The Prevalence of Hyperuricemia and the Association Between Hyperuricemia and Age in Patients with Psychiatric Disorders to a General Hospital: A Cross-Section Study.

Purpose: In clinical work, it has been found that the prevalence of hyperuricemia (HUA) is significantly higher in younger patients with psychiatric disorders, but there are few studies in this area. The present study aims to evaluate the prevalence of HUA and the relationship between the HUA and age in hospitalized patients with psychiatric disorders in the real world, and to provide a theoretical basis for clinical staff to pay attention to the metabolic indicators of younger patients and for future related studies. Methods: This is a cross-sectional evaluation of a cohort of 1761 patients with psychiatric disorders of hospitalized. The categories of disorders designed for study included: Depression, Bipolar disorder, Schizophrenia, Anxiety, Obsessive-Compulsive disorder, Acute and transient psychotic disorder, Dissociative(conversion) disorders, Conduct disorders and Tic disorders. In addition, based on age, the participants are stratified into three groups. The authors used Kruskal-Wallis tests, chi-square tests, and multiple linear logistic regression to verify the relationship between HUA and age among hospitalized patients with psychiatric disorders. Results: Overall, the estimated prevalence of HUA was 35.4%. The prevalence of HUA was significantly higher in individuals with 17 years and under compared to those with 45 years and above (P < 0.001). After adjusting for confounders, the prevalence of HUA remained higher at 17 years and under than at 45 years and above. Bipolar disorder can lead to an increased prevalence of HUA (P<0.05). Conclusion: The prevalence of HUA was higher in hospitalized patients with psychiatric disorders, and the prevalence was inversely proportional to age.

Hydrangea-like TiO2/Bi2MoO6 porous nanoflowers triggering highly sensitive electrochemical immunosensing to tumor marker.

Rapid and sensitive detection of carcinoembryonic antigen (CEA) is of great significance for cancer patients. Here, molybdenum (Mo) was doped into bismuth oxide (Bi2O3) by one-pot hydrothermal method forming porous tremella Bi2MoO6 nanocomposites with a larger specific surface area than the spherical structure. Then, a new kind of hydrangea-like TiO2/Bi2MoO6 porous nanoflowers (NFs) was prepared by doping titanium into Bi2MoO6, where titanium dioxide (TiO2) grew in situ on the surface of Bi2MoO6 nanoparticles (NPs). The hydrangea-like structure provides larger specific surface area, higher electron transfer ability and biocompatibility as well as more active sites conducive to the attachment of anti-carcinoembryonic antigen (anti-CEA) to TiO2/Bi2MoO6 NFs. A novel label-free electrochemical immunosensor was then constructed for the quantitative detection of CEA using TiO2/Bi2MoO6 NFs as sensing platform, showing a good linear relationship with CEA in the concentration range 1.0 pg/mL ~ 1.0 mg/mL and a detection limit of 0.125 pg/mL (S/N = 3). The results achieved with the designed immunosensor are comparable with many existing immunosensors used for the detection of CEA in real samples.

Advancing e-commerce user purchase prediction: Integration of time-series attention with event-based timestamp encoding and Graph Neural Network-Enhanced user profiling.

In recent years, the global e-commerce landscape has witnessed rapid growth, with sales reaching a new peak in the past year and expected to rise further in the coming years. Amid this e-commerce boom, accurately predicting user purchase behavior has become crucial for commercial success. We introduce a novel framework integrating three innovative approaches to enhance the prediction model's effectiveness. First, we integrate an event-based timestamp encoding within a time-series attention model, effectively capturing the dynamic and temporal aspects of user behavior. This aspect is often neglected in traditional user purchase prediction methods, leading to suboptimal accuracy. Second, we incorporate Graph Neural Networks (GNNs) to analyze user behavior. By modeling users and their actions as nodes and edges within a graph structure, we capture complex relationships and patterns in user behavior more effectively than current models, offering a nuanced and comprehensive analysis. Lastly, our framework transcends traditional learning strategies by implementing advanced meta-learning techniques. This enables the model to autonomously adjust learning parameters, including the learning rate, in response to new and evolving data environments, thereby significantly enhancing its adaptability and learning efficiency. Through extensive experiments on diverse real-world e-commerce datasets, our model demonstrates superior performance, particularly in accuracy and adaptability in large-scale data scenarios. This study not only overcomes the existing challenges in analyzing e-commerce user behavior but also sets a foundation for future exploration in this dynamic field. We believe our contributions provide significant insights and tools for e-commerce platforms to better understand and cater to their users, ultimately driving sales and improving user experiences.

