Toxicological evaluation and preliminary exposure assessment on glycerol monocaprylate.

As a commonly used food preservative, glycerol monocaprylate (GMC) has limited information and lacked a comprehensive risk assessment. In this study, we conducted in vitro genotoxicity tests, a 90-day subchronic toxicity study, and dietary exposure assessment in China. Rats (n=10/sex/group) were orally administered GMC at doses of 1.02, 2.04, and 4.08 g/kg BW/day along with a water and corn oil for 90 days, including satellite groups (n =5/sex/group) in the control groups and 4.08 g/kg BW dose group for observation after 90 days. Body weight, food consumption, hematology, serum biochemistry, urinalysis, endocrine hormone level and other metrics were examined. GMC did not exhibit genotoxicity based on the genotoxicity tests results, and an acceptable daily intake (ADI) of 40.8 mg/kg BW/day was established based on the 90-day subchronic toxicity study. Estimated daily intake of GMC for general population and consumer population in China were 0.99 mg/kg BW/day and 3.19 mg/kg BW/day respectively, which were significantly lower than the ADI. Our findings suggest that GMC does not pose a known health risk to Chinese consumers at the current usage level.

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains.

Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.

Dual-Functional AIE Fluorescent Probe for Visualization of Lipid Droplets and Photodynamic Therapy of Cancer.

Abnormal lipid droplets (LDs) are known to be intimately bound with the occurrence and development of cancer, allowing LDs to be critical biomarkers for cancers. Aggregation-induced emission luminogens (AIEgens), with efficient reactive oxygen species (ROS) production performance, are prime photosensitizers (PSs) for photodynamic therapy (PDT) with imaging. Therefore, the development of dual-functional fluorescent probes with aggregation-induced emission (AIE) characteristics that enable both simultaneous LD monitoring and imaging-guided PDT is essential for concurrent cancer diagnosis and treatment. Herein, we reported the development of a novel LD-targeting fluorescent probe (TDTI) with AIE performance, which was expected to realize the integration of cancer diagnosis through LD visualization and cancer treatment via PDT. We demonstrated that TDTI, with typical AIE characteristics and excellent photostability, could target LDs with high specificity, which enables the dynamic tracking of LDs in living cells, specific imaging of LDs in zebrafish, and the differentiation of cancer cells from normal cells for cancer diagnosis. Meanwhile, TDTI exhibited fast ROS generation ability (achieving equilibrium within 60 s) under white light irradiation (10 mW/cm2). The cell apoptosis assay revealed that TDTI effectively induced growth inhibition and apoptosis of HeLa cells. Further, the results of PDT in vivo indicated that TDTI had a good antitumor effect on the tumor-bearing mice model. Collectively, these results highlight the potential utility of the dual-functional fluorescent probe TDTI in the integrated diagnosis and treatment of cancer.

Spatial and temporal variations in the pollution status and sources of mercury in the Jiaozhou bay.

In the past few decades, mercury (Hg) discharged into the coastal bays of China has significantly increased; however, long-term trends regarding the pollution status and sources of Hg in these bays have yet to be clear. Focusing on this issue, surface sediments and core sediments were collected in the Jiaozhou Bay (JZB), a typical bay highly affected by human activities in China, to analyze the concentrations and stable isotopic composition of Hg. Total mercury (THg) concentrations in surface sediment varied from 7 to 163 ng/g, with higher levels located in the eastern JZB, possibly attributed to intensive industrial and population density. THg in sediment cores 14 and 20 displayed fluctuating increasing trends from 1936 to 2019, reflecting the deterioration of Hg pollution. In contrast, THg in sediment core 28 near the river mouth exhibited a declining trend, possibly due to the river dam construction. Using a stable isotope mixing model, contributions of various sources (atmospheric, riverine, and industrial emissions) to Hg in the JZB were estimated. The results showed that industrial emissions were the main source (over 50%) of mercury in the JZB in 2019. Sediment cores recorded an increase in industrial Hg due to early industrialization and Reform and Opening-up before 2000. In addition, sediment core 20 demonstrated a rise in the percentage of riverine Hg due to land reclamation at the bay's mouth during 2000-2007.

Distinct resting-state functional connectivity of the anterior cingulate cortex subregions in first-episode schizophrenia.

