The association between problematic short video use and suicidal ideation and self-injurious behaviors: the mediating roles of sleep disturbance and depression.

BACKGROUND: Prior work suggests that problematic short video use was associated with adverse psychological, physiological, and educational outcomes. With the prevailing of short video platforms, the potential relationships between this problematic behavior and suicidal ideation and self-injurious behaviors have yet to be thoroughly examined. Besides, considering the potential dual nature of problematic short video use, particularly its positive aspects, a potential mechanism may exist linking such problematic behavior to SI and SIBs, ultimately driving individuals towards extreme outcomes. Nevertheless, such mediation paths have not been rigorously examined. Thus, the current study aimed to investigate their relationships and delve into the underlying mechanism, specifically identifying potential mediators between sleep disturbance and depression. METHODS: A quantitative cross-sectional study design was employed to model data derived from a large sample of first- and second-year university students residing in mainland China (N = 1,099; Mage = 19.80 years; 51.7% male). RESULTS: Results showed that problematic short video use has a dual impact on SI and SIBs. On the one hand, problematic short video use was directly related to the decreased risk of suicidal ideation, attempts, and NSSI. On the other hand, such problematic behavior was indirectly associated with the increased risk of NSSI through sleep disturbance, and it indirectly related to the elevated risk of suicidal ideation, attempts, and NSSI through depression. Besides, on the whole, problematic short video use was positively associated with NSSI but not suicidal ideation and attempts. CONCLUSIONS: These findings indicated that problematic short video use had a dual impact on SI and SIBs. Consequently, it is paramount to comprehend the genuine magnitude of the influence that such problematic behavior holds over these intricate psychological conditions.

Pubertal exposure to Microcystin-LR arrests spermatogonia proliferation by inducing DSB and inhibiting SIRT6 dependent DNA repair in vivo and in vitro.

The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2 µg/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition.

Enhanced bacterial cellulose production in Gluconacetobacter xylinus by overexpression of two genes (bscC and bcsD) and a modified static culture.

Bacterial cellulose (BC), a nanostructured material, is renowned for its excellent properties. However, its production by bacteria is costly due to low medium utilization and conversion rates. To enhance the yield of BC, this study aimed to increase BC yield through genetic modification, specifically by overexpressing bcsC and bcsD in Gluconacetobacter xylinus, and by developing a modified culture method to reduce medium viscosity by adding water during fermentation. As a result, BC yields of 5.4, 6.2, and 6.8 g/L were achieved from strains overexpressing genes bcsC, bcsD, and bcsCD, significantly surpassing the yield of 2.2 g/L from wild-type (WT) strains. In the modified culture, the BC yields of all four strains increased by >1 g/L with the addition of 20 mL of water during fermentation. Upon comparing the properties of BC, minimal differences were observed between the WT and pbcsC strains, as well as between the static and modified cultures. In contrast, BC produced by strains overexpressing bcsD had a denser microstructural network and exhibited demonstrated higher tensile strength and elongation-to-break. Compared to WT, BC from bcsD overexpressed strains also displayed enhanced crystallinity, higher degree of polymerization and improved thermal stability.

Deciphering the anammox microbial community succession with humic acid exposure to optimize large anammox granules for robust nitrogen removal.

The robustness of the anaerobic ammonia oxidation (anammox) process in treating wastewater with high concentrations of humic acids (HAs), including landfill leachate and sludge anaerobic digestion liquid, has been paid great attention. This study revealed that the anammox sludge granule size of 1.0-2.0 mm could be robust under the HA exposure with high concentrations. The total nitrogen removal efficiency (NRE) was 96.2% at the HA concentration of 20-100 mg/L, while the NRE was 88.5% at the HA concentration of 500 mg/L, with reduced by 7.7%. The increased extracellular polymeric substances (EPS) content which was stimulated by the HA exposure favored the formation of large granules (1.0-2.0 mm) by enveloping medium and micro granules (0.2-1.0 mm). The abundance of anammox bacteria Candidatus Brocadia was found to be higher (14.2%) in large anammox granules sized 1.0-2.0 mm, suggesting a potentially high anammox activity. However, the abundance of denitrifiers Denitratisoma increased by 4.3% in ultra-large anammox granules sized >2.0 mm, which could be attributed to the high EPS content for heterotrophic denitrifiers metabolism as organic matter. The feedback mechanism of the anammox community for maintaining the ecological function under the HA exposure resulted in a closely related microbial community, with positive and negative correlations in the ecological network increased by 64.3%. This study revealed that the HA exposure of the anammox system resulted in the anammox granules of 1.0-2.0 mm size being the dominant granules with robust nitrogen removal, providing significant guidance for the optimization of anammox granules for an efficient treatment of HA-containing wastewater in anammox applications.

Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs.

Emerging immunotherapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell (CAR-T) therapy have revolutionized cancer treatment and have improved the survival of patients with multiple cancer types. Despite this success many patients are unresponsive to these treatments or relapse following treatment. CRISPR activation and knockout (KO) screens have been used to identify novel single gene targets that can enhance effector T cell function and promote immune cell targeting and eradication of tumors. However, cancer cells often employ multiple genes to promote an immunosuppressive pathway and thus modulating individual genes often has a limited effect. Paralogs are genes that originate from common ancestors and retain similar functions. They often have complex effects on a particular phenotype depending on factors like gene family similarity, each individual gene's expression and the physiological or pathological context. Some paralogs exhibit synthetic lethal interactions in cancer cell survival; however, a thorough investigation of paralog pairs that could enhance the efficacy of cancer immunotherapy is lacking. Here we introduce a sensitive computational approach that uses sgRNA sets enrichment analysis to identify cancer-intrinsic paralog pairs which have the potential to synergistically enhance T cell-mediated tumor destruction. We have further developed an ensemble learning model that uses an XGBoost classifier and incorporates features such as gene characteristics, sequence and structural similarities, protein-protein interaction (PPI) networks, and gene coevolution data to predict paralog pairs that are likely to enhance immunotherapy efficacy. We experimentally validated the functional significance of these predicted paralog pairs using double knockout (DKO) of identified paralog gene pairs as compared to single gene knockouts (SKOs). These data and analyses collectively provide a sensitive approach to identify previously undetected paralog pairs that can enhance cancer immunotherapy even when individual genes within the pair has a limited effect.

Brazing of TC4 Alloy Using Ti-Zr-Ni-Cu-Sn Amorphous Braze Fillers.

In order to address the issues of excessive brittle intermetallic compounds (IMC) formation in the TC4 brazed joints, two types of novel Ti-Zr-Cu-Ni-Sn amorphous braze fillers were designed. The microstructure and shear strength of the TC4/Ti-Zr-Ni-Cu-Sn/TC4 brazed joints were studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffractometer (XRD) and electronic universal materials testing machine. The results show that the optimized Ti35Zr25Ni15Cu20Sn5 braze filler whose chemical composition is closer to the eutectic point possesses a lower melting point compared with the equiatomic Ti23.75Zr23.75Ni23.75Cu23.75Sn5. This was beneficial to the sufficient diffusion of Cu and Ni elements with the base metal during brazing and reduces the residual (Ti,Zr)2(Ni,Cu) content in the joint, which helps to improve the joint performance. The room-temperature and high-temperature shear strength of the TC4 brazed joints using the near eutectic component Ti35Zr25Ni15Cu20Sn5 filler reached a maximum of 472 MPa and 389 MPa at 970 °C/10 min, which was 66% and 48% higher than that of the TC4 joints brazed with the equiatomic Ti23.75Zr23.75Ni23.75Cu23.75Sn5 braze filler. Microstructural evolution and the corresponding mechanical response were in-depth discussed.

Magnetic fibrin nanofiber hydrogel delivering iron oxide magnetic nanoparticles promotes peripheral nerve regeneration.

Peripheral nerve injury is a debilitating condition that have a profound impact on the overall quality of an individual's life. The repair of peripheral nerve defects continues to present significant challenges in the field. Iron oxide magnetic nanoparticles (IONPs) have been recognized as potent nanotools for promoting the regeneration of peripheral nerves due to their capability as biological carriers and their ability to template the hydrogel structure under an external magnetic field. This research used a fibrin nanofiber hydrogel loaded with IONPs (IONPs/fibrin) to promote the regeneration of peripheral nerves in rats. In vitro examination of PC12 cells on various concentrations of IONPs/fibrin hydrogels revealed a remarkable increase in NGF and VEGF expression at 2% IONPs concentration. The biocompatibility and degradation of 2% IONPs/fibrin hydrogel were assessed using the in vivo imaging system, demonstrating subcutaneous degradation within a week without immediate inflammation. Bridging a 10-mm sciatic nerve gap in Sprague Dawley rats with 2% IONPs/fibrin hydrogel led to satisfactory morphological recovery of myelinated nerve fibers. And motor functional recovery in the 2% IONPs/fibrin group was comparable to autografts at 6, 9 and 12 weeks postoperatively. Hence, the composite fibrin hydrogel incorporating 2% IONPs exhibits potential for peripheral nerve regeneration.

