Synovial fibroblasts are critical for maintaining homeostasis in major autoimmune diseases involving joint inflammation, including osteoarthritis and rheumatoid arthritis. However, little is known about the interactions among different cell subtypes and the specific sets of signaling pathways and activities that they trigger. Using social network analysis, pattern recognition, and manifold learning approaches, we identified patterns of single-cell communication in OA (osteoarthritis) and RA (rheumatoid arthritis). Our results suggest that OA and RA have distinct cellular communication patterns and signaling pathways. The LAMININ (Laminin) and COLLAGEN (Collagen) pathways predominate in osteoarthritis, while the EGF (Epidermal growth factor), NT (Neurotrophin) and CDH5 (Cadherin 5) pathways predominate in rheumatoid arthritis, with a central role for THY1 (Thy-1 cell surface antigen) ⁺CDH11 (Cadherin 11) ⁺ cells. The OA opens the PDGF (Platelet-derived growth factors) pathway (driver of bone angiogenesis), the RA opens the EGF pathway (bone formation) and the SEMA3 (Semaphorin 3A) pathway (involved in immune regulation). Interestingly, we found that OA no longer has cell types involved in the MHC complex (Major histocompatibility complex) and their activity, whereas the MHC complex functions primarily in RA in the presentation of inflammatory antigens, and that the complement system in OA has the potential to displace the function of the MHC complex. The specific signaling patterns of THY1⁺CDH11⁺ cells and their secreted ligand receptors are more conducive to cell migration and lay the foundation for promoting osteoclastogenesis. This subpopulation may also be involved in the accumulation of lymphocytes, affecting the recruitment of immune cells. Members of the collagen family (COL1A1 (Collagen Type I Alpha 1 Chain), COL6A2 (Collagen Type VI Alpha 2 Chain) and COL6A1 (Collagen Type VI Alpha 1 Chain)) and transforming growth factor (TGFB3) maintain the extracellular matrix in osteoarthritis and mediate cell migration and adhesion in rheumatoid arthritis, including the PTN (Pleiotrophin) / THBS1 (Thrombospondin 1) interaction. Increased understanding of the interaction networks between synovial fibroblast subtypes, particularly the shared and unique cellular communication features between osteoarthritis and rheumatoid arthritis and their hub cells, should help inform the design of therapeutic agents for inflammatory joint disease.

Chemotherapy-induced gastrointestinal dysfunction (CIGD) is a multifactorial clinical syndrome that substantially limits treatment tolerance, continuity, and quality of life in patients with cancer. Although targeted therapy and immunotherapy have expanded therapeutic options, chemotherapy remains a cornerstone of cancer treatment, and its gastrointestinal toxicities continue to pose major clinical challenges. Current evidence indicates that CIGD arises not from isolated lesions, but from interconnected pathological processes involving oxidative stress, mucosal barrier disruption, gut microbiota dysbiosis, immune amplification, and enteric nervous system (ENS) remodeling. In particular, microbiota-immune interactions and ENS-associated neuroimmune alterations may contribute to the persistence and amplification of tissue injury. Existing management strategies are still focused largely on symptom control and often do not adequately address the underlying biological drivers of dysfunction. In this review, we summarize the major mechanistic modules involved in CIGD and discuss a conceptual translational framework for mechanism-informed intervention. This framework includes: (1) targeted approaches aimed at interrupting key pathogenic loops, such as oxidative injury, microbial metabolite-related toxicity, and barrier dysfunction; (2) parameterizable integrative Western and Chinese medicine approaches, in which acupuncture and Chinese herbal formulae are considered as testable adjunctive modules alongside evidence-based supportive care; and (3) stratified management informed by interindividual variation in genetic background, drug metabolism, and microbiome features. On this basis, we further propose a working "niche medicine" framework that views CIGD as dysregulation of multicellular and molecular microenvironments across the gut ecosystem. This perspective may help connect mechanistic research with longitudinal monitoring, patient stratification, and multimodal intervention design, and may support a shift in CIGD management from predominantly symptomatic relief toward mechanism-guided restoration and recovery.

