Diabetic neuropathy and Charcot neuroarthropathy (CN) may compromise lower limb skeletal integrity. We performed a comprehensive comparative assessment of foot bone across multiple hierarchical parameters at nano, meso and micro scale orders.

Acute kidney injury (AKI) has become a global public health problem that seriously endangers human health, the treatment for AKI is mainly supportive and there is no targeted, efficient and low-toxicity treatment.

Hyperinflammatory diseases arise from excessive immune activation, causing tissue damage and systemic inflammation. Regulatory T (Treg) cells play a key role in maintaining immune homeostasis, but their function or numbers may be impaired in pathological conditions. Conventional immunosuppressive therapies often fail to restore immune balance and are associated with significant adverse effects. An emerging therapeutic strategy involves the use of chimeric antigen receptor (CAR)-engineered Tregs to suppress aberrant immune responses. However, antigen-specific CAR-Tregs may be insufficient due to the heterogeneity of inflammatory diseases. Universal CAR-Tregs (UniCAR-Tregs), which may recognize broad immune markers, represent a more flexible and potentially effective alternative. In this study, second- and third-generation UniCAR constructs containing a monomeric streptavidin extracellular domain were introduced into human thymus-derived Tregs (thyTregs) via lentiviral transduction. The phenotype and transcriptomic profile of engineered thyTregs were characterized and compared to unmodified controls. Their suppressive capacity was assessed in vitro using a mixed lymphocyte reaction with a biotinylated intermediary, followed by evaluation in a preclinical graft-versus-host disease (GvHD) mouse model. CARs incorporating CD28 co-stimulation resulted in non-specific activation or failed to enhance suppression. In contrast, the UniCAR41BB construct more specifically activated thyTregs and augmented their suppressive function. In vivo, UniCAR41BB thyTregs delayed GvHD onset and improved survival. This study demonstrates, for the first time, that thyTregs can be effectively transduced without compromising their regulatory phenotype. Furthermore, second-generation UniCAR41BB construct enhances antigen-dependent suppressive function, highlighting its potential as a versatile therapeutic platform for GvHD and other inflammatory disorders.

Acute lung injury (ALI), especially when resulting from trauma-associated hemorrhagic shock (THS), is a life-threatening condition with limited treatment options and high mortality. Understanding the molecular mechanisms driving ALI in this context is essential to identify reliable biomarkers and therapeutic targets. This study aimed to explore the transcriptomic alterations and protein interaction networks in a rat model of THS-induced ALI using RNA sequencing and bioinformatics tools. RNA-seq analysis was performed on lung tissues from five THS-induced and five normal rats. Analysis revealed 1003 differentially expressed genes, including 365 upregulated and 638 downregulated. Functional enrichment pointed to significant involvement of pathways related to oxidative stress, hypoxia response, neutrophil degranulation, ferroptosis, and immune activation. Protein-protein interaction network analysis identified four key gene modules, with Module 3 notably associated with iron metabolism and neutrophilic inflammation. Hub genes such as Cd163, Nqo1, Gclc, Lcn2, and Mmp8 were identified as central regulators and validated in independent samples (three THS-induced and three controls). Lcn2 and cathepsins (CTSS, CTSK, CTSL) emerged as particularly relevant for their multifaceted roles in inflammation, iron homeostasis, and matrix remodeling. These findings provide novel insights into the immunometabolic dysregulation underlying THS-induced ALI and suggest promising molecular targets for future therapeutic interventions aimed at mitigating lung injury in critically injured trauma patients.

The global incidence rate of Crohn's disease (CD) is rising, with mesenteric adipose tissue (MAT) playing a pivotal role in CD progression, particularly in fibrosis development. This study aimed to identify key genes in MAT that contribute to CD progression, thereby providing insights for potential therapeutic strategies.

Understanding the associations between genetic markers, serological subsets and clinical manifestations in patients with Systemic lupus erythematosus (SLE) may elucidate disease mechanisms and inform personalised treatment strategies. This study aimed to classify SLE patients into distinct subsets based on autoantibody profiles and to examine associations with clinical and genetic characteristics, focusing on key risk loci.

Acute kidney injury (AKI) represents a significant public health challenge, marked by high rates of incidence and mortality. PANoptosis, a multifaceted process of cell death, involves complex interactions between pyroptosis, apoptosis, and necroptosis. This mechanism mediates cell death via the PANoptosome complex, which combines components from multiple cell death pathways. The therapeutic potential of targeting PANoptosis for AKI treatment is increasingly promising. In this review, we explore recent progress in the understanding of PANoptosis in AKI and examine possible therapeutic targets.

