Adverse childhood experiences and cognitive function in later life: the sequential mediating roles of education level and adult loneliness.

Background: This study assesses the impact of adverse childhood experiences (ACEs) on the cognitive function of older adults. Furthermore, it examines the potential underlying mechanism involving education level and the subjective "feeling of loneliness" (FOL). Methods: Analyzing a population-based cohort sample from the China Health and Retirement Longitudinal Study database, 8,365 subjects aged 45 or older were interviewed in 2018. Ten ACEs indicators were measured using life history questionnaires assessed at 2014. FOL was assessed using a single item from 10-item Center for Epidemiological Studies Depression Scale (CESD-10). Cognitive function was assessed using a structured questionnaire comprising four dimensions: memory, orientation, computation, and visuospatial abilities. Results: In the fully adjusted model, which accounted for age, gender, marital status, smoke, drink, rural residence, and education levels of both mothers and fathers, the linear regression analysis indicated that ACEs were inversely associated the lower education level (B = -0.058, 95% CI = -0.090, -0.026, p < 0.001), and ACEs were found to be linked to an elevated risk of FOL (B = 0.072, 95% CI = 0.056, 0.089, p < 0.001). In addition, ACEs was not significantly associated with cognitive function (B = -0.047, 95% CI = -0.108, 0.015, p = 0.136), but FOL was significantly associated with cognitive function (B = -0.483, 95% CI = -0.561, -0.404, p < 0.001). Mediation analysis revealed that education level and FOL sequentially and partially mediated the association between ACEs and the total cognitive score, with a proportion mediated of 52.58%. Limitations: The evaluation of ACEs exposure was based on binary response options. This method limited our ability to explore various dimensions of adversity, such as ages of occurrence, severity, frequency, duration, and the extent of psychological effects at the time. Furthermore, the assessment of loneliness relied on a single item from the CESD-10, introducing a potential source of measurement error. Conclusion: Our study unveils a substantial association between ACEs and education level, as well as with FOL and cognitive function in the older adults. Moreover, education level and FOL serve as sequential mediating factors in the relationship between ACEs and cognitive function.

Machine learning-based prediction of diabetic patients using blood routine data.

Diabetes stands as one of the most prevalent chronic diseases globally. The conventional methods for diagnosing diabetes are frequently overlooked until individuals manifest noticeable symptoms of the condition. This study aimed to address this gap by collecting comprehensive datasets, including 1000 instances of blood routine data from diabetes patients and an equivalent dataset from healthy individuals. To differentiate diabetes patients from their healthy counterparts, a computational framework was established, encompassing eXtreme Gradient Boosting (XGBoost), random forest, support vector machine, and elastic net algorithms. Notably, the XGBoost model emerged as the most effective, exhibiting superior predictive results with an area under the receiver operating characteristic curve (AUC) of 99.90% in the training set and 98.51% in the testing set. Moreover, the model showcased commendable performance during external validation, achieving an overall accuracy of 81.54%. The probability generated by the model serves as a risk score for diabetes susceptibility. Further interpretability was achieved through the utilization of the Shapley additive explanations (SHAP) algorithm, identifying pivotal indicators such as mean corpuscular hemoglobin concentration (MCHC), lymphocyte ratio (LY%), standard deviation of red blood cell distribution width (RDW-SD), and mean corpuscular hemoglobin (MCH). This enhances our understanding of the predictive mechanisms underlying diabetes. To facilitate the application in clinical and real-life settings, a nomogram was created based on the logistic regression algorithm, which can provide a preliminary assessment of the likelihood of an individual having diabetes. Overall, this research contributes valuable insights into the predictive modeling of diabetes, offering potential applications in clinical practice for more effective and timely diagnoses.

Urban greenspace types and climate factors jointly drive the microbial community structure and co-occurrence network.

