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PubMed2026

Effects of umbilical cord mesenchymal stem cell-derived exosomes on periodontal ligament stem cells: An exploratory study.

OBJECTIVE: To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (UCMSCs) at two osteogenic induction stages (undifferentiated and late-stage) differentially affect periodontal ligament stem cells (PDLSCs), and to explore the potential molecular basis. DESIGN: UCMSCs and PDLSCs were isolated and cultured. Exosomes were harvested from undifferentiated UCMSCs (Exo-D0) and UCMSCs after 14 days of osteogenic induction (Exo-D14). PDLSCs were treated with both exosome types. Proliferation and migration were analyzed using EdU and scratch assays, the latter under serum-free conditions. Early osteogenic differentiation was assessed by alkaline phosphatase staining and quantitative reverse transcription PCR (qRT-PCR). Differentially expressed miRNAs were identified by high-throughput sequencing and further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: Both exosome types promoted PDLSC migration. Exo-D0 enhanced early osteogenic differentiation, whereas Exo-D14 enhanced proliferation but reduced early osteogenic marker expression. Sequencing identified 21 differentially expressed miRNAs (13 upregulated, 8 downregulated). Bioinformatic prediction suggested that the putative target genes were enriched in Ras signal transduction, regulation of kinase activity, and focal adhesion, and further predicted significant enrichment in the MAPK, Ras, and PI3K-Akt signaling pathways, which are central to cell proliferation and osteogenic differentiation. CONCLUSIONS: Exosomes from undifferentiated and osteogenically induced UCMSCs exerted distinct effects on PDLSCs, potentially associated with differentially packaged miRNAs. These findings offer a basis for hypotheses about exosome-mediated mechanisms and support matching exosome sources to the intended therapeutic outcome as potential cell-free strategies for periodontal tissue regeneration and alveolar bone repair.

Humans↗

PubMed2026

Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5 wt%) and increasing Sr contents (0.5, 1.0, 1.5 wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-α and TGF-β; with an enhanced TNF-α secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

Animals↗

PubMed2026

Comparison of posterior cellular bonegraft options for single-level lumbar spinal fusion: a randomized trial.

BACKGROUND: Iliac bone autograft (IBG) is osteoinductive/osteogenic/osteoconductive but requires an additional harvesting procedure with known morbidities. Bone morphogenic protein (BMP) is osteoinductive and effective in obtaining fusion but is used off label for posterior fusion, has multiple side effects, and is expensive. Stem cell bone products, both auto- and allograft are attractive osteoinductive alternatives that avoid morbidity related to the graft donor site and may have a better safety profile than BMP. Morcelized allograft bone is osteoconductive but not osteoinductive or osteogenic. PURPOSE: Evaluate and compare the effectiveness of 6 types of viable or osteoinductive bone graft material in obtaining a solid posterior spinal fusion (PSF) for single level anterior/posterior lumbar spinal fusion. The bone grafts were IBG, BMP, autogenous stem cells (MSC) from concentrated bone marrow aspirate (BMA), allograft MSC from bone marrow, adipose tissue, or amniotic fluid, combined with inert cancellous allograft (Allo). STUDY DESIGN/SETTING: Prospective, single-blinded randomized study of 6 cohorts and inert historical control. PATIENT SAMPLE: Elective anterior-posterior lumbar spinal fusion of 175 patients. OUTCOME MEASURES: Assessments included pre and postoperative back and leg pain (VAS) scores, pain drawing, disability (ODI) scores, pain medication usage, and 1-year postoperative thin-cut CT scans (read by blinded radiologists). METHODS: Patients who were surgical candidates for a 1-level anterior/posterior lumbar fusion were randomized to 1 of 6 types of posterior bone graft alternatives: IBG, BMP, BMA, allograft MSC derived from bone marrow combined with morcelized Allo (cAlloBone), adipose derived MSC combined with morcelized Allo (cAlloFat), or amnion derived MSC combined with morcelized Allo (cAlloAm). Historical Allo patients served as a negative control group. Each group (n 27) had prospective outcomes and were followed for a minimum of 2 years. Fusion rate and outcomes were compared and referenced to Allo group. RESULTS: All but 5 patients had a solid ASF. The posterior fusion rates were 98% for IBG, 94% for BMP, 85% for BMA, 67% for cAlloBone, 64% for cAlloFat, 62% for cAlloAm, and 50% for Allo. Outcomes were significantly improved for all measures for all groups and there was no difference between groups except cAlloFat had slightly greater improvement in back pain in the 7-12 month follow-up period. BMP was the most expensive graft material; cellular allografts had a high-cost relative to fusion rate. CONCLUSIONS: For single level ASF/PSF, the PSF fusion rate was significantly greater for IBG and BMP followed by BMA. Various allograft MSC bone graft options resulted in lower fusion rates but may be greater than Allo. Outcomes were uniformly improved regardless of the type of graft used or the fusion status of the posterior fusion as long as the interbody fusion was solid. If bone graft cost savings is a consideration for PSF, then IBG has the greatest radiographic value, and Allo the greatest clinical value as long as the anterior interbody fusion is solid.