The anterior cingulate cortex (ACC) is a heterogeneous region of the brain's limbic system that regulates cognitive and emotional processing, and is frequently implicated in schizophrenia. This study aims to characterize resting-state functional connectivity (rsFC) profiles of three subregions of ACC in patients with first-episode schizophrenia and healthy controls. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were collected from 60 first-episode schizophrenia (FES) patients and 60 healthy controls (HC), and the subgenual ACC (sgACC), pregenual ACC (pgACC), and dorsal ACC (dACC) were selected as seed regions from the newest automated anatomical labeling atlas 3 (AAL3). Seed-based rsFC maps for each ACC subregion were generated and compared between the two groups. The results revealed that compared to the HC group, the FES group showed higher rsFC between the pgACC and bilateral lateral orbitofrontal cortex (lOFC), and lower rsFC between the dACC and right posterior OFC (pOFC), the medial prefrontal gyrus (MPFC), and the precuneus cortex (PCu). These findings point to a selective functional dysconnectivity of pgACC and dACC in schizophrenia and provide more accurate information about the functional role of the ACC in this disorder.

Model construction and drug therapy of primary ovarian insufficiency by ultrasound-guided injection.

BACKGROUND: Clinically, hormone replacement therapy (HRT) is the main treatment for primary ovarian insufficiency (POI). However, HRT may increase the risk of both breast cancer and cardiovascular disease. Exosomes derived from human umbilical cord mesenchymal stem cell (hUC-MSC) have been gradually applied to the therapy of a variety of diseases through inflammation inhibition, immune regulation, and tissue repair functions. However, the application and study of hUC-MSC exosomes in POI remain limited. METHODS: Here, we first constructed four rat animal models: the POI-C model (the "cyclophosphamide-induced" POI model via intraperitoneal injection), the POI-B model (the "busulfan-induced" POI model), the POI-U model (the "cyclophosphamide-induced" POI model under ultrasonic guidance), and MS model (the "maternal separation model"). Second, we compared the body weight, ovarian index, status, Rat Grimace Scale, complications, and mortality rate of different POI rat models. Finally, a transabdominal ultrasound-guided injection of hUC-MSC exosomes was performed, and its therapeuticy effects on the POI animal models were evaluated, including changes in hormone levels, oestrous cycles, ovarian apoptosis levels, and fertility. In addition, we performed RNA-seq to explore the possible mechanism of hUC-MSC exosomes function. RESULTS: Compared with the POI-C, POI-B, and MS animal models, the POI-U model showed less fluctuation in weight, a lower ovarian index, fewer complications, a lower mortality rate, and a higher model success rate. Second, we successfully identified hUC-MSCs and their exosomes, and performed ultrasound-guided intraovarian hUC-MSCs exosomes injection. Finally, we confirmed that the ultrasound-guided exosome injection (termed POI-e) effectively improved ovarian hormone levels, the oestrous cycle, ovarian function, and fertility. Mechanically, hUC-MSCs may play a therapeutic role by regulating ovarian immune and metabolic functions. CONCLUSIONS: In our study, we innovatively constructed an ultrasound-guided ovarian drug injection method to construct POI-U animal models and hUC-MSC exosomes injection. And we confirmed the therapeutic efficacy of hUC-MSC exosomes on the POI-U animal models. Our study will offer a better choice for new animal models of POI in the future and provides certain guidance for the hUC-MSCs exosome therapy in POI patients.

Sensory omics combined with mathematical modeling for integrated analysis of retronasal Muscat flavor in table grapes.

This study focused on analyzing the aroma formation mechanism of retronasal muscat flavor in table grapes. The sensory characteristics and fragrance components of table grape juice with different intensities of Muscat were investigated using GC-Quadrupole-MS, quantitative descriptive analysis and three-alternate forced choice. Free monoterpenoids were the main contributors to the retronasal Muscat flavor. The contribution of Muscat compounds to this flavor was quantified by Stevens coefficient, the most and the least sensitive compounds to concentration changes were citronellol and linalool, respectively. To predict the Muscat flavor intensity by mathematical modeling, established a model between Muscat flavor intensity and monoterpenoids concentration, and an optimal partial least squares regression model with a linear relationship between natural logarithms was obtained. These findings provide reference for understanding the formation mechanism of specific aromas in fruits and provide a basis for the development and quality control of processed products such as Muscat flavor grape juice.

