SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion.

The secretory pathway of eukaryotic cells packages cargo proteins into COPII-coated vesicles for transport from the endoplasmic reticulum (ER) to the Golgi. We now report that complete genetic deficiency for the COPII component SEC24A is compatible with normal survival and development in the mouse, despite the fundamental role of SEC24 in COPII vesicle formation and cargo recruitment. However, these animals exhibit markedly reduced plasma cholesterol, with mutations in Apoe and Ldlr epistatic to Sec24a, suggesting a receptor-mediated lipoprotein clearance mechanism. Consistent with these data, hepatic LDLR levels are up-regulated in SEC24A-deficient cells as a consequence of specific dependence of PCSK9, a negative regulator of LDLR, on SEC24A for efficient exit from the ER. Our findings also identify partial overlap in cargo selectivity between SEC24A and SEC24B, suggesting a previously unappreciated heterogeneity in the recruitment of secretory proteins to the COPII vesicles that extends to soluble as well as trans-membrane cargoes. DOI:http://dx.doi.org/10.7554/eLife.00444.001

Supporting Left-Behind Children in China: A Systematic Review of Literature on Library Services

Left-behind children are minors under the age of sixteen whose parents migrate elsewhere for work or whose sole guardian lacks the ability to provide adequate care. They represent a unique yet vulnerable population group in China. Libraries play a vital role in serving left-behind children by ensuring equal access to information and promoting educational equity and social inclusion. Following a systematic literature review approach, we analyzed 31 relevant articles from four major Chinese academic databases: CNKI (China National Knowledge Infrastructure), Wanfang, VIP (Chinese Science and Technology Journal Database), and DuXiu. Based on content analysis of the included literature, we identified the following key findings: (1) The included articles primarily focus on left-behind children’s interpersonal and socioeconomic vulnerabilities that lead to deficits in family education and limitations in school education; (2) Left-behind children’s library needs center on space accessibility, reading resources, emotional support, and information literacy development; (3) Current library services for this group face challenges such as low public awareness of library services, inadequate resources and collections, and ineffective service delivery; (4) Rural libraries should not operate alone but collaborate with schools, village reading centers, public libraries, publishers, government agencies, and social organizations to build integrated educational systems for left-behind children; and (e) It is important to activate rural communities’ internal dynamics by encouraging knowledgeable left-behind youth to provide intergenerational knowledge exchange with younger peers and senior populations, thereby elevating rural cultural ecosystems. This systematic review offers practical implications for improving library services for left-behind children and advancing information equality in China

Lignin‐derived hard carbon anode with a robust solid electrolyte interphase for boosted sodium storage performance

Hard carbon is regarded as a promising anode candidate for sodium-ion batteries due to its low cost, relatively low working voltage, and satisfactory specific capacity. However, it still remains a challenge to obtain a high-performance hard carbon anode from cost-effective carbon sources. In addition, the solid electrolyte interphase (SEI) is subjected to continuous rupture during battery cycling, leading to fast capacity decay. Herein, a lignin-based hard carbon with robust SEI is developed to address these issues, effectively killing two birds with one stone. An innovative gas-phase removal-assisted aqueous washing strategy is developed to remove excessive sodium in the precursor to upcycle industrial lignin into high-value hard carbon, which demonstrated an ultrahigh sodium storage capacity of 359 mAh g−1. It is found that the residual sodium components from lignin on hard carbon act as active sites that controllably regulate the composition and morphology of SEI and guide homogeneous SEI growth by a near-shore aggregation mechanism to form thin, dense, and organic-rich SEI. Benefiting from these merits, the as-developed SEI shows fast Na+ transfer at the interphases and enhanced structural stability, thus preventing SEI rupture and reformation, and ultimately leading to a comprehensive improvement in sodium storage performance

Exploring the molecular landscape of osteosarcoma through PTTG family genes using a detailed multi-level methodology