The benefits of urban green space are socially widely recognized as a direct link between plant-microbe interactions and the maintenance of biodiversity, community stability, and ecosystem functioning. Nevertheless, there is a lack of knowledge about the factors influencing microbial communities in urban green spaces, especially those related to phyllosphere epiphytes and stem epiphytes. In this study, we analyzed the microbial community assembly in leaf and stem bark samples collected from Square, Road, Campus, and Park. Illumina sequecing of 16S amplicons was performed to characterize microbial diversity and composition. The α-diversity was significantly higher in the bark epiphytic community, compared to the phyllosphere. Moreover, urban greenspaces'type altered the way communities gathered. The main soil and air properties factors of the urban greenhouse (e.g. soil temperature, atmospheric moisture, air temperature) were shaping the characteristics of bacterial communities on the leaf surface and bark epiphytic. In addition, in the co-occurrence network analysis, keystone taxa were not mostly observed in abundant species, which may be necessary to maintain ecosystem functions. Finally, our findings provide a deeper understanding of the ecological dynamics and microbial interactions within plant phyllosphere and stem epiphytes microbiomes.

USP14 deficiency inhibits neointima formation following vascular injury via degradation of Skp2 protein.

Ubiquitin-proteasome system (UPS) is involved in vascular smooth muscle cell (VSMC) proliferation. Deubiquitinating enzymes (DUBs) have an essential role in the UPS-regulated stability of the substrate; however, the function of DUBs in intimal hyperplasia remains unclear. We screened DUBs to identify a protein responsible for regulating VSMC proliferation and identified USP14 protein that mediates cancer development, inflammation, and foam cell formation. USP14 promotes human aortic smooth muscle cell and A7r5 cell growth in vitro, and its inhibition or deficiency decreases the intimal area in the mice carotid artery ligation model. In addition, USP14 stabilizes Skp2 expression by decreasing its degradation, while Skp2 overexpression rescues USP14 loss-induced issues. The current findings suggested an essential role of USP14 in the pathology of vascular remodeling, deeming it a promising target for arterial restenosis therapy.

Schizandrin A enhances the sensitivity of gastric cancer cells to 5-FU by promoting ferroptosis.

Schizandrin A (Sch A) exert anticancer and multidrug resistance-reversing effects in a variety of tumors, but its effect on 5-fluorouracil (5-Fu) in gastric cancer (GC) cells remains unclear. The aim of the present study was to examine the resistance-reversing effect of Schizandrin A and assess its mechanisms in 5-Fu-resistant GC cells.5-Fu-sensitive GC cells were treated with 5-Fu and 5-Fu-resistant GC cells AGS/5-Fu and SGC7901/5-Fu were were established. These cells were stimulated with Schizandrin A alone or co-treated with 5-Fu and their effect on tumor cell growth, proliferation, migration, invasion and ferroptosis-related metabolism were investigated both in vitro and in vivo. A number of additional experiments were conducted in an attempt to elucidate the molecular mechanism of increased ferroptosis. The results of our study suggest that Schizandrin A in combination with 5-Fu might be useful in treating GC by reverse drug resistance. It was shown that Schizandrin A coadministration suppressed metastasis and chemotherapy resistance in 5-Fu-resistant GC cells through facilitating the onset of ferroptosis, which is an iron-dependent form of cell death, which was further demonstrated in a xenograft nude mouse model. Mechanistically, Schizandrin A co-administration synergistically increased the expression of transferin receptor, thus iron accumulates within cells, leading to lipid peroxidation, which ultimately results in 5-Fu-resistant GC cells death. The results of this study have provided a novel strategy for increasing GC chemosensitivity, indicating Schizandrin A as a novel ferroptosis regulator. Mechanistically, ferroptosis is induced by Schizandrin A coadministration via increasing transferrin receptor expression.

Unraveling Immune Heterogeneity across Pan-Cancer and Deep Insights in Lung Adenocarcinoma based on Alternative Splicing.

