Olfactory toxicity of tetrabromobisphenol A to the goldfish Carassius auratus.

Tetrabromobisphenol A (TBBPA) is one of the most extensively used brominated flame retardants and its increasing use in consumer products has raised concerns about its ecotoxicity. Given the ubiquity of TBBPA in aquatic environments, it is inevitable that these chemicals will enter the olfactory chambers of fish via water currents. Nevertheless, the olfactory toxicity of TBBPA to aquatic organisms and the underlying toxic mechanisms have yet to be elucidated. Therefore, we investigated the olfactory toxicity of TBBPA in the goldfish Carassius auratus, a model organism widely used in sensory biology. Results showed that exposure to TBBPA resulted in abnormal olfactory-mediated behaviors and diminished electro-olfactogram (EOG) responses, indicating reduced olfactory acuity. To uncover the underlying mechanisms of action, we examined the structural integrity of the olfactory epithelium (OE), expression levels of olfactory G protein-coupled receptors (GPCRs), enzymatic activities of ion transporters, and fluctuations in neurotransmitters. Additionally, comparative transcriptomic analysis was employed to investigate the molecular mechanisms further. Our study demonstrates for the first time that TBBPA at environmentally relevant levels can adversely affect the olfactory sensitivity of aquatic organisms by interfering with the transmission of aqueous stimuli to olfactory receptors, impeding the binding of odorants to their receptors, disrupting the olfactory signal transduction pathway, and ultimately affecting the generation of action potentials.

[Engineering and application of Komagataella phaffii as a cell factory].

Nowadays, engineered Komagataella phaffii plays an important role in the biosynthesis of small molecule metabolites and protein products, showing great potential and value in industrial productions. With the development and application of new editing tools such as CRISPR/Cas9, it has become possible to engineer K. phaffii into a cell factory with high polygenic efficiency. Here, the genetic manipulation techniques and objectives for engineering K. phaffii are first summarized. Secondly, the applications of engineered K. phaffii as a cell factory are introduced. Meanwhile, the advantages as well as disadvantages of using engineered K. phaffii as a cell factory are discussed and future engineering directions are prospected. This review aims to provide a reference for further engineering K. phaffii cell factory, which is supposed to facilitate its application in bioindustry.

PD-1+ IFN-γ+ subset of CD8+ T cell in circulation predicts response to anti-PD-1 therapy in NSCLC.

Background: Treatment with programmed cell death protein-1 (PD-1) antibodies has minimal response rates in patients with non-small cell lung cancer (NSCLC), and, actually, they are treated with chemotherapy combined with anti-PD-1 therapy clinically. Reliable markers based on circulating immune cell subsets to predict curative effect are still scarce. Methods: We included 30 patients with NSCLC treated with nivolumab or atezolizumab plus platinum drugs between 2021 and 2022. Whole blood was collected at baseline (before treatment with nivolumab or atezolizumab). The percentage of circulating PD-1+ Interferon-γ (IFN-γ+) subset of CD8+ T cell was determined by flow cytometry. The proportion of PD-1+ IFN-γ+ was calculated after gating on CD8+ T cells. Neutrophil/lymphocyte ratio (NLR), relative eosinophil count (%), and Lactate dehydrogenase (LDH) concentration at baseline of included patients were extracted from electronic medical records. Results: The percentage of circulating PD-1+ IFN-γ+ subset of CD8+ T cell at baseline in responders was significantly higher than those in non-responders (P < 0.05). Relative eosinophil count (%) and LDH concentration in responders showed no significance between non-responders and responders. NLR in responders was significantly lower than those in non-responders (P < 0.05). Receiver operation characteristic (ROC) analysis found that the areas under the ROC curve for PD-1+ IFN-γ+ subset of CD8+ T cell and NLR were 0.7781 (95% CI, 0.5937-0.9526) and 0.7315 (95% CI, 0.5169-0.9461). Moreover, high percentage of PD-1+ IFN-γ+ subset in CD8+ T cells was relevant to long progression-free survival in patients with NSCLC treated with chemotherapy combined with anti-PD-1 therapy. Conclusion: The percentage of circulating PD-1+ IFN-γ+ subset of CD8+ T cell could be a potential marker at baseline to predict early response or progression in patients with NSCLC receiving chemotherapy combined with anti-PD-1 therapy.

