Neuroimaging features of cognitive impairments in schizophrenia and major depressive disorder.

Cognitive dysfunctions are one of the key symptoms of schizophrenia (SZ) and major depressive disorder (MDD), which exist not only during the onset of diseases but also before the onset, even after the remission of psychiatric symptoms. With the development of neuroimaging techniques, these non-invasive approaches provide valuable insights into the underlying pathogenesis of psychiatric disorders and information of cognitive remediation interventions. This review synthesizes existing neuroimaging studies to examine domains of cognitive impairment, particularly processing speed, memory, attention, and executive function in SZ and MDD patients. First, white matter (WM) abnormalities are observed in processing speed deficits in both SZ and MDD, with distinct neuroimaging findings highlighting WM connectivity abnormalities in SZ and WM hyperintensity caused by small vessel disease in MDD. Additionally, the abnormal functions of prefrontal cortex and medial temporal lobe are found in both SZ and MDD patients during various memory tasks, while aberrant amygdala activity potentially contributes to a preference to negative memories in MDD. Furthermore, impaired large-scale networks including frontoparietal network, dorsal attention network, and ventral attention network are related to attention deficits, both in SZ and MDD patients. Finally, abnormal activity and volume of the dorsolateral prefrontal cortex (DLPFC) and abnormal functional connections between the DLPFC and the cerebellum are associated with executive dysfunction in both SZ and MDD. Despite these insights, longitudinal neuroimaging studies are lacking, impeding a comprehensive understanding of cognitive changes and the development of early intervention strategies for SZ and MDD. Addressing this gap is critical for advancing our knowledge and improving patient prognosis.

Striatum and globus pallidus structural abnormalities in schizophrenia: A retrospective study of the different stages of the disease.

BACKGROUND: The basal ganglia are important structures for the release of dopamine in the limbic circuits of the midbrain, and the striatum and globus pallidus are the major nuclei of the basal ganglia, and the dysfunction of these regions has been the basis of many models that have attempted to explain the underlying mechanisms of schizophrenia symptoms. The purpose of this study was to investigate the changes in the volume of the striatum subregion and globus pallidus in three different stages of schizophrenia, and to analyze whether these volume changes were related to antipsychotic drugs and schizophrenia symptoms. METHODS: In this study, we investigated the volume of the striatum and globus pallidus in patients with schizophrenia at three different stages. The study included 57 patients with first-episode schizophrenia (FSZ), 51 patients with early-stage schizophrenia (ESZ), 86 patients with chronic schizophrenia (CSZ), and 191 healthy controls (HC), all of whom underwent structured magnetic resonance imaging (MRI) scans. Covariance analysis was performed using SPSS 26.0 was used for covariance analysis to determine whether there were significant differences in striatal subregion and globus pallidus volume between groups, and stratified analysis was used to further eliminate the effect of age on brain volume. Finally, the correlation analysis between the region of interest and the cumulative dose of antipsychotic drugs and psychotic symptoms was performed. RESULTS: The comparison between the different stages of the illness showed significant volume differences in the left caudate nucleus (lCAU) (F = 2.665, adjusted p = 0.048), left putamen (lPUT) (F = 12.749, adjusted p < 0.001), left pallidum (lPAL) (F = 41.111, adjusted p < 0.001), and right pallidum (rPAL) (F = 14.479, adjusted p < 0.001). Post-hoc analysis with corrections showed that the volume differences in the lCAU subregion disappeared. Further stratified analysis controlling for age showed that compared with the HC, the lPAL (t = 4.347, p < 0.001) was initially significantly enlarged in the FSZ group, the lPUT (t = 4.493, p < 0.001), rPUT (t = 2.190, p = 0.031), lPAL (t = 7.894, p < 0.001), and rPAL (t = 4.983, p < 0.001) volumes were all significantly increased in the ESZ group, and the lPUT (t = 3.314, p = 0.002), lPAL (t = 6.334, p < 0.001), and rPAL (t = 3.604, p < 0.001) subregion volumes were also significantly increased in the CSZ group. Correlation analysis showed that lPUT and bilateral globus pallidus were associated with cumulative dose of antipsychotics, but were not associated with clinical symptoms in each subregion. CONCLUSION: The findings suggest that different subregions of the striatum and globus pallidus show significant volume differences at different stages of schizophrenia compared to HC. These volume differences may be strong radiographic evidence for schizophrenia. In addition, the lPAL was the only significantly different brain region observed in the FSZ group, suggesting that it may be a sensitive indicator of early brain structural changes in schizophrenia. Finally, our findings support the hypothesis that antipsychotic drugs have an effect on the volume of brain structures.