This study aims to employ magnetic particle imaging (MPI) for in vivo tracking and quantitative assessment of targeting capability of CLDN18.2-specific CAR-T cells. CLDN18.2-targeted CAR-T cells were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic particle imaging (MPI), and with the near-infrared fluorescent dye DiR for fluorescence molecular imaging (FMI) before infusion. SPIONs-labeled and unlabeled CAR-T cells were administered intravenously to NOD/SCID mice bearing HGC27 xenograft tumors, either independently or in combination with anti-PD-L1 (aPD-L1) antibody (n = 3 for imaging and n = 5 for treatment). The FMI and MPI successfully monitored the dynamic migration and tumor targeting of CAR-T cells towards CLDN18.2-overexpressing tumors. On the fifth day post-infusion, the MPI signal of SPIONs-labeled CAR-T cells was significantly higher in the tumor than that of labeled normal T cells. MPI combined with FMI successfully monitored the targeting of CLDN18.2-specific CAR-T cells in gastric cancer, providing a potential framework for evaluating CAR-T therapy combined with aPD-L1 immunotherapy.

Despite recent significant therapeutic progress, cardiovascular diseases (CVD) remain an unmet clinical, economic, and social burden worldwide. Cell-based therapies have been proposed as therapeutic strategies, however, the overall efficacy was modest.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease involving production of autoantibodies by B cells. This study aimed at identifying novel drug targets using a computational algorithm to select targets and thereafter validate the top ranked 11 targets by siRNA knockdown in a primary B cell maturation assay.

The appendix, a component of the gut-associated lymphoid tissue enriched with B lymphocytes, plays a pivotal role in intestinal mucosal immunity. Previous studies have indicated that prior appendectomy may prevent the onset of ulcerative colitis (UC); however, its therapeutic role in UC remains unclear, and prophylactic appendectomy is not a realistic approach to prevent UC. In this study, we confirmed that appendectomy alleviates dextran sodium sulphate (DSS)-induced chronic murine colitis and further demonstrated that appendiceal B (APB) lymphocytes exacerbate colonic inflammation by migrating to the colon via the CCL20-CCR6 axis and facilitating colonic CD4 T cell-mediated T helper 1 (Th1) and T helper 17 (Th17) immune responses. Single-cell sequencing of colonic tissues revealed IgG B cell-skewed responses in patients with UC, and APB cell expansion was positively correlated with disease severity. Immunofluorescence co-staining suggested that colonic B cells of UC patients related to the appendix. These findings highlight the therapeutic potential of appendectomy and B cell-targeted immunotherapy in UC treatment and further introduce the hypothesis that UC with appendiceal orifice inflammation may represent a distinct subtype of the disease.

Adaptive thermogenesis, particularly via the β3-adrenergic receptor (ADRB3)-protein kinase A catalytic subunit α (PKA Cα)-uncoupling protein 1 (UCP1) pathway, promotes energy expenditure and contributes to metabolic homeostasis, thereby establishing this pathway as a promising therapeutic target for metabolic disorders associated with excessive energy intake. In this study, we aimed to evaluate the therapeutic potential of adeno-associated virus (AAV)-mediated gene therapy targeting thermogenic pathways in metabolic tissues for the treatment of obesity-related dysfunctions. We demonstrated that adipocyte-specific overexpression of UCP1 improved glucose tolerance. Similarly, ADRB3 overexpression significantly enhanced glucose tolerance. Furthermore, ectopic expression of UCP1 in hepatocytes and myofibers also led to improved glucose tolerance. These findings highlight the potential of AAV-mediated gene therapy targeting the ADRB3-PKA Cα-UCP1 axis as a promising strategy for the treatment of obesity-associated metabolic disorders.

Peritoneal metastasis is a leading cause of death in gastric cancer (GC) patients, highlighting the need for early diagnosis and high-risk population identification. While circulating tumor DNA(ctDNA) and circulating tumor cells (CTC) have been widely studied in blood, their role in peritoneal lavage fluid (PLF) remains unexplored.

Diabetic kidney disease (DKD) is a main cause of end-stage renal disorder, yet its pathogenesis is still incompletely understood. Ferroptosis has been implicated in DKD progression; however, its regulatory mechanisms remain unclear. Phosphoglycerate dehydrogenase (PHGDH), a key enzyme in serine biosynthesis, has been minimally studied in DKD development. To elucidate the roles of PHGDH in ferroptosis and its underlying mechanism in podocytes and DKD, we conducted this study. Our findings demonstrate that PHGDH deficiency exacerbates podocyte injury, characterized by cytoskeletal disorganization, and promotes ferroptosis in both podocytes and DKD renal tissues. Conversely, PHGDH overexpression alleviates podocyte injury, reduces ferroptosis, and improves renal function in DKD mice. Mechanistically, we identified that PHGDH mediates ferroptosis by regulating SLC7A11 expression, a key ferroptosis-related protein. Specifically, PHGDH stabilizes Y-box binding protein 1 (YB1) by inhibiting its K48-linked ubiquitination and degradation, thereby enhancing SLC7A11 mRNA stability and expression. In conclusion, our study reveals a novel PHGDH-YB1-SLC7A11 regulatory axis that is responsible for suppressing ferroptosis and protecting against podocyte and renal injury in DKD. Our findings shed new light into the molecular mechanism underlying ferroptosis in DKD and highlight PHGDH as a therapeutic target for mitigating ferroptosis-mediated renal damage.