Daily life affective dynamics as transdiagnostic predictors of mental health symptoms: An ecological momentary assessment study.

BACKGROUND: Affective dynamics have been identified as a correlate of a broad span of mental health issues, making them key candidate transdiagnostic factors. However, there remains a lack of knowledge about which aspects of affective dynamics - especially as they manifest in the course of daily life - relate to a general risk for mental health issues versus specific symptoms. METHODS: We leverage an ecological momentary assessment (EMA) study design with four measures per day over a two-week period to explore how negative affect levels, inertia, lability, and reactivity to provocation and stress in the course of daily life relate to mental health symptoms in young adults (n = 256) in the domains of anxiety, depression, psychosis-like symptoms, behaviour problems, suicidality, and substance use. RESULTS: Dynamic structural equation modelling (DSEM) suggested that negative affect levels in daily life were associated with depression, anxiety, indirect and proactive aggression, psychosis, anxiety, and self-injury; negative affective lability was associated with depression, physical aggression, reactive aggression, suicidal ideation, and ADHD symptoms; negative affective inertia was associated with depression, anxiety, physical aggression, and cannabis use; and emotional reactivity to provocation was related to physical aggression. LIMITATIONS: The cross-sectional design, the limited span of mental health issues included, and the convenience nature and small size of the sample are limitations. CONCLUSIONS: Findings suggest that a subset of mental health symptoms have shared negative affective dynamics patterns. Longitudinal research is needed to rigorously examine the directionality of the effects underlying the association between affective dynamics and mental health issues.

MCL attenuates atherosclerosis by suppressing macrophage ferroptosis via targeting KEAP1/NRF2 interaction.

BACKGROUND: Micheliolide (MCL), which is the active metabolite of parthenolide, has demonstrated promising clinical application potential. However, the effects and underlying mechanisms of MCL on atherosclerosis are still unclear. METHOD: ApoE-/- mice were fed with high fat diet, with or without MCL oral administration, then the plaque area, lipid deposition and collagen content were determined. In vitro, MCL was used to pretreat macrophages combined by ox-LDL, the levels of ferroptosis related proteins, NRF2 activation, mitochondrial function and oxidative stress were detected. RESULTS: MCL administration significantly attenuated atherosclerotic plaque progress, which characteristics with decreased plaque area, less lipid deposition and increased collagen. Compared with HD group, the level of GPX4 and xCT in atherosclerotic root macrophages were increased in MCL group obviously. In vitro experiment demonstrated that MCL increased GPX4 and xCT level, improved mitochondrial function, attenuated oxidative stress and inhibited lipid peroxidation to suppress macrophage ferroptosis induced with ox-LDL. Moreover, MCL inhibited KEAP1/NRF2 complex formation and enhanced NRF2 nucleus translocation, while the protective effect of MCL on macrophage ferroptosis was abolished by NRF2 inhibition. Additionally, molecular docking suggests that MCL may bind to the Arg483 site of KEAP1, which also contributes to KEAP1/NRF2 binding. Furthermore, Transfection Arg483 (KEAP1-R483S) mutant plasmid can abrogate the anti-ferroptosis and anti-oxidative effects of MC in macrophages. KEAP1-R483S mutation also limited the protective effect of MCL on atherosclerosis progress and macrophage ferroptosis in ApoE-/- mice. CONCLUSION: MCL suppressed atherosclerosis by inhibiting macrophage ferroptosis via activating NRF2 pathway, the related mechanism is through binding to the Arg483 site of KEAP1 competitively.

Hepatocyte-specific CCAAT/enhancer binding protein α restricts liver fibrosis progression.