Zinc-ion Anchor Induced Highly Reversible Zn Anodes for High Performance Zn-ion Batteries.

Unstable Zn interface with serious detrimental parasitic side-reactions and uncontrollable Zn dendrites severely plagues the practical application of aqueous zinc-ion batteries. The interface stability was closely related to the electrolyte configuration and Zn2+ depositional behavior. In this work, a unique Zn-ion anchoring strategy is originally proposed to manipulate the coordination structure of solvated Zn-ions and guide the Zn-ion depositional behavior. Specifically, the amphoteric charged ion additives (denoted as DM), which act as zinc-ion anchors, can tightly absorb on the Zn surface to guide the uniform zinc-ion distribution by using its positively charged -NR4+ groups. While the negatively charged -SO3- groups of DM on the other hand, reduces the active water molecules within solvation sheaths of Zn-ions. Benefiting from the special synergistic effect, Zn metal exhibits highly ordered and compact (002) Zn deposition and negligible side-reactions. As a result, the advanced Zn||Zn symmetric cell delivers extraordinarily 7000 hours long lifespan (0.25 mAh cm-2, 0.25 mAh cm-2). Additionally, based on this strategy, the NH4V4O10llZn pouch-cell with low negative/positive capacity ratio (N/P ratio=2.98) maintains 80.4% capacity retention for 180 cycles. A more practical 4 cm*4 cm sized pouch-cell could be steadily cycled in a high output capacity of 37.0 mAh over 50 cycles.

Survival mechanisms of circulating tumor cells and their implications for cancer treatment.

Metastasis remains the principal trigger for relapse and mortality across diverse cancer types. Circulating tumor cells (CTCs), which originate from the primary tumor or its metastatic sites, traverse the vascular system, serving as precursors in cancer recurrence and metastasis. Nevertheless, before CTCs can establish themselves in the distant parenchyma, they must overcome significant challenges present within the circulatory system, including hydrodynamic shear stress (HSS), oxidative damage, anoikis, and immune surveillance. Recently, there has been a growing body of compelling evidence suggesting that a specific subset of CTCs can persist within the bloodstream, but the precise mechanisms of their survival remain largely elusive. This review aims to present an outline of the survival challenges encountered by CTCs and to summarize the recent advancements in understanding the underlying survival mechanisms, suggesting their implications for cancer treatment.

Millimeter wave-based patient setup verification and motion tracking during radiotherapy.

BACKGROUND: Position verification and motion monitoring are critical for safe and precise radiotherapy (RT). Existing approaches to these tasks based on visible light or x-ray are suboptimal either because they cannot penetrate obstructions to the patient's skin or introduce additional radiation exposure. The low-cost mmWave radar is an ideal solution for these tasks as it can monitor patient position and motion continuously throughout the treatment delivery. PURPOSE: To develop and validate frequency-modulated continuous wave (FMCW) mmWave radars for position verification and motion tracking during RT delivery. METHODS: A 77 GHz FMCW mmWave module was used in this study. Chirp Z Transform-based (CZT) algorithm was developed to process the intermediate frequency (IF) signals. Absolute distances to flat Solid Water slabs and human shape phantoms were measured. The accuracy of absolute distance and relative displacement were evaluated. RESULTS: Without obstruction, mmWave based on the CZT algorithm was able to detect absolute distance within 1 mm for a Solid Water slab that simulated the reflectivity of the human body. Through obstructive materials, the mmWave device was able to detect absolute distance within 5 mm in the worst case and within 3.5 mm in most cases. The CZT algorithm significantly improved the accuracy of absolute distance measurement compared with Fast Fourier Transform (FFT) algorithm and was able to achieve submillimeter displacement accuracy with and without obstructions. The surface-to-skin distance (SSD) measurement accuracy was within 8 mm in the anterior of the phantom. CONCLUSIONS: With the CZT signal processing algorithm, the mmWave radar is able to measure the absolute distance to a flat surface within 1 mm. But the absolute distance measurement to a human shape phantom is as large as 8 mm at some angles. Further improvement is necessary to improve the accuracy of SSD measurement to uneven surfaces by the mmWave radar.

