Bead-based spontaneous Raman codes for multiplex immunoassay.

In the immunoassay process, for fulfilling the need to identify multiple analytes in a small amount of complex sample matrix, it is desirable to develop highly efficient and specific multiplex suspension array technology. Raman coding strategy offers an attractive solution to code the suspension arrays by simply combing narrow spectral bands with stable signal intensities through solid-phase synthesis on the resin beads. Based on this strategy, we report the bead-based spontaneous Raman codes for multiplex immunoassay. The study resulted in superior selectivity of the Raman-encoded beads for binding with single and multiple analytes, respectively. With the use of mixed types of Raman-encoded immunoassay beads, multiple targets in small amounts of samples were identified rapidly and accurately. By confirming the feasibility of bead-based spontaneous Raman codes for multiplex immunoassay, we anticipate this novel technology to be widely applied in the near future.

Hydromorphone combined with ropivacaine for erector spinae plane block in patients undergoing modified radical mastectomy: A prospective randomized controlled trial.

BACKGROUND: Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast surgery patients. METHODS: In this study, breast cancer patients undergoing modified radical mastectomy were randomized into 3 groups for anesthesia (30 patients in each group): standard general (group C), Erector Spinae Plane Block (ESPB) with ropivacaine (group R), and ESPB with ropivacaine plus hydromorphone (group HR). Diagnosis: Breast cancer patients. Postsurgery, pain levels, IL-6, anesthetic doses, additional analgesia needs, and recovery milestones were compared to evaluate the efficacy of the ESPB enhancements. RESULTS: The 3 groups were not significantly different in baseline characteristics, operation time, number of cases with postoperative nausea, and serum IL-6 concentrations at T1 (the time of being returned to the ward after surgery). At T2 (at 6:00 in the next morning after surgery), the serum IL-6 concentration in group HR was significantly lower than that in groups R and C (P < .05); the intraoperative doses of remifentanil, sufentanil, and propofol were significantly lower in groups HR and R than those in group C (P < .05); Groups HR and R had significantly lower visual analog scale scores at T3 (4 hours postoperatively), T4 (12 hours postoperatively), and T5 (24 hours postoperatively) than those in group C (P < .05); the proportions of patients receiving postoperative remedial analgesia were significantly lower in groups HR and R than in group C (P < .05); groups HR and R had significantly lower proportions of patients with postoperative nausea than group C (P < .05); the time to the first anal exhaust and the time to the first ambulation after surgery were significantly shorter in groups HR and R than those in group C (P < .05). CONCLUSION: Hydromorphone combined with ropivacaine for ESPB achieved a greater postoperative analgesic effect for patients receiving MRM under general anesthesia. The combined analgesia caused fewer adverse reactions and inhibited the expression level of the inflammatory factor IL-6 more effectively, thereby facilitating postoperative recovery. ESPB using hydromorphone with ropivacaine improved pain control post-MRM, reduced adverse effects, and more effectively suppressed IL-6, enhancing recovery.

HIF-2α inhibition disrupts leukemia stem cell metabolism and impairs vascular microenvironment to enhance chronic myeloid leukemia treatment.

Leukemic stem cells (LSCs) in chronic myeloid leukemia (CML) contribute to treatment resistance and disease recurrence. Metabolism regulates LSCs, but the mechanisms remain elusive. Here, we show that hypoxia-inducible factor 2α (HIF-2α) is highly expressed in LSCs in mouse and human CML and increases after tyrosine kinase inhibitor (TKI) treatment. Deletion of HIF-2α suppresses disease progression, reduces LSC numbers, and enhances the efficacy of TKI treatment in BCL-ABL-induced CML mice. Mechanistically, HIF-2α deletion reshapes the metabolic profile of LSCs, leading to increased production of reactive oxygen species (ROS) and apoptosis in CML. Moreover, HIF-2α deletion decreases vascular endothelial growth factor (VEGF) expression, thereby suppressing neovascularization in the bone marrow of CML mice. Furthermore, pharmaceutical inhibition of HIF-2α by PT2399 attenuates disease progression and improves the efficacy of TKI treatment in both mouse and human CML. Overall, our findings highlight the role of HIF-2α in controlling the metabolic state and vascular niche remodeling in CML, suggesting it is a potential therapeutic target to enhance TKI therapy.