Humans↗

PubMed2026

Genome-wide characterization of the TGF-β superfamily identifies bmp15, gdf9, and gsdf as sex-biased candidate regulators of gonadal differentiation in the synchronous hermaphrodite Plectropomus leopardus.

The transforming growth factor-β (TGF-β) superfamily plays conserved roles in vertebrate reproduction and gonadal sex differentiation. However, its genomic repertoire and sex-biased expression patterns remain unclear in the leopard coral grouper (Plectropomus leopardus), a species with synchronous hermaphroditism. Here, we performed a genome-wide identification of the TGF-β superfamily, identifying 42 genes from the chromosome-level genome. Phylogenetic and synteny analyses indicated that segmental duplication under purifying selection contributed to family expansion. Expression profiling across multiple tissues and four gonadal developmental stages (undifferentiated, 120 dph; early differentiated, 15 months; mature testis, 3 years; mature ovary, 3 years) identified eight gonad-enriched genes, among which bmp15 and gdf9 exhibited pronounced female-biased expression, with transcripts localized exclusively to the oocyte cytoplasm, particularly in stage II-III oocytes. In contrast, gsdf showed male-biased expression and was localized in spermatogenic cells of the testis. These reciprocal expression patterns indicate that bmp15/gdf9 and gsdf are candidate factors associated with gonadal sex differentiation. Our study provides the first comprehensive characterization of the TGF-β superfamily in P. leopardus and highlights bmp15, gdf9, and gsdf as candidate sex-differentiation factors in this hermaphroditic species.

Animals↗

PubMed2026

Hippocampal teneurin-4 knockdown promotes depression-like behavioral phenotypes by disrupting oligodendrocyte differentiation in mice.

Depression is one of the most prevalent mental disorders worldwide. The limited clinical efficacy of current antidepressants highlights identifying new therapeutic targets. Emerging evidence suggests that dysfunction of oligodendrocyte lineage cells contributes to the pathophysiology of depression. Teneurin-4 (Tenm4), a transmembrane protein that promotes oligodendrocyte differentiation and myelination, has been implicated in psychiatric disorders in genome-wide association studies; however, its causal role remains unclear. To determine whether Tenm4 contributes to depressive-like behavioral phenotypes, we examined Tenm4 protein expression in mice exposed to repeated forced swimming stress and generated hippocampal Tenm4 knockdown (Tenm4KD) mice. Chronic stress reduced Tenm4 expression levels in the hippocampus. Mice with hippocampus-specific Tenm4KD exhibited depressive-like behaviors, accompanied by reduced hippocampal myelin basic protein. Importantly, administration of clemastine, a myelin formation promoter, inhibited the reduction of myelin and attenuated depression-like behavioral phenotypes. Immunohistochemical analysis showed that Tenm4KD significantly decreased the number of mature oligodendrocyte cells and increased in the number of oligodendrocyte precursor cells, without changes in the total number of oligodendrocyte lineage cells. This study provides the first evidence that hippocampal Tenm4 deficiency induces depression-like behavior phenotypes through impaired oligodendrocyte differentiation and promoting demyelination. Our results identify Tenm4 as a molecular regulator of stress-induced behavioral phenotypes and suggest that it might represent a potential therapeutic target for mood disorders associated with demyelination.

Animals↗

PubMed2026

Transcriptomic insights into temperature regulation of proliferation and differentiation in skeletal muscle cells of Nibea albiflora.

