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Abstract Knowing provoking factors of vitiligo progression and how to avoid them is essential to the successful self-management of vitiligo. Cultivating a positive attitude is also essential to avoid focusing on the negative aspects of the disease and to fuel proactive practice. This study aims to evaluate the knowledge, attitudes, and practices (KAP) of vitiligo patients and identify related factors. The study recruited 517 (54.55% male) adult vitiligo patients in Beijing and Nanjing. The mean knowledge, attitude, and practice scores were 5.45 ± 2.74 (possible range: 0–10), 23.15 ± 6.78 (possible range: 8–40), and 37.13 ± 6.78 (possible range: 10–50), respectively. Mediation analysis indicated that knowledge (β = 0.24, P = 0.023), attitude (β=-0.28, P

Autophagic activation in immune cells, gut microbiota dysbiosis, and metabolic abnormalities have been reported separately as characteristics of systemic lupus erythematosus (SLE). Elucidating the crosstalk among the immune system, commensal microbiota, and metabolites is crucial to understanding the pathogenesis of autoimmune diseases. Emerging evidence shows that basophil activation plays a critical role in the pathogenesis of SLE; however, the underlying mechanisms remain largely unknown. Here, we investigated the effects of autophagic inhibition on the pathogenesis of basophils in SLE using Autophagy-related gene 5 (Atg5) knockout (Atg5−/−) as an autophagic inhibitor. Specifically, we knocked out basophilic Atg5 in vivo to investigate its impact on lupus metabolism. Furthermore, Atg5−/− basophils were transferred to basophil-depleted MRL/MpJ-Faslpr (MRL/lpr) mice to study their effect on disease metabolism. Metagenomic and targeted metabolomic sequencing results indicated considerable reduction in the levels of plasma autoantibodies and inflammatory cytokines in the Atg5−/− basophil transfer group compared with that in the control group. Transplanting Atg5−/− basophils improved the gut microbiota balance in MRL/lpr mice, increasing the abundance of beneficial bacteria, such as Ligilactobacillus murinus and Faecalitalea rodentium, and reducing that of potentially pathogenic bacteria such as Phocaeicola salanitronis. The transplantation of Atg5-deficient basophils improved lupus symptoms by modulating lipid and amino acid metabolism. This improvement was linked to changes in the gut microbiota, particularly an increase in Ligilactobacillus murinus and Faecalitalea rodentium populations. These microbial shifts are believed to promote the production of beneficial metabolites, such as γ-linolenic acid and oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine, while reducing the levels of harmful metabolites such as arginine. These alterations in the metabolic profile contribute to the alleviation of lupus symptoms. Collectively, these findings reveal a novel role of basophil autophagy in SLE, highlighting its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Mitochondrial homeostasis plays a crucial role in the pathogenesis of osteoarthritis (OA), a chronic musculoskeletal disorder characterized by articular cartilage degeneration and chondrocyte apoptosis. However, molecular mechanisms underlying the association between mitophagy and OA remain unclear. Here, we aimed to investigate the role of the autophagy receptor protein optineurin (OPTN) in OA, and explore the effects of dietary intervention on OA symptoms and its relationship with OPTN-mediated mitophagy. Our findings showed the downregulation of OPTN in patients with OA. Using an Optn-knockout mouse model, we demonstrated that OPTN deficiency leads to impaired mitophagy, resulting in the accumulation of damaged mitochondria, increased production of reactive oxygen species, and chondrocyte apoptosis. Furthermore, fasting prevented OA progression by activating OPTN-mediated mitophagy and maintaining mitochondrial homeostasis in mice. The present study revealed a novel mechanism by which OPTN-mediated mitophagy influences chondrocytes and the OA phenotype in Optn-knockout mice, suggesting that OPTN-mediated mitophagy plays a crucial role in OA development and progression. This study provides new insights into the pathogenesis of OA and offers a potential avenue for the development of novel drugs targeting OPTN to mitigate OA progression. OPTN-mediated mitophagy plays a key role in OA progression. OPTN deficiency leads to mitochondrial damage and chondrocyte apoptosis, while fasting alleviates OA by activating OPTN-mediated mitophagy, offering a potential therapeutic target for OA [ABSTRACT FROM AUTHOR]