Causal relationships between body mass index, low-density lipoprotein and bone mineral density: Univariable and multivariable Mendelian randomization.

SUMMARY: Utilizing the Mendelian randomization technique, this research clarifies the putative causal relationship between body mass index (BMI) andbone mineral density (BMD), and the mediating role of low-density lipoprotein (LDL). The implications of these findings present promising opportunities for enhancing our understanding of complex bone-related characteristics and disorders, offering potential directions for treatment and intervention. OBJECTIVE: The objective of this study is to examine the correlation between BMI and BMD, while exploring the intermediary role of LDL in mediating the causal impact of BMI on BMD outcomes via Mendelian randomization. METHODS: In this study, we employed genome-wide association study (GWAS) data on BMI, LDL, and BMD to conduct a comparative analysis using both univariate and multivariate Mendelian randomization. RESULTS: Our study employed a two-sample Mendelian randomization design. Considering BMI as the exposure and BMD as the outcome, our results suggest that BMI may function as a potential protective factor for BMD (ß = 0.05, 95% CI 1.01 to 1.09, P = 0.01). However, when treating LDL as the exposure and BMD as the outcome, our findings indicate LDL as a risk factor for BMD (ß = -0.04, 95% CI 0.92 to 0.99, P = 0.04). In our multivariate Mendelian randomization (MVMR) model, the combined influence of BMI and LDL was used as the exposure for BMD outcomes. The analysis pointed towards a substantial protective effect of LDL on BMD (ß = 0.08, 95% CI 0.85 to 0.97, P = 0.006). In the analysis of mediation effects, LDL was found to mediate the relationship between BMI and BMD, and the effect was calculated at (ß = 0.05, 95% CI 1.052 to 1.048, P = 0.04). CONCLUSION: Our findings suggest that BMI may be considered a protective factor for BMD, while LDL may act as a risk factor. Moreover, LDL appears to play a mediatory role in the causal influence of BMI on BMD.

Hydrophilic Fraction of Dissolved Organic Matter Largely Facilitated Microplastics Photoaging: Insights from Redox Properties and Reactive Oxygen Species.

Dissolved organic matter (DOM) exists widely in natural water, which inevitably influences microplastic (MP) photoaging. Nevertheless, the impacts of DOM fractions with diverse molecular structures on MP photoaging remain to be elucidated. This study explored the photoaging mechanisms of polylactic acid (PLA)-MPs and polystyrene (PS)-MPs in the presence of DOM and its subfractions (hydrophobic acid (HPOA), hydrophobic neutral (HPON), and hydrophilic (HPI)). Across DOM fractions, HPI exhibited the highest electron accepting capacity (23 µmol e- (mg C)-1) due to its abundant tannin-like species (36.8%) with carboxylic groups, which facilitated more reactive oxygen species generation (particularly hydroxyl radical), leading to the strongest photoaging rate of two MPs by HPI. However, the sequences of bond cleavage during photoaging of each MPs were not clearly shifted as revealed by two-dimensional infrared correlation spectra. Inconspicuous effects on the extent of PS- and PLA-MPs photoaging were observed for HPOA and HPON, respectively. This was mainly ascribed to the occurrence of inhibitory mechanisms (e.g., light-shielding and quenching effect) counteracting the reactive oxygen species-promoting effects. The findings identified the HPI fraction of DOM for promoting PS- and PLA-MPs photoaging rate and first constructed a link among DOM molecular structures, redox properties, and effects on MP photoaging.

Protective effect of Lactiplantibacillus plantarum CCFM8661 against heavy metal mixture-induced liver and kidney injury in mice.