Release of damaged mitochondrial DNA: A novel factor in stimulating inflammatory response.

Mitochondrial DNA (mtDNA) is a circular double-stranded genome that exists independently of the nucleus. In recent years, research on mtDNA has significantly increased, leading to a gradual increase in understanding of its physiological and pathological characteristics. Reactive oxygen species (ROS) and other factors can damage mtDNA. This damaged mtDNA can escape from the mitochondria to the cytoplasm or extracellular space, subsequently activating immune signaling pathways, such as NLR family pyrin domain protein 3 (NLRP3), and triggering inflammatory responses. Numerous studies have demonstrated the involvement of mtDNA damage and leakage in the pathological mechanisms underlying various diseases including infectious diseases, metabolic inflammation, and immune disorders. Consequently, comprehensive investigation of mtDNA can elucidate the pathological mechanisms underlying numerous diseases. The prevention of mtDNA damage and leakage has emerged as a novel approach to disease treatment, and mtDNA has emerged as a promising target for drug development. This article provides a comprehensive review of the mechanisms underlying mtDNA-induced inflammation, its association with various diseases, and the methods used for its detection.

The impact of childhood trauma on Adolescent Depressive Symptoms: the Chain Mediating role of borderline personality traits and self-control.

BACKGROUND: The adolescent depression associated with childhood trauma has been confirmed, but the underlying mechanisms remain unclear. This study aims to explore the chain-mediated role of borderline personality traits and self-control in the relationship between childhood trauma and adolescent depression. METHODS: A cross-sectional study was conducted on 2,664 students from a senior high school through online questionnaires from October to December 2022 in Henan, China. Childhood Trauma Questionnaire-Short Form, Borderline Personality Dimension of Personality Diagnostic Questionnaire-4, Self-Control Scale, and Children's Depression Inventory were used to measure childhood trauma, borderline personality traits, and self-control. RESULTS: The prevalence of depression in adolescents was 21.17%, while the prevalence of borderline personality was 12.00%. childhood trauma (r = 0.50, p < 0.001) and borderline personality traits (r = 0.60, p < 0.001) were positively correlated with adolescent depressive symptoms, while self-control was negatively correlated with depressive symptoms (r = - 0.50, p < 0.001). Borderline personality traits and Self-control both play a mediating role in childhood trauma and depressive symptoms, and the mediating effect values are 0.116 (95%CI = [0.098, 0.137]), and 0.022 (95%CI = [0.012, 0.032]) respectively. The chain mediating effect of borderline personality traits and self-control on the relationship between childhood trauma and depressive symptoms was significant (effect value: 0.034, 95%CI = [0.028, 0.042]). CONCLUSIONS: Childhood trauma can predict depressive symptoms in adolescents due to the formation of borderline personality traits and the reduction of self-control. These findings are important for understanding the formation of personality traits, self-control abilities and coping strategies shaped by traumatic experiences in adolescents.

Improvement of nucleotide content of Cordyceps tenuipes by Schisandra chinensis: fermentation process optimization and application prospects.

