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BackgroundSuicidal ideation serves as a sensitive predictive indicator for non-suicidal self-injury （NSSI） behavior， and NSSI behavior brings profound effects to both mental and physical health of senior high school students. Existing studies have made exploration on the relationship among insomnia， anxiety and NSSI behavior in the general population， but the internal mechanism of NSSI behavior in senior high school students with suicidal ideation requires further study.ObjectiveTo explore the pathway of anxiety between insomnia and NSSI behavior in senior high school students， so as to provide references for the intervention on NSSI behavior in such demographic.MethodsFrom December 10 to 15， 2021， cluster sampling was adopted to select 2 572 senior high school students across three senior high schools in Hubei Province as the research objects. Assessment was conducted by using Insomnia Severity Index （ISI）， Generalized Anxiety Disorder Scale-7 item （GAD-7） and Adolescents Self-Harm Scale. Spearman correlation analysis was conducted to examine the correlation among scores of scales finished by senior high school students with suicidal ideation. Model 4 from the SPSS 20.0 Process 4.2 was employed to test the mediating path of anxiety between insomnia and NSSI behavior.ResultsA total of 2 421 valid questionnaires （94.13%） were recovered， which revealed 554 cases （22.88%） with suicidal ideation and 408 cases （16.85%） with NSSI behavior. The scores of ISI， GAD-7 and Adolescents Self-Harm Scale of senior high school students with suicidal ideation were higher than those of students without suicidal ideation （Z=17.124， 20.611， 21.314， P

Both seed germination and subsequent seedling establishment are key checkpoints during the life cycle of seed plants, yet flooding stress markedly inhibits both processes, leading to economic losses from agricultural production. Here, we report that melatonin (MT) seed priming treatment enhances the performance of seeds from several crops, including soybean, wheat, maize, and alfalfa, under flooding stress. Transcriptome analysis revealed that MT priming promotes seed germination and seedling establishment associated with changes in abscisic acid (ABA), gibberellin (GA), and reactive oxygen species (ROS) biosynthesis and signaling pathways. Real‐time quantitative RT‐PCR (qRT‐PCR) analysis confirmed that MT priming increases the expression levels of GA biosynthesis genes, ABA catabolism genes, and ROS biosynthesis genes while decreasing the expression of positive ABA regulatory genes. Further, measurements of ABA and GA concentrations are consistent with these trends. Following MT priming, quantification of ROS metabolism‐related enzyme activities and the concentrations of H2O2 and superoxide anions (O2−) after MT priming were consistent with the results of transcriptome analysis and qRT‐PCR. Finally, exogenous application of GA, fluridone (an ABA biosynthesis inhibitor), or H2O2 partially rescued the poor germination of non‐primed seeds under flooding stress. Collectively, this study uncovers the application and molecular mechanisms underlying MT priming in modulating crop seed vigor under flooding stress. [ABSTRACT FROM AUTHOR]

The automotive industry appears to be a particularly attractive application case for blockchain technology adoption. Blockchain is one of the innovations that has much potential to change current business processes in German original equipment manufacturers (OEMs) and enable new services for their customers. This paper combines collective case study and in-depth interviews to explore the potentials and existing challenges of blockchain technology-based applications at German OEMs. The results suggest that blockchain applications have advantages in aggregating product information, securing transaction information, and establishing a reliable supply chain. Based on the TOE (technology, organisation and environment) model, our case study shows that the biggest obstacles for blockchain technology adoption in the automotive supply chain include: technology immaturity, lack of guidance and industry standards, non-cooperation of chain members, and legislative ambiguity. Based on auto manufacturers investigated, blockchain technology is perceived to have great potentials in reducing process costs, ensure product quality, and enhance the automotive supply chain's visibility and digitisation. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have shown great potential for the treatment of liver injuries, and the therapeutic efficacy greatly depends on their homing to the site of injury. In the present study, we detected significant upregulation of hepatocyte growth factor (HGF) in the serum and liver in mice with acute or chronic liver injury. In vitro study revealed that upregulation of miR-9-5p or miR-221-3p promoted the migration of human MSCs (hMSCs) toward HGF. Moreover, overexpression of miR-9-5p or miR-221-3p promoted hMSC homing to the injured liver and resulted in significantly higher engraftment upon peripheral infusion. hMSCs reduced hepatic necrosis and inflammatory infiltration but showed little effect on extracellular matrix (ECM) deposition. By contrast, hMSCs overexpressing miR-9-5p or miR-221-3p resulted in not only less centrilobular necrosis and venous congestion but also a significant reduction of ECM deposition, leading to obvious improvement of hepatocyte morphology and alleviation of fibrosis around central vein and portal triads. Further studies showed that hMSCs inhibited the activation of hepatic stellate cells (HSCs) but could not decrease the expression of TIMP-1 upon acute injury and the expression of MCP-1 and TIMP-1 upon chronic injury, while hMSCs overexpressing miR-9-5p or miR-221-3p led to further inactivation of HSCs and downregulation of all three fibrogenic and proinflammatory factors TGF-β, MCP-1, and TIMP-1 upon both acute and chronic injuries. Overexpression of miR-9-5p or miR-221-3p significantly downregulated the expression of α-SMA and Col-1α1 in activated human hepatic stellate cell line LX-2, suggesting that miR-9-5p and miR-221-3p may partially contribute to the alleviation of liver injury by preventing HSC activation and collagen expression, shedding light on improving the therapeutic efficacy of hMSCs via microRNA modification. [ABSTRACT FROM AUTHOR]