Myogenesis involves sequential stages of muscle satellite cell activation, myoblast proliferation, differentiation, and fusion into multinucleated myotubes. Teleost muscle exhibits indeterminate growth and is highly sensitive to environmental temperature, yet the underlying mechanisms by which temperature regulate proliferation and differentiation remain poorly understood. In this study, we established a primary skeletal muscle cell culture from the yellow drum (Nibea albiflora), an economically important marine fish, and integrated morphological observations with comparative transcriptomics analysis to characterize cellular and molecular responses at 28 °C and 20 °C during both proliferation and differentiation stages. Phenotypic analysis revealed that 28 °C significantly enhanced both myoblast proliferation and myogenic differentiation ability compared with 20 °C. Transcriptomic profiling revealed that at 28 °C, differentiation upregulated extracellular matrix(ECM) organization, calcium signaling, and sarcomere assembly, while proliferation enhanced focal adhesion, growth factor signaling, and lipid metabolism. At 20 °C, differentiation was characterized by glutathione metabolism, and ferroptosis, while proliferation involved cytokine-cytokine receptor interaction and negative regulation of signal transduction. Core myogenic regulatory factors (MRFs), particularly myogenin, were strongly upregulated at 28 °C during the differentiation stage, serving as an internal control. Based on these findings, we propose a testable model that elevated temperature coordinates Ca2+-dependent MRF activation with ECM-integrin signaling to drive sarcomere assembly and muscle growth. Key differentially expressed genes (DEGs) regulating myogenesis in N. albiflora were also identified. This study provides a mechanistic framework for temperature adaptation in teleost skeletal muscle and identifies candidate genes for functional validation and marker-assisted selection, as well as a rationale for temperature management strategies to improve aquaculture yield of N. albiflora.

Animals↗

PubMed2026

Combining neuromelanin-sensitive MRI and quantitative susceptibility mapping for enhanced diagnosis and differentiation of parkinson's disease: A systematic review.

BACKGROUND: Loss of dopaminergic neurones and iron deposition in the substantia nigra pars compacta (SNpc) are two major pathological hallmarks of Parkinson's disease (PD). Such changes can be visualised by advanced techniques including neuromelanin-sensitive MRI (NM-MRI) and quantitative susceptibility mapping (QSM). This systematic review investigates the diagnostic performance and methodological development of the integrated use of NM-MRI and QSM in PD. METHODS: The systematic search was performed in four databases (Scopus, PubMed, ScienceDirect, and Web of Science) according to the PRISMA 2020 guidelines until July 2026. Bias was assessed using QUADAS-2 and certainty of evidence was assessed using GRADE. RESULTS: Seventeen studies with 2228 participants were included. Combined NM-MRI and QSM consistently showed reduced neuromelanin volume/contrast and increased iron deposition in the SNpc of PD patients compared to healthy controls. Multimodal integration yielded a significant improvement in diagnostic accuracy (AUC values 0.86-0.99), and was able to successfully differentiate PD. Recent methodological advances included simultaneous acquisition sequences (e.g. MTC-GRE, STAGE, setMag) and AI-driven automated segmentation, which led to significantly reduced scan times and improved reproducibility. CONCLUSION: The combination of NM-MRI and QSM has a synergistic effect and provides powerful complementary biomarkers for the diagnosis and differential diagnosis of PD.

Humans↗

PubMed2026

Integrated transcriptomic and metabolomic analysis of fluoride tolerance-related pathways and differentially expressed genes in silkworm strain XSKD.

XueSong KD (XSKD) silkworm strain exhibits prominent fluoride tolerance, yet the underlying molecular mechanisms of fluoride tolerance remains unclear. In the present study, fourth-instar pre-molting XSKD silkworms were used as experimental materials for integrated transcriptomic and untargeted metabolomic analyses. In total, 572 differentially expressed genes and 90 differential metabolites were screened. GO enrichment and KEGG enrichment based on the hypergeometric distribution model revealed that 13-Hydroxy-9Z,11E-octadecadienoic acid (13-(S)-HODE) acts as the core differential metabolite, which is significantly enriched in the linoleic acid metabolism pathway. Within this pathway, LOC101737302 and CYP338A1 display opposite expression trends and show correlations with pathway metabolites. Based on multi-omics data, this study preliminarily characterizes the lipid metabolic response under fluoride stress, providing omics dataset support for further in-depth exploration of the molecular mechanism of fluoride tolerance in silkworms.