Alternative splicing (AS) participates in tumor development and tumor microenvironment formation. However, the landscape of immune infiltrating AS events (IIASE) in pan-cancer and mechanisms of AS in lung adenocarcinoma (LUAD) have not been comprehensively characterized. We systematically profiled the IIASE landscape of pan-cancer using data from The Cancer Genome Atlas (TCGA), analyzing both commonalities and specific characteristics among different cancer types. We found that AS events tend to occur specifically in one cancer type rather than in multiple cancer types. AS events were used to classify 512 LUAD samples into two subtypes by unsupervised clustering: aberrant splicing subtype (ABS) and immune infiltrating subtype (IIS). The two subtypes showed significant differences in clinicopathology, prognosis, transcriptomics, genomics and immune microenvironment. We constructed a classification signature comprising 10 genes involved in 14 AS events using Logistic regression. The robustness of the signature was validated in three independent datasets using survival analysis. To explore AS mechanisms in LUAD, we constructed subtype-specific co-expression networks using Pearson correlation analysis. AS event of AKT3 regulated by splicing factor ENOX1 was associated with poor prognosis in LUAD. Overall, we outline AS events associated with immune infiltration in pan-cancer and this study provides insights into AS mechanisms in LUAD patient classification.

Polar Bloch points in strained ferroelectric films.

Topological domain structures have drawn great attention as they have potential applications in future electronic devices. As an important concept linking the quantum and classical magnetism, a magnetic Bloch point, predicted in 1960s but not observed directly so far, is a singular point around which magnetization vectors orient to nearly all directions. Here we show polar Bloch points in tensile-strained ultrathin ferroelectric PbTiO3 films, which are alternatively visualized by phase-field simulations and aberration-corrected scanning transmission electron microscopic imaging. The phase-field simulations indicate local steady-state negative capacitance around the Bloch points. The observation of polar Bloch points and their emergent properties consequently implies novel applications in future integrated circuits and low power electronic devices.

Decreased resting-state functional connectivity and brain network abnormalities in the prefrontal cortex of elderly patients with Parkinson's disease accompanied by depressive symptoms.

This study aimed to explore the brain network characteristics in elderly patients with Parkinson's disease (PD) with depressive symptoms. Thirty elderly PD patients with depressive symptoms (PD-D) and 26 matched PD patients without depressive symptoms (PD-NOD) were recruited based on HAMD-24 with a cut-off of 7. The resting-state functional connectivity (RSFC) was conducted by 53-channel functional near-infrared spectroscopy (fNIRS). There were no statistically significant differences in MMSE scores, disease duration, Hoehn-Yahr stage, daily levodopa equivalent dose, and MDS-UPDRS III between the two groups. However, compared to the PD-NOD group, the PD-D group showed significantly higher MDS-UPDRS II, HAMA-14, and HAMD-24. The interhemispheric FC strength and the FC strength between the left dorsolateral prefrontal cortex (DLPFC-L) and the left frontal polar area (FPA-L) was significantly lower in the PD-D group (FDR p < 0.05). As for graph theoretic metrics, the PD-D group had significantly lower degree centrality (aDc) and node efficiency (aNe) in the DLPFC-L and the FPA-L (FDR, p < 0.05), as well as decreased global efficiency (aEg). Pearson correlation analysis indicated moderate negative correlations between HAMD-24 scores and the interhemispheric FC strength, FC between DLPFC-L and FPA-L, aEg, aDc in FPA-L, aNe in DLPFC-L and FPA-L. In conclusion, PD-D patients show decreased integration and efficiency in their brain networks. Furthermore, RSFC between DLPFC-L and FPA-L regions is negatively correlated with depressive symptoms. These findings propose that targeting DLPFC-L and FPA-L regions via non-invasive brain stimulation may be a potential intervention for alleviating depressive symptoms in elderly PD patients.