Metabolic dysfunction-associated steatohepatitis (MASH) - previously described as nonalcoholic steatohepatitis (NASH) - is a major driver of liver fibrosis in humans, while liver fibrosis is a key determinant of all-cause mortality in liver disease independent of MASH occurrence. CCAAT/enhancer binding protein α (CEBPA), as a versatile ligand-independent transcriptional factor, has an important function in myeloid cells, and is under clinical evaluation for cancer therapy. CEBPA is also expressed in hepatocytes and regulates glucolipid homeostasis; however, the role of hepatocyte-specific CEBPA in modulating liver fibrosis progression is largely unknown. Here, hepatic CEBPA expression was found to be decreased during MASH progression both in humans and mice, and hepatic CEBPA mRNA was negatively correlated with MASH fibrosis in the human liver. CebpaΔHep mice had markedly enhanced liver fibrosis induced by a high-fat, high-cholesterol, high-fructose diet or carbon tetrachloride. Temporal and spatial hepatocyte-specific CEBPA loss at the progressive stage of MASH in CebpaΔHep,ERT2 mice functionally promoted liver fibrosis. Mechanistically, hepatocyte CEBPA directly repressed Spp1 transactivation to reduce the secretion of osteopontin, a fibrogenesis inducer of hepatic stellate cells. Forced hepatocyte-specific CEBPA expression reduced MASH-associated liver fibrosis. These results demonstrate an important role for hepatocyte-specific CEBPA in liver fibrosis progression, and may help guide the therapeutic discoveries targeting hepatocyte CEBPA for the treatment of liver fibrosis.

One Health: Insights from Organizational & Social, Technology Assessment and Human Factors Perspectives.

OBJECTIVES: To offer diverse but complementary perspectives on how biomedical and health informatics can be informed by and help to achieve the vision of One Health. METHODS: Overview of key considerations and critical discussion of common themes, barriers and opportunities, based on collaborative review by International Medical Informatics Association (IMIA) working group members active in related fields. RESULTS: Health and care systems are complex sociotechnical systems that need explicit design and implementation strategies to align with the goals of One Health. The evidence-based health informatics paradigm and associated frameworks for evaluation of digital health technologies need to broaden their scope to take full account of the One Health approach. Informatics has specific contributions to make to One Health, for example by improved user experience reducing energy consumption and effective app design enhancing medication adherence. CONCLUSIONS: One Health is inherently intertwined with ergonomic, sociotechnical and evaluation perspectives in biomedical and health informatics. Health is a planetary issue that requires interdisciplinary collaborative action. The theories and principles of biomedical and health informatics offer many opportunities to transform digital health technology to better serve the One Health agenda.

Transcriptome analysis for the restrained stem development of the wheat mutant dms / Desenvolvimento e análise de transcriptoma de uma haste de trigo mutante dms

ABSTRACT: Wheat (Triticum aestivum L.) stem development significantly affects grain yield. The dwarf plants (D) of wheat mutant dms was less than 30cm. Here, we were to explore the molecular basis for the restrained stem development of the dwarf plants. The results were reached by compare the young spikes and stems transcriptomes of the tall (T) and D plants of mutant dms. We identified 663 genes highly expressed in stem tips. We identified 997 differentially expressed genes (DEGs) in stem tips between T and D, 403 DEGs were significantly related with stem development. Most biological processes in stem tips on dwarf plants were significantly suppressed, such as phytohormone signaling etc. The sequencing analysis results were confirmed by quantitatively analysis the expression profiles of fourteen key DEGs via real-time QRT-PCR. We identified a group genes related to wheat stem development, identified a group DEGs related to the restrained stem development of D plants of dms. The suppressed phytohormone signaling, carbohydrate transport and metabolism were the major causal factors leading to dwarf plants of D. Our dataset provides a useful resource for investigating wheat stem development.

RESUMO: O desenvolvimento da haste do trigo (Triticum aestivum L.) afeta significativamente o rendimento dos grãos. A partir disso, empregou-se a base molecular para o desenvolvimento de uma haste de variedade de trigo. Os resultados foram alcançados ao conferir as hastes de um mutante de trigo DMS. Identificou-se 663 genes altamente expressos na haste; 997 genes (DEGs) diferentemente expressos em hastes entre T e D e; 403 DEGs foram significativamente diferentes. A maioria dos processos biológicos de caule tipo não plantas foram significativamente suprimidas, com o fito hormônio de sinalização. Os resultados da análise de sequencia foram confirmados pela expressão quantitativa de perfis de catorze chave DEGs através de qRT-PCR em tempo real. Nota-se um grupo de genes relacionados com a haste de trigo de desenvolvimento. Identificou-se um grupo DEGs relacionados com o desenvolvimento de um tronco D plantas de DMS. O fito hormônio de sinalização, transporte e metabolismo de hidratos de carbono foram os principais fatores suscetíveis das plantas anão de D. Nosso conjunto de dados fornece um recurso útil para investigar o desenvolvimento do caule de trigo.