Disclosing Support-Size-Dependent Effect on Ambient Light-Driven Photothermal CO2 Hydrogenation over Nickel/Titanium Dioxide.

The size of support in heterogeneous catalysts can strongly affect the catalytic property but is rarely explored in light-driven catalysis. Herein, we demonstrate the size of TiO2 support governs the selectivity in photothermal CO2 hydrogenation by tuning the metal-support interactions (MSI). Small-size TiO2 loading nickel (Ni/TiO2 -25) with enhanced MSI promotes photo-induced electrons of TiO2 migrating to Ni nanoparticles, thus favoring the H2 cleavage and accelerating the CH4 formation (227.7 mmol g-1 h-1 ) under xenon light-induced temperature of 360 °C. Conversely, Ni/TiO2 -100 with large TiO2 prefers yielding CO (94.2 mmol g-1 h-1 ) due to weak MSI, inefficient charge separation, and inadequate supply of activated hydrogen. Under ambient solar irradiation, Ni/TiO2 -25 achieves the optimized CH4 rate (63.0 mmol g-1 h-1 ) with selectivity of 99.8 %, while Ni/TiO2 -100 exhibits the CO selectivity of 90.0 % with rate of 30.0 mmol g-1 h-1 . This work offers a novel approach to tailoring light-driven catalytic properties by support size effect.

Evaluating the Role of Functional Groups in the Selective Capture of Ag(I) onto UiO-66-Type Metal-Organic Frameworks.

UiO-66-type metal-organic frameworks have been considered as promising adsorbents for capturing Ag(I) from wastewater. However, uncertainties persist regarding the specific absorptivity of individual functional groups to the UiO-66 framework structure. In this study, UiO-66-type metal-organic frameworks (UiO-66-X), featuring diverse functional groups (X = -(OH)2, -(COOH)2, -NO2, -NH2, -SO3H, -(SH)2), were synthesized in situ for Ag(I) capture. The findings revealed that functionalization significantly enhanced the adsorption capacity of Ag(I). Notably, quantitative analysis showed that 1 mol of -SH functional group onto the UiO-66 framework structure can adsorb 0.73 mol of Ag(I) ions, surpassing those of -COOH, -OH, -NH2, -SO3H, and -NO2 by 2.4-, 3.5-, 3.8-, 9.1-, and 24.3-fold, respectively. This represents the first assessment of the adsorption capacity of functionalized UiO-66 for Ag(I) based on each effective functional group, addressing limitations in traditional unit mass calculations. Further, the adsorption mechanism of UiO-66-X for selectively capturing Ag(I) was elucidated through experimental and theoretical analyses. Additionally, selectivity and practical applications confirm that UiO-66-(SH)2 exhibits strong anti-interference ability, whether in natural water bodies with complex compositions or in industrial wastewater under harsh conditions. We anticipate that this study will enhance our understanding of structure-performance dependencies of multivariate MOFs for designing novel adsorbents for Ag(I) capture.

