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This study considered the role of coal as China’s basic energy source and examines the development of the coal industry. We focused on the intelligent development of coal mines, and introduced the “Chinese mode” of intelligent mining in underground coal mines, which uses complete sets of technical equipment to propose classification and grading standards. In view of the basic characteristics and technical requirements of intelligent coal mine systems, we established a digital logic model and propose an information entity and knowledge map construction method. This involves an active information push strategy based on a knowledge demand model and an intelligent portfolio modeling and distribution method for collaborative control of coal mines. The top-level architecture of 5G+ intelligent coal mine systems combines intelligent applications such as autonomous intelligent mining, human–machine collaborative rapid tunneling, unmanned auxiliary transportation, closed-loop safety control, lean collaborative operation, and intelligent ecology. Progress in intelligent mining technology was described in terms of a dynamic modified geological model, underground 5G network and positioning technology, intelligent control of the mining height and straightness of the longwall working face, and intelligent mining equipment. The development of intelligent coal mines was analyzed in terms of its imbalances, bottlenecks, and the compatibility of large-scale systems. Implementation ideas for promoting the development of intelligent coal mines were proposed, such as establishing construction standards and technical specifications, implementing classification and grading standards according to mining policy, accelerating key technology research, and building a new management and control model.

A growing body of research suggests that social or physical activity can affect the risk of Major depressive disorder (MDD). However, the bidirectional relationship between them remains to be clarified further, especially between inactivity and MDD. Here, we performed a two-sample Mendelian Randomization analysis using genetic variants associated with social/physical activities and MDD, and assessed the mediating effect of obesity-related measures and brain imaging phenotypes. The dataset on MDD, social activities, and physical activities included 500,199; 461,369; 460,376 individuals, respectively. Information regarding body mass index (BMI), body fat percentage (BFP), IDPs for 454,633; 461,460; 8,428 participants, respectively. We identified bidirectional causal relationships between sport clubs or gyms, strenuous sports, heavy do-it-youself, other exercises and MDD. We also observed that leisure/social inactivity (odds ratio [OR] = 1.64; P = 5.14 × 10−5) or physical inactivity (OR = 3.67; P = 1.99 × 10−5) caused an increased risk of MDD, which were partially mediated by BMI or BFP and masked by the weighted-mean orientation dispersion index of left acoustic radiation or volume of right caudate. Furthermore, we discovered that MDD increased the risk of leisure/social inactivity (OR = 1.03; P = 9.89 × 10−4) or physical inactivity (OR = 1.01; P = 7.96 × 10−4). In conclusions, we found that social/physical activities reduced the risk of MDD, while MDD in turn hindered social/physical activities. Inactivity may increase the risk of MDD, which was mediated or masked by brain imaging phenotypes. These results help to understand the manifestations of MDD and provide evidence and direction for the advancement of intervention and prevention.

To investigate the association between overt hepatic encephalopathy (OHE) and liver pathology after transjugular intrahepatic portosystemic shunt (TIPS) creation in cirrhotic patients. From July 2015 to April 2024, 73 patients from 4 hospitals in China who received TIPS creation and liver biopsy were retrospectively enrolled in this study. Based on whether OHE occurred within 3 months after TIPS creation, the patients were categorized into OHE (n = 29) and non-OHE (n = 44) groups. The liver pathology was assessed by hematoxylin-eosin (H&E), Sirius red staining, immunohistochemistry, and immunofluorescence. Liver pathology by H&E staining showed typical features of liver cirrhosis (including disordered structure and pseudolobule formation) in all the patients. No marked difference was observed in extracellular matrix (ECM) deposition between the OHE and non-OHE groups. However, the patients in the OHE group had a higher level of liver and systemic inflammation than in the non-OHE group. And there was a strong correction between intrahepatic macrophage infiltration and serum inflammatory indicators. Additionally, the OHE group had more liver neovascularization, which was consistent with liver inflammation. The emergence of OHE after TIPS creation is closely associated with liver pathology, especially in liver inflammation and angiogenesis, but not in ECM deposition.