Human health and the ecological balance are both gravely threatened by heavy metal pollution brought on by global industrialization. Probiotics are thought to represent a novel class of medicinal products for reducing heavy metal toxicity. Though simultaneous poisoning of numerous heavy metals is more prevalent, the majority of current studies on probiotics in the treatment of heavy metal poisoning concentrate on a single heavy metal. Thus, a mouse damage model was created in this investigation using five heavy metals (Pb, Cd, Hg, Cr, and As), and Lactiplantibacillus plantarum CCFM8661 was utilized as an intervention therapy. The oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT), antioxidant capacity (T-AOC), and malondialdehyde (MDA), were evaluated in the blood, liver, and kidney tissues of mice throughout the experiment by tracking changes in body weight. Additionally, the amounts of five heavy metals were measured in the liver and kidney tissues. The alleviation of tissue damage and the detoxifying activity of L. plantarum CCFM8661 in mice with combined heavy metal intoxication were assessed by histopathological examination of liver and kidney tissues. Results revealed that during the test period, L. plantarum CCFM8661 significantly reduced the content of MDA and the contents of Pb, Cd, Hg, Cr, and As in liver and kidney tissues, while also significantly increasing weight gain and the activities of SOD, CAT, and T-AOC in mouse blood, liver, and kidney tissues compared to the model group. Mouse liver and kidney tissue damage from combined heavy metal exposure was considerably lessened by L. plantarum CCFM8661 when compared to the model group, according to H&E staining. This study demonstrates that L. plantarum CCFM8661 may be utilized as a useful intervention for the treatment of combined heavy metal poisoning by efficiently reducing the harm that heavy metals do to the body and maintaining bodily health.

Dietary Inflammatory Index and Cognitive Function: Findings from a Cross-Sectional Study in Obese Chinese Township Population from 45 to 75 Years.

Background and Objective: Cognitive dysfunction is highly prevalent in obese people, and food is a key factor in obesity, and dietary inflammatory index (DII) can reflect whether diet has anti-inflammatory or pro-inflammatory potential. In addition, dietary fatty acid consumption is linked to inflammation, obesity, and cognitive impairment. Erythrocyte membrane fatty acids can reflect dietary fatty acid intake. Our hypothesis was that erythrocyte membrane fatty acids might have a significant impact on the relationship between DII and cognition in obese individuals, and we designed experiments to test the hypothesis. Methods: In three villages in Beijing, we collected 579 respondents from individuals 45 to 75 years old and categorized them by body mass index. The Montreal Cognitive Assessment (MoCA) score and DII score was calculated and gas chromatography was used to measure the proportion of erythrocyte membrane fatty acids. The relationship between the DII score and cognition was examined using multiple linear regression and binary logistic regression. Mediation analysis can help to understand the causal chain between variables, deeply explore the internal relationship and mechanism of action between variables. So a multiple chain mediation model was developed to investigate the mediating factors between the DII score and cognitive association. Results: According to adjusted linear regression, higher DII scores were linked to lower MoCA scores in the obese group. The negative correlation between DII score and cognitive function score remains in binary linear regression. We discovered through mediation analysis that erythrocyte membrane fatty acids mediate the detrimental link between DII and cognitive function in obese individuals. Conclusion: We propose that higher DII scores in obese people are associated with a decline in cognitive function. In addition, this effect might be mediated via the fatty acids in the erythrocyte membrane.

Construction of glutathione-responsive paclitaxel prodrug nanoparticles for image-guided targeted delivery and breast cancer therapy.

Paclitaxel (PTX) remains an essential drug in the treatment of breast cancer. To improve metabolic stability and real-time monitoring of drug location, we develop a visualized nano-prodrug. Novel hyaluronic acid (HA)-coated glutathione (GSH)-sensitive chitosan (CS)-based nano-prodrug (HA/TPE-CS-SS-PTX NPs) with aggregation-induced emission effects (AIE) were accomplished. The prodrug NPs (drug loading 29.32%, particle size 105 nm, regular sphericity) exhibit excellent fluorescence stability. The prodrug NPs could target tumor cells with high expression of CD44 and decompose in the presence of high concentrations of glutathione. In vitro evaluations revealed that the prodrug NPs have significant cytotoxicity on 4T1 cells, and due to their excellent AIE characteristics, their position in cells can be tracked. Moreover, the prodrug NPs also shown superior anti-tumor effects in vivo experimental. Overall, the HA/TPE-CS-SS-PTX NPs we constructed have excellent bio-imaging capabilities and can be served as a potential nanomedicine for PTX delivery against breast cancer.

Integration Analysis of Single-Cell Multi-Omics Reveals Prostate Cancer Heterogeneity.