Abdominal aortic aneurysm (AAA) is an age-related, life-threatening condition characterized by the expansion of the abdominal aorta. Serum C-reactive protein (CRP) levels are a prognostic marker for AAA, and CRP accelerates tissue injury when deposited in damaged cell membranes in its monomeric form (mCRP). We previously showed that mCRP deposits in eroded atherosclerotic regions are associated with increases in inflammatory cell infiltration and aortic diameter. To investigate the changes in inflammatory-stromal cellular landscape associated with mCRP deposition, we used Co-Detection by Indexing (CODEX) tissue imaging with 31 nucleotide-barcoded antibodies and single-cell-based unsupervised clustering. AAA cases were categorized into High-CRP (n = 6) and Low-CRP (n = 3) groups based on serum levels and immunohistochemistry scores of mCRP. We identified 47 distinct immune and stromal cell types, revealing significant differences in protein expression between groups. In AAA, stromal cells decreased while immune cells increased. High-CRP cases showed increased M1-like and Ki67 proliferating macrophages, and reduced αSMA cells, whereas Low-CRP cases exhibited intensified fibrosis with CD163Ki67 proliferating M2-like macrophages. Spatial neighborhood enrichment analysis highlighted the close proximity of CD4FOXP3PDL1 T cells to specific clusters: (1) CD57granzyme B cytotoxic NK cells, (2) CD31HLA-A endothelial cells, (3) CD45lymphocytes/CD31 endothelial cells, and (4) CD45CD20B cells in High-CRP cases. Our findings demonstrate the varying distribution of immune cells and vascular wall phenotypes in AAA according to mCRP deposition levels. Targeting inflammation, specifically the immune cells, macrophages, and fibrosis affected by mCRP, may represent a novel approach to halting the pathogenesis of AAA.

AKI and CKD are major global health problem, which closely connected and promote each other. The mechanism may be related to maladaptive repair after renal tubular injury. FAK is a non-receptor tyrosine kinase located at the intersection of multiple cell signal transduction pathways. Previous studies have suggested that FAK may be involved in the repair process after kidney injury, but its role and mechanism in the process of AKI to CKD need to be further elucidated. In this study, we found that FAK was up-regulated in AKI to CKD and mainly localized in renal collecting ducts. Therefore, we generated renal collecting duct specific FAK knockout mice, which were treated with RIRI and UUO models to simulate the progression of AKI and CKD. This study for the first time found that the specific knockout of FAK in renal collecting duct can reduce oxidative stress and inflammatory response in the early stage of kidney injury, improve renal function, inhibit renal fibrosis, and significantly prolong the survival time of mice. In terms of mechanism, FAK knockout in renal collecting duct may affect inflammatory cell infiltration through KLF5 signaling pathway, regulate the trend of adaptive repair and maladaptive repair of renal tubular cells after injury, and promote the damaged kidney tubules restore health. Therefore, this study confirmed that loss of FAK function in the renal collecting duct can delay the progression of AKI to CKD by inhibiting inflammation-regulated maladaptive kidney repair, which providing a novel potential strategy for the clinical treatment of AKI to CKD.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by microvascular damage, immune dysregulation, and tissue fibrosis. While lymphocyte-platelet (PLT) complexes have been implicated in autoimmune diseases, their role in SSc is not well understood.

Interleukin-34, a ligand of CD115, controls Langerhans cells and microglia homeostasis and acts as regulatory cytokine. Here, we describe an unexpected role for IL-34 in metabolic homeostasis. We show that IL-34 is constitutively expressed by human β-cell and mouse islets of Langerhans. β-cell specific genetic invalidation of Il34 in mice (IL-34) impaired glucose tolerance associated with increased inflammation in islets of Langerhans during aging. This phenotype was exacerbated when IL-34 mice were subjected to a high-fat diet, suggesting a role for IL-34 in controlling local inflammation. Accordingly, in the presence of pro-inflammatory cytokines, ex vivo murine islets of Langerhans exhibited a decreased insulin synthesis, which was restored in the presence of IL-34. Finally, we observed that the levels of Il-34 mRNA were elevated in islets of Langerhans from type 2 diabetic donors. Collectively, these results identify IL-34 as a major regulator of pancreas inflammation.

Acute respiratory distress syndrome (ARDS) is characterised by severe inflammation and pulmonary edema, often leading to respiratory failure. This study aims to develop a stable and relevant rabbit model of severe ARDS using hydrochloric acid (HCl) aspiration and ventilator-induced lung injury (VILI).

Calorie restriction holds the potential in alleviating metabolic disorders and inflammation. However, the effects of intermittent caloric restriction (ICR) on cardiometabolic diseases remain poorly understood. In this study, we aim to assess the protective role of ICR in both prediabetic and diabetic heart injury.