Biology-Basel最新文献

Olfaction plays a central role in mammalian social behavior, yet its contribution to group coordination remains poorly understood. Here, we show that olfactory impairment in adult C57BL/6J mice (Mus musculus) leads to the spontaneous emergence of structured group behavior not observed in controls. Mice with disrupted olfactory input consistently engaged in close-contact interactions that increased over time. We quantified these events and found that aggregation occurred significantly more often than expected by chance, with olfaction-impaired mice exhibiting coordinated dyadic, triadic, and quartet configurations that were spatially enriched, temporally stable, and showed consistent patterns of progression between the states. Unsupervised behavioral modeling revealed that these formations were preceded by structured approach and stationing behaviors. Our findings suggest that olfactory input is a key contributor to maintaining typical social dynamics, and that its absence may lead to altered patterns of group interaction potentially driven by reduced sensory input. This work positions olfaction as a key scaffold for social structure and offers a novel framework for understanding how animals adapt to sensory loss in complex group settings.

Influenza's pandemic threat is driven by antigenic drift, which limits the efficacy of conventional vaccines. To address this challenge, we established a clinical serum-anchored computational design pipeline for a broad-spectrum multi-epitope mRNA vaccine (MEMV), bridging the gap between pure in silico design and clinical applicability. Using 36 longitudinal sera (d0/d28/d365) from 12 well-characterized human cohorts (6 vaccine recipients and 6 influenza patients) and high-density antibody-peptide microarrays, we empirically identified 12 immunodominant B-cell linear epitopes from the nucleoprotein (NP) of influenza A (H1N1/H3N2) and B viruses. These experimentally validated epitopes were combined with in silico-predicted conserved helper T-lymphocyte (HTL)/cytotoxic T-lymphocyte (CTL) epitopes (from NP/HA/NA) to construct MEMVs candidates, ensuring high antigenicity, non-toxicity, and 95.63% global HLA coverage. Molecular docking and 100 ns molecular dynamics (MD) simulations confirmed favorable conformational compatibility between MEMVs and Toll-like receptor 3 (TLR3) in silico immunization via C-ImmSim predicted robust B/T-cell responses and protective cytokine (IFN-γ/IL-10) production. Collectively, this pipeline shortens the preliminary design cycle for influenza vaccines, provides a standard epitope-combination strategy, and offers direct targets for follow-up in vitro/in vivo experiments.

Retinol-binding protein 4 (RBP4), an adipokine secreted by adipose tissues, has been implicated in metabolic inflammation and insulin resistance. Type 2 diabetes (T2D) is a recognized risk factor for osteoarthritis, with both conditions characterized by chronic low-grade inflammation, suggesting potential links between metabolic disorder and joint degeneration. This study aimed to investigate whether inflammatory and metabolic stresses regulate RBP4 expression and function in joint-related cells. Murine immature chondrocyte cells (iMACs) and the mouse AT805 teratocarcinoma cell line, clone 5, that differentiates into chondrogenic cells (ATDC5), were used as in vitro models for chondrocyte cells. Rbp4 mRNA expression increased during differentiation of iMACs, with 3.6- and 2.2-fold elevations observed on days 7 and 14, respectively (p < 0.01 vs. undifferentiated controls). Inflammatory stimulation with interleukin-6 (IL-6) significantly increased Rbp4 mRNA expression in ATDC5 cells (p < 0.05 vs. vehicle), along with elevated expression of catabolic and inflammatory mediators, including monocyte chemoattractant protein-1 (Mcp1), cyclooxygenase-2 (Cox2), and matrix metalloproteinase-3 (Mmp3) (p < 0.05 vs. vehicle). Pharmacological inhibition of RBP4 using fenretinide (FEN) attenuated chondrogenic differentiation marker expression, reduced glycosaminoglycan synthesis during chondrogenic differentiation, and mitigated high-glucose-induced catabolic responses, as indicated by reduced Mcp2 (p = 0.04) and Mmp13 (p = 0.01) expression in ATDC5 cells treated with FEN compared with cells treated with the vehicle under high-glucose conditions. Furthermore, in RAW 264.7 cells, a murine macrophage cell line commonly used as an in vitro model for osteoclastogenesis, FEN significantly reduced the expression of osteoclast differentiation markers, dendritic cell-specific transmembrane protein (DC-Stamp), nuclear factor of activated T-cells, cytoplasmic 1 (Nf-atc1), cathepsin k (Cath.k), and tartrate-resistant acid phosphatase (Trap) under osteoclastogenic conditions (p < 0.01 vs. vehicle). Collectively, these findings suggest that RBP4 functions as a metabolic-inflammatory mediator influencing both cartilage and bone-remodeling processes. This study reveals a previously unrecognized role of RBP4 in regulating osteoclast-associated pathways. Targeting RBP4 may, therefore, represent a promising therapeutic strategy for delaying or preventing osteoarthritis progression, particularly in metabolically compromised conditions.