Prostate cancer (PCa) is an extensive heterogeneous disease with a complex cellular ecosystem in the tumor microenvironment (TME). However, the manner in which heterogeneity is shaped by tumors and stromal cells, or vice versa, remains poorly understood. In this study, single-cell RNA sequencing, spatial transcriptomics, and bulk ATAC-sequence are integrated from a series of patients with PCa and healthy controls. A stemness subset of club cells marked with SOX9highARlow expression is identified, which is markedly enriched after neoadjuvant androgen-deprivation therapy (ADT). Furthermore, a subset of CD8+CXCR6+ T cells that function as effector T cells is markedly reduced in patients with malignant PCa. For spatial transcriptome analysis, machine learning and computational intelligence are comprehensively utilized to identify the cellular diversity of prostate cancer cells and cell-cell communication in situ. Macrophage and neutrophil state transitions along the trajectory of cancer progression are also examined. Finally, the immunosuppressive microenvironment in advanced PCa is found to be associated with the infiltration of regulatory T cells (Tregs), potentially induced by an FAP+ fibroblast subset. In summary, the cellular heterogeneity is delineated in the stage-specific PCa microenvironment at single-cell resolution, uncovering their reciprocal crosstalk with disease progression, which can be helpful in promoting PCa diagnosis and therapy.

Analysis of T-lymphocyte subsets and risk factors in children with tuberculosis.

BACKGROUND: Tuberculosis (TB) is not only related to infection but also involves immune factors. This study explores the changes in T-lymphocyte subsets in children with TB who are human immunodeficiency virus (HIV)-negative and examines their relationship using chest computed tomography (CT) scans. Additionally, the study identifies risk factors for severe TB (STB) in children and establishes relevant risk prediction models. METHODS: We recruited 235 participants between 2018 and 2022, comprising 176 paediatric patients with TB who were HIV-negative and 59 age-matched children with bacterial community-acquired pneumonia (CAP). We quantitatively analysed and compared T-lymphocyte subsets between the two groups and among different types of TB infection. Both univariate and multivariate analyses of clinical and laboratory characteristics were conducted to identify independent risk factors for STB in children and to establish a risk prediction model. RESULTS: The absolute counts of CD3, CD4 and CD8 T-cells in children with TB infection decreased significantly compared with bacterial CAP. The percentage of CD8 T-cells increased, whereas the percentage of CD4 T-cells did not change significantly. The absolute count of CD3, CD4 and CD8 T-cells in extrapulmonary TB (EPTB) was significantly higher than in extra-respiratory TB, with unchanged subset percentages. According to chest CT lesion classification, CD4 T-cell counts decreased significantly in S3 compared with S1 or S2, with no significant change in CD3 and CD8 T-cell counts and percentages. No significant differences were observed in lymphocyte subset counts and percentages between S1 and S2. Univariate analyses indicated that factors such as age, symptom duration, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate, prealbumin level, albumin level, globulin level, albumin/globulin (A/G) ratio, high-sensitivity C-reactive protein (Hs-CRP) level and CD4 and CD8 T-cell counts are associated with STB. Multivariate logistic regression analysis revealed that age, Hs-CRP level, NLR, symptom duration and A/G ratio are independent risk factors for STB in children. Increased age, Hs-CRP levels and NLR, along with decreased A/G, correlate with increased susceptibility to STB. A nomogram model, based on these independent risk factors, demonstrated an area under the receiver operating characteristics curve of 0.867 (95% CI: 0.813-0.921). Internal verification confirmed the model's accuracy, with the calibration curve approaching the ideal and the Hosmer-Lemeshow goodness-of-fit test showing consistent results (χ2 = 12.212, p = 0.142). CONCLUSION: In paediatric patients with TB, the absolute counts of all lymphocyte subsets were considerably reduced compared with those in patients with bacterial CAP. Clinicians should consider the possibility of EPTB infection in addition to respiratory infections in children with TB who have higher CD3, CD4 and CD8 T-cell counts than the ERTB group. Furthermore, CD4 T-cell counts correlated closely with the severity of chest CT lesions. Age, symptom duration, A/G ratio, Hs-CRP level and NLR were established as independent risk factors for STB. The nomogram model, based on these factors, offers effective discrimination and calibration in predicting STB in children.

Association of lipid-lowering drugs with osteoarthritis outcomes from a drug-target Mendelian randomization study.