Objectives: BCL2 family proteins have been widely studied over the past decade due to their essential roles in apoptosis, oncogenesis and anti‐cancer therapy. However, the similarities and differences in the spatial pattern of the BCL2 gene family within the context of chromatin have not been well characterized. We sought to fill this knowledge gap by assessing correlations between gene alteration, gene expression, chromatin accessibility, and clinical outcomes in gynaecologic and breast cancer.Materials and methods: In this study, the molecular characteristics of the BCL2 gene family in gynaecologic cancer were systematically analysed by integrating multi‐omics datasets, including transcriptomics, chromatin accessibility, copy number variation, methylomics and clinical outcome.Results: We evaluated spatiotemporal associations between long‐range regulation peaks and tumour heterogeneity. Differential expression of the BCL2 family was coupled with widespread chromatin accessibility changes in gynaecologic cancer, accompanied by highly heterogeneous distal non‐coding accessibility surrounding the BCL2L1 gene loci. A relationship was also identified between gene expression, gene amplification, enhancer signatures, DNA methylation and overall patient survival. Prognostic analysis implied clinical correlations with BAD, BIK and BAK1. A shared protein regulatory network was established in which the co‐mutation signature of TP53 and PIK3CA was linked to the BCL2L1 gene.Conclusions: Our results provide the first systematic identification of the molecular features of the BCL2 family under the spatial pattern of chromatin in gynaecologic and breast cancer. These findings broaden the therapeutic scope of the BCL2 family to the non‐coding region by including a significantly conserved distal region overlaying an enhancer.

The patterns of communication among different chondrocyte subtypes in human cartilage degeneration and regeneration help us understand the microenvironment of osteoarthritis and optimize cell-targeted therapies. Here, a single-cell transcriptome dataset of chondrocytes is used to explore the synergistic and communicative patterns of different chondrocyte subtypes. We collected 1600 chondrocytes from 10 patients with osteoarthritis and analyzed the active communication patterns for the first time based on network analysis and pattern recognition at the single-cell level. Manifold learning and quantitative contrasts were performed to analyze conserved and specific communication pathways. We found that ProCs (Proliferative chondrocytes), ECs (Effector chondrocytes), preHTCs (Prehypertrophic chondrocytes), HTCs (Hypertrophic chondrocytes), and FCs (Fibrocartilage chondrocytes) are more active in incoming and outgoing signaling patterns, which is consistent with studies on their close functional cooperation. Among them, preHTCs play multiple roles in chondrocyte communication, and ProCs and preHTCs have many overlapping pathways. These two subtypes are the most active among all chondrocyte subtypes. Interestingly, ECs and FCs are a pair of "mutually exclusive" subtypes, of which ECs are predominant in incoming patterns and FCs in outgoing patterns. The active signaling pathways of ECs and FCs largely do not overlap. COLLAGEN and LAMININ are the main pivotal pathways, which means they are very important in the repair and expansion of joint homeostasis. Notably, only preHTCs assume multiple roles (including sender, receiver, mediator, and influencer) and are involved in multiple communication pathways. We have examined their communication patterns from the perspective of cellular interactions, revealed the relationships among different chondrocyte subtypes, and, in particular, identified a number of active subtypes and pathways that are important for targeted therapy in the osteoarthritic microenvironment. Our findings provide a new research paradigm and new insights into understanding chondrocyte activity patterns in the osteoarthritic microenvironment.

Psoriasis, a complex and recurrent chronic inflammatory skin disease involving various inflammatory cell types, requires effective cell communication to maintain the homeostatic balance of inflammation. However, patterns of communication at the single-cell level have not been systematically investigated. In this study, we employed social network analysis tools, pattern recognition, and manifold learning to compare molecular communication features between psoriasis cells and normal skin cells. Utilizing a process that facilitates the discovery of cell type-specific regulons, we analyzed internal regulatory networks among different cells in psoriasis. Advanced techniques for the quantitative detection of non-targeted proteins in pathological tissue sections were employed to demonstrate protein expression. Our findings revealed a synergistic interplay among the communication signals of immune cells in psoriasis. B-cells were activated, while Langerhans cells shifted into the primary signaling output mode to fulfill antigen presentation, mediating T-cell immunity. In contrast to normal skin cells, psoriasis cells shut down numerous signaling pathways, influencing the balance of skin cell renewal and differentiation. Additionally, we identified a significant number of active cell type-specific regulons of resident immune cells around the hair follicle. This study unveiled the molecular communication features of the hair follicle cell-psoriasis axis, showcasing its potential for therapeutic targeting at the single-cell level. By elucidating the pattern of immune cell communication in psoriasis and identifying new molecular features of the hair follicle cell-psoriasis axis, our findings present innovative strategies for drug targeting to enhance psoriasis treatment.