Childhood maltreatment stands out as a pivotal risk factor for depression, with gene-by-environment interaction serving as a crucial mechanism. Here we perform genome-wide interaction analyzes of childhood maltreatment in the UK Biobank, integrating methylation evidence through colocalization analysis and identifying associated brain structure abnormalities from childhood to adulthood. A genome-wide significant genomic region interacting with childhood maltreatment is identified at 8p11.21 ( IDO2 rs7846217, P  = 2.02e–08), implicating the tryptophan-kynurenine pathway. Colocalization analysis reveals that IDO2 rs11777027, rs2340953 and rs28631334 are associated with depression in individuals exposed to childhood maltreatment and colocalize with methylation signals in both blood and brain for IDO2 . These interactions affect cortical thickness of the left supramarginal gyrus in children ( P  = 9.72e–04) and adults ( P  = 1.34e–04), as well as cortical volume in the right angular gyrus in children ( P  = 1.02e–04). Furthermore, the interactions significantly predict new-onset depression at a 2-year follow-up in children. Stunted increase in cortical thickness of the left middle-anterior cingulate gyrus and sulcus significantly mediates the interaction between childhood maltreatment and IDO2 on childhood depression. These interactions also moderate antidepressant treatment efficacy at 4–6 weeks. Childhood maltreatment interacts with genes to increase depression risk. Here, Sun et al. use a genome-wide approach to identify variants of IDO2 associated with depression in individuals who have undergone child maltreatment.

Background Protein phosphatase 2 C (PP2C) proteins play crucial roles in plant growth, development, and stress responses. However, PP2C gene family members in Ipomoea trifida (wild relative of sweet potato) have not been comprehensively investigated, thereby limiting our understanding of their functions. Results We identified 91 PP2C genes ( ItfPP2C1–91 ) that were unevenly distributed across all 15 I. trifida chromosomes. On the basis of a phylogenetic analysis, these genes were classified into 13 subfamilies, with subfamilies E, A, and D containing the most genes. Conserved motif and gene structure analyses revealed subfamily-specific patterns, with motif 2 identified as the most conserved motif. Numerous promoter cis-acting elements related to hormone responses and stress tolerance were identified. Tissue-specific ItfPP2C expression patterns were observed, with several genes expressed at high levels in all examined tissues, while other genes were expressed in specific tissues. Under drought conditions, most PP2C genes had upregulated expression levels, with significant increases in ItfPP2C15 , 16 , 30 , and 77 (subfamily A) expression suggesting that they may be key drought-responsive candidate genes. In response to a stem nematode infection, ItfPP2C30 , ItfPP2C77 , and ItfPP2C89 were differentially expressed between resistant and susceptible varieties. Moreover, ItfPP2C90 expression was significantly induced in Z22 and L9 at 12 h. Hence, these genes may be involved in disease resistance. A protein interaction network analysis identified proteins that may interact with ItfPP2C30 and ItfPP2C77, most of which were ABA receptors (PYLs) and kinases (SnRK2s). Conclusions Our comprehensive analysis of the PP2C gene family in I. trifida provides valuable insights into their evolutionary relationships, structural features, and potential functions related to growth and stress responses. ItfPP2C30 and ItfPP2C77 were identified as promising candidates for improving both drought and nematode resistance, with the encoded proteins potentially interacting with PYL and SnRK2 proteins in stress-related signaling pathways.

Background Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function. Methods Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months’ ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 μm (PM 2.5 ). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility. Results Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM 2.5 interactive effect ( P FWE  = 0.028), indicating that PM 2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM 2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network ( P FDR  < 0.05). In those genetically predisposed to MDD, increased PM 2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed. Conclusions Our cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network.

Background Adverse childhood experiences (ACEs) have been considered significant drivers of negative mental health and cognitive outcomes. However, identifying clear neurobiological signatures of ACEs has been challenging due to limited sample sizes, participant heterogeneity, and methodological variability. Methods A whole-brain meta-analysis was conducted to identify functional, structural, and overlapping brain alterations in ACEs-exposed individuals compared to unexposed controls, using a large sample (functional analysis: 63 studies, 3549 participants; structural analysis: 38 studies, 2919 participants). Subgroup analyses were performed based on age, adversity type, diagnostic status, and functional magnetic resonance imaging task domains, providing a more nuanced aspect of ACEs’ effect on neurodevelopment. Furthermore, the BrainMap-derived task activation maps, atlas-based nuclear imaging-derived neurotransmitter maps, and postmortem gene expression profiles were integrated to examine spatial correlations between ACEs-related brain abnormalities and downstream behavioral processes, disease domains, and upstream receptor/transporter distributions and gene expression. Results ACEs-exposed individuals exhibited significantly increased functional activity in the amygdala, increased gray matter volume (GMV) in the parahippocampal gyrus, and reduced GMV in the inferior frontal gyrus and supramarginal gyrus, with overlapping abnormalities observed in the parahippocampal gyrus. Subgroup analyses revealed distinct brain alterations. Furthermore, specific associations were identified between structural alterations and the distribution of dopaminergic, serotonergic, and GABAergic neurotransmitter systems. Enrichment analyses further emphasized the profound impact of ACEs on neurodevelopment, immunometabolism, and psychopathological trajectories. Conclusions These findings characterize the neural substrates of ACEs, providing valuable insights into their impact on neurodevelopment and suggesting potential targets for ACEs-related disorders.