Although metal-free hydrosilylation of siloxanes is essential for the industrial preparation of organosilicon compounds due to its unique advantages, such as the avoidance of the use and residue of precious metals, efficient metal-free silicon hydrogenation reactions are still rare. Herein, we report a straightforward visible light-driven metal-free hydrosilylation reaction based on siloxanes and silicon vinyl groups, catalyzed by the synergistic effect of the organic photooxidation catalyst 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile and the base N,N′-diisopropylethylamine, which undergo electron transfer and selectively induce Si–H activation during catalysis. After optimization, the silicon vinyl conversion rate in the hydrosilylation reaction exceeded 99% without using any traditional hydrogen atom transfer reagents. Mechanistic studies based on experimental data and theoretical calculations revealed that the reaction proceeds through a free radical reaction and is thermodynamically feasible. The proposed methodology efficiently affords linear polymer formation via a stepwise growth approach. Furthermore, it can crosslink commercial high-molecular-weight polyvinyl silicone oil with disiloxane, realizing the gelation of the material. [ABSTRACT FROM AUTHOR]

In this study, a novel cost-effective methodology was developed to enhance the gas barrier properties and permselectivity of unfilled natural rubber (NR)/polybutadiene rubber (BR) composites through the construction of a heterogeneous structure using pre-vulcanized powder rubber to replace traditional fillers. The matrix material is composed of a blend of NR and BR, which is widely used in tire manufacturing. By incorporating pre-vulcanized trans-1,4-poly(isoprene-co-butadiene) (TBIR) rubber powder (pVTPR) with different cross-linking densities and contents, significant improvements in the gas barrier properties and CO2 permselectivity of the NR/BR/pVTPR composites were observed. The results indicated that compared to NR/BR/TBIR composites prepared through direct blending of NR, BR, and TBIR, the NR/BR/pVTPR composites exhibited markedly superior gas barrier properties. Increasing the cross-linking density of pVTPR resulted in progressive enhancement of the gas barrier properties of the NR/BR/pVTPR composite. For example, the addition of 20 phr pVTPR with a cross-linking density of 346 mol/m3 resulted in a 79% improvement in the oxygen barrier property of NR/BR/pVTPR compared to NR/BR, achieving a value of 5.47×10−14 cm3·cm·cm−2·s−1·Pa−1. Similarly, the nitrogen barrier property improved by 76% compared to NR/BR, reaching 2.4×10−14 cm3·cm·cm−2·s−1·Pa−1, which is 28 % higher than the conventional inner liner material brominated butyl rubber (BIIR, PN2=3.32×10−14 cm3·cm·cm−2·s−1·Pa−1). Owing to its low cost, exceptional gas barrier properties, superior adhesion to various tire components, and co-vulcanization capabilities, the NR/BR/pVTPR composite has emerged as a promising alternative to butyl rubber in the inner liner of tires. Furthermore, by fine-tuning the cross-linking density of pVTPR, the high-gas-barrier NR/BR/pVTPR composites also demonstrated remarkable CO2 permselectivity, with a CO2/N2 selectivity of 61.4 and a CO2/O2 selectivity of 26.12. This innovation provides a novel strategy for CO2 capture and separation, with potential applications in future environmental and industrial processes. The multifunctional NR/BR/pVTPR composite, with its superior gas barrier properties and CO2 permselectivity, is expected to contribute to the development of safer, greener, and more cost-effective transportation solutions. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy activation in renal tubular epithelial cells protects against acute kidney injury (AKI). However, the role of immune cell autophagy, such as that involving macrophages, in AKI remains unclear. In this study, we discovered that macrophage autophagy was an adaptive response during AKI as mice with macrophage-specific autophagy deficiency (atg5−/−) exhibited higher serum creatinine, more severe renal tubule injury, increased infiltration of ADGRE1/F4/80+ macrophages, and elevated expression of inflammatory factors compared to WT mice during AKI induced by either LPS or unilateral ischemia-reperfusion. This was further supported by adoptive transfer of atg5−/− macrophages, but not WT macrophages, to cause more severe AKI in clodronate liposomes-induced macrophage depletion mice. Similar results were also obtained in vitro that bone marrow-derived macrophages (BMDMs) lacking Atg5 largely increased pro-inflammatory cytokine expression in response to LPS and IFNG. Mechanistically, we uncovered that atg5 deletion significantly upregulated the protein expression of TARM1 (T cell-interacting, activating receptor on myeloid cells 1), whereas inhibition of TARM1 suppressed LPS- and IFNG-induced inflammatory responses in atg5−/− RAW 264.7 macrophages. The E3 ubiquitin ligases MARCHF1 and MARCHF8 ubiquitinated TARM1 and promoted its degradation in an autophagy-dependent manner, whereas silencing or mutation of the functional domains of MARCHF1 and MARCHF8 abolished TARM1 degradation. Furthermore, we found that ubiquitinated TARM1 was internalized from plasma membrane into endosomes, and then recruited by the ubiquitin-binding autophagy receptors TAX1BP1 and SQSTM1 into the autophagy-lysosome pathway for degradation. In conclusion, macrophage autophagy protects against AKI by inhibiting renal inflammation through the MARCHF1- and MARCHF8-mediated degradation of TARM1. Abbreviations: AKI, acute kidney injury; ATG, autophagy related; Baf, bafilomycin A1; BMDMs, bone marrow-derived macrophages; CCL2/MCP-1, C-C motif chemokine ligand 2; CHX, cycloheximide; CQ, chloroquine; IFNG, interferon gamma; IL, interleukin; IR, ischemia-reperfusion; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; LPS, lipopolysaccharide; MARCHF, membrane associated ring-CH-type finger; NC, negative control; NFKB, nuclear factor of kappa light polypeptide gene enhancer in B cells; NLRP3, NLR family, pyrin domain containing 3; NOS2, nitric oxide synthase 2, inducible; Rap, rapamycin; Wort, wortmannin; RT-qPCR, real-time quantitative polymerase chain reaction; Scr, serum creatinine; SEM, standard error of mean; siRNA, small interfering RNA; SYK, spleen tyrosine kinase; TARM1, T cell-interacting, activating receptor on myeloid cells 1; TAX1BP1, Tax1 (human T cell leukemia virus type I) binding protein 1; TECs, tubule epithelial cells; TNF, tumor necrosis factor; WT, wild type. [ABSTRACT FROM AUTHOR]