BACKGROUND: Osteoarthritis (OA), a prevalent musculoskeletal disorder, has been suggested to have a potential association with metabolic syndrome, particularly lipid metabolism. Studies exploring the effects of lipid-lowering drugs on OA have yielded conflicting results. OBJECTIVE: This study employed a drug-targeted Mendelian randomization approach to investigate the association between genetically predicted lipid-modulating effects of commonly targeted lipid-lowering agents and the risk of OA, with the aim of providing a theoretical foundation for the use of lipid-lowering drugs in OA treatment. METHODS: Employing Mendelian randomization (MR) analysis, we examined the potential causal relationship between lipid-lowering drugs and OA. Genetic variants associated with LDL cholesterol levels were selected from the GWAS summary data, and a series of statistical analyses, including inverse-variance weighted (IVW), weighted median (WM), and MR-Egger, were performed to estimate causal effects. RESULTS: We observed significant associations between genetically proxied lipid-lowering drug targets and OA risk. Notably, HMGCR-mediated LDL cholesterol showed an association with overall OA of the hip or knee (OR = 0.865, 95%CI: 0.762 to 0.983, p = 0.026, q = 0.07) and knee osteoarthritis specifically (OR = 0.746, 95%CI: 0.639 to 0.871, p = 2.180×10-4, q = 0.004). PCSK9-mediated LDL cholesterol also demonstrated an association with OA of the hip or knee (OR = 0.915, 95%CI: 0.847 to 0.988, p = 0.023, q = 0.07) and knee osteoarthritis (OR = 0.901, 95%CI: 0.821 to 0.990, p = 0.03, q = 0.07). NPC1L1-mediated LDL cholesterol showed a positive association with OA of the hip or knee (OR = 1.460, 95%CI: 1.127 to 1.890, p = 0.004, q = 0.033). Furthermore, LDLR-mediated LDL cholesterol demonstrated an association with OA of the hip or knee (OR = 0.882, 95%CI: 0.788 to 0.988, p = 0.03, q = 0.07) and hip osteoarthritis (OR = 0.867, 95%CI: 0.769 to 0.978, p = 0.02, q = 0.07). CONCLUSIONS: These findings provide preliminary evidence for the potential therapeutic use of lipid-lowering drugs in OA treatment. Further investigation is needed to validate these findings and explore the precise mechanisms underlying the observed associations.

SHP-1 inhibition targets leukaemia stem cells to restore immunosurveillance and enhance chemosensitivity by metabolic reprogramming.

Leukaemia stem cells (LSCs) in acute myeloid leukaemia present a considerable treatment challenge due to their resistance to chemotherapy and immunosurveillance. The connection between these properties in LSCs remains poorly understood. Here we demonstrate that inhibition of tyrosine phosphatase SHP-1 in LSCs increases their glycolysis and oxidative phosphorylation, enhancing their sensitivity to chemotherapy and vulnerability to immunosurveillance. Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-ß-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Moreover, the upregulation of PFKP promotes MYC degradation and, consequently, reduces the immune evasion abilities of LSCs. Overall, our study demonstrates that targeting SHP-1 disrupts the metabolic balance in LSCs, thereby increasing their vulnerability to chemotherapy and immunosurveillance. This approach offers a promising strategy to overcome LSC resistance in acute myeloid leukaemia.

Adjunctive efficacy of Bifidobacterium animalis subsp. lactis XLTG11 for functional constipation in children.

Functional constipation (FC) can seriously affect the physical and mental health of children. The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. lactis XLTG11 in treating FC in children through a randomized, double-blinded, placebo-controlled approach. Eligible children were randomized into either the intervention group (IG, n = 65, receiving conventional treatment with probiotics) or the control group (CG, n = 66, receiving conventional treatment without probiotics). The primary outcome measure was fecal frequency. Fecal gut microbiota analysis and PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) were used to predict gene family abundances based on 16S information. Over the course of treatment, the weekly frequency of feces within each group increased significantly (F = 41.97, p < 0.001). The frequency of feces (times/week (t/w)) in the IG was significantly higher than that in the CG (3.69 ± 2.62 t/w vs.3.18 ± 1.43 t/w, 4.03 ± 2.54 t/w vs. 2.89 ± 1.39 t/w and 3.74 ± 2.36 t/w vs. 2.94 ± 1.18 t/w and 3.45 ± 1.98 vs. 3.17 ± 1.41 t/w for the 1st, 2nd, 3rd, and 4th week after intervention, respectively) (F = 7.60, p = 0.0067). After the intervention, dominate species shifted to Bifidobacterium longum, Bifidobacterium breve, and Escherichia coli in the IG. Additionally, genes related to short-chain fatty acid (SCF) metabolism were upregulated, while methane metabolism was downregulated. Administration of XLTG11 at a dose of 1 × 1010 CFU/day to children increased fecal frequency, induced beneficial changes in gut microbiota, and regulated SCFs and methane metabolism-related genes.