Piper longum L. ameliorates gout through the MAPK/PI3K-AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Gout, a painful joint disease with a prevalence ranging from 0.86% to 2.2% in China over the past decade. Traditional medicine has long utilized the medicinal and edible Piper longum L. (PL) fruit spikes for treating gout and other joint conditions like rheumatoid arthritis. However, the exact mechanisms behind its effectiveness remain unclear. AIM OF THE STUDY: This study aimed to investigate the potential of alcoholic extracts from PL fruit spikes as a safe and effective treatment for gout. We used a combined network pharmacology and experimental validation approach to evaluate the mechanisms behind the anti-gout properties of PL. MATERIALS AND METHODS: UPLC-Q/TOF-MS analysis determined the major components of PL. Subsequently, network pharmacology analysis predicted potential molecular targets and related signaling pathways for the anti-gout activity of PL. Molecular docking simulations further explored the interactions between PL compounds and proteins and characterized the properties of potential bioactive secondary metabolites. Mouse models of air pouch inflammation and hyperuricemia were further established, and the anti-gout mechanism of PL was confirmed by examining the expression of proteins related to the MAPK and PI3K-AKT pathways in the tissue. RESULTS: Our analysis revealed 220 bioactive secondary metabolites within PL extracts. Network pharmacology and molecular docking results indicated that these metabolites primarily combat gout by modulating the PI3K-AKT and MAPK signaling pathways. In vivo experiments have also proven that PL at a dose of 100 mg/kg can optimally reduce acute inflammation of gout and kidney damage caused by high uric acid. The anti-gout mechanism involves the PI3K-AKT/MAPK signaling pathway and its downstream NF-κB pathway. CONCLUSION: This study provides compelling evidence for PL's therapeutic potential in gout management by modulating key inflammatory pathways. The findings offer a strong foundation for future clinical exploration of PL as a gout treatment option.

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, China in 2019.

Objective: This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A (RVA) in the Pearl River Delta region of Guangdong Province, China. Methods: This study included individuals aged 28 days-85 years. A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens, including RVA, using a Gastrointestinal Pathogen Panel, followed by genotyping, virus isolation, and complete sequencing to assess the genetic diversity of RVA. Results: The overall RVA infection rate was 14.59% (103/706), with an irregular epidemiological pattern. The proportion of co-infection with RVA and other pathogens was 39.81% (41/103). Acute gastroenteritis is highly prevalent in young children aged 0-1 year, and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea. G9P[8] (58.25%, 60/103) was found to be the predominant genotype in the RVA strains, and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis. Recombination analysis showed that gene reassortment events, selection pressure, codon usage bias, gene polymorphism, and post-translational modifications (PTMs) occurred in the G9P[8] and G3P[8] strains. Conclusion: This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China, further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity. Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Isolation, purification, and biological activities of polysaccharides from Amorpha fruticosa flowers.

The extraction, isolation, structural characterisation and biological activities of polysaccharides from Amorpha fruticosa flowers were investigated. First, the crude polysaccharide AFP was extracted, and two major purified polysaccharide fractions AFP-2 and AFP-3 were isolated. The molecular weight and monosaccharide compositions of AFP-2 and AFP-3 were determined. Then the antioxidant activities of AFP, AFP-2 and AFP-3 were assessed by DPPH radical, ß-Carotene bleaching and hydroxyl radical assays. All three tested polysaccharides showed good antioxidant activity while AFP was the strongest one. The study also showed that AFP, AFP-2 and AFP-3 have good tyrosinase inhibition, moisture absorption and retention activities. The results will provide a helpful reference for the application of polysaccharide from Amorpha fruticosa flowers as a natural cosmetic ingredient.

Tuning the Fermi Level of Graphene by Two-Dimensional Metals for Raman Detection of Molecules.

