Current research on pathological retinal neovascularization primarily focuses on growth factors, inflammation, and endothelial signaling pathways. However, increasing attention is being directed toward disruptions in the retinal immune microenvironment. Therefore, deciphering the immune-angiogenic interplay could uncover therapeutic avenues for neovascular disorders. Through integrative analyses of single-cell RNA sequencing from human fibrovascular membranes and multicohort clinical datasets, we identified neutrophil infiltration as an independent risk factor for diabetic retinopathy progression. Mechanistically, activated microglia preceded and potentiated neutrophil infiltration by secreting galectin-3 (GAL3), establishing a self-amplifying feedback loop that sustained microglial activation and drove pathological angiogenesis in mice with oxygen-induced retinopathy (OIR). To therapeutically disrupt this loop, we engineered a photocurable hydrogel for the sustained intravitreal delivery of GAL3 and vascular endothelial growth factor (VEGF)-neutralizing antibodies, which effectively suppressed aberrant angiogenesis in mice with OIR. Together, these findings reinforce the concept of retinal neovascularization as an immunovascular disorder and underscore the therapeutic potential of microenvironment-modulating strategies using biomaterials.

The efficacy of cell-based therapeutics is often compromised by host immune recognition of implanted cells and biomaterials, resulting in fibrotic encapsulation and loss of function. Here, we address this challenge with an immunomodulatory cell-based therapy, in which alginate-encapsulated retinal pigment epithelial cells continuously secrete cytokines to locally modulate the implant microenvironment. In a healthy rodent model, the localized production of interleukin-10 (IL-10) or IL-12 from encapsulated cytokine-producing cells prevented foreign body response to alginate capsules. Mechanistically, treatment was associated with reduced expression of profibrotic genes and immune shifts consistent with macrophage and T cell regulation, supporting a cytokine-mediated mitigation of foreign body response. In a diabetic murine model (streptozotocin-induced C57BL/6J), coimplantation of human islets with IL-10-producing cells attenuated pericapsular fibrosis, preserved islet viability, and restored normoglycemia for up to 100 days (4.76 times longer than islets alone). Notably, IL-10-producing cells were also effective in enabling the durability and function of encapsulated cells in a healthy nonhuman primate, showing translational feasibility. Collectively, these findings suggest that localized cytokine delivery can reduce fibrotic encapsulation and support durable graft function, offering a path to lessen reliance on systemic immunosuppression in islets transplantation and other implantable biomaterial therapies.

Recent clinical trials have shown that dual GLP-1R/GCGR agonists, including mazdutide and cotadutide, provide kidney benefits in patients with type 2 diabetes and CKD, suggesting a potential contribution of GCGR activation to these renal effects. However, whether GCGR directly confers renoprotection and the underlying mechanisms remain unclear. Here, using tubule-specific GCGR loss- and gain-of-function mouse models and human kidney samples, we show that tubular GCGR signaling exerts an important renoprotective role in DKD. Tubular GCGR expression is reduced in humans and mice with DKD and correlates with worse kidney function and increased renal injury. Genetic ablation of tubular GCGR markedly exacerbates DKD and induces pronounced phospholipid accumulation within enlarged lysosomes. Mechanistically, GCGR loss disrupts its association with the V-ATPase V1A subunit ATP6V1A, compromises V1-V0 assembly, and thereby impairs lysosomal acidification. This defect leads to impaired phospholipid hydrolysis and protease maturation, blockade of autophagic flux, and ultimately tubular cell injury. In vivo, ATP6V1A overexpression markedly reverses GCGR deficiency-induced lysosomal dysfunction and DKD progression. Consistently, re-expression of tubular GCGR via AAV9 restores lysosomal function, reduces phospholipid accumulation, and mitigates renal injury in DKD. Together, these findings provide genetic evidence for the renoprotective role of tubular GCGR in DKD, delineate a kidney-intrinsic GCGR-ATP6V1A-lysosome axis that protects tubular integrity, and extend prior GCGR-in-kidney observations into a more concrete GCGR-lysosome mechanism.

BACKGROUND Septic shock is highly prevalent in clinical practice. Some cases present insidiously and have poor prognoses. We report a case of a patient with a dislodged catheter who developed septic shock during a cystostomy procedure. CASE REPORT Our patient was a 76-year-old man with a history of hypertension, type 2 diabetes mellitus, and cerebral infarction. He had been confined to bed for a long time following a cerebral infarction and had impaired consciousness. One year prior, he developed urinary retention due to benign prostatic hyperplasia. As he did not undergo surgical treatment, a long-term indwelling urinary catheter was subsequently placed. He initially presented to the emergency department of our hospital at 8: 30 PM on November 1, 2025, 8 hours after accidental urethral catheter dislodgement. A cystostomy was recommended, but he refused and left against medical advice. At approximately 8: 00 AM on November 2, 2025, he returned to the hospital and consented to cystostomy. During the procedure, he developed septic shock. Postoperatively, he was transferred to the intensive care unit for further treatment. Three days later, the family decided to discontinue active treatment and took the patient home. Follow-up revealed that the patient died 2 days after discharge. CONCLUSIONS This case highlights the critical importance of early infection screening and prompt sepsis recognition prior to surgical procedures in elderly, frail, and catheter-dependent patients. It also highlights the importance of keeping the catheter unobstructed and ensuring proper home care.