Small-cell lung cancer (SCLC) is the most lethal histologic subtype of lung cancer. It is characterized by rapid tumor growth and early metastatic dissemination, resulting in an extremely poor prognosis. The addition of immunotherapy to standard chemotherapy has led to a modest improvement in survival for patients with extensive-stage disease. However, the overall clinical benefit remains limited due to both primary and acquired resistance to immunotherapy. Indeed, the efficacy of immune checkpoint inhibitors is influenced by multiple factors, including tumor heterogeneity, an immunosuppressive tumor microenvironment, and intrinsic molecular characteristics of the disease. In recent years, active research has been conducted to identify and therapeutically overcome resistance mechanisms to immunotherapy, and accumulating suggestive evidence is lighting the way for new strategies for clinical management of patients with SCLC. In this review article, we summarize and discuss the substantial obstacle to immunotherapy clinical efficacy, with a particular emphasis on the published and ongoing clinical trials that investigated the potential strategies to overcome mechanisms of resistance to immunotherapy. Moreover, we report and discuss the new therapeutic approaches tested, especially the use of antibody-drug conjugates, bi-specific antibodies, adoptive cell therapies and combination strategies.

Global climate problems and the sharp decline in biodiversity have attracted widespread attention. Orchids, as the "flagship" species of biodiversity, are important indicators of ecological changes. This study took Chongqing as the study area and conducted a comprehensive survey of orchids through field investigation combined with data review to clarify Chongqing's diversity distribution pattern. The distribution of orchids was characterized by "high in the east and low in the west, high in the north and low in the south" horizontally. Vertically, the distribution was characterized by an obvious "unimodal distribution", with higher abundance in the low and middle altitude areas of 500-1499 m. The minimum temperature of the coldest month (Bio6), isothermality (Bio3), altitude (Bio20), and precipitation of the wettest season (Bio16) were the main environmental factors affecting the distribution of the orchid habitat. The suitable habitat of orchids would be greatly reduced in the future (2070SSP-585), and the suitable habitat tends to migrate to the high-altitude areas; therefore, we should pay more attention to the conservation and sustainable use of orchid plant resources.

Salt stress is a major environmental constraint affecting plant growth and productivity. Crop wild relatives provide valuable genetic resources for stress tolerance, yet transcriptomic information for forest-derived wild species remains limited. In this study, we analyzed transcriptional responses of V. hirsuta, a crop wild relative (CWR) of legumes, after seven days of salt stress using de novo transcriptome sequencing. Seedlings were exposed to salt stress, and differentially expressed genes (DEGs) were identified between control (Vh_S0) and salt-treated (Vh_S7) plants using an FDR-adjusted threshold (q < 0.05). Gene Ontology and KEGG enrichment analyses revealed that salt-responsive DEGs were mainly involved in regulatory signaling, metabolic adjustment, redox-related processes, and macromolecular organization. Up- and down-regulated DEGs showed distinct yet overlapping enrichment patterns, indicating complex transcriptional reprogramming under salt stress. Transcription factor analysis identified bHLH, MYB, bZIP, NAC, and WRKY families as major regulators, with many families containing both up- and down-regulated members. Notably, genes associated with Na⁺/K⁺ homeostasis were consistently up-regulated and validated by qRT-PCR. These results suggest that continuous seven days salt stress adaptation in V. hirsuta involves coordinated regulation of signaling pathways, transcriptional networks, and transporter-mediated ion homeostasis, providing a valuable transcriptomic resource for crop wild relatives.