Nucleotides are important components and the main indicators for judging Cordyceps quality. In this paper, the mixed fermentation process of Schisandra chinensis and Cordyceps tenuipes was systematically studied, and it was proposed that the fermentation products aqueous extract (S-ZAE) had antioxidant activity and anti-AChE ability. Herein, the results of a single factor showed that S. chinensis, yeast extract, inoculum amount, and pH had significant effects on nucleotide synthesis. The fermentation process optimization results were 3% glucose, 0.25% KH2PO4, 2.1% yeast extract, and S. chinensis 0.49% (m/v), the optimal fermentation conditions were 25℃, inoculum 5.8% (v/v), pH 3.8, 6 d. The yield of total nucleotides in the scale-up culture was 0.64 ± 0.027 mg/mL, which was 10.6 times higher than before optimization. S-ZAE has good antioxidant and anti-AChE activities (IC50 0.50 ± 0.050 mg/mL). This fermentation method has the advantage of industrialization, and its fermentation products have the potential to become good functional foods or natural therapeutic agents.

Precise Structural Analysis of Neutral Glycans Using Aerolysin Mutant T240R Nanopore.

Glycans play vital roles in nearly all life processes of multicellular organisms, and understanding these activities is inseparable from elucidating the biological significance of glycans. However, glycan research has lagged behind that of DNA and protein due to the challenges posed by structural heterogeneity and isomerism (i.e., structures with equal molecular weights) the lack of high-efficiency structural analysis techniques. Nanopore technology has emerged as a sensitive single-molecule biosensor, shining a light on glycan analysis. However, a significant number of glycans are small and uncharged, making it challenging to elicit identifiable nanopore signals. Here we introduce a R-binaphthyl tag into glycans, which enhances the cation-π interaction between the derivatized glycan molecules and the nanopore interface, enabling the detection of neutral glycans with an aerolysin nanopore. This approach allows for the distinction of di-, tri-, and tetrasaccharides with monosaccharide resolution and has the potential for group discrimination, the monitoring of enzymatic transglycosylation reactions. Notably, the aerolysin mutant T240R achieves unambiguous identification of six disaccharide isomers, trisaccharide and tetrasaccharide linkage isomers. Molecular docking simulations reveal that multiple noncovalent interactions occur between residues R282, K238, and R240 and the glycans and R-binaphthyl tag, significantly slowing down their translocation across the nanopore. Importantly, we provide a demonstration of the kinetic translocation process of neutral glycan isomers, establishing a solid theoretical foundation for glycan nanopore analysis. The development of our technology could promote the analysis of glycan structural isomers and has the potential for nanopore-based glycan structural determination and sequencing.

Depression and the risk of dementia and all-cause mortality among Japanese older adults: A 9-year longitudinal study from JAGES.

BACKGROUND: This study aims to investigate the association and dose-response relationship between depression, dementia, and all-cause mortality based on a national cohort study of elderly people in Japan. METHODS: We conducted a longitudinal study of 44,546 participants aged ≥65 from 2010-2019 Japanese Gerontological Evaluation Study (JAGES). The Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms and the long-term care insurance (LTCI) was used to assess dementia. Fine-gray models and Cox proportional hazard models were used to explore the effect of depression severity on the incidence of dementia and all-cause mortality, respectively. Causal mediation analysis (CMA) to explore the extent of association between dementia-mediated depression and all-cause mortality. RESULTS: We found that both minor and major depressive symptoms were associated with the increased cumulative incidence of dementia and all-cause mortality, especially major depressive symptoms (P < 0.001). The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia were 1.25 (1.19-1.32) for minor depressive symptoms and 1.42 (1.30-1.54) for major depressive symptoms in comparison to non-depression; P for trend < 0.001. The multivariable-adjusted HRs and 95% CIs for all-cause mortality were 1.27 (1.21-1.33) for minor depressive symptoms and 1.51 (1.41-1.62) for major depressive symptoms in comparison to non-depression; P for trend < 0.001. Depression has a stronger impact on dementia and all-cause mortality among the younger group. In addition, dementia significantly mediated the association between depression and all-cause mortality. DISCUSSION: Interventions targeting major depression may be an effective strategy for preventing dementia and premature death.