Specific heterozygous pathogenic variants in LMNA have been reported in patients with Dunnigan-type familial partial lipodystrophy (FPLD2), while other variants cause autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD). FPLD2 is characterized by variable loss of subcutaneous fat from the extremities and trunk, and AD-EDMD is characterized by early joint contractures, proximal muscle weakness, and cardiac conduction defects. Previously, only 2 families have been reported with combined features of FPLD2 and AD-EDMD.

To report the overlapping phenotype of both FPLD2 and AD-EDMD in 5 families with heterozygous LMNA variants.

Clinical, anthropometric, laboratory, and genotyping data of affected subjects from 5 families with female probands presenting with FPLD2 and AD-EDMD phenotypes were collected.

Affected individuals (8 females, ages 18-57 years; 3 males, ages 25-41 years) harbored heterozygous p.T528R, p.R527P, p.R541P, or p.R453W LMNA variants. Five females and 2 males had joint contractures and proximal muscle weakness, and 4 females and 1 male had pacemaker-defibrillator implantation for cardiac arrhythmias, confirming AD-EDMD. Subcutaneous fat loss from the extremities confirming FPLD2 was observed in all females but only in 2 males. Four females had diabetes mellitus and hypertriglyceridemia, and 1 male had hypertriglyceridemia. Two females, 50 and 58 years old, died due to aspiration pneumonia and cerebrovascular accident, respectively, and one 40-year-old male died of alcoholic liver disease.

Our report brings attention to the frequent co-occurrence of FPLD2 and AD-EDMD. In the future, all patients with AD-EDMD should be carefully evaluated for clinical signs of lipodystrophy and metabolic complications.

To examine the association between branched-chain α-keto acids (BCKAs) and pancreatic steatosis in patients with type 2 diabetes (T2DM).

This cross-sectional study was conducted from January 2023 to March 2025. Upper abdominal computerized tomography was performed, pancreatic volume (PV), PV index (PVI), CT attenuation of pancreas (CTA_P), and CTA_p/s were then calculated. Levels of serum BCKAs and BCAAs were determined by ELISA kits. Partial correlation and linear regression analysis were performed to investigate the relationship between BCKA and pancreatic parameters. Mediating models were employed to explore the role of BMI in the relationship between BCKA and pancreatic parameters.

There were significant differences in median PV, PVI, CTAp, and CTAp/s according to BCKA tertiles (all p < 0.05). BCKAs were positively associated with PV and PVI but negatively correlated with CTAp and CTAp/s after adjustment for age and gender (all P < 0.05). Linear regression analysis showed that BCKA was associated with PV, CTAp, and CTAp/s after adjustment for confounders in all models (Model 1, Model 2, Model 3) (all P < 0.05). There existed no significant association of BCAA with pancreatic parameters after adjustment for confounders. Mediation analysis suggested that BMI played approximately 20% indirect effect in the relationship between BCKAs and PV or CTAp/s.

Serum BCKAs rather than BCAAs were associated with PV and CTAp in T2DM patients, indicating an association between BCAA malmetabolism and pancreatic steatosis. Additionally, obesity may serve as a mediator between BCKAs and pancreatic steatosis, which should be validated by prospective cohort.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the destruction of pancreatic β cells, leading to lifelong insulin dependence and an increased risk of severe complications. Three-dimensional stem cells (3D SCs) culture systems have emerged as a superior alternative by more accurately mimicking the in vivo microenvironment and enhancing stemness maintenance, regenerative efficiency, and paracrine secretion. However, studies exploring the application of 3D SCs in T1D remain limited. Here, we developed a novel serum- and cytokine-free orbital-shaking system. It enables efficient and large-scale reprogramming of somatic cells into 3D embryonic-like stem cell spheroids (Sph-Es) characterized by robust pluripotency and improved safety. To enhance therapeutic utility, Sph-Es were irradiated and transduced with INS-expressing adenoviral vectors to generate Sph-R-Ins, allowing transient insulin production without permanent genomic modification. In STZ-induced T1D mice, Sph-R-Ins improved glycemic control and glucose tolerance and increased mouse insulin and C-peptide responses, indicating improved endogenous islet function. Donor-cell tracking analyses showed no pancreatic engraftment, supporting an indirect mode of action. Additional transcriptomic, immunological, and ex vivo studies indicated that the therapeutic benefit was accompanied by ECM-related signaling changes, reduced inflammatory infiltration, enhanced M2 macrophage polarization and Treg-associated immune regulation, improved metabolic signaling, and spheroid-derived paracrine support of islet function. Together, these findings establish a mechanically guided 3D stem cell-gene therapy platform with both endocrine and immunometabolic benefits in T1D.