Effects of Zhuang medicine compound Xiancao Granule on diabetic kidney disease: A multi-omics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic kidney disease (DKD) poses a severe threat to human health. Compound Xiancao Granule (CXCG), a classic Zhuang medicinal formula, is reported as highly effective in treating DKD. However, the mechanisms underlying the action of CXCG in DKD remain unclear. AIM OF THE STUDY: This study aimed to investigate the mechanisms of action of CXCG against DKD using multi-omics analysis, including 16s rRNA sequencing, metabolomics, and transcriptomics. MATERIALS AND METHODS: The chemical compounds of CXCG were identified using ultra-high- performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry analysis. A rat model of DKD was established by combining nephrectomy of the left kidney, high-fat diet, and streptozotocin. The therapeutic effects of CXCG on DKD were assessed based on body weight, blood glucose level, renal function, inflammatory cytokine levels, and histological staining. Subsequently, 16s rRNA sequencing, liquid chromatography-tandem mass spectrometry untargeted metabolomic profiling, and RNA sequencing analysis were used to investigate the mechanisms of action of CXCG in DKD. Spearman's correlation analysis was performed to elucidate the correlations between efficacy indicators, gut microbiota, metabolites, and inflammation-related genes. RESULTS: A total of 118 compounds were identified in CXCG. CXCG significantly ameliorated glucose metabolism disorders, improved renal function, attenuated inflammation, and delayed renal pathological changes in DKD rats. CXCG modulated gut microbiota dysbiosis, including Alloprevotella, Oscillibacter, Anaeroplasma, Anaerotruncus, and Faecalibacterium. In addition, metabolic disruption in DKD rats was regulated by CXCG, which is involved in the metabolism of carbohydrates and amino acids. Transcriptome analysis showed that CXCG affected DKD mainly by regulating inflammation-related genes and pathways, such as the PI3K/Akt and MAPK signaling pathways. Furthermore, there were significant correlations between efficacy indicators, gut microbiota, metabolites, and genes. CONCLUSION: This multi-omics association study provides novel insights into the effects of CXCG on DKD by remodeling the gut microbiota structure and restoring the metabolic homeostasis through the regulation of carbohydrate metabolism, amino acid metabolism, and inflammation-related pathways, highlighting a potential therapeutic strategy for DKD.

Ferroptosis: A new view on the prevention and treatment of diabetic kidney disease with traditional Chinese medicine.

Diabetic kidney disease is one of the complications of diabetes mellitus, which can eventually progress to end-stage kidney disease. The increasing prevalence of diabetic kidney disease has brought huge economic burden to society and seriously jeopardized public health. Ferroptosis is an iron-dependent, non-apoptosis-regulated form of cell death. The regulation of ferroptosis involves different molecular mechanisms and multiple cellular metabolic pathways. In recent years, ferroptosis has been proved to be closely related to the occurrence and development of diabetic kidney disease, and can interact with pathological changes such as fibrosis, inflammation, oxidative stress, and disorders of glucose and lipid metabolism, destroying the structure, form and function of the inherent cells of the kidney, and promoting the progression of the disease. Traditional Chinese medicine has a long history of treating diabetic kidney disease with remarkable curative effect. Current scholars have shown that the oral administration of traditional Chinese medicine and the external treatment of Chinese medicine can regulate GPX4, Nrf2, ACSL4, PTGS2, TFR1 and other key signaling molecules, curb ferroptosis, and prevent the progressive deterioration of diabetic kidney disease. In this paper, the mechanism of ferroptosis and diabetic kidney disease and the prevention and treatment of traditional Chinese medicine are analyzed and summarized, in order to provide new ideas and new plans for the treatment of diabetic kidney disease.

A comparative study of interhemispheric functional connectivity in major depression and schizophrenia.

BACKGROUND: Major depressive disorder (MDD) and schizophrenia (SZ) are serious psychiatric disorders that, despite exhibiting different diagnostic criteria, exhibit significant overlap regarding the biological and clinical features of affected patients. While prior evidence has shown that interhemispheric functional connectivity (FC) is abnormal in MDD and SZ, the particular similarities and differences that unify and characterize MDD and SZ regarding these interhemispheric FC patterns remain to be characterized. This study was thus designed to conduct an in-depth analysis of MDD- and SZ-related patterns of interhemispheric FC. METHODS: This study enrolled MDD patients, SZ patients, and normal control (NC) individuals (n = 36 each). Resting-state functional MRI (rs-fMRI) studies of these patients were conducted, after which voxel-mirrored homotopic connectivity (VMHC) was used to analyze the preprocesses rs-fMRI data. The VMHC values in these different values were then compared through one-way ANOVAs and post hoc analyses. RESULTS: Significant differences were observed in both the striatum and middle frontal gyrus (MFG) when comparing these three groups. Through pairwise comparisons, MDD patients but not SZ patients exhibited reduced MFG VMHC values relative to the NC individuals. Conversely, striatum VMHC values significantly increased in SZ patients relative to NC individuals and MDD patients. CONCLUSION: These results support the interhemispheric functional disconnection hypothesis as a basis for the pathogenesis of MDD and SZ. The observed differences in interhemispheric FC in the MFG and striatum of MDD and SZ patients will offer a neuroimaging basis that can aid in the differential diagnosis of these debilitating conditions.

DUSP22 suppresses tumor progression by directly dephosphorylating AKT in non-small cell lung cancer.

Protein kinase B (AKT) plays a pivotal in regulating cell migration, proliferation, apoptosis, and survival, making it a prominent target for anticancer therapy. While the kinase activity of AKT has been extensively explored, its dephosphorylation have largely remained uncharted. Herein, we aimed to unravel the molecular mechanisms governing AKT dephosphorylation, with a specific emphasis on dual-specificity phosphatases DUSP22. Our investigation sought to shed light on the potential of DUSP22 as a potential therapeutic target for non-small cell lung cancer (NSCLC). To determine the expression level of DUSP22 in NSCLC cell lines, the gene expression profiling interactive analysis (GEPIA) and Oncomine database were searched. Additionally, the effect of DUSP22 on patient survival was analyzed with Kaplan-Meier database. Antitumor effects of DUSP22 were tested in A549 and H1299 cell lines. Experiments are based on: (1) cell viability determined by the cell counting kit-8 assay and colony-formation assay; (2) cell migratory ability assessed through the scratch assay and the transwell migration assay; (3) the mechanism behind the antitumor effects of DUSP22 dissected with co-immunoprecipitation (Co-IP) and in vitro kinase assays. Our study revealed a significant downregulation of DUSP22 in both NSCLC cell lines and tissues. Meanwhile, survival rate analysis results demonstrated that reduced DUSP22 expression was correlated with poorer overall survival in lung cancer patients. Moreover, DUSP22 exhibited an inhibitory effect on the cell viability and migratory capacity of A549 and H1299 cells. This inhibition was accompanied by the decrease in the phosphorylation of AKT and p38. Mechanistically, the phosphatase domain of DUSP22 interacted with AKT, resulting in the inhibition of AKT phosphorylation. This inhibitory effect was contingent upon the phosphatase activity of DUSP22. These findings provide compelling evidence that DUSP22 directly interacted with AKT, leading to the dephosphorylation of AKT at S473 and T308 residues, ultimately curbing the proliferation and migration of lung cancer cells. Additionally, our results also highlight a preclinical rationale for utilizing DUSP22 as a prognostic marker in NSCLC.

The role of SIRT3 in mediating the cognitive deficits and neuroinflammatory changes associated with a developmental animal model of schizophrenia.

The neuroinflammatory state may contribute to the pathogenesis of many mental disorders including schizophrenia. Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for activation of proteins involved in mitochondria quality control, such as Sirtuin3 (SIRT3). Our previous study has found that NAD+ supplement could rescue early life stress (ELS)-induced neuroinflammation and down-regulation of SIRT3 in adult offspring. However, it is unclear whether SIRT3 is the key to the neuroprotective effects of NAD+ supplement in this animal model of schizophrenia. The present study used 24 h maternal separation (MS) as ELS to Wistar rat pups on the postnatal day (PND) 9. Schizophrenia-like behaviors and memory impairments were detected by behavioral tests. Microglial activation, pro-inflammatory cytokine expression, and NAD+/SIRT3 expression were detected in the prefrontal cortex and hippocampus. Meanwhile, NAM (a precursor of NAD+), and the SIRT3 activator Honokiol (HNK), and the SIRT3 inhibitor 3-TYP were used as an intervention in vivo. Our results showed that ELS could induce schizophrenia-like behaviors and M1 microglial activation, NAD+ decline, lower expression of SIRT3, and increased acetylated superoxide dismutase 2 expression at the adult stage. NAD+ supplement or HNK administration could block this process and normalize the behavioral alterations of the MS animals. 3-TYP administration in the control group and the NAM-treated MS rats caused M1 microglial activation and cognitive deficits. Our results demonstrated that SIRT3 mediated the stabilizing effect of NAD+ on normalizing M1 microglial activation and behavioral phenotypes in MS rats.

Exploration of Inflammatory Biomarkers and Psychological Cardiovascular Disease Risk Factors Among Community Dwelling Adults: A Gender Comparison Study.