Animals↗

PubMed2026

Stage shift, histological differentiation, and survival patterns of lung squamous cell carcinoma versus adenocarcinoma in low-dose CT screening.

BACKGROUND: Whether LDCT-associated stage shift translates into similar survival patterns across lung cancer histologies remains uncertain. We compared stage shift, histological differentiation, tumor characteristics, and survival between lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) in the National Lung Screening Trial. METHODS: Among participants diagnosed with LUSC or LUAD, stage distribution and histological differentiation were compared between LDCT and chest X-ray (CXR) arms. Survival among diagnosed cases was measured from randomization. Multivariable models tested screening arm-by-histology interactions. Screen-detected LDCT tumors were compared by histology. RESULTS: During 6.5 years of median follow-up, 498 LUAD and 249 LUSC cases were diagnosed in the LDCT arm, and 374 and 212, respectively, were diagnosed in the CXR arm. LDCT was associated with higher odds of stage I disease for LUAD (adjusted odds ratio [aOR], 2.48; 95% CI 1.88-3.28) and LUSC (aOR, 1.71; 95% CI 1.17-2.48), without significant interaction (P = 0.116). LDCT was associated with lower hazard of lung cancer-specific death among diagnosed LUAD cases (adjusted hazard ratio [aHR], 0.54; 95% CI 0.43-0.66), but not among diagnosed LUSC cases (aHR, 1.04; 95% CI 0.78-1.39; P for interaction<0.001). LUSC had lower screening sensitivity, more frequent detection in annual screening rounds, greater prediagnostic tumor size increase, and fewer well-differentiated stage I tumors than LUAD. CONCLUSION: LDCT was associated with stage shift for both subtypes, but favorable survival patterns among diagnosed cases were mainly observed for LUAD. Lower screening sensitivity, greater prediagnostic tumor size increase, and poorer histological differentiation may help explain why stage shift did not translate into similar survival patterns for LUSC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00047385.

Humans↗

PubMed2026

Comparative analyses of olfactory receptor repertoires in Schizothorax fish based on the chromosome-level genomes: Implications for regulatory roles of dietary differentiation and ploidy variation.

The olfactory receptor (OR) genes constitute the molecular basis of fish olfaction, mediating survival behaviors and environmental adaptation while coevolving with habitat-driven evolution. Schizothorax, a cyprinid genus endemic to the Qinghai-Tibetan Plateau, exhibits remarkable dietary divergence and ploidy variation in response to plateau environmental changes, which presumably facilitates the adaptive evolution of OR genes. However, the evolutionary patterns of OR genes associated with trophic divergence and ploidy variation in this genus remain unclear. In this study, three species were selected: the herbivorous diploid S. macropogon, the carnivorous diploid S. lantsangensis, and the herbivorous tetraploid S. curvilabiatus. S. macropogon possessed 142 OR genes (92.25% functional), primarily located on chromosomes 14 and 24, with the fewest sequence clusters. Such compact gene repertoire and highly overlapping chromosomal clusters indicated specialization for a herbivorous olfactory niche. S. lantsangensis contained 127 OR genes (93.70% functional), concentrated on chromosomes 4 and 5, with fewer sequence clusters and a scattered distribution, reflecting evolution of OR genes under carnivorous feeding habits. The herbivorous tetraploid S. curvilabiatus exhibited striking features: 316 OR genes (94.30% functional), the most subfamilies, unique ε and κ OR subfamilies, and species-specific motifs. These characteristics revealed that ploidy, rather than herbivory, dominated OR gene evolution. In conclusion, dietary differentiation and ploidy variation together drove olfactory adaptive evolution in Schizothorax, providing new insights into vertebrate OR gene ecological adaptation.

Animals↗

PubMed2026

Distinct cell morphotypes of Aureobasidium melanogenum ZN exhibit differential functional profiles in promoting maize growth.