The effectiveness of fire needle therapy in the treatment of recurrent aphthous stomatitis: A systematic review and meta-analysis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is common in clinical practice and imposes both physical and psychological distress on patients. OBJECTIVE: This study aimed to evaluate the clinical effectiveness of fire needle therapy for the treatment of RAS, providing a basis for clinical decision-making. METHODS: Eight databases, in both Chinese and English, were searched from their inception until December 2022. All randomized controlled trials (RCTs) that utilized fire needle therapy, either alone or combined with other treatments for RAS, were considered. Data evaluation and extraction were conducted independently by 2 authors. RESULTS: The revised Cochrane Risk of Bias Version 2 tool was employed to assess the risk of bias in the included RCTs. A meta-analysis was conducted using Review Manager 5.4 and Stata 15.0. Nine RCTs involving 1469 patients were selected for inclusion. The meta-analysis revealed that, compared to a non-fire-needle control group (primarily utilizing vitamin and transfer factor treatments), fire needle therapy for RAS significantly improved the total effective rate (relative risk = 1.25, 95% confidence interval [CI] [1.14, 1.36], P < .00001), reduced the visual analogue scale score (mean difference = -1.68, 95% CI [-1.82, -1.53], P < .0001), diminished the Traditional Chinese Medicine symptom score (standardized mean difference = -1.20, 95% CI [-1.76, -0.65], P < .0001), and shortened the healing time (mean difference = -1.66, 95% CI [-2.73, -0.59], P = .002). Notably, there was no significant difference in the recurrence rate between the groups (relative risk = -0.18, 95% CI [-0.36, 0.01], P = .06). Further subgroup analysis on total efficacy rate was performed based on variables such as experimental group intervention, control group intervention, and duration of therapy to explore potential sources of heterogeneity. CONCLUSION: Fire needle therapy appears to be a clinically effective treatment for RAS, offering benefits such as pain alleviation, symptom improvement based on the Traditional Chinese Medicine parameters, and faster recovery. Nonetheless, the overall quality of the RCTs available raises concerns. Future research, involving high-quality RCTs, is essential to confirm the clinical efficacy and safety of this treatment. Registration number: PROSPERO (CRD42023387973).

Biotoxicity dynamic change and key toxic organics identification of coal chemical wastewater along a novel full-scale treatment process.

It is particularly important to comprehensively assess the biotoxicity variation of industrial wastewater along the treatment process for ensuring the water environment security. However, intensive studies on the biotoxicity reduction of industrial wastewater are still limited. In this study, the toxic organics removal and biotoxicity reduction of coal chemical wastewater (CCW) along a novel full-scale treatment process based on the pretreatment process-anaerobic process-biological enhanced (BE) process-anoxic/oxic (A/O) process-advanced treatment process was evaluated. This process performed great removal efficiency of COD, total phenol, NH4+-N and total nitrogen. And the biotoxicity variation along the treatment units was analyzed from the perspective of acute biotoxicity, genotixicity and oxidative damage. The results indicated that the effluent of pretreatment process presented relatively high acute biotoxicity to Tetrahymena thermophila. But the acute biotoxicity was significantly reduced in BE-A/O process. And the genotoxicity and oxidative damage to Tetrahymena thermophila were significantly decreased after advanced treatment. The polar organics in CCW were identified as the main biotoxicity contributors. Phenols were positively correlated with acute biotoxicity, while the nitrogenous heterocyclic compounds and polycyclic aromatic hydrocarbons were positively correlated with genotoxicity. Although the biotoxicity was effectively reduced in the novel full-scale treatment process, the effluent still performed potential biotoxicity, which need to be further explored in order to reduce environmental risk.