Childhood cancer survivors (CCS) are at risk for health-related and social challenges that can extend far into adulthood. However, CCS' trajectories are heterogeneous. As a potential influencing factor, the present work investigated adult romantic attachment in conjunction with their relationship perceptions and experiences and help-seeking behavior. CCS (N = 633, aged 24-49 years) were recruited in cooperation with the nationwide German Childhood Cancer Registry (GCCR). Participants underwent a comprehensive medical examination at the study centre. Validated self-report questionnaires (including the ECR-RD8, PHQ-9, F-SozU K6, UCLA 3-item loneliness scale) and further items regarding help-seeking behavior were applied. Adult romantic attachment orientations were substantially related to CCS' relationships in adulthood: Both more attachment anxiety and avoidance were linked to higher loneliness (r = 0.471, p < .001; r = 0.320, p < .001) and lower perceived social support (r = -0.349, p < .001; r = -0.300, p < .001). While 20.2% of CCS reported a need for psychosocial support, only 7.3% reported currently using a professional support offer. Lastly, attachment orientations also played a role in whether CCS voiced such a need when experiencing distress: Attachment anxiety moderated the relationship between suicidal ideation and the expression of a need for support, diminishing help-seeking. The findings emphasize the importance of integrating attachment-informed approaches in the long-term care of CCS. Tailored interventions addressing the interpersonal and emotional needs shaped by attachment styles could enhance resilience and mitigate barriers to seeking psychosocial support.

Objective: To investigate the correlation between advanced lung cancer inflammation index (ALI) and renal pathological activity index (AI) in lupus nephritis (LN) patients, and to evaluate its predictive value for moderate-to-severe renal pathological activity. Methods: This cross-sectional study retrospectively included 279 LN patients who underwent renal biopsy at the First Affiliated Hospital of Xi'an Jiaotong University from January 1, 2017, to December 31, 2024. The median age of the patients was 34.0 (27.0, 45.0) years, and 234 (83.9%) were female. Based on the AI, patients were divided into a low-activity group (n=177) and a moderate-to-severe activity group (n=102). Logistic regression analysis was performed to identify the influencing factors for moderate-to-severe AI. Correlation analysis was used to explore the relationship between ALI and clinical indicators. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive value of ALI for moderate-to-severe AI. Results: The ALI level in the moderate-to-severe activity group was significantly lower than that in the low-activity group (15.4 vs. 18.8, P<0.001). Multivariate logistic regression analysis showed that the 2000 Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score (OR=5.54, P<0.001) and serum creatinine (OR=1.01, P=0.007) were risk factors for moderate-to-severe AI; whereas hemoglobin (OR=0.98, P=0.001) and ALI (OR=0.97, P=0.048) were protective factors. Correlation analysis revealed that ALI was negatively correlated with AI (r=-0.31, P<0.001), and positively correlated with body mass index, hemoglobin, albumin, complement C4, and IgG. ALI was negatively correlated with SLEDAI-2K, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), serum creatinine, blood urea nitrogen, and C-reactive protein. ROC curve analysis demonstrated that the area under the curve (AUC) of ALI for predicting moderate-to-severe AI was 0.658 (95%CI 0.592-0.724, P<0.001). The optimal cutoff value was 13.14, with a sensitivity of 72.8% and a specificity of 55.9%. The proportion of patients with moderate-to-severe LN in the ALI <13.14 group was significantly higher than that in the ALI ≥13.14 group (50.9% vs. 27.7%, P<0.001). Conclusions: ALI is closely correlated with renal pathological AI in LN and serves as a protective factor against moderate-to-severe AI. ALI holds certain predictive value and may serve as a non-invasive auxiliary tool for evaluating renal pathological activity in LN.

Lung cancer associated with cystic airspaces (LCCA) is a rare and distinct subtype of lung cancer. Patients are often without specific clinical symptoms in the early stage, and the radiological features can be easily confused with pulmonary bullae, benign pulmonary cysts, and other cystic lung lesions, resulting in a high rate of missed diagnosis and misdiagnosis. We report the case of a middle-aged woman with LCCA pathologically confirmed following surgical resection. A chest computed tomography (CT) scan performed during a routine health examination initially revealed an air-containing lesion adjacent to the oblique fissure in the right lower lobe, measuring approximately 1.1 cm×0.8 cm. Serial CT examinations over a 12-year period demonstrated gradual evolution of the lesion, with the development of a lobulated contour, interlobar pleural indentation, and vascular convergence, raising suspicion for malignancy. The patient subsequently underwent surgical resection. Based on histopathological and immunohistochemical findings, the lesion was finally diagnosed as invasive lung adenocarcinoma (lepidic predominant, 60%; acinar, 30%; papillary, 10%). No evidence of tumor recurrence or metastasis was observed during postoperative outpatient follow-up.