Surface-Enhanced Raman Spectroscopy-Based Detection of EMT-Related Targets in Endometrial Cancer: Potential for Diagnosis and Prognostic Prediction.

Epithelial-mesenchymal transformation (EMT) is one of the important mechanisms of malignancy in endometrial cancer, and detection of EMT targets is a key challenge to explore the mechanism of endometrial carcinoma (EC) malignancy and discover novel therapeutic targets. This study attempts to use surface-enhanced Raman spectroscopy (SERS), a highly sensitive, ultrafast, and highly specific analytical technology, to rapidly detect microRNA-200a-3p and ZEB1 in endometrial cancer cell lines. The silver nanoparticles were decorated with iodine and calcium ions, can capture the SERS fingerprints of microRNA-200a-3p and ZEB1 protein, and effectively avoid the interference of impurity signals. At the same time, the method has high sensitivity for the detection of the above EMT targets, and the lowest detection limits for microRNA-200a-3p and ZEB1 are 4.5 pmol/mL and 10 ng/mL, respectively. At the lowest detection concentration, the method still has high stability. In addition, principal component analysis can not only identify microRNA-200a-3p and ZEB1 protein from a variety of EMT-associated microRNA and proteins but also identify them in the total RNA and total protein of endometrial cancer cell lines and normal endometrial epithelial cell lines. This study modified silver nanoparticles with iodine and calcium ions and for the first time captured the fingerprints of EMT-related targets microRNA-200a-3p and ZEB1 at the same time without label, and the method has high sensitivity and stability. This SERS-based method has immense potential for elucidating the molecular mechanisms of EMT-related EC, as well as identifying biomarkers for malignant degree and prognosis prediction.

In vitro simulated digestion and fermentation characteristics of pectic polysaccharides from fresh passion fruit (Passiflora edulis f. flavicarpa L.) peel.

In this study, two pectic polysaccharides (PFP-T and PFP-UM) were extracted from fresh passion fruit peels using three-phase partitioning (TPP) and sequential ultrasound-microwave-assisted TPP methods, respectively, and their effects on the in vitro gastrointestinal digestion and fecal fermentation characteristics were examined. The results indicate that gastrointestinal digestion has a minimal effect on the physicochemical and structural characteristics of PFP-T and PFP-UM. However, during in vitro fecal fermentation, both undigested PFP-T and PFP-UM are significantly degraded and utilized by intestinal microorganisms, showing increased the total relative abundance of Firmicutes and Bacteroidota in the intestinal flora. Notably, compared with PFP-UM, PFP-T better promoted the reproduction of beneficial bacteria such as Prevotella, Megasphaera and Dialister, while suppressed the growth of harmful genera including Escherichia-Shigella, producing higher content of short-chain fatty acids. Therefore, our findings suggest that PFP-T derived from passion fruit peel has potential as a dietary supplement for promoting intestinal health.

Deep Learning Radiomics Model of Contrast-Enhanced CT for Differentiating the Primary Source of Liver Metastases.