Graphene-enhanced Raman scattering (GERS) offers great opportunities to achieve optical sensing with a high uniformity and superior molecular selectivity. The GERS mechanism relies on charge transfer between molecules and graphene, which is difficult to manipulate by varying the band alignment between graphene and the molecules. In this work, we synthesized a few atomic layers of metal termed two-dimensional (2D) metal to precisely and deterministically modify the graphene Fermi level. Using copper phthalocyanine (CuPc) as a representative molecule, we demonstrated that tuning the Fermi level can significantly improve the signal enhancement and molecular selectivity of GERS. Specifically, aligning the Fermi level of graphene closer to the highest occupied molecular orbital (HOMO) of CuPc results in a more pronounced Raman enhancement. Density functional theory (DFT) calculations of the charge density distribution reproduce the enhanced charge transfer between CuPc molecules and graphene with a modulated Fermi level. Extending our investigation to other molecules such as rhodamine 6G, rhodamine B, crystal violet, and F16CuPc, we showed that 2D metals enabled Fermi level tuning, thus improving GERS detection for molecules and contributing to an enhanced molecular selectivity. This underscores the potential of utilizing 2D metals for the precise control and optimization of GERS applications, which will benefit the development of highly sensitive, specific, and reliable sensors.

A study of new labor market entrants' job satisfaction trajectories during a series of consecutive job changes.

Previous research on the psychological effect of job change has revealed a honeymoon-hangover pattern during the turnover process. However, there is a dearth of evidence on how individuals react and adapt to multiple job changes over their working lives. This study distinguishes adaptation to a single job change in the short term from adaptation to the process of job change in the long term. Drawing on two large-scale, long-running panel data sets from Britain and Australia, it examined how job satisfaction trajectory evolved as individuals made a series of consecutive job changes since they first entered the labor market. Our fixed effect analyses show that in both countries, individuals experienced a stronger honeymoon effect with each successive job change, before gradually reverting to their baseline job satisfaction. In short, the amplitude of the honeymoon-hangover effect increased across multiple job changes. By distinguishing "adaptation to change" from "change in adaptation," this study generates original insights into the role of job mobility in facilitating career development and extends set point theory from understanding the impact of single life events to recurring life events. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Integrating somatic mutation profiles with structural deep clustering network for metabolic stratification in pancreatic cancer: a comprehensive analysis of prognostic and genomic landscapes.

Pancreatic cancer is a globally recognized highly aggressive malignancy, posing a significant threat to human health and characterized by pronounced heterogeneity. In recent years, researchers have uncovered that the development and progression of cancer are often attributed to the accumulation of somatic mutations within cells. However, cancer somatic mutation data exhibit characteristics such as high dimensionality and sparsity, which pose new challenges in utilizing these data effectively. In this study, we propagated the discrete somatic mutation data of pancreatic cancer through a network propagation model based on protein-protein interaction networks. This resulted in smoothed somatic mutation profile data that incorporate protein network information. Based on this smoothed mutation profile data, we obtained the activity levels of different metabolic pathways in pancreatic cancer patients. Subsequently, using the activity levels of various metabolic pathways in cancer patients, we employed a deep clustering algorithm to establish biologically and clinically relevant metabolic subtypes of pancreatic cancer. Our study holds scientific significance in classifying pancreatic cancer based on somatic mutation data and may provide a crucial theoretical basis for the diagnosis and immunotherapy of pancreatic cancer patients.

Mandibular alveolar bone thickness in untreated Class I subjects with different vertical skeletal patterns: a cone-beam computed tomography study.