Patients with rheumatic disease (RD) are at high risk for cardiovascular disease (CVD), which is the leading non-communicable chronic disease cause of death worldwide. Inflammatory biomarkers and psychological health status are reliable predictors of CVD in patients with RD. The primary aim of this study was to compare the inflammatory biomarkers and psychological CVD risk factors (CRFs) between a group of community-dwelling adults with RD and CRFs and a group of their peers with CRFs only. The secondary aim of this study was to analyze and compare the collected data by gender in the RD group. Data were collected and analyzed from 355 participants, with the 135 participants with physician-diagnosed RD assigned to the RD group and the remainder (n = 220) assigned to the comparison group. The measures used included a demographic datasheet, medical information, serum homocysteine (Hcy) levels, high sensitive C-reactive protein (hs-CRP) levels, and depression and global sleep-quality scale scores. The RD group had higher ratios of hypertension and depression diagnoses than the comparison group. The gender analysis of the RD group found significantly more-severe sleep disturbances in women than men and a significantly higher mean value of Hcy in men than women. The women in the RD group were significantly older, less educated, and less employed than their male counterparts and thus may be presumed to at higher risk of health illiteracy. Gender-tailored interventions to modify the risk factors of CVD identified in this study for patients with RD are recommended.

High-quality nursing benefits patients with emergency trauma undergoing surgical debridement and suturing and helps relieve pain.

OBJECTIVE: This study was designed to explore the clinical value of high-quality nursing in patients with emergency trauma undergoing surgical debridement and suture and its effects on pain relief. METHODS: The clinical data of 181 patients with emergency trauma who received surgical debridement and suture in Shangrao Municipal Hospital from January 2020 to December 2021 were analyzed retrospectively. Among them, patients who received routine nursing were assigned to a control group (n=85), and those who received high-quality nursing were assigned to an observation group (n=96). The neurologic rating scale (NRS) was adopted to evaluate the pain in the two groups before operation and at 1 d, 3 d, and 7 d after the operation. The rescue time and examination time in the two groups were recorded and analyzed, and the effective rescue rate and postoperative complications of the two groups were compared. In addition, the MOS 36-item short-form health survey (SF-36) was employed to evaluate the quality of life (QoL) of the two groups, and a self-designed nursing satisfaction questionnaire was adopted to evaluate and compare the nursing satisfaction in the two groups. The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate the status of anxiety and depression. In addition, independent risk factors for poor prognosis were analyzed by multivariate logistic regression. RESULTS: Before surgery and at 1 d after surgery, the NRS scores of the two groups were not significantly different, while at 3 d and 7 d after surgery, the NRS scores decreased significantly in both groups, and the observation group exhibited significantly lower NRS scores than the control group on these two days. There was no significant difference in the SAS and SDS scores between the two groups before nursing, while after nursing, the scores decreased significantly in both groups, and the decreases in the observation group were more significant than those of the control group. The observation group consumed a significantly shorter rescue time and examination time than the control group, and the observation group showed a significantly higher effective rescue rate than the control group. In addition, the observation group demonstrated a lower incidence of complications than the control group after surgery, and a higher QoL score than the control group. Moreover, the observation group exhibited a higher nursing satisfaction rate than the control group. Age, time from injury to medical treatment, and injury site were risk factors impacting the prognosis of patients, and age was an independent risk factor for prognosis. CONCLUSION: In patients with emergency trauma undergoing surgical debridement and suture, high-quality nursing can substantially contribute to lower pain, shorter rescue time, higher success rate of rescue, better QoL, and nursing satisfaction, and fewer complications. Therefore, high-quality nursing is worthy of clinical application.

A Machine Learning Analysis of Big Metabolomics Data for Classifying Depression: Model Development and Validation.