BackgroundOsteosarcoma (OS) poses a significant clinical challenge, necessitating a comprehensive exploration of its molecular underpinnings.MethodsThis study explored the roles of PTTG family genes (PTTG1, PTTG2, and PTTG3P) in OS, employing a multifaceted approach encompassing molecular experiments, including OS cell lines culturing, RT-qPCR, bisulfite and Whole Exome Sequencing (WES) and in silico experiments, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets-based validation, overall survival, gene enrichment, functional assays, and molecular docking analyses.ResultsOur findings reveal a consistent up-regulation of PTTG genes in OS cell lines, supported by RT-qPCR experiments and corroborated across various publically available expression datasets databases. Importantly, ROC curve analyses highlight their potential as diagnostic markers. Moving beyond expression profiles, we unveil the epigenetic landscape by demonstrating significant hypomethylation of CpG islands associated with PTTG genes in OS. The negative correlation between methylation status and mRNA expression emphasizes the regulatory role of promoter methylation in PTTG gene expression. Contrary to expectations, genetic mutations in PTTG genes are rare in OS, with only benign mutations observed. Moreover, functional assays also confirmed the oncogenic roles of the PTTG gene in the development of OS. Lastly, we also revealed that Calcitriol is the most appropriate drug that can be utilized to treat OS in the context of PTTG genes.ConclusionThe identification of PTTG genes as potential diagnostic markers and their association with epigenetic alterations opens new avenues for understanding OS pathogenesis and developing targeted therapies. As we navigate the complex landscape of OS, this study contributes essential insights that may pave the way for improved diagnostic and therapeutic strategies in its management

Multivitamin supplementation as a potential adjunctive therapy in post-cardiac arrest: insights from a multicenter retrospective analysis of MIMIC-IV and eICU-CRD

BackgroundCardiac arrest (CA) remains a global health challenge, with low survival rates despite advances in resuscitation. There is a need for novel therapies to improve post-resuscitation outcomes, and the potential role of multivitamin supplementation in this context remains underexplored.MethodsThis multi-center, retrospective observational study examined the association between multivitamin supplementation and clinical outcomes in CA patients. Data were derived from two publicly available critical care databases: the Medical Information Mart for Intensive Care IV (MIMIC-IV) as the training cohort and the eICU Collaborative Research Database (eICU-CRD) as the validation cohort. Adult CA patients were identified and categorized based on whether they received multivitamin supplementation during hospitalization. The primary outcome was in-hospital mortality, with ICU and 28-day mortality as secondary outcomes. Kaplan–Meier survival analysis, propensity score matching (PSM), and inverse probability treatment weighting (IPTW) were used to adjust for confounding variables. A stepwise Cox proportional hazards model evaluated the association between multivitamin use and mortality. Subgroup analyses were conducted based on age, gender, disease severity scores, and comorbidities. Stratified analyses were also performed for patients hospitalized ≥5 days, comparing outcomes between those receiving multivitamins for <5 days vs. ≥5 days.ResultsIn the MIMIC-IV cohort, 223 patients received multivitamins and 890 did not; in the eICU-CRD cohort, 174 received multivitamins and 2,455 did not. Patients receiving multivitamin supplementation had significantly higher survival rates for both in-hospital and 28-day mortality (p < 0.01). After PSM and IPTW adjustment, multivitamin use remained significantly associated with lower mortality in both cohorts. In the fully adjusted Cox model, hazard ratios for in-hospital mortality were 0.56 (95% CIs: 0.45–0.70), 0.47 (95% CIs: 0.35–0.62), and 0.52 (95% CIs: 0.42–0.65) in the original, PSM, and IPTW analyses, respectively (all p < 0.01). Subgroup analysis showed stronger effects in patients aged <65 years. Prolonged supplementation (≥5 days) was linked to better survival.ConclusionAcross two large critical care cohorts, multivitamin supplementation was associated with lower mortality after adjustment, consistent with a potential adjunctive role in post-cardiac arrest care

Plant Responses to Different Grazing Intensities in the Missouri Coteau of North Dakota

Report assessing the effect that grazing intensity has on Kentucky bluegrass (Poa pratensis) in the Coteau region of North Dakota; examins seed banks in areas of light grazing intensity and extreme grazing intensity

Detection of phosphatidylserine in the plasma membrane of single apoptotic cells using electrochemiluminescence

Phosphatidylserine in the plasma membrane of single apoptotic cells was detected using luminol electrochemiluminescence.</p

Basic psychological need satisfaction as mediators in the Relationship between Valuing Time over Money and Happiness

The current study will investigate the mediating roles of basic psychological need satisfaction (BNPS; including autonomy, relatedness, and competence) in the relationship between valuing time over money (VTOM) and happiness. It aims to explore the underlying mechanism between VTOM and happiness