RATIONALE AND OBJECTIVES: To develop and validate a deep learning radiomics (DLR) model based on contrast-enhanced computed tomography (CT) to identify the primary source of liver metastases. MATERIALS AND METHODS: In total, 657 liver metastatic lesions, including breast cancer (BC), lung cancer (LC), colorectal cancer (CRC), gastric cancer (GC), and pancreatic cancer (PC), from 428 patients were collected at three clinical centers from January 2018 to October 2023 series. The lesions were randomly assigned to the training and validation sets in a 7:3 ratio. An additional 112 lesions from 61 patients at another clinical center served as an external test set. A DLR model based on contrast-enhanced CT of the liver was developed to distinguish the five pathological types of liver metastases. Stepwise classification was performed to improve the classification efficiency of the model. Lesions were first classified as digestive tract cancer (DTC) and non-digestive tract cancer (non-DTC). DTCs were divided into CRC, GC, and PC and non-DTCs were divided into LC and BC. To verify the feasibility of the DLR model, we trained classical machine learning (ML) models as comparison models. Model performance was evaluated using accuracy (ACC) and area under the receiver operating characteristic curve (AUC). RESULTS: The classification model constructed by the DLR algorithm showed excellent performance in the classification task compared to ML models. Among the five categories task, highest ACC and average AUC were achieved at 0.563 and 0.796 in the validation set, respectively. In the DTC and non-DTC and the LC and BC classification tasks, AUC was achieved at 0.907 and 0.809 and ACC was achieved at 0.843 and 0.772, respectively. In the CRC, GC, and PC classification task, ACC and average AUC were the highest, at 0.714 and 0.811, respectively. CONCLUSION: The DLR model is an effective method for identifying the primary source of liver metastases.

Changes of PK/PD of Meropenem in patients with abdominal septic shock and exploration of clinical rational administration plan: a prospective exploratory study.

This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.

NETosis-Inspired Cell Surface-Constrained Framework Nucleic Acids Traps (FNATs) for Cascaded Extracellular Recognition and Cellular Behavior Modulation.

Upon pathogenic stimulation, activated neutrophils release nuclear DNA into the extracellular environment, forming web-like DNA structures known as neutrophil extracellular traps (NETs), which capture and kill bacteria, fungi, and cancer cells. This phenomenon is commonly referred to as NETosis. Inspired by this, we introduce a cell surface-constrained web-like framework nucleic acids traps (FNATs) with programmable extracellular recognition capability and cellular behavior modulation. This approach facilitates dynamic key chemical signaling molecule recognition such as adenosine triphosphate (ATP), which is elevated in the extracellular microenvironment, and triggers FNA self-assembly. This, in turn, leads to in situ tightly interwoven FNAs formation on the cell surface, thereby inhibiting target cell migration. Furthermore, it activates a photosensitizer-capturing switch, chlorin e6 (Ce6), and induces cell self-destruction. This cascade platform provides new potential tools for visualizing dynamic extracellular activities and manipulating cellular behaviors using programmable in situ self-assembling DNA molecular devices.

Increased serum interleukin-41 correlates with disease severity in myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease mediated by pathogenic antibodies produced by abnormally activated B cells, resulting in neuromuscular junction transmission dysfunction. Interleukin-41 (IL-41) is a novel immunomodulatory cytokine that has been implicated in various metabolic, inflammatory, and autoimmune diseases. The role of IL-41 in MG is still unclear up to now, our study aimed to investigate the level of IL-41 in MG patients and its correlation with clinical features and inflammatory indicators. METHODS: Totally, 60 MG patients and 30 healthy controls (HC) were recruited. Baseline data and laboratory parameters were routinely recorded through electronic medical systems. IL-41 levels were measured by enzyme-linked immunosorbent assay. Proportions of T-cell and B-cell subsets and natural killer cells were analyzed by flow cytometry. The correlation between serum IL-41 and MG related parameters was investigated, and the clinical value of IL-41 in the diagnosis of MG was evaluated by receiver operator characteristic curve (ROC) analysis. RESULTS: Serum IL-41 levels in MG patients were higher than in HC, and were higher in Myasthenia Gravis Foundation of America (MGFA) III + IV group than that in MGFA I + II group. Serum IL-41 was positively correlated with MG-specific activities of daily living scale (MG-ADL), MGFA classification, platelet to lymphocyte ratio (PLR), and proportion of CD19+ B cells, while it was negatively correlated with high-sensitive C-reactive protein (hs-CRP) and circulatory plasma cells in MG patients. Serum IL-41 levels increased in patients who were treated with efgartigimod during the first cycle of therapy. However, compared to disease initiation, serum IL-41 levels decreased when clinical features steadily improved. ROC analysis showed that IL-41 had a diagnostic value for MG. CONCLUSION: The present findings suggested that serum IL-41 was increased in MG patients and was positively associated with the severity of the disease. IL-41 may be essential to the immunopathological mechanism of MG and a potential biomarker for MG.