It has been confirmed in clinic that Qingxin Zishen Prescription (QZP) is effective and safe in relieving vasomotor symptoms. However, its active components have not been elucidated. In this study, a method based on ultra-performance liquid chromatography quadrupole-time of flight mass spectrometry (UPLC-Q-TOF MS) was developed to identify the plasma absorbed components of QZP. After continuous intragastric administration of 48.5 g/kg QZP for 3 days to female SD rats, plasma samples were collected and then pre-treated by solid phase extraction (SPE) to remove proteins in plasma. Then, chromatographic separation of the plasma samples was performed on an Agilent ZORBAX SB C18 column (4.6 mm×100 mm, 1.8 µm) using a gradient elution with a mobile phase composed of 0.1% formic acid aqueous solution (A) and methanol-acetonitrile (1:1, V/V, B) prior to MS analysis. The column temperature was kept at 40 ℃. The MS and MS2 analysis were performed with the electrospray ionization (ESI) source under both positive and negative ion modes from m/z 100 to 1300. Intelligent dynamic background deduction, information dependent acquisition and highly sensitive mode were used to collect the data. According to the accurate m/z values of MS and MS2 information, data from reference substance and related literature, the absorbed components in plasma were identified. In total, forty prototypes from QZP are identified and inferred in the plasma samples, including 27 alkaloids, 9 iridoid glycosides, 2 flavonoid carbon glycosides, 1 phenolic acid and 1 fatty acid. Among them, alkaloids are mainly from Nelumbo nucifera Gaertn, Coptis chinensis Franch, Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou, and Uncaria rhynchophylla (Miq.) Miq. ex Havil. Iridoid glycosides are mainly from Rehmannia glutinosa Libosch. and Cornus officinalis Sieb. et Zucc. Furthermore, the fragmentation pathways and characteristic fragment ions of iridoid glycosides and dibenzylisoquinoline alkaloids were summarized. This study provides not only a rapid and comprehensive analysis method for the plasma absorbed components of QZP, but also a scientific fundamental for elucidating the material basis of action of QZP.