Sympatric species share identical geographical spaces, climatic conditions and survival pressures. Comparative chloroplast genomes among Anna and Lysionotus sympatric species enable exploration of genome-wide evolutionary dynamics of sympatric species. In this study, we assembled and annotated 10 complete chloroplast genomes, representing sympatric species distributed along the Sino-Vietnamese border. We conducted a comparison of chloroplast genomes, characterized their adaptive evolution and used multiple methods to clarify their phylogenetic relationships. Key findings included the following: 1. The number of CDs, rRNA and tRNA varied among different species, whereas they were relatively conserved between the two genera; 2. psaB-psaA, trnL-UAG and ndhD-psaC were identified as potential molecular markers for Anna species, with clpP and ycf1 proposed as effective molecular markers for Lysionotus species; 3. the types of simple sequence repeats (SSRs) and large sequence repeats (LRSs) showed a higher conservation in Lysionotus compared with Anna; 4. the codon usage preferences of the two genera showed convergent evolutionary trends and natural selection played a dominant role, with ycf1 and atpH being confirmed as significantly positively selected genes; 6. phylogenetic analyses using multiple approaches (ML, BI and NJ) consistently verified that Anna and Lysionotus each formed a well-supported monophyletic group. This study offers molecular insights into adaptation and differentiation patterns among distinct plant genera inhabiting the same extreme habitat.

This study provides the first insights into the biology of the blue crab Callinectes sapidus in the Loukkos Estuary, based on 461 individuals collected between December 2022 and November 2023. Results indicate a well-structured invasive population. Carapace width ranged from 52 to 201 mm (mean ± SD: 121.7 ± 25.4 mm) and total weight from 12 to 512 g (128.2 ± 76.6 g). Morphometric analyses revealed pronounced sexual dimorphism, with males larger and heavier than females. Size structure shifted seasonally, with smaller crabs dominating spring-summer samples and larger crabs in winter. Biometric relationships were significant and indicated negative allometric growth in both sexes. The sex ratio was strongly male-biased (M/F = 2.72). Condition factor varied with season and sex, peaking in summer and reaching minima in autumn. Female maturity exhibited marked seasonality: immature females prevailed from spring to autumn, whereas mature females occurred mainly in winter. Logistic modeling estimated size at 50% maturity (L₅₀) at 126.7 mm carapace width in females. Results suggest that Loukkos Estuary functions primarily as a nursery and growth area for C. sapidus and provide essential baseline information for future monitoring and management of this invasive species.

This study aimed to explore genetic variants associated with serum albumin (ALB) levels in Chinese winter sports athletes using genome-wide association analysis (GWAS) and to investigate potential regulatory mechanisms using bioinformatics annotation. A total of 382 Chinese winter sports athletes were recruited. ALB levels were compared between elite and non-elite athletes. GWAS was conducted using PLINK v1.9, with ALB as the phenotype and sex, age, and principal components as covariates. Associated SNPs were annotated using GTEx and SNPnexus. No significant differences were observed in ALB levels between elite and non-elite male or female athletes, and ALB levels in all groups followed a normal distribution. We identified 113 SNPs reaching a suggestive significance threshold (p < 1 × 10^-5), with per-variant variance explained estimates (7.11-11.76%) reflecting model fit within this cohort. A stepwise regression model highlighted nine candidate SNPs that together explained 51.1% of ALB variance in the study sample. Functional annotation suggested that several variants show eQTL or sQTL signals in tissues relevant to ALB biology (e.g., liver and kidney), and pathway enrichment analyses implicated amino acid and hormone metabolism. Overall, these findings are hypothesis-generating; independent replication in additional and ancestry-matched cohorts (and follow-up functional studies) is required to confirm the robustness of the associations and clarify causal mechanisms.

The proper regulation of signaling pathways, including WNT signaling, during early embryonic development is critical for whole-organism development. In particular, maternally enriched WNTs play critical roles in cell cleavage and axis formation through non-canonical and canonical pathways during early embryogenesis. However, early developmental processes related to maternal WNTs and their underlying mechanisms have remained unstudied in avian species. In this study, we investigated WNT signaling-mediated early development in the chicken embryo. We found that WNT4 and WNT6, different ligands from other species, exhibited expression patterns consistent with maternal enrichment in chicken. The chemical inhibition of maternal WNT signaling in intrauterine embryos led to aberrant zygotic expression of WNT8C, which is important for primitive streak formation. Combined with in vitro functional studies, we demonstrated that WNT4 increased WNT8C expression through the non-canonical JNK pathway and that WNT8C subsequently promoted the canonical β-catenin pathway. Our results indicate that maternal WNT4 activates zygotic WNT8C and potentially regulates embryonic polarity in chicken.