The impact of social media has been significant on various aspects of life, particularly mental health. Growing concerns about the adverse effects of social media use have prompted the exploration of experimental interventions, defined as digital detox interventions. However, it remains unclear whether digital detox interventions are effective for mental health outcomes. The aim of this study was to provide comprehensive insights into the effects of digital detox interventions on various mental health outcomes, including depression, life satisfaction, stress, and mental well-being. Following the PRISMA guidelines, systematic searches were carried out in online databases, including PubMed and ScienceDirect, within the publication range of 2013 and 2023. A total of 2578 titles and abstracts were screened, and 10 studies were included in the analysis. A risk of bias assessment was conducted using RoB 2.0 and the Newcastle-Ottawa scale, while statistical analysis was conducted using RevMan 5.4.1. Our data indicated a significant effect of digital detox in mitigating depression with the standardized mean difference (SMD: -0.29; 95%CI: -0.51, -0.07, p=0.01). No statistically significant effects were discerned in terms of life satisfaction (SMD: 0.20; 95%CI: -0.12, 0.52, p=0.23), stress (SMD: -0.31; 95%CI: -0.83, 0.21, p=0.24), and overall mental well-being (SMD: 0.04; 95%CI: -0.54, 0.62, p=0.90). These data underscore the nuanced and selective influence of digital detox on distinct facets of mental health. In conclusion, digital detox interventions significantly reduce depressive symptoms, suggesting that intentional reduction or cessation of digital engagement may help alleviate contributing factors. However, no statistically significant effects were observed in mental well-being, life satisfaction, and stress. This discrepancy may be due to the complex nature of these constructs, involving various factors beyond the scope of digital detox interventions.

Significance Statement: Nuclear translocation of dendrin is observed in injured podocytes, but the mechanism and its consequence are unknown. In nephropathy mouse models, dendrin ablation attenuates proteinuria, podocyte loss, and glomerulosclerosis. The nuclear translocation of dendrin promotes c-Jun N-terminal kinase phosphorylation in podocytes, altering focal adhesion and enhancing cell detachment–induced apoptosis. We identified mediation of dendrin nuclear translocation by nuclear localization signal 1 (NLS1) sequence and adaptor protein importin-α. Inhibition of importin-α prevents nuclear translocation of dendrin, decreases podocyte loss, and attenuates glomerulosclerosis in nephropathy models. Thus, inhibiting importin-α–mediated nuclear translocation of dendrin is a potential strategy to halt podocyte loss and glomerulosclerosis. Background: Nuclear translocation of dendrin is observed in the glomeruli in numerous human renal diseases, but the mechanism remains unknown. This study investigated that mechanism and its consequence in podocytes. Methods: The effect of dendrin deficiency was studied in adriamycin (ADR) nephropathy model and membrane-associated guanylate kinase inverted 2 (MAGI2) podocyte-specific knockout (MAGI2 podKO) mice. The mechanism and the effect of nuclear translocation of dendrin were studied in podocytes overexpressing full-length dendrin and nuclear localization signal 1–deleted dendrin. Ivermectin was used to inhibit importin-α. Results: Dendrin ablation reduced albuminuria, podocyte loss, and glomerulosclerosis in ADR-induced nephropathy and MAGI2 podKO mice. Dendrin deficiency also prolonged the lifespan of MAGI2 podKO mice. Nuclear dendrin promoted c-Jun N-terminal kinase phosphorylation that subsequently altered focal adhesion, reducing cell attachment and enhancing apoptosis in cultured podocytes. Classical bipartite nuclear localization signal sequence and importin-α mediate nuclear translocation of dendrin. The inhibition of importin-α/β reduced dendrin nuclear translocation and apoptosis in vitro as well as albuminuria, podocyte loss, and glomerulosclerosis in ADR-induced nephropathy and MAGI2 podKO mice. Importin-α3 colocalized with nuclear dendrin in the glomeruli of FSGS and IgA nephropathy patients. Conclusions: Nuclear translocation of dendrin promotes cell detachment–induced apoptosis in podocytes. Therefore, inhibiting importin-α–mediated dendrin nuclear translocation is a potential strategy to prevent podocyte loss and glomerulosclerosis.

Biofilm formation is a key factor in the persistence and recurrence of otorhinolaryngology (ORL) infections, driving antimicrobial resistance and treatment failure. Chronic conditions, such as rhinosinusitis, otitis media and tonsillitis, are linked to biofilm‑producing pathogens, forming protective extracellular matrices that shield bacteria from immune defenses and antibiotics. The present review explores emerging pharmacological strategies to disrupt biofilm integrity and improve treatment outcomes. Strategies such as quorum sensing inhibitors, antibiofilm peptides, enzymatic dispersal agents, and drug repurposing can potentially disrupt biofilms and counter‑resistance mechanisms. Furthermore, novel therapies (including nanotechnology‑based drug delivery systems, phage therapy and immunomodulation) offer innovative alternatives for managing biofilm‑associated infections. However, clinical implementation remains challenging. Future research should prioritize optimizing drug formulations, refining delivery techniques, and exploring synergistic combinations to enhance biofilm eradication. Implementing these innovative strategies can improve the management of chronic ORL infections, reducing recurrence rates and enhancing patient outcomes.

In many cells and tissues, including the glomerular filtration barrier, scaffold proteins are critical in optimizing signal transduction by enhancing structural stability and functionality of their ligands. Recently, mutations in scaffold protein membrane-associated guanylate kinase inverted 2 (MAGI-2) encoding gene were identified among the etiology of steroid-resistant nephrotic syndrome. MAGI-2 interacts with core proteins of multiple pathways, such as transforming growth factor-β signaling, planar cell polarity pathway, and Wnt/β-catenin signaling in podocyte and slit diaphragm. Through the interaction with its ligand, MAGI-2 modulates the regulation of apoptosis, cytoskeletal reorganization, and glomerular development. This review aims to summarize recent findings on the role of MAGI-2 and some other scaffold proteins, such as nephrin and synaptopodin, in the underlying mechanisms of glomerulopathy.

Despite advances in diabetes management, there is an urgent need for novel therapeutic strategies since the current treatments remain insufficient in halting the progression of diabetic nephropathy-diabetic kidney disease (DN-DKD). This review is mainly addressed on the pivotal role of endothelin-1 in the pathophysiology of DN, with a specific focus on its effects on podocytes and the glomerular filtration barrier. Endothelin-1 promotes mesangial cell proliferation, sclerosis, and direct podocyte injury via the activation of endothelin type A and B receptors, that drive the progression of glomerulosclerosis in DN-DKD. Endothelin receptor antagonists, including drugs like atrasentan and sparsentan, have demonstrated nephroprotective effects in experimental models by reducing proteinuria and podocyte injury. The therapeutic potential to slow the progression of DN to end-stage kidney disease (ESKD) of these endothelin receptor antagonists in clinical practice is currently under evaluation. However, fluid retention and increased risk of heart failure associated with endothelin receptor antagonists need careful consideration. This review aims to provide an in-depth analysis of the pathophysiological role of endothelin and the emerging therapeutic implications of targeting this pathway in DN-DKD and discusses efficacy, safety, and the possibility of combining the new generation of endothelin receptor antagonists with the standard treatment of CKD and DN-DKD. Graphical abstract

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin–angiotensin–aldosterone system and chronic inflammation, may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions, placing them in the spectrum of RAS–MAPK-driven neoplasms, which were until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumours, such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumours includes clinical symptoms involving chronic bone pain and laboratory findings of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically, both lesions are characterized by clustered osteoclasts in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumours.