Disrupting circadian control of autophagy induces podocyte injury and proteinuria.

The circadian clock influences a wide range of biological process and controls numerous aspects of physiology to adapt to the daily environmental changes caused by Earth's rotation. The kidney clock plays an important role in maintaining tubular function, but its effect on podocytes remains unclear. Here, we found that podocytes expressed CLOCK proteins, and that 2666 glomerular gene transcripts (13.4%), including autophagy related genes, had 24-hour circadian rhythms. Deletion of Clock in podocytes resulted in 1666 gene transcripts with the loss of circadian rhythm including autophagy genes. Podocyte-specific Clock knockout mice at age three and eight months showed deficient autophagy, loss of podocytes and increased albuminuria. Chromatin immunoprecipitation (ChIP) sequence analysis indicated autophagy related genes were targets of CLOCK in podocytes. ChIP-PCR further confirmed Clock binding to the promoter regions of Becn1 and Atg12, two autophagy related genes. Furthermore, the association of CLOCK regulated autophagy with chronic sleep fragmentation and diabetic kidney disease was analyzed. Chronic sleep fragmentation resulted in the loss of glomerular Clock rhythm, inhibition of podocyte autophagy, and proteinuria. Rhythmic oscillations of Clock also disappeared in high glucose treated podocytes and in glomeruli from diabetic mice. Finally, circadian differences in podocyte autophagy were also abolished in diabetic mice. Deletion Clock in podocytes aggravated podocyte injury and proteinuria in diabetic mice. Thus, our findings demonstrate that clock-dependent regulation of autophagy may be essential for podocyte survival. Hence. loss of circadian controlled autophagy may play an important role in podocyte injury and proteinuria.

Self-Polymerized Spiro-Type Interfacial Molecule toward Efficient and Stable Perovskite Solar Cells.

In the pursuit of highly efficient perovskite solar cells, spiro-OMeTAD has demonstrated recorded power conversion efficiencies (PCEs), however, the stability issue remains one of the bottlenecks constraining its commercial development. In this study, we successfully synthesize a novel self-polymerized spiro-type interfacial molecule, termed v-spiro. The linearly arranged molecule exhibits stronger intermolecular interactions and higher intrinsic hole mobility compared to spiro-OMeTAD. Importantly, the vinyl groups in v-spiro enable in situ polymerization, forming a polymeric protective layer on the perovskite film surface, which proves highly effective in suppressing moisture degradation and ion migration. Utilizing these advantages, poly-v-spiro-based device achieves an outstanding efficiency of 24.54 %, with an enhanced open-circuit voltage of 1.173 V and a fill factor of 81.11 %, owing to the reduced defect density, energy level alignment and efficient interfacial hole extraction. Furthermore, the operational stability of unencapsulated devices is significantly enhanced, maintaining initial efficiencies above 90 % even after 2000 hours under approximately 60 % humidity or 1250 hours under continuous AM 1.5G sunlight exposure. This work presents a comprehensive approach to achieving both high efficiency and long-term stability in PSCs through innovative interfacial design.

Interface Dipole Management of D-A-Type Molecules for Efficient Perovskite Solar Cells.

Interfacial engineering of perovskite films has been the main strategies in improving the efficiency and stability of perovskite solar cells (PSCs). In this study, three new donor-acceptor (D-A)-type interfacial dipole (DAID) molecules with hole-transporting and different anchoring units are designed and employed in PSCs. The formation of interface dipoles by the DAID molecules on the perovskite film can efficiently modulate the energy level alignment, improve charge extraction, and reduce non-radiative recombination. Among the three DAID molecules, TPA-BAM with amide group exhibits the best chemical and optoelectrical properties, achieving a champion PCE of 25.29 % with the enhanced open-circuit voltage of 1.174 V and fill factor of 84.34 %, due to the reduced defect density and improved interfacial hole extraction. Meanwhile, the operational stability of the unencapsulated device has been significantly improved. Our study provides a prospect for rationalized screening of interfacial dipole materials for efficient and stable PSCs.

Association between cognitive function and skeletal muscle in patients undergoing maintenance hemodialysis.

Background: Patients on hemodialysis have a higher burden of cognitive impairment than individuals of the same age in the general population. Studies have found a link between cognition and skeletal muscle function. However, few studies have investigated these associations and the underlying mechanisms in patients on hemodialysis. Methods: A total of 166 patients on hemodialysis were enrolled in this longitudinal study. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scores. Skeletal muscle indicators were evaluated using Inbody S10. Plasma brain-derived neurotrophic factor (BDNF) concentrations were measured by enzyme-linked immunosorbent assay. The primary outcome was a change in the MoCA scores. A mediation analysis was performed to examine the indirect effect of skeletal muscle on cognitive decline through BDNF. Results: Among the 166 patients, the average age was 49.9 ± 11.2 years. Of these patients with a median follow-up of 1,136 days, 133 participated in the study. We defined MoCA scores decreased by ≥2 points at 3 years from the baseline measurement as cognitive decline (CD). Compared to the cognitively unchanged group, patients with CD had significantly lower fat-free mass, soft lean mass, skeletal muscle mass, and skeletal muscle index (all P<0.05). After adjusting for potential confounders, skeletal muscle indicators were protective predictors of CD. A significant increase in plasma BDNF levels was observed in the CD group. Mediation analysis suggested that BDNF played a mediating role of 20-35% between cognitive impairment and skeletal muscle. Conclusion: Skeletal muscle is a protective predictor of CD in patients undergoing dialysis. BDNF mediates the relationship between cognitive impairment and skeletal muscle function.

Photocatalytic degradation of perfluorooctanoic acid (PFOA) from water: A mini review.

Perfluorooctanoic acid (PFOA) has drawn increasing attention as a highly persistent organic pollutant. The inherent stability, rigidity and potential toxicities characteristics make it a challenge to develop efficient technologies to eliminate it from water. Photocatalytic technology, as one advanced method, has been widely used in the degradation of PFOA in water. In this review, recent progress in the design of photocatalysts including doping, defects engineering, heterojunction and surface modification to boost the photocatalytic performance toward PFOA is summarized. The relevant degradation mechanisms were also discussed in detail. Finally, future prospect and challenges are proposed. This review may provide new guidelines for researchers to design much more efficient photocatalysts applied in the elimination of PFOA.