Transcriptomic and metabolomic analyses reveals keys genes and metabolic pathways in tea (Camellia sinensis) against six-spotted spider mite (Eotetranychus Sexmaculatus).

BACKGROUND: Six-spotted spider mite (Eotetranychus sexmaculatus) is one of the most damaging pests of tea (Camellia sinensis). E. sexmaculatus causes great economic loss and affects tea quality adversely. In response to pests, such as spider mites, tea plants have evolved resistance mechanisms, such as expression of defense-related genes and defense-related metabolites. RESULTS: To evaluate the biochemical and molecular mechanisms of resistance in C. sinensis against spider mites, "Tianfu-5" (resistant to E. sexmaculatus) and "Fuding Dabai" (susceptible to E. sexmaculatus) were inoculated with spider mites. Transcriptomics and metabolomics based on RNA-Seq and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) technology were used to analyze changes in gene expression and metabolite content, respectively. RNA-Seq data analysis revealed that 246 to 3,986 differentially expressed genes (DEGs) were identified in multiple compared groups, and these DEGs were significantly enriched in various pathways, such as phenylpropanoid and flavonoid biosynthesis, plant-pathogen interactions, MAPK signaling, and plant hormone signaling. Additionally, the metabolome data detected 2,220 metabolites, with 194 to 260 differentially abundant metabolites (DAMs) identified in multiple compared groups, including phenylalanine, lignin, salicylic acid, and jasmonic acid. The combined analysis of RNA-Seq and metabolomic data indicated that phenylpropanoid and flavonoid biosynthesis, MAPK signaling, and Ca2+-mediated PR-1 signaling pathways may contribute to spider mite resistance. CONCLUSIONS: Our findings provide insights for identifying insect-induced genes and metabolites and form a basis for studies on mechanisms of host defense against spider mites in C. sinensis. The candidate genes and metabolites identified will be a valuable resource for tea breeding in response to biotic stress.

Association between erythrocyte membrane fatty acids and gut bacteria in obesity-related cognitive dysfunction.

Obesity increases the risk of cognitive impairment and dementia, and the gut microbiota can affect brain cognitive function and obesity through a variety of pathways such as the gut-brain axis. This study aimed to discover how fatty acid affect cognitive function by regulating intestinal flora in obesity. Obese subjects were recruited for cognitive function assessment, and participants were divided into obese group with cognitive impairment (MCI, n = 49) and obese cognitively normal group (Non_MCI, n = 55). In the erythrocyte membrane, the proportion of polyunsaturated fatty acids (PUFA), linoleic acid (C18:2 n-6) and arachidonic acid (C20:4 n-6) and n-6/n-3 ratio was higher in the MCI group than in the Non_MCI group. However, the α-linolenic acid (C18:3 n-3) percentage of the erythrocyte membrane was lower in the MCI group. We found that Coriobacteriales_Incertae_Sedis was positively correlated with erythrocyte membrane C20:4 n-6 and n-6 PUFA and negatively correlated with cognitive scores in obese patients. In addition, several of the functional pathways we predicted were significantly different in the MCI and Non_MCI groups. Higher levels of n-6/n-3 polyunsaturated fatty acids ratio in the erythrocyte membranes may influence the inflammatory response in the organism causing obesity induced cognitive damage. Moreover, high levels of n-6/n-3 polyunsaturated fatty acids ratio may also affect the intestinal flora of obese patients, which in turn may affect the cognitive function of obese patients.

Glucocorticoid receptor regulates the epithelial-mesenchymal transition process through GR/ZEB1/E-cad and is involved in breast cancer endocrine drug resistance-a bioinformatics analysis.

Background: Studies have shown that there is a connection between estrogen receptor (ER) and glucocorticoid receptor (GR), which can impact the epithelial-mesenchymal transition (EMT) process and contribute to endocrine resistance in breast cancer. However, the specific mechanism is unclear. It is crucial to investigate this mechanism further. Methods: This study aimed to confirm the role of GR in breast cancer endocrine resistance. Based on our hypothesis, GR is linked to a gene involved in the EMT process, and thus contributes to endocrine resistance in breast cancer. We obtained survival data and GR expression data from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Additionally, we gathered GR expression data from Gene Expression Omnibus (GEO). Using Cytoscape, we constructed a protein-protein interaction (PPI) network and identified key genes. Data of Vimentin, E-cad, and Wnt/ß-catenin expression were obtained from The Cancer Genome Atlas (TCGA). We used the co-expression method to identify key proteins. UALCAN and cBioPortal were utilized to verify the function of the key protein. Results: In ER+ breast cancer, GR (P=3.12780899271121E-08) and zinc finger E-box binding homeobox 1 (ZEB1) (P=1.716157E-01) were lowly expressed and down-regulated genes of GR differentially expressed genes were enriched in cell adhesion molecules. We screened for the key protein ZEB1 and found high levels of it was positively associated with prolonged recurrence-free survival (RFS) in patients receiving endocrine therapy (P=0.0024), while high levels of E-cad were negatively associated (P=0.0038). GR expression was positively associated with ZEB1 (Spearman =0.29, P=8.50e-21), negatively associated with E-cad (Spearman =-0.13, P=5.17e-5), and negatively associated with the SETD1B (Spearman =-0.14, P=1.527e-5), a gene downstream of ZEB1. In contrast, ZEB1 expression was negatively correlated with E-cad (Spearman =-0.081, P=3.132e-3) and negatively correlated with SET domain-containing 1B (SETD1B) (Spearman =-0.177, P=9.07e-11). Conclusions: In ER+ breast cancers, GR expression is suppressed, and the EMT process is inhibited by suppressing ZEB1 expression and thus promoting E-cad expression. For the investigation of endocrine medication resistance in breast cancer, it is crucial to identify the mechanisms by how GR participates in the EMT process.

Soil bacterial community composition in rice-turtle coculture systems with different planting years.

The rice-turtle coculture system is the most special rice-fish integrated farming system. In this study, we selected four paddy fields, including a rice monoculture paddy and three rice-turtle paddies with different planting years, to investigate the soil bacterial community composition with Illumina MiSeq sequencing technology. The results indicated that the contents of soil available nitrogen (AN), soil available phosphorus (AP) and soil organic matter (OM) in 9th year of rice-turtle paddy (RT9) were increased by 5.40%, 51.11% and 23.33% compared with rice monoculture paddy (CK), respectively. Significant differences of Acidobacteria, Desulfobacteria, Crenarchaeota were observed among the different rice farming systems. The relative abundance of Methylomonadaceae, Methylococcaceae and Methylophilaceae in RT9 was significantly higher than that in other treatments. RT9 had significantly lower relative abundance of Acidobacteria, but significantly higher relative abundance of Proteobacteria than other treatments. Redundancy analysis showed that soil AN and AP contents were the major factors influencing the abundance of the dominant microbes, wherein Methylomonadaceae, Methylococcaceae and Methylophilaceae were positively correlated with OM. The findings revealed the rice-turtle coculture system in the 9th year had higher soil nutrients and soil bacterial diversity, but there was also a risk of increasing methane emissions.

PlantCHRs: A comprehensive database of plant chromatin remodeling factors.

The Snf2 protein family is a group of ATP-dependent chromatin remodeling factors (CHRs) that play an essential role in gene expression regulation. In plants, Snf2 is involved in growth, development, as well as stress resistance. However, only a very limited number of experimentally validated Snf2 have been identified and reported, while the majority remaining undiscovered in most species . In this study, we predicted 3135 Snf2 proteins and 8398 chromatin remodeling complex (CRC) subunits in diverse plant species, and constructed the Plant Chromatin Remodeling Factors Database (PlantCHRs, http://www.functionalgenomics.cn/PlantCHRs/), which provide a comprehensive resource for researchers to access information about plant CHRs. We also developed an online tool capable of predicting CHRs and CRC subunits. Moreover, we investigated the distribution of Snf2 proteins in different species and observed a significant increase in the number of Snf2 proteins and the diversity of the Snf2 subfamily during the evolution, highlighting their evolutionary importance. By analyzing the expression patterns of the Snf2 genes in different tissues of maize and Arabidopsis, we found that the Snf2 proteins may show some conservation across different species in regulating plant growth and development. Over the all, we established a comprehensive database for plant CHRs, which will facilitate the researches on plant chromatin remodeling.