FvMYB108, a MYB Gene from Fragaria vesca, Positively Regulates Cold and Salt Tolerance of Arabidopsis.

MYB (myoblast) protein comes in large quantities and a wide variety of types and plays a role in most eukaryotes in the form of transcription factors (TFs). One of its important functions is to regulate plant responses to various stresses. However, the role of MYB TFs in regulating stress tolerance in strawberries is not yet well understood. Therefore, in order to investigate the response of MYB family members to abiotic stress in strawberries, a new MYB TF gene was cloned from Fragaria vesca (a diploid strawberry) and named FvMYB108 based on its structural characteristics and evolutionary relationships. After a bioinformatics analysis, it was determined that the gene belongs to the R2R3-MYB subfamily, and its conserved domain, phylogenetic relationships, predicted protein structure and physicochemical properties, subcellular localization, etc. were analyzed. After qPCR analysis of the expression level of FvMYB108 in organs, such as the roots, stems, and leaves of strawberries, it was found that this gene is more easily expressed in young leaves and roots. After multiple stress treatments, it was found that the target gene in young leaves and roots is more sensitive to low temperatures and salt stimulation. After these two stress treatments, various physiological and biochemical indicators related to stress in transgenic Arabidopsis showed corresponding changes, indicating that FvMYB108 may be involved in regulating the plant's ability to cope with cold and high-salt stress. Further research has found that the overexpression of this gene can upregulate the expression of AtCBF1, AtCOR47, AtERD10, and AtDREB1A related to low-temperature stress, as well as AtCCA1, AtRD29a, AtP5CS1, and AtSnRK2.4 related to salt stress, enhancing the ability of overexpressed plants to cope with stress.

Long-term saline water irrigation affected soil carbon and nitrogen cycling functional profiles in the cotton field.

Saline water irrigation (SWI) plays an important role in alleviating water resource shortages. At the same time, the salt input of irrigation water affects soil microorganisms which participate in various ecological processes of terrestrial ecosystems. However, the responses of soil microbial functional potential to long-term SWI remains unclear. Therefore, Metagenomics method was utilized in cotton fields under long-term SWI to reveal the microbial functional profiles associated with soil carbon and nitrogen cycles. Results indicated that SWI impacted the microbial functional profiles of soil carbon and nitrogen cycles in the cotton fields significantly. Especially, irrigation water salinity inhibited the relative abundances of sacC and vanB, which are soil carbon degradation genes. SWI also affected the functional gene abundance of nitrogen degradation, dissimilatory nitrate reduction, and nitrification. Moreover, SWI significantly increased the abundance of Candidatus_Cloacimonetes in both carbon and nitrogen cycles. In the discussion, we used person analysis found that soil salinity, pH, and ammonium nitrogen were important factors affecting the abundance of functional genes and microbial taxa. Overall, this study indicated that long-term SWI significantly influenced specific microbial functional genes and taxa abundance, which may lead to predictable outcomes for soil carbon and nitrogen cycling, and is of great importance in exploring the impact of SWI on soil environments.

The Pharmacogenetic Variability Associated With the Pharmacokinetics and Pharmacodynamics of Rivaroxaban in Healthy Chinese Subjects: A National Multicenter Exploratory Study.