Exploring the diagnostic value of endothelial cell and angiogenesis-related genes in Hashimoto's thyroiditis based on transcriptomics and single cell RNA sequencing.

(1) BACKGROUND: Hashimoto's thyroiditis (HT) can cause angiogenesis in the thyroid gland. However, the molecular mechanism of endothelial cells and angiogenesis related genes (ARGs) has not been extensively studied in HT. (2) METHODS: The HRA001684, GSE29315 and GSE163203 datasets were included in this study. Using single-cell analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, machine learning algorithms and expression analysis for exploration. And receiver operator characteristic (ROC) curves was draw. Gene set enrichment analysis (GSEA) was utilized to investigate the biological function of the biomarkers. Meanwhile, we investigated into the relationship between biomarkers and different types of immune cells. Additionally, the expression of biomarkers in the TCGA-TC dataset was examined and the mRNA-drug interaction network was constructed. (3) RESULTS: We found 14 cell subtypes were obtained in HT samples after single-cell analysis. A total of 5 biomarkers (CD52, CD74, CD79A, HLA-B and RGS1) were derived, and they had excellent diagnostic performance. Then, 27 drugs targeting biomarkers were predicted. The expression analysis showed that CD74 and HLA-B were significantly up-regulated in HT samples. (4) CONCLUSION: In this study, 5 biomarkers (CD52, CD74, CD79A, HLA-B and RGS1) were screened and their expressions in endothelial cells was compared to offer a new reference for the recognition and management of HT.

Escape sites from the endo-lysosomal trafficking route manipulate exocytosis of nanoparticles in polar epithelium.

The endo-lysosomal pathway is a major barrier for the trans-epithelial transport of nanoparticles (NPs), but escape strategies could facilitate trans-epithelial delivery. Based on the polarization properties of the epithelium, different escape compartments may result in different exocytosis fates of NPs and further affect the delivery efficiency. Therefore, optimizing the escape sites is critical for trans-epithelial delivery. Here, commonly used PEG-coated-poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles were fabricated as model nanoparticles (MNPs) and the intestinal epithelium was chosen as the polarized epithelium. The MNPs were incubated with different endosomolytic agents for early endosomal escape, late endosomal escape and lysosomal escape, respectively. According to in vitro and in vivo studies, MNPs escaping from early endosomes and late endosomes exhibited stronger capacity for trans-epithelial transport than those escaping from lysosomes. By further probing into the mechanism, we surprisingly found that although MNPs escaping from early endosomes quickly egressed from the apical side of epithelia, they were subsequently followed by "reuptake" via caveolae and trafficked through the endoplasmic reticulum-Golgi apparatus (ER/GA) secretory pathway, achieving efficient trans-epithelial transport; MNPs escaping from late endosomes, which were located near the nucleus, were prone to enter the ER/GA for efficient basolateral exocytosis. However, MNPs escaping from lysosomes were detained within cells by autophagosomes. Collectively, our research suggested that early endosomes and late endosomes were ideal escape sites for trans-epithelial delivery.