Black yeast-like fungi of the genus Aureobasidium exhibit morphological plasticity, but whether distinct cellular states within the same genetic background are associated with different plant growth-promoting functions remains unclear. Here, yeast-like cells (YL), swollen cells (SC), and chlamydospores (CH) of Aureobasidium melanogenum ZN were characterized. YL was associated mainly with siderophore production and laccase activity, SC with extracellular polysaccharide accumulation, and CH with phosphate mobilization and higher ammonia and IAA production. Whole-genome and comparative genomic analyses revealed a shared repertoire related to nutrient acquisition, auxin-associated metabolism, extracellular oxidation, and carbohydrate remodeling, with expansions in nutrient- and cell-surface-related gene families. Transcriptomic and metabolomic analyses showed distinct deployment of these capacities, with CH exhibiting broad reprogramming of tryptophan-associated, nitrogen, phosphate, central-carbon, and amino-acid metabolism. In maize, CH at the optimal inoculation concentration of 105 CFU·mL-1 produced the strongest growth promotion, increasing plant height, dry biomass, root length, root surface area, and root volume by 58.6%, 365.1%, 191.0%, 194.3%, and 222.4%, respectively. Consistent with this pronounced growth phenotype, maize root transcriptomics showed coordinated CH-induced responses involving root development, nutrient transport, redox regulation, and root-interface remodeling. Root-zone tracking showed greater short-term stability and persistence of CH. These findings identify cellular state as an important functional dimension of Aureobasidium-plant interactions and provide a basis for developing fungal inoculants with defined beneficial cellular states.

Zea mays↗

PubMed2026

Genome-wide scans reveal candidate genes associated with wing morph differentiation in Tetrix japonica.

Wing dimorphism is an important dispersal-related trait in insects, but its genomic basis remains poorly understood in pygmy grasshoppers. Here, we integrated genome-wide single-nucleotide polymorphism (SNP) analyses, population structure inference, selection scans, and functional annotation to investigate genomic differentiation between long- and short-winged Tetrix japonica. Principal component analysis (PCA), ADMIXTURE, and phylogenetic analyses revealed weak genome-wide separation between morphs, indicating differentiation on a largely shared genetic background. Genome-wide scans based on the fixation index (FST), nucleotide diversity ratios, and Tajima's D, using 50-kb non-overlapping windows and empirical top-5% outlier thresholds, identified multiple candidate regions across seven chromosomes. The broader long- and short-winged candidate sets spanned 9.35 Mb and 9.37 Mb and directly overlapped 82 and 77 genes, respectively. Candidate genes were associated with signaling/hormone regulation, membrane transport, metabolism, cytoskeletal organization, extracellular matrix structure, and development. Short-winged candidate genes were significantly enriched for ABC-type transporter activity and ATP hydrolysis activity. Because all individuals originated from a single laboratory-maintained population with weak genome-wide structure, these regions should be regarded as candidate loci from a screening-stage analysis that require validation in independent populations and by functional assays, rather than as confirmed targets of selection.

Animals↗

PubMed2026

Mitochondrial translocation of DNMT3L suppresses oxidative phosphorylation and restrains megakaryopoiesis.

DNMT3L, a catalytically inactive member of the DNA methyltransferase family, is identified here as a negative regulator of megakaryopoiesis. In K562 cells undergoing PMA-induced megakaryocytic differentiation, DNMT3L protein levels declined progressively, and shRNA-mediated depletion enhanced differentiation, whereas overexpression attenuated it. Consistent with these findings, Dnmt3l-knockout mice exhibited elevated peripheral blood platelet counts and expanded bone marrow megakaryocytes. Mechanistically, megakaryocytic differentiation triggered rapid mitochondrial translocation of DNMT3L within 6 h; mitochondrial DNMT3L suppressed oxidative phosphorylation (OXPHOS) capacity and ATP production and downregulated mitochondrial-encoded genes spanning Complex I, III, IV, and ATP synthase, without altering mitochondrial DNA copy number. This metabolic suppression was mediated through compartment-specific remodeling of DNMT3L-containing protein complexes: upon differentiation, DNMT3L selectively dissociated from DNMT1 and DNMT3B in mitochondria, relieving the repressive constraint on OXPHOS, whereas in the nucleus DNMT3L remained associated with DNMT3A, which concomitantly accumulated during differentiation. These findings reveal a previously unrecognized mechanism by which a catalytically inactive epigenetic co-regulator spatially redistributes to coordinate mitochondrial metabolic output with nuclear epigenetic control, thereby facilitating terminal megakaryocytic maturation.

Animals↗

PubMed2026

Non-parametric differential methylation analysis characterizes histotype-specific promoter regions in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a heterogenous disease with frequent late-stage diagnosis and high mortality rates, for which no reliable screening tests exist. In recent years, epigenetic biomarkers in the form of DNA methylation in CpG-rich regions have gained increased attention in the scientific community due to their robust nature and accessibility, allowing for diagnosis without the need for invasive surgery. In this study, we investigated the aberrant methylation of promoter regions in early stage EOC through non-parametric methods, with the purpose of characterizing candidate epigenetic biomarkers. The approach was used on a cohort of early stage EOC samples, and results were compared to existing programs for differential methylation. Significant regions were then used to construct a CpG panel for stratifying EOC histotypes through predictive classification in external data. Identified promoter regions were highly reproducible across cohorts, and the constructed CpG model stratified histotypes in external cohorts through predictive classification. Comparisons against other DMP and DMR callers showed a degree of homogeneity between results but also revealed promoter regions that were overlooked despite clear signs of aberrant methylation. Finally, EOC histotypes were found to differ in their methylation distribution types, and results indicate that methods sensitive to non-normally distributed data may be poorly suited to compare groups with different distribution types. The non-parametric approach identified aberrantly methylated promoter regions that were highly reproducible across cohorts. Results from predictive classification indicate that these regions may be useful for the purpose of EOC histotype stratification.

Humans↗

PubMed2026

Differential contributions of mt-Tr and Cs variants to developmental cochlear defects and mitochondrial dysfunction in A/J mice.

A/J mice exhibit early-onset hearing loss linked to Cdh23, mitochondrial tRNA-Arg (mt-Tr), and citrate synthase (Cs) variants. Although developmental cochlear defects have been identified in juvenile A/J mice, the hierarchical contributions of mt-Tr versus Cs remain unclear. Using reciprocal intercross-derived strains to decouple mitochondrial haplotypes from nuclear factors, we demonstrate that the mitochondrial background is the primary determinant of auditory dysfunction. Mice with A/J mtDNA (AXB strains) displayed significantly higher ABR thresholds, accelerated hair cell attrition, and severe stereocilia dysmorphology compared to those with B6 mtDNA (BXA strains), occurring largely independently of the Cs genotype. While the Cs mutation exacerbated hearing loss, its impact was secondary to that of the dominant mitochondrial background. Systemic behavioral assessments and mitochondrial assays confirmed that A/J mitochondria exert a more profound metabolic impact than the Cs mutation. Our findings establish that the mitochondrial genomic background, with the mt-Tr locus as a prominent candidate variant, serves as the principal driver of developmental cochlear defects and early-onset hearing loss in A/J mice, while the nuclear Cs mutation acts as a synergistic modifier. This study underscores the critical role of mitonuclear crosstalk in inner ear maturation and provides new insights into the etiology of hereditary hearing loss.

Animals↗

PubMed2026

A chromosomal gtrB homolog and dam differentially contribute to dry-heat and high hydrostatic pressure resistance in Salmonella enterica.

Salmonella enterica can persist in low-moisture foods and shows enhanced dry-heat resistance under low water activity, posing significant food safety challenges. However, the genetic basis of extreme dry-heat resistance and its relationship with other processing stresses remain unclear. In this study, twelve S. enterica strains were screened for dry-heat treatment at 60 °C and 80 °C, with S. Infantis CICC21649 identified as the most resistant strain. Comparative genomics and transcriptional analysis identified candidate genes related to envelope integrity and regulation, including gtrB and dam. Deletion of the chromosomal gtrB homolog reduced dry-heat resistance, producing an additional 0.91-log10 reduction relative to the parent strain at 80 °C. Deletion of dam caused broader stress sensitivity, reducing resistance to both dry heat and high hydrostatic pressure, with the stronger phenotype observed under high hydrostatic pressure. Proteomic analysis of the chromosomal gtrB homolog mutant revealed broad alterations in envelope-associated proteins, transport functions, oxidative stress pathways, and central metabolism under dry-heat stress. These findings indicate that the chromosomal gtrB homolog is an important contributor to extreme dry-heat resistance, whereas dam contributes to resistance against both dry-heat and high hydrostatic pressure, likely through a broader regulatory role in stress adaptation. These results reveal distinct structural and regulatory layers underlying stress adaptation in S. enterica and provide practical guidance for low-moisture food processing by highlighting the need to account for strain-dependent and stress-specific resistance during process validation.