PURPOSE: This study aimed to explore the pharmacogenetic variability associated with the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in healthy Chinese subjects. METHODS: This was a multicenter study that included 304 healthy adults aged 18 to 45 years with unknown genotypes. All participants were administered a single dose of rivaroxaban at 10 mg, 15 mg, or 20 mg. PK and PD parameters were measured, and exome-wide association analysis was conducted. FINDINGS: Sixteen SNPs located on 11 genes influenced the AUC0-t. Among these, the 3 most influential genes were MiR516A2, PARP14, and MIR618. Thirty-six SNPs from 28 genes were associated with the PD of rivaroxaban. The 3 most influential genes were PKNOX2, BRD3, and APOL4 for anti-Xa activity, and GRIP2, PLCE1, and MLX for diluted prothrombin time (dPT). Among them, BRD3 played an important role in both the PK and PD of rivaroxaban. Anti-Xa activity (ng/mL) differed significantly among subjects with BRD3 rs467387: 145.1 ± 55.5 versus 139.9 ± 65.1 versus 164.0 ± 68.6 for GG, GA, and AA carriers, respectively (P = 0.0002). IMPLICATIONS: This study found that that the regulation of the BRD3 gene might affect the PK and PD of rivaroxaban, suggesting that it should be studied as a new pharmacologic target. The correlation between this gene locus and clinical outcomes has yet to be verified in patients undergoing clinical treatment.

Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides.

Quinoxaline 1,4-di-N-Oxides (QdNOs) have been used as synthetic antimicrobial agents in animal husbandry and aquaculture. The metabolism and potential toxicity have been also concerns in recently years. The metabolism investigations showed that there were 8 metabolites of Carbadox (CBX), 34 metabolites of Cyadox (CYA), 33 metabolites of Mequindox (MEQ), 35 metabolites of Olaquindox (OLA), and 56 metabolites of Quinocetone (QCT) in different animals. Among them, Cb3 and Cb8, M6, and O9 are metabolic residual markers of CBX, MEQ and OLA, which are associated with N → O reduction. Toxicity studies revealed that QdNOs exhibited severe tumorigenicity, cytotoxicity, and adrenal toxicity. Metabolic toxicology showed that toxicity of QdNOs metabolites might be related to the N → O group reduction, and some metabolites exhibited higher toxic effects than the precursor, which could provide guidance for further research on the metabolic toxicology of QdNOs and provide a wealth of information for food safety evaluation.

Prediction of the benign and malignant nature of masses in COPD background based on Habitat-based enhanced CT radiomics modeling: A preliminary study.

BACKGROUND: It is difficult to differentiate between chronic obstructive pulmonary disease (COPD)-peripheral bronchogenic carcinoma (COPD-PBC) and inflammatory masses. OBJECTIVE: This study aims to predict COPD-PBC based on clinical data and preoperative Habitat-based enhanced CT radiomics (HECT radiomics) modeling. METHODS: A retrospective analysis was conducted on clinical imaging data of 232 cases of postoperative pathological confirmed PBC or inflammatory masses. The PBC group consisted of 82 cases, while the non-PBC group consisted of 150 cases. A training set and a testing set were established using a 7:3 ratio and a time cutoff point. In the training set, multiple models were established using clinical data and radiomics texture changes within different enhanced areas of the CT mass (HECT radiomics). The AUC values of each model were compared using Delong's test, and the clinical net benefit of the models was tested using decision curve analysis (DCA). The models were then externally validated in the testing set, and a nomogram of predicting COPD-PBC was created. RESULTS: Univariate analysis confirmed that female gender, tumor morphology, CEA, Cyfra21-1, CT enhancement pattern, and Habitat-Radscore B/C were predictive factors for COPD-PBC (P< 0.05). The combination model based on these factors had significantly higher predictive performance [AUC: 0.894, 95% CI (0.836-0.936)] than the clinical data model [AUC: 0.758, 95% CI (0.685-0.822)] and radiomics model [AUC: 0.828, 95% CI (0.761-0.882)]. DCA also confirmed the higher clinical net benefit of the combination model, which was validated in the testing set. The nomogram developed based on the combination model helped predict COPD-PBC. CONCLUSION: The combination model based on clinical data and Habitat-based enhanced CT radiomics can help differentiate COPD-PBC, providing a new non-invasive and efficient method for its diagnosis, treatment, and clinical decision-making.