An herbal formulation "Shugan Xiaozhi decoction" ameliorates methionine/choline deficiency-induced nonalcoholic steatohepatitis through regulating inflammation and apoptosis-related pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Shugan Xiaozhi (SGXZ) decoction is a traditional Chinese medicine used for treating nonalcoholic steatohepatitis (NASH). It has been used clinically for over 20 years and proved to be effective; however, the molecular mechanism underlying the effects of SGXZ decoction remains unclear. AIM OF THE STUDY: We analyzed the chemical components, core targets, and molecular mechanisms of SGXZ decoction to improve NASH through network pharmacology and in vivo experiments. MATERIALS AND METHODS: The chemical components, core targets, and related signaling pathways of SGXZ decoction intervention in NASH were predicted using network pharmacology. Molecular docking was performed to verify chemical components and their core targets. The results were validated in the NASH model treated with SGXZ decoction. Mouse liver function was assessed by measuring ALT and AST levels. TC and TG levels were determined to evaluate lipid metabolism, and lipid deposition was assessed via oil red O staining. Mouse liver damage was determined via microscopy following hematoxylin and eosin staining. Liver fibrosis was assessed via Masson staining. Western blot (WB) and immunohistochemical (IHC) analyses were performed to detect inflammation and the expression of apoptosis-related proteins, including IL-1ß, IL-6, IL-18, TNF-α, MCP1, p53, FAS, Caspase-8, Caspase-3, Caspase-9, Bax, Bid, Cytochrome c, Bcl-2, and Bcl-XL. In addition, WB and IHC were used to assess protein expression associated with the TLR4/MyD88/NF-κB pathway. RESULTS: Quercetin, luteolin, kaempferol, naringenin, and nobiletin in SGXZ decoction were effective chemical components in improving NASH, and TNF-α, IL-6, and IL-1ß were the major core targets. Molecular docking indicated that these chemical components and major core targets might interact. KEGG pathway analysis showed that the pathways affected by SGXZ decoction, primarily including apoptosis and TLR4/NF-κB signaling pathways, interfere with NASH. In vivo experiments indicated that SGXZ decoction considerably ameliorated liver damage, fibrosis, and lipid metabolism disorder in MCD-induced NASH mouse models. In addition, WB and IHC verified the underlying molecular mechanisms of SGXZ decoction as predicted via network pharmacology. SGXZ decoction inhibited the activation of apoptosis-related pathways in MCD-induced NASH mice. Moreover, SGXZ decoction suppressed the activation of TLR4/MyD88/NF-κB pathway in MCD-induced NASH mice. CONCLUSION: SGXZ decoction can treat NASH through multiple targets and pathways. These findings provide new insights into the effective treatment of NASH using SGXZ decoction.

Secondary metabolites in host pears defense against two fruit borers and cytochrome-P450-mediated counter-defense.

Herbivorous insects have evolved metabolic strategies to survive the challenges posed by plant secondary metabolites (SMs). This study reports an exploration of SMs present in pears, which serve as a defense against invasive Cydia pomonella and native Grapholita molesta and their counter-defense response. The feeding preferences of fruit borers are influenced by the softening of two pear varieties as they ripen. The content of SMs, such as quercetin and rutin, increases due to feeding by fruit borers. Notably, quercetin levels only increase after C. pomonella feeding. The consumption of SMs affects the growth of fruit borer population differently, potentially due to the activation of P450 genes by SMs. These two fruit borers are equipped with specific P450 enzymes that specialize in metabolizing quercetin and rutin, enabling them to adapt to these SMs in their host fruits. These findings provide valuable insights into the coevolution of plants and herbivorous insects.

Decoding the Reactivity Enhancement of Ln2Ce2O7 Compounds (Ln = Yb, Y, Tb, and Gd) for Soot Combustion: The Remarkable Contribution of Variable Valence A-Sites.

The impact of variable valence A-sites on the redox property and reactivity of Ln2Ce2O7 compounds in soot particulate combustion has been investigated. It was observed that Yb2Ce2O7, Y2Ce2O7, and Gd2Ce2O7 formed a rare earth C-type phase, while Tb2Ce2O7 formed a solid solution phase. Both Tb2Ce2O7 and Yb2Ce2O7 possess dual valence state A-sites, resulting in significantly more surface vacancies. Additionally, the advantageous solid solution phase structure of Tb2Ce2O7 leads to even more surface vacancies than Yb2Ce2O7, which is crucial to generate active oxygen sites. Moreover, the introduction of NO into the reaction feed enhances combustion activity by producing active surface monodentate nitrates. A catalyst with higher numbers of surface vacancies exhibits improved NO oxidation ability and better NO2 utilization efficiency. Consequently, the Tb2Ce2O7 compound demonstrates not only the best soot combustion activity, but also an optimal NOx-assistance effect. Therefore, it is concluded that variable valence A-site is the intrinsic factor to improve the reactivity of Ln2Ce2O7 catalysts.