Causal effects of human serum metabolites on occurrence and progress indicators of chronic kidney disease: a two-sample Mendelian randomization study.

Background: Chronic kidney disease (CKD) is often accompanied by alterations in the metabolic profile of the body, yet the causative role of these metabolic changes in the onset of CKD remains a subject of ongoing debate. This study investigates the causative links between metabolites and CKD by leveraging the results of genomewide association study (GWAS) from 486 blood metabolites, employing bulk two-sample Mendelian randomization (MR) analyses. Building on the metabolites that exhibit a causal relationship with CKD, we delve deeper using enrichment analysis to identify the metabolic pathways that may contribute to the development and progression of CKD. Methods: In conducting the Mendelian randomization analysis, we treated the GWAS data for 486 metabolic traits as exposure variables while using GWAS data for estimated glomerular filtration rate based on serum creatinine (eGFRcrea), microalbuminuria, and the urinary albumin-to-creatinine ratio (UACR) sourced from the CKDGen consortium as the outcome variables. Inverse-variance weighting (IVW) analysis was used to identify metabolites with a causal relationship to outcome. Using Bonferroni correction, metabolites with more robust causal relationships are screened. Additionally, the IVW-positive results were supplemented with the weighted median, MR-Egger, weighted mode, and simple mode. Furthermore, we performed sensitivity analyses using the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out (LOO) test. Pathway enrichment analysis was conducted using two databases, KEGG and SMPDB, for eligible metabolites. Results: During the batch Mendelian randomization (MR) analyses, upon completion of the inverse-variance weighted (IVW) approach, sensitivity analysis, and directional consistency checks, 78 metabolites were found to meet the criteria. The following four metabolites satisfy Bonferroni correction: mannose, N-acetylornithine, glycine, and bilirubin (Z, Z), and mannose is causally related to all outcomes of CKD. By pathway enrichment analysis, we identified eight metabolic pathways that contribute to CKD occurrence and progression. Conclusion: Based on the present analysis, mannose met Bonferroni correction and had causal associations with CKD, eGFRcrea, microalbuminuria, and UACR. As a potential target for CKD diagnosis and treatment, mannose is believed to play an important role in the occurrence and development of CKD.

Quadratus lumborum block versus transversus abdominis plane block for postoperative analgesia in patients undergoing abdominal surgeries: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Abdominal surgery is common and is associated with severe postoperative pain. The transverse abdominal plane (TAP) block is considered an effective means for pain control in such cases. The quadratus lumborum (QL) block is another option for the management of postoperative pain. The aim of this study was to conduct a meta-analysis and thereby evaluate the efficacy and safety of QL blocks and TAP blocks for pain management after abdominal surgery. METHODS: We comprehensively searched PubMed, EMBASE, EBSCO, the Cochrane Library, Web of Science and CNKI for randomized controlled trials (RCTs) that compared QL blocks and TAP blocks for pain management in patients undergoing abdominal surgery. All of the data were screened and evaluated by two researchers. RevMan5.3 was adopted for the meta-analysis. RESULTS: A total of 8 RCTs involving 564 patients were included. The meta-analysis showed statistically significant differences between the two groups with respect to postoperative pain scores at 2 h (standardized mean difference [Std.MD] = - 1.76; 95% confidence interval [CI] = - 2.63 to - 0.89; p < .001), 4 h (Std.MD = -0.77; 95% CI = -1.36 to - 0.18; p = .01),6 h (Std.MD = -1.24; 95% CI = -2.31 to - 0.17; p = .02),12 h (Std.MD = -0.70; 95% CI = -1.27 to - 0.13; p = .02) and 24 h (Std.MD = -0.65; 95% CI = -1.29 to - 0.02; p = .04); postoperative morphine consumption at 24 h (Std.MD = -1.39; 95% CI = -1.83 to - 0.95; p < .001); and duration of postoperative analgesia (Std.MD = 2.30; 95% CI = 1.85 to 2.75; p < .001). There was no statistically significant difference between the two groups with regard to the incidence of postoperative nausea and vomiting (PONV) (RR = 0.55;95% CI = 0.27 to 1.14;p = 0.11). CONCLUSION: The QL block provides better pain management with less opioid consumption than the TAP block after abdominal surgery. In addition, there are no differences between the TAP block and QL block with respect to PONV.