The joint effects of prenatal exposure to PM2.5 constituents and reduced fetal growth on children's accelerated growth in the first 3 years: a birth cohort study.

BACKGROUND: Prenatal fine particulate matter (PM2.5) constituents exposure and reduced fetal growth may be risk factors for accelerated growth in early childhood, an important indicator for lifelong health. OBJECTIVE: The study investigated whether the joint effects are present between PM2.5 constituents and reduced fetal growth. METHODS: The study was embedded in a birth cohort in China, including 5424 mother-child pairs. Prenatal PM2.5 and its constituents' [organic carbon (OC), elementary carbon (EC), ammonium (NH4+), nitrate (NO3-), and sulfate (SO42-)] concentrations were estimated based on maternal residential addresses. Fetal growth was evaluated by fetal growth trajectory in utero and preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). Children's accelerated growth was defined as body mass index (BMI) Z-score change of >0.67 between birth and 3 years. Generalized logistic regression was used to analyze the effects of prenatal PM2.5 constituents exposure and fetal growth on children's accelerated growth. Joint effect was tested on multiplicative scale and additive scale with the relative excess risk due to interaction (RERI). RESULTS: Children with lower fetal growth trajectory, PTB, LBW, and SGA had increased odds of children's accelerated growth, with odds ratios (ORs) ranging from 1.704 to 11.605. Compared with lower exposure (≤median), higher exposure (>median) of PM2.5, OC, and SO42- were significantly associated with increased odds of children's accelerated growth, varying in ORs from 1.163 to 1.478. Prenatal exposure to OC had joint effects with lower fetal growth on children's accelerated growth. We observed that the interaction was statistically significant on an additive scale in OC and lower fetal growth trajectory (RERI: 0.497, 95% CI: 0.033,0.962). IMPACT: Fine particulate matter (PM2.5) is a huge threat to human health worldwide, causing 6.7 million death globally in 2019. According to the theory of DOHaD, prenatal PM2.5 exposure could influence early childhood growth, which is important for lifelong health. We found that prenatal exposure to PM2.5, OC, and SO42- was associated with higher risk of accelerated childhood growth in the first 3 years. More importantly, reduced fetal growth moderated these associations. Our findings highlight the need for policies and interventions on PM2.5 constituents to improve lifelong health, especially for those vulnerable populations with reduced fetal growth.

Electroacupuncture Promotes Angiogenesis in Mice with Cerebral Ischemia by Inhibiting miR-7.

OBJECTIVE: To observe the angiogenesis effect of electroacupuncture (EA) at Shuigou acupoint (GV 26) in the treatment of cerebral ischemia, and explore the value of miRNA-7 (miR-7) in it. METHODS: First, 48 mice were randomly divided into sham operation, middle cerebral artery occlusion (MCAO) model, and EA treatment groups. Then 9 mice were divided into carrier control group, miR-7 knockout group and miR-7 overexpression group (n=3 each group). Finally, 20 mice were divided into model and carrier control group, model and miR-7 knockout group, EA treatment and carrier control group and EA treatment and miR-7 overexpression group, with 3-6 mice in each group. The MCAO model was established in the MCAO and EA groups. Neurological deficit score and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate the severity of cerebral ischemia. Hematoxylin-eosin staining was used to describe basic pathological changes. Immunohistochemistry was used to quantify cerebral microvessel density. Real-time PCR and Western blot were used to detect the expression of miR-7 and its downstream target genes Krüppel-like factor 4/vascular endothelial growth factor (KLF4/VEGF) and angiopoietin-2 (ANG-2) in the ischemic cerebral cortex. RESULTS: After EA, neurological deficit scores and infarction volumes decreased, and the density of cerebral microvessels increased. In the MCAO group, miR-7 expression was higher than that in the sham group (P<0.01). After EA at GV 26, miR-7 expression decreased (P<0.01) and the expression of downstream target genes KLF4/VEGF and ANG-2 increased as compared with the MCAO group (P<0.01). After EA combined with overexpression of miR-7, the expression of downstream target genes KLF4/VEGF and ANG-2 decreased compared to the control EA group (P<0.01). After miR-7 knockdown, the expression of KLF4/VEGF and ANG-2 increased (P<0.05 or P<0.01). CONCLUSIONS: EA could promote angiogenesis in MCAO mice likely by inhibiting the expression of miR-7 and relieving inhibition of downstream target genes KLF4/VEGF and ANG-2.