Causal effects of neuroticism on postpartum depression: a bidirectional mendelian randomization study.

PURPOSE: Postpartum depression (PPD) brings adverse and serious consequences to both new parents and newborns. Neuroticism affects PPD, which remains controversial for confounding factors and reverse causality in cross-sectional research. Therefore, mendelian randomization (MR) study has been adopted to investigate their causal relationship. METHODS: This study utilized large-scale genome-wide association study genetic pooled data from three major databases: the United Kingdom Biobank, the European Bioinformatics Institute, and the FinnGen databases. The causal analysis methods used inverse variance weighting (IVW). The weighted median, MR-Egger method, MR-PRESSO test, and the leave-one-out sensitivity test have been used to examine the results' robustness, heterogeneity, and horizontal pleiotropy. The fixed effect model yielded the results of meta-analysis. RESULTS: In the IVW model, a meta-analysis of the MR study showed that neuroticism increased the risk of PPD (OR, 1.17; 95% CI, 1.11-1.25, p < 0.01). Reverse analysis showed that PPD could not genetically predict neuroticism. There was no significant heterogeneity or horizontal pleiotropy bias in this result. CONCLUSION: Our study suggests neuroticism is the risk factor for PPD from a gene perspective and PPD is not the risk factor for neuroticism. This finding may provide new insights into prevention and intervention strategies for PPD according to early detection of neuroticism.

Breaking Continuously Packed Bimetallic Sites to Singly Dispersed on Nonmetallic Support for Efficient Hydrogen Production.

We have synthesized Pt1Zn3/ZnO, also termed 0.01 wt %Pt/ZnO-O2-H2, as a catalyst containing singly dispersed single-atom bimetallic sites, also called a catalyst of singly dispersed bimetallic sites or a catalyst of isolated single-atom bimetallic sites. Its catalytic activity in partial oxidation of methanol to hydrogen at 290 °C is found to be 2-3 orders of magnitude higher than that of Pt-Zn bimetallic nanoparticles supported on ZnO, 5.0 wt %Pt/ZnO-N2-H2. Selectivity for H2 on Pt1Zn3/ZnO reaches 96%-100% at 290-330 °C, arising from the uniform coordination environment of single-atom Pt1 in singly dispersed single-atom bimetallic sites, Pt1Zn3 on 0.01 wt %Pt/ZnO-O2-H2, which is sharply different from various coordination environments of Pt atoms in coexisting PtxZny (x ≥ 0, y ≥ 0) sites on Pt-Zn bimetallic nanoparticles. Computational simulations attribute the extraordinary catalytic performance of Pt1Zn3/ZnO to the stronger adsorption of methanol and the lower activation barriers in O-H dissociation of CH3OH, C-H dissociations of CH2O to CO, and coupling of intermediate CO with atomic oxygen to form CO2 on Pt1Zn3/ZnO as compared to those on Pt-Zn bimetallic nanoparticles. It demonstrates that anchoring uniform, isolated single-atom bimetallic sites, also called singly dispersed bimetallic sites on a nonmetallic support can create new catalysts for certain types of reactions with much higher activity and selectivity in contrast to bimetallic nanoparticle catalysts with coexisting, various metallic sites MxAy (x ≥ 0, y ≥ 0). As these single-atom bimetallic sites are cationic and anchored on a nonmetallic support, the catalyst of singly dispersed single-atom bimetallic sites is different from a single-atom alloy nanoparticle catalyst. The critical role of the 0.01 wt %Pt in the extraordinary catalytic performance calls on fundamental studies of the profound role of a trace amount of a metal in heterogeneous catalysis.