Three semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, Simeoni, Jumbe, and Hybrid, were used for the efficacy translation of RC88 from preclinical to clinical. RC88 is a mesothelin‐targeting antibody–drug conjugate for malignant solid tumor. In the preclinical study, the relationship between PKs and PDs was determined using the xenograft mouse model derived from ovarian cancer and lung cancer cell lines. A secondary parameter representing the efficacy index of the drug, termed as tumor static concentration (TSC), was calculated using the three semimechanistic PK/PD models. A mechanism‐based target‐mediated drug disposition model was used to predict the human PKs. TSC from mice and predicted human PK were integrated to predict human efficacy dose. Results showed that 2 cell lines were sensitive to drugs, and the predicted efficacy dose was between 0.82 and 1.96 mg/kg q1w.

Optimizing paroxetine therapy for major depressive disorder (MDD) requires effective prediction models for treatment efficacy and therapeutic drug monitoring (TDM). This study aimed to develop prediction models for treatment remission and steady-state concentration (Css) of paroxetine, elucidate the role of CYP2D6 activity score (AS) in predicting Css, establish associations between adverse drug reactions (ADRs) and Css, and validate and update the therapeutic reference range (TRR) for patients with MDD in the Han Chinese population. We conducted a post-hoc analysis of an 8-week multicenter prospective cohort study involving 530 Han Chinese patients with MDD. Logistic regression models were developed to predict treatment remission at the eighth week and Css as a binary variable (within/outside TRR of 20–65 ng/ml). The model for predicting treatment remission demonstrated an AUC of 0.707, while the model for Css achieved an AUC of 0.615. Associations between ADRs and Css were assessed using logistic regression, adjusted for sex and age. Patients with Css within 20–65 ng/ml were more likely to achieve remission (OR = 1.655, 95% CI: 1.109–2.489) and less likely to experience ADRs (OR = 0.460, 95% CI: 0.203–0.961). Additionally, those with lower AS were more likely to maintain Css within this range (OR = 0.638, 95% CI: 0.461–0.878). ROC analysis further established an updated TRR of 20.8–52.5 ng/ml considering both treatment remission and ADRs. Our findings enhance paroxetine treatment and monitoring, underscoring the potential of CYP2D6 AS and Css as predictors for Css and treatment remission, respectively.

A glass frit containing Li 2 O–MgO–ZnO–B 2 O 3 –SiO 2 component was used to explore the low-temperature sintering behaviors and microwave dielectric characteristics of tri-rutile MgTa 2 O 6 ceramics in this study. The good low-firing effects are presented due to the high matching relevance between Li 2 O–MgO–ZnO–B 2 O 3 –SiO 2 glass and MgTa 2 O 6 ceramics. The pure tri-rutile MgTa 2 O 6 structure remains unchanged, and high sintering compactness can also be achieved at 1150°C. We found that the Li 2 O–MgO–ZnO–B 2 O 3 –SiO 2 glass not only greatly improves the low-temperature sintering characteristics of MgTa 2 O 6 ceramics but also maintains a high (quality factor ( Q ) × resonance frequency ( f )) value while still improving the temperature stability. Typically, great microwave dielectric characteristics when added with 2wt% Li 2 O–MgO–ZnO–B 2 O 3 –SiO 2 glass can be achieved at 1150°C: dielectric constant, ε r = 26.1; Q × f = 34267 GHz; temperature coefficient of resonance frequency, τ f = −8.7 × 10 −6 /°C.