Microbial communities exhibit distinct diversities and assembly mechanisms in rainwater and tap-water storage systems.

Roof-harvested rainwater stored for potable and nonpotable usages represent a clean and sustainable water supply resource. However, the microbial dynamics and mechanisms of community assembly in long-termed operated rainwater storage systems remain elusive. In this study, characteristics of microbial communities in different habitats were systematically compared within rainwater and tap-water simulated storage systems (SWSSs) constructed with different tank materials (PVC, stainless steel and cement). Distinct microbial communities were observed between rainwater and tap-water SWSSs for both water and biofilm samples (ANOSIM, p < 0.05), with lower diversity indexes noted in rainwater samples. Notably, a divergent potential pathogen profile was observed between rainwater and tap-water SWSSs, with higher relative abundances of potential pathogens noted in rainwater SWSSs. Moreover, tank materials had a notable impact on microbial communities in rainwater SWSSs (ANOSIM, p < 0.05), rather than tap-water SWSSs, illustrating the distinct interplay between water chemistry and engineering factors in shaping the SWSS microbiomes. Deterministic processes contributed predominantly to the microbial community assembly in cement rainwater SWSSs and all tap-water SWSSs, which might be ascribed to the high pH levels in cement rainwater SWSSs and low-nutrient levels in all tap-water SWSSs, respectively. However, microbial communities in the PVC and stainless-steel rainwater SWSSs were mainly driven by stochastic processes. Overall, the results provided insights to the distinct microbial assembly mechanisms and potential health risks in stored roof-harvested rainwater, highlighting the importance of developing tailored microbial management strategies for the storage and utilization of rainwater.

Pathogenic mycobacterium upregulates cholesterol 25-hydroxylase to promote granuloma development via foam cell formation.

Pathogenic mycobacteria orchestrate the complex cell populations known as granuloma that is the hallmark of tuberculosis. Foam cells, a lipid-rich cell-type, are considered critical for granuloma formation; however, the causative factor in foam cell formation remains unclear. Atherosclerosis is a chronic inflammatory disease characterized by the abundant accumulation of lipid-laden-macrophage-derived foam cells during which cholesterol 25-hydroxylase (CH25H) is crucial in foam cell formation. Here, we show that M. marinum (Mm), a relative of M. tuberculosis, induces foam cell formation, leading to granuloma development following CH25H upregulation. Moreover, the Mm-driven increase in CH25H expression is associated with the presence of phthiocerol dimycocerosate, a determinant for Mm virulence and integrity. CH25H-null mice showed decreased foam cell formation and attenuated pathology. Atorvastatin, a recommended first-line lipid-lowering drug, promoted the elimination of M. marinum and concomitantly reduced CH25H production. These results define a previously unknown role for CH25H in controlling macrophage-derived foam cell formation and Tuberculosis pathology.

Metabolic subtypes and immune landscapes in esophageal squamous cell carcinoma: prognostic implications and potential for personalized therapies.