Hydrostatic Pressure↗

PubMed2026

Studies on functional differentiation of xpr1a and xpr1b genes in zebrafish.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is known to be involved in various biological processes, including phosphate homeostasis, cellular signaling, brain and vascular mineralization, whereas its specific contribution to bone development remains incompletely characterized. Due to genome duplication in teleosts, zebrafish Danio rerio possess two paralogous genes of XPR1 namely xpr1a and xpr1b, whose functional divergence remains unclear. The amino acid sequence similarity between zebrafish xpr1a and xpr1b was 83.26%. In situ hybridization demonstrated overlapping localization in the head and spinal cord at 24-48 hpf, while diverged by 72 hpf, with xpr1a becoming restricted to the head while xpr1b persisted in both regions. CRISPR/Cas9 was used to generate xpr1a and xpr1b mutants. The xpr1a mutants are comparatively healthy, viable but with mild growth reduction, whereas the xpr1b mutants display high mortality, reduced body length and severe vertebral deformities. Interestingly, all the double mutants died at the embryonic stage. Moreover, to further investigate the molecular and regulatory mechanisms, we conducted comparative transcriptome analysis on bone and brain tissues from xpr1b+/+ and xpr1b-/- zebrafish. In bone tissue, 6749 DEGs were identified, comprising 3846 upregulated and 2903 downregulated genes. These DEGs were mainly enriched in the MAPK signaling pathway, Wnt signaling pathway, cysteine and methionine metabolism, and ECM-receptor interaction. RT-qPCR validated results showed that seven osteogenesis-related genes (col1a1a, sp7, runx2b, col1a2, col1a1b, alp1 and entpd5), and two phosphate homeostasis related genes (slc20a2 and pdgfba), which are essential for skeletal mineralization and phosphate homeostasis, exhibited significantly downregulated expression in bone tissue of xpr1b mutant zebrafish. These results highlight the pivotal role of xpr1b in regulating skeletal mineralization and phosphate metabolism, thereby elucidating the functional specialization of XPR1 paralogs while providing a theoretical basis for understanding bone developmental mechanism in teleost vertebrates.

Animals↗

PubMed2026

Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), established biomarkers of neuroaxonal injury and astroglial pathology, are frequently only assessed in blood, which limits conclusions regarding their origin. Bi-compartmental analyses of CSF and serum may help differentiate central or peripheral origin of biomarker elevation. Moreover, studies on NfL and GFAP in distinct neuroinfectious disease (NID) phenotypes, particularly those based on real-world cohorts, are limited. This retrospective monocentric study analyzed CSF and serum from patients with (meningo-)encephalitis/myelitis (TI+; n = 48), meningitis (TI-; n = 80), (cranial) nerve palsies/polyradiculitis (PND; n = 61), and 113 non-neuroinflammatory/non-neurodegenerative controls. A bi-compartmental model using scatter plots and simple linear regression was applied to assess the origin of blood biomarker levels and discriminate between central and peripheral pathology. CSF and serum NfL and GFAP z-scores were significantly higher in TI+ compared with TI- (CSF-GFAP p < 0.001/sGFAP p = 0.0083; CSF-NfL p = 0.003/sNfL p = 0.0004). TI+ and PND differed only in GFAP levels, which were higher in TI+ (CSF-GFAP p = 0.0049/sGFAP p = 0.003). The overall group effect (p ≤ 0.003) and principal findings remained significant after adjustment for age, sex, QAlb, and time since (symptom) onset to LP. Bi-compartmental analysis revealed simultaneous elevation of CSF and serum NfL in TI+, indicating predominantly central origin, whereas PND demonstrated a shift toward higher sNfL levels suggesting peripheral origin. Higher clinical severity (modified Rankin Scale 3-5) was associated with elevated serum and CSF GFAP and NfL (sGFAP p = 0.012/sNfL p = 0.002; CSF-GFAP p < 0.0001/CSF-NfL p = 0.0001), which also predicted unfavorable outcome at discharge (sGFAP p = 0.006/sNfL p = 0.004; CSF-GFAP p = 0.003/CSF-NfL p = 0.012). NfL and GFAP were associated with brain/myelon involvement in NID, predominantly reflecting central pathology. Despite strong CSF-serum correlations, bi-compartmental approaches provide additional insight into biomarker origin and disease compartment.

Humans↗