BACKGROUND: Many metabolomics studies of depression have been performed, but these have been limited by their scale. A comprehensive in silico analysis of global metabolite levels in large populations could provide robust insights into the pathological mechanisms underlying depression and candidate clinical biomarkers. METHODS: Depression-associated metabolomics was studied in 2 datasets from the UK Biobank database: participants with lifetime depression (N = 123,459) and participants with current depression (N = 94,921). The Whitehall II cohort (N = 4744) was used for external validation. CatBoost machine learning was used for modeling, and Shapley additive explanations were used to interpret the model. Fivefold cross-validation was used to validate model performance, training the model on 3 of the 5 sets with the remaining 2 sets for validation and testing, respectively. Diagnostic performance was assessed using the area under the receiver operating characteristic curve. RESULTS: In the lifetime depression and current depression datasets and sex-specific analyses, 24 significantly associated metabolic biomarkers were identified, 12 of which overlapped in the 2 datasets. The addition of metabolic features slightly improved the performance of a diagnostic model using traditional (nonmetabolomics) risk factors alone (lifetime depression: area under the curve 0.655 vs. 0.658 with metabolomics; current depression: area under the curve 0.711 vs. 0.716 with metabolomics). CONCLUSIONS: The machine learning model identified 24 metabolic biomarkers associated with depression. If validated, metabolic biomarkers may have future clinical applications as supplementary information to guide early and population-based depression detection.

An outcomes-based module education via flipped classroom enhances undergraduate oral histopathology learning.

INTRODUCTION: Oral histopathology is a bridge course connecting oral basic medicine and clinical dentistry. However, the application of outcomes-based education via flipped classroom (FC) in oral histopathology has not been well explored. This study has assessed the efficacy of outcomes-based education via FC in undergraduate oral histopathology module learning in Nanjing Medical University of China. MATERIALS AND METHODS: A total of 214 third-year students were enrolled and assigned to the FC group of the batch 2022-23 (n = 110) and the traditional classroom (TC) group of the batch 2021-22 (n = 104) to participate the oral histopathology sessions respectively in the study. The FC group were required to preview the online course materials pre-class, followed by in-class quizz, in-class interactive group discussion, and slides microscopic observation. The outcomes-based formative and summative assessments for FC were designed. The TC group attended traditional laboratory class for the same glass slides microscopic observation. In addition, a questionnaire was performed to investigate the satisfaction of learning. Along with this, the performances of FC group in written theory tests and oral histopathology slide tests were compared with TC group. RESULTS: Students in the FC group gained significantly final higher scores of the course than those in the TC group (score: 83.79 ± 11 vs. 76.73 ± 10.93, P<0.0001). Data from the student questionnaires indicated a preference for outcomes-based module education via FC. In the questionnaires, most students considered outcomes-based module education via FC to be beneficial to learning motivation, knowledge comprehension, critical thinking and teamwork. FC group had a higher level of satisfaction with oral histopathology teaching than TC group (satisfaction score: 4.599 ± 0.1027 vs. 4.423 ± 0.01366, P<0.01). CONCLUSION: An outcomes-based module education via FC has a promising effect on undergraduate oral histopathology education.

The mechanism effects of root exudate on microbial community of rhizosphere soil of tree, shrub, and grass in forest ecosystem under N deposition.

Forests are composed of various plant species, and rhizosphere soil microbes are driven by root exudates. However, the interplay between root exudates, microbial communities in the rhizosphere soil of canopy trees, understory shrubs, grasses, and their responses to nitrogen (N) deposition remains unclear. Pinus tabulaeformis, Rosa xanthina, and Carex lancifolia were used to investigate root exudates, rhizosphere soil microbial communities, and their responses to N application in forest ecosystem. Root exudate abundances of P. tabulaeformis were significantly higher than that of R. xanthina and C. lancifolia, with carbohydrates dominating P. tabulaeformis and R. xanthina root exudates, fatty acids prevailing in C. lancifolia root exudates. Following N application, root exudate abundances of P. tabulaeformis and R. xanthina initially increased before decreasing, whereas those of C. lancifolia decreased. Microbial number of rhizosphere soil of C. lancifolia was higher than that of P. tabulaeformis and R. xanthina, but there was insignificant variation of rhizosphere soil microbial diversity among plant species. N application exerted promotional and inhibitory impacts on bacterial and fungal numbers, respectively, while bacterial and fungal diversities were increased by N application. Overall, N application had negative effects on root exudates of P. tabulaeformis, inhibiting rhizosphere soil microbial populations. N application suppressed rhizosphere soil microbial populations by increasing root exudates of R. xanthina. Conversely, N application elevated nutrient content in the rhizosphere soil of C. lancifolia, reducing root exudates and minimally promoting microbial populations. This study highlights the importance of understory vegetation in shaping soil microbial communities within forests under N deposition.