BACKGROUND: This study aimed to identify metabolic subtypes in ESCA, explore their relationship with immune landscapes, and establish a metabolic index for accurate prognosis assessment. METHODS: Clinical, SNP, and RNA-seq data were collected from 80 ESCA patients from the TCGA database and RNA-seq data from the GSE19417 dataset. Metabolic genes associated with overall survival (OS) and progression-free survival (PFS) were selected, and k-means clustering was performed. Immune-related pathways, immune infiltration, and response to immunotherapy were predicted using bioinformatic algorithms. Weighted gene co-expression network analysis (WGCNA) was conducted to identify metabolic genes associated with co-expression modules. Lastly, cell culture and functional analysis were performed using patient tissue samples and ESCA cell lines to verify the identified genes and their roles. RESULTS: Molecular subtypes were identified based on the expression profiles of metabolic genes, and univariate survival analysis revealed 163 metabolic genes associated with ESCA prognosis. Consensus clustering analysis classified ESCA samples into three distinct subtypes, with MC1 showing the poorest prognosis and MC3 having the best prognosis. The subtypes also exhibited significant differences in immune cell infiltration, with MC3 showing the highest scores. Additionally, the MC3 subtype demonstrated the poorest response to immunotherapy, while the MC1 subtype was the most sensitive. WGCNA analysis identified gene modules associated with the metabolic index, with SLC5A1, NT5DC4, and MTHFD2 emerging as prognostic markers. Gene and protein expression analysis validated the upregulation of MTHFD2 in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA. CONCLUSION: The established metabolic index and identified metabolic genes offer potential for prognostic assessment and personalized therapeutic interventions for ESCA, underscoring the importance of targeting metabolism-immune interactions in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA.

Effects of the ApoE genotype on cognitive function in aging mice fed with a high-fat diet and the protective potential of n-3 polyunsaturated fatty acids.

The ApoE4 allele is the strongest genetic determinant for Alzheimer's disease (AD), while obesity is a strong environmental risk for AD. The modulatory effect of the ApoE genotype on aging-related cognitive function in tandem with a high-fat diet (HFD) remains uncertain. This study aimed to elucidate the effects of ApoE3/ApoE4 genotypes in aged mice exposed to a HFD, and the benefits of n-3 polyunsaturated fatty acids (PUFAs) from fish oil. Remarkably, the HFD led to weight gain and lipid accumulation, more pronounced in ApoE3 mice, while ApoE4 mice experienced exacerbated cerebral insulin resistance, neuroinflammation, and oxidative stress. Critically, n-3 PUFAs modulated the cerebral insulin signaling via the IRS-1/AKT/GLUT4 pathway, mitigated microglial hyperactivity, and reduced IL-6 and MDA levels, thereby counteracting cognitive deficits. These findings highlight the contrasting impacts of ApoE genotypes on aging mice exposed to a HFD, supporting n-3 PUFAs as a strategic nutritional intervention for brain health, especially for ApoE4 carriers.

Prognostic and chemotherapeutic response prediction by proliferation essential gene signature: Investigating POLE2 in bladder cancer progression and cisplatin resistance.

Background: Bladder cancer (BLCA) is the most common genitourinary malignancy. Proliferation essential genes (PEGs) are crucial to the survival of cancer cells. This study aimed to build a PEG signature to predict BLCA prognosis and treatment efficacy. Methods: BLCA PEGs and differentially expressed PEGs were identified using DepMap and TCGA-BLCA datasets, respectively. Based on the prognostic analysis of the differentially expressed PEGs, a PEG model was constructed. Subsequently, we analyzed the relationship between the PEG signature and prognosis of BLCA patients as well as their response to chemotherapy. Finally, we performed random forest analysis to target and functional experiments to validate the most significant PEG which is associated with BLCA progression. CCK-8, invasion, migration, and chemosensitivity assays were performed to assess effects of gene knockdown on BLCA cell proliferation, invasion and migration abilities, and cisplatin chemosensitivity. Results: We screened 10 prognostic PEGs from 201 differentially expressed PEGs and used them to construct a PEG signature model. Patients with high PEG signature score (PEGs-high) exhibited worse OS and lower sensitivity to chemotherapy than those with PEGs-low. We also found significant correlations between the PEG score and previously defined BLCA molecular subtypes. This suggests that the PEG score may effectively predict the molecular subtypes which have distinct clinical outcomes. Random forest analysis revealed that POLE2 (DNA polymerase epsilon subunit 2) was the most significant PEG differentiating BLCA tissue and normal tissue. Bioinformatic analysis and an immunohistochemistry staining assay confirmed that POLE2 was significantly up-regulated in tumor tissues and was associated with poor survival in BLCA patients. Moreover, POLE2 knockdown inhibited the ability of cell clone formation, proliferation, invasion, immigration and IC50 of cisplatin. Conclusion: The PEG signature acts as a potential predictor for prognosis and chemotherapy response in BLCA patients. POLE2 is a key PEG and plays a remarkable role in promoting the malignant progression and cisplatin resistance of BLCA.