In this work, Cu-doped O3-Na[Fe1/3Ni1/3Mn1/3]1-xCuxO2 cathodes were studied to enhance the structure stability and air stability. XPS analysis reveals that Cu-doping changes the electronic structure of Mn, thus enhancing the electrochemical performance of the NFM. The Cu-doped O3-Na[Fe1/3Ni1/3Mn1/3]0.95Cu0.05O2 (NFMC-0.05) cathode remains a capacity of 81.6 mAh g−1 at 10 C and keeps a capacity retention of 80.7% after 200 cycles at 0.5 C, while the undoped O3-NaFe1/3Ni1/3Mn1/3O2 (NFM) can only remain a capacity of 59.9 mAh g−1 at 10 C and keep a capacity retention of 68.9% after 200 cycles at 0.5 C. The 9-day air-exposed NFMC-0.05 exhibits a higher capacity of 97.3 mAh g−1 than the 9-day air-exposed NFM (58 mAh g−1) at 0.1 C, showing greatly enhanced air stability. Moreover, Cu-doping reduces the Rct value and the polarization, leading to a significant improvement in electronic conductivity. These results confirm that a small quantity (5 at. %) of Cu-doping improves the structural stability and air stability of the material, leading to the excellent electrochemical performance. [ABSTRACT FROM AUTHOR]

Background: Stroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis. Methods: SalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted. Results: SalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke. Conclusions: SalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke. [ABSTRACT FROM AUTHOR]

The microstructure and compressive properties of the 7xxx series aluminum alloy (Al – 12.44Zn – 3.22Mg – 1.13Cu – 0.19Zr – 0.12Sr) reinforced with SiC whiskers via squeeze casting are investigated after aging treatments T6-1, T6-2, T6I4-1, and T6I4-2. For this purpose, the effect of four kinds of aging heat treatments on the properties of the aluminum metal matrix composites (AMMCs) is studied systematically through Vickers hardness and room temperature compressive testing. The microstructure is analyzed by optical microscopy, scanning electron microscopy, and x-ray diffraction. The experimental results show that the hardness of the AMMCs after four kinds of aging processes has different degrees of improvement compared to no-aging. After the T6-1, T6-2, T6I4-1, and T6I4-2 aging processes, the hardness of the composites is 325, 278, 306, and 345.8 HV, respectively. The additional T6-2 aging treatment provides the highest compressive strength and compressive strain, about 747 MPa and 7%, respectively, as well as a maximum dislocation strengthening of approximately 86.89 MPa. [ABSTRACT FROM AUTHOR]

The performance of solid solution aging treatment on aluminum matrix composites prepared by powder metallurgy and reinforced with 6061 aluminum alloy powder as matrix; meanwhile, nano silicon carbide particles (nm SiCp), submicron silicon carbide particles (1 µm SiCp) and Ti particles were studied. The Al/SiCp composite powder was prepared by high-energy ball milling, and then cold-pressed, sintered, hot-extruded, and then heat-treated with different solution temperatures and aging times for the extruded composites. Optical microscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy (EDS), X-ray diffractometer (XRD) and extrusion testing were used to analyze and test the microstructure and mechanical properties of aluminum matrix composites. The results show that after the multi-stage solid solution at 530 °C×2 h+535 °C×2 h+540 °C×2 h, the particles are mainly equiaxed grains and uniformly distributed. There is no reinforcement agglomeration, and the surface is dense and the insoluble phase is basically dissolved. In the matrix, the strengthening effect is good, and the hardness and compressive strength are 179.43 HV and 680.42 MPa, respectively. Under this solution process, when the aluminum matrix composites are aged at 170 °C for 10 h, the hardness and compressive strength can reach their peaks and increase to 195.82 HV and 721.48 MPa, respectively. [ABSTRACT FROM AUTHOR]