Summary: Transforming growth factor β (TGF-β) is well known to play paradoxical roles in tumorigenesis as it has both growth-inhibitory and pro-metastatic effects. However, the underlying mechanisms of how TGF-β drives the opposing responses remain largely unknown. Here, we report that ERBB4, a member of the ERBB receptor tyrosine kinase family, specifically promotes TGF-β′s metastatic response but not its anti-growth response. ERBB4 directly phosphorylates Tyr162 in the linker region of SMAD4, which enables SMAD4 to achieve a higher DNA-binding ability and potentiates TGF-β-induced gene transcription associated with epithelial-to-mesenchymal transition (EMT), cell migration, and invasion without affecting the genes involved in growth inhibition. These selective effects facilitate lung cancer metastasis in mouse models. This discovery sheds light on the previously unrecognized role of SMAD4 as a substrate of ERBB4 and highlights the selective involvement of the ERBB4-SMAD4 regulatory axis in tumor metastasis.

ABSTRACT This study aimed to assess the correlation between estimated pulse wave velocity (ePWV) and mortality rates related to all‐cause and cardiovascular disease (CVD) among individuals diagnosed with chronic kidney disease (CKD) in the United States. A total of 4669 participants with CKD were identified from the National Health and Nutrition Examination Survey conducted between 1999 and 2018. We calculated the incidence of CKD using an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2. Our study examined the association between ePWV and mortality risk based on weighted Kaplan–Meier plots and multivariate Cox regression. Linear testing between ePWV and mortality from all causes and CVD was performed using restricted cubic splines and Cox regression. This study included 4669 patients with CKD from the NHANES, representing 37 million Americans with CKD. There was a mean age of 71.9 years, and 48.1% of participants were male. With every increase of 1 m/s in ePWV measurement, there is a corresponding 31% (hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.28–1.34) increase in the rate of mortality from all causes and a 32% (HR: 1.32, 95% CI: 1.27–1.37) increase in the rate of mortality from CVD. A significantly higher rate of cardiovascular and all‐cause mortality was observed in patients with CKD with elevated ePWV than in those with lower ePWV, as shown in the weighted Kaplan–Meier plots. Patients with CKD have a significant relationship between ePWV and all‐cause and cardiovascular mortality.

Plant communities are composed of species that differ both in functional traits and evolutionary histories. As species' functional traits partly result from their individual evolutionary history, we expect the functional diversity of communities to increase with increasing phylogenetic diversity. This expectation has only been tested at local scales and generally for specific growth forms or specific habitat types, for example, grasslands. Here we compare standardized effect sizes for functional and phylogenetic diversity among 1,781,836 vegetation plots using the global sPlot database. In contrast to expectations, we find functional diversity and phylogenetic diversity to be only weakly and negatively correlated, implying a decoupling between these two facets of diversity. While phylogenetic diversity is higher in forests and reflects recent climatic conditions (1981 to 2010), functional diversity tends to reflect recent and past climatic conditions (21,000 years ago). The independent nature of functional and phylogenetic diversity makes it crucial to consider both aspects of diversity when analysing ecosystem functioning and prioritizing conservation efforts., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Bottlebrush block copolymers (BBCPs) are a unique class of materials that contain a backbone with densely grafted and chemically distinct polymeric side chains. The nonlinear architecture of BBCPs provides numerous degrees of freedom in their preparation, including control over key parameters such as grafting density, side chain length, block arrangement, and overall molecular weight. This uniquely branched structure provides BBCPs with several important distinctions from their linear counterparts, including sterically induced side chain and backbone conformations, rapid and large self-assembled nanostructures, and reduced or eliminated entanglement effects (assuming sufficient grafting density and that the molecular weight of the side chains is below their respective entanglement molecular weight). These distinctions allow access to large domain sizes, very rapid assembly, and the ability to preferentially add additives and/or precursors to one domain, thereby enabling the efficient fabrication of a wide range of advanced materials and devices. BBCPs have been utilized to create finely controlled and well-ordered nanostructures for use in applications, such as photonic crystals, drug delivery systems, energy conversion, energy storage devices, and key components in surface coatings. To further deploy BBCPs as templates for the formation of precise nanostructures, having a thorough understanding of their synthesis, self-assembly, and templating is necessary. To explore and understand the self-assembly and subsequent applications of BBCPs, this review emphasizes the physics of self-assembly for BBCPs (including architectural, rheological, and thermodynamic considerations) and structure-property relationships between BBCPs and their resulting nanostructures. Lastly, we provide an overview of current research trends using BBCPs in energy storage, energy conversion, photonic, 3D printing, and drug delivery applications. We aim to provide researchers with the fundamentals of BBCP self-assembly in their use as nanostructured materials to continue their development of advanced materials.