heterogeneity in HA formulations, short follow-up periods, and inconsistent reporting of periodontal defect morphology. Future research should focus on standardized, well-designed preclinical and clinical studies integrating histological, radiographic, immunological, and microbiological assessments to distinguish true periodontal regeneration from repair and to optimize HA-based strategies tailored to specific defect configurations. Full article

Tachykinins (TKs), a conserved family of neuropeptides, play critical roles in regulating multiple physiological processes such as feeding and energy metabolism in insects. This study identified the TK gene (ApTK) from the Chinese oak silkworm, Antheraea pernyi, an economically important insect species. Bioinformatic analysis showed that ApTK possesses four FX₁GX₂R motifs (X₁ and X₂ represent variable amino acid residues), comprising FMGVR, FYGVR, FIGVR, and FFGMR, in the C-terminus and shares a close phylogenetic relationship with TKs from Bombyx mori and Manduca sexta. Tissue-specific expression profiling demonstrated that ApTK was mainly expressed in the brain and midgut. Starvation–refeeding experiments showed that the expression of ApTK was significantly upregulated during food deprivation and returned to baseline after refeeding, evincing its involvement in hunger signaling. RNA interference (RNAi)-mediated knockdown of ApTK led to a significant increase in larval body weight and increased levels of triglyceride, glycogen, and trehalose, indicating enhanced energy storage. Collectively, these results demonstrate that ApTK acts as a key regulator in restraining feeding and modulating energy homeostasis in A. pernyi. Our findings provide insights into the neuroendocrine mechanisms underlying feeding behavior and energy metabolism in A. pernyi. Full article

Background and aim: Alterations in immune signaling have emerged as a key factor contributing to Parkinson’s disease pathophysiology. Increasing evidence also suggests that MASLD and Parkinson’s disease may share common immunological mechanisms. Among these, TLR4 has been linked to immune surveillance processes and inflammatory responses in both the central nervous system and the liver. The aim of our study was to delineate TLR4-mediated immune networks underpinning the molecular overlap between MASLD and Parkinson’s disease. Methods: Disease–disease and gene–disease associations were systematically retrieved from the DisGeNet database to map TLR4-related molecular networks across both conditions. Functional enrichment analyses were subsequently applied to identify biological pathways significantly associated with TLR4, including potential gene–drug interactions. Guided by these results, a scoping review of the literature was undertaken to summarize existing evidence addressing TLR4-dependent mechanisms in MASLD and Parkinson’s disease. Results: DisGeNet analysis indicated 978 shared genes and 39 SNPs shared between both diseases. TLRs, including TLR4-associated coreceptors such as CD14, are among these shared genes. Among these, TLR4 and its missense SNP rs4986791 emerged as key shared immunometabolic nodes linking both diseases. Among the shared SNPs identified in both diseases, we focused on TLR4, where the common variant was rs4986791. Gene set enrichment analysis revealed multiple biological processes associated with cytokine signaling, inflammation, and fibrogenesis. Gene–drug enrichment analysis identified statins and fibrates among the compounds enriched in TLR4-containing networks. Conclusions: These findings support a role for TLR4-associated pathways in linking immunometabolic processes across MASLD and Parkinson’s disease. Disruption of these pathways is associated with aberrant inflammatory regulation, with tissue-specific effects further contributing to the distinct molecular pathology observed in each condition. Consequently, modulation of TLR4 signaling represents a plausible strategy for the development or repositioning of disease-modifying interventions applicable to both conditions. Full article