Change in neighborhood socioeconomic status and childhood weight status and body composition from birth to adolescence.

BACKGROUND: We aim to assess the associations between the change in neighborhood socioeconomic score (SES) between birth and 6 years and childhood weight status and body composition from 6 to 13 years. METHODS: Data for 3909 children from the Generation R Study, a prospective population-based cohort in the Netherlands were analyzed. The change in neighborhood SES between birth and 6 years was defined as static-high, static-middle, static-low, upward, and downward mobility. Child body mass index (BMI), overweight and obesity (OWOB), fat mass index (FMI) and lean mass index (LMI) were measured at age 6, 10, and 13 years. The associations were explored using generalized estimating equations. The effect modification by child sex was examined. RESULTS: In total, 19.5% and 18.1% of children were allocated to the upward mobility and downward mobility neighborhood SES group. The associations between the change in neighborhood SES and child weight status and body composition were moderated by child sex (p < 0.05). Compared to girls in the static-high group, girls in the static-low group had relatively higher BMI-SDS (ß, 95% confidence interval (CI): 0.24, 0.09-0.40) and higher risk of OWOB (RR, 95% CI: 1.98, 1.35-2.91), together with higher FMI-SDS (ß, 95% CI: 0.27, 0.14-0.41) and LMI-SDS (ß, 95% CI: 0.18, 0.03-0.33). The associations in boys were not significant. CONCLUSIONS: An increased BMI and fat mass, and higher risk of OWOB from 6 to 13 years were evident in girls living in a low-SES neighborhood or moving downward from a high- to a low-SES neighborhood. Support for children and families from low-SES neighborhoods is warranted.

Long-term saline water irrigation has the potential to balance greenhouse gas emissions and cotton yield in North China plain.

Saline water has proven to be one of the alternative sources of freshwater for agricultural irrigation in water-scarce areas. However, the changes in farmland ecology caused by saline water irrigation remain unclear. In this study, six irrigation water salinities (CK: 1.3 dS m-1, S1: 3.4 dS m-1, S2: 7.1 dS m-1, S3: 10.6 dS m-1, S4: 14.1 dS m-1, S5: 17.7 dS m-1) were set in a three-year (2019, 2021-2022) experiment to investigate their effects on soil environment and greenhouse gas emissions in cotton fields under long-term saline water irrigation. Results show that soil salinity in the same layer increased as increasing water salinity. Soil moisture of S3-S5 increased significantly by 4.99-12.94%. There was no significant difference in soil organic matter content between CK and S1. Saline water irrigation increased soil ammonium nitrogen content by 0.57-49.26%, while decreasing nitrate nitrogen content by 1.43-32.03%. Soil CO2 and N2O emissions and CH4 uptake were lower in S1-S5 than in CK at different cotton growth stages. In addition, saline water irrigation reduced the global warming potential by 6.93-53.86%. A structural equation model was developed to show that soil salinity, moisture, and ammonium nitrogen content were negatively correlated with global warming potential, while organic matter and nitrate nitrogen had positive effects on global warming potential. Considering the comprehensive perspectives of gas emissions and cotton yield, irrigation water with salinity less than 10.6 dS m-1 could effectively reduce greenhouse gas emissions from cotton fields while maintaining stable cotton yields in the experimental area and similar region.