Transplanted mesenchymal stem cells (MSCs) can significantly aid in repairing spinal cord injuries (SCI) by migrating to and settling at the injury site. However, this process is typically inefficient, as only a small fraction of MSCs successfully reach the target lesion area. During SCI, the increased expression and secretion of hepatocyte growth factor (HGF) act as a chemoattractant that guides MSC migration. Nonetheless, the precise mechanisms by which HGF influences MSC migration are not fully understood. This study focused on unraveling the molecular pathways that drive MSC migration towards the SCI site in response to HGF. It was found that HGF can activate β-catenin signaling in MSCs either by phosphorylating LRP6 or by suppressing GSK3β phosphorylation through the AKT and ERK1/2 pathways, or by enhancing the expression and nuclear translocation of TCF4. This activation leads to elevated Nedd9 expression, which promotes focal adhesion formation and F-actin polymerization, facilitating chemotactic migration. Transplanting MSCs during peak HGF expression in injured tissues substantially improves nerve regeneration, reduces scarring, and enhances hind limb mobility. Additionally, prolonging HGF release can further boost MSC migration and engraftment, thereby amplifying regenerative outcomes. However, inhibiting HGF/Met or interfering with β-catenin or Nedd9 signaling significantly impairs MSC engraftment, obstructing tissue repair and functional recovery. Together, these findings provide a theoretical basis and practical strategy for MSC transplantation therapy in SCI, highlighting the specific molecular mechanisms by which HGF regulates β-catenin signaling in MSCs, ultimately triggering their chemotactic migration., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Previous studies have shown the anti-inflammatory effect of 25-hydroxyvitamin D (25(OH)D) and the crucial roles of high-sensitive C reactive protein (hsCRP) and novel inflammatory markers (red blood cell distribution width-platelet count ratio (RDWPCR), mean platelet volume-platelet count ratio (MPVPCR), neutrophil-lymphocyte ratio (NLR) and white blood cell-neutrophil ratios (WBCNR)) in several diseases, but scarce data explored the associations of 25(OH)D with hsCRP and novel inflammatory markers. This study aimed to investigate these associations in children., Design: Cross-sectional study., Setting: Children in China., Participants: 10141 children (mean age 14.6 months) were included., Primary and Secondary Outcome Measures: HsCRP, red blood cell distribution width, platelet count, mean platelet volume, neutrophil, lymphocyte and white blood cell were measured., Results: Overall, serum 25(OH)D was inversely associated with hsCRP and novel inflammatory biomarkers. In multivariable analysis, serum 25(OH)D was inversely associated with hsCRP and novel inflammatory biomarkers (Q quartile (Q) 4 vs Q1: 1129.75 vs 2090.99 for hsCRP; 4246.94 vs 6829.89 for RDWPCR; 4863.57 vs 5545.66 for MPVPCR; 4345.76 vs 6507.46 for NLR; 2418.84 vs 2868.39 for WBCNR). Similar results also were observed in stratified analyses by sex (boys and girls). Moreover, serum 25(OH)D was inversely associated with elevated inflammation levels. After adjustment for other potential covariates, inverse associations between serum 25(OH)D and elevated inflammation levels were still observed. The corresponding ORs (95% CI) were 0.05 (0.04, 0.06) for hsCRP, 0.13 (0.11, 0.15) for RDWPCR, 0.74 (0.64, 0.85) for MPVPCR, 0.11 (0.09, 0.13) for NLR and 0.57 (0.49, 0.66) for WBCNR in the fourth quartile compared with the first quartile, respectively., Conclusions: Generally, the graded and inverse associations of serum 25(OH)D with hsCRP and four novel inflammatory markers (RDWPCR, MPVPCR, NLR and WBCNR) were observed. The present study provided further support for the anti-inflammatory effects of 25(OH)D., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Immunotherapy confers little to no benefit in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Mechanistic insights suggested that epidermal growth factor receptor (EGFR) antibody plus irinotecan might augment the tumor immune response in mCRC. Therefore, we conducted a proof-of-concept, single-arm, phase 2 study (ChiCTR identifier: ChiCTR2000035642) of a combination treatment regimen including tislelizumab (anti-PD-1), cetuximab (anti-EGFR) and irinotecan in 33 patients with MSS and RAS wild-type (WT) mCRC who were previously treated with ≥2 lines of therapy. The primary endpoint was met, with a confirmed objective response rate of 33%. As secondary endpoints, the disease control rate was 79%, and the median progression-free survival and overall survival were 7.3 and 17.4 months respectively. Among the 33 patients, 32 (97.0%) had treatment-related adverse events (AEs). Three (9.1%) reported grade ≥ 3 AEs, including rash (n = 1), neutropenia (n = 2). The post-hoc evaluation of dynamic circulating tumor DNA using next generation sequencing and the analysis of peripheral immune proteomics landscape using Olink revealed that lower variant allele frequency (VAF) at baseline, greater reduction in VAF on treatment, and a hot peripheral macroenvironment were associated with the treatment response independently. Our study showed the antitumor activity of tislelizumab, cetuximab, and irinotecan combination with a tolerable safety profile in previously treated MSS and RAS WT mCRC., (© 2024. The Author(s).)