OBJECTIVE: To evaluate the mandibular alveolar bone thickness in untreated skeletal Class I subjects with different vertical skeletal patterns. MATERIALS AND METHODS: A total of 50 preorthodontic treatment cone-beam computed tomography (CBCT) images of a skeletal Class I Chinese population with near-normal occlusion were selected. The buccal and lingual alveolar bone thicknesses of mandibular canines to second molars were measured at 2 mm below the cementoenamel junction (CEJ), mid-root, and root apex levels. Differences in the measurements were analyzed with Mann-Whitney U-test. The correlation between alveolar bone thickness and the sella-nasion-mandibular plane (SN-MP) angle was calculated using Pearson correlation coefficients and linear regression analysis. RESULTS: Buccal alveolar bone was thinner on all mandibular canines to first molars but thicker on second molars in comparison with lingual alveolar bone. Buccal alveolar bone was within 1 mm at the levels of 2 mm below CEJ and mid-root for the canines and first premolars. Significant differences were detected among subjects with different vertical patterns, with a negative correlation between the SN-MP angle and alveolar thickness, especially in the canine and premolar regions. The thinnest buccal and lingual alveolar bone were detected in the high-angle group canine region (0.50 mm at the levels of 2 mm below CEJ and mid-root for the buccal side, 0.90 mm at the level of 2 mm below the CEJ for the lingual side). CONCLUSIONS: To avoid periodontal complications, buccal-lingual movement of the mandibular canines and first premolars should be limited, especially in high-angle patients.

To use or not to use? Understanding doctoral students' acceptance of ChatGPT in writing through technology acceptance model.

While artificial intelligence-based chatbots have demonstrated great potential for writing, little is known about whether and how doctoral students accept the use of ChatGPT in writing. Framed with Technology Acceptance Model, this study investigated doctoral students' acceptance toward ChatGPT in writing and the factors that influence it. The questionnaire survey revealed a high intention to use ChatGPT in writing among doctoral students in China. The findings further indicated that attitude was a significant predictor of behavioural intention to use ChatGPT in writing and mediated the impacts of perceived usefulness and perceived ease of use on it. Perceived ease of ChatGPT use was in turn influenced by students' past ChatGPT use experience. This study provides powerful evidence for the applicability of Technology Acceptance Model in the acceptance of ChatGPT in writing. The results have significant implications for leveraging ChatGPT for writing in higher education.

Childhood trauma and suicide risk in hospitalized patients with schizophrenia: the sequential mediating roles of pandemic related post-traumatic stress symptoms, sleep quality, and psychological distress.

Introduction: Stressful global situation due to the COVID-19 pandemic caused a tremendous impact on mental health in hospitalized patients with schizophrenia. The mediating roles of psychological impact related to COVID-19, sleep quality, and psychological distress were investigated in the association between childhood trauma and suicidal risk in hospitalized patients with schizophrenia. Methods: We analyzed cross-sectional data of 147 patients with schizophrenia and 189 healthy controls (HCs). Results: Histories of childhood trauma and schizophrenia were good predictors of COVID-19-related psychological impact, global sleep quality, and psychological distress. Moreover, the series mediation model showed that the effect of childhood trauma on suicidal risk in hospitalized patients with schizophrenia was totally sequential mediated by the psychological impact of COVID-19, sleep quality, and psychological distress. Conclusion: Clinicians need to recognize the increased suicidal risk associated with COVID-19-related psychological distress in schizophrenia patients with a history of childhood trauma.

Design of Efficient Oxygen Reduction Reaction Catalysts with Single Transition Metal Atom on N-Doped Graphdiyne.

The revelation of the underlying structure-property relationship of single-atom catalysts (SACs) is a fundamental issue in the oxygen reduction reaction (ORR). Here we present systematic theoretical and experimental investigations of various N-doped graphdiyne (NGDY) supported transition metals (TMs) to shed light on this relationship. Calculation results indicate that the TMs' comprehensive activities follow the order of Pd@NGDY > Ni@NGDY > Co@NGDY > Fe@NGDY, which fits well with our experimental conclusion. Moreover, detailed structure-property relationship (194 in total) analysis suggests that the key-species binding stability (ΔG*OH), the d-orbital center (εd/εd-a) and charge transfer (ΔQTM/ΔQTM-a) of the active metal before/after reactants adsorption and the bond length of TM-O (LTM-O) as descriptors can well reflect the intermediate binding stability or ORR activity on different TM-SACs. Specifically, the change trend of catalytic activity is opposite to that of intermediate binding stability, meaning that too strongly bonded *OOH, *O, and *OH intermediates are unfavorable for ORR.