Emerging N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and 6PPD quinone in paired human plasma and urine from Tianjin, China: Preliminary assessment with demographic factors.

With increasing concerns about N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and 6PPD-quinone (6PPD-Q), relevant environmental investigations and toxicological research have sprung up in recent years. However, limited information could be found for human body burden assessment. This work collected and analyzed 200 samples consisting of paired urine and plasma samples from participants (50 male and 50 female) in Tianjin, China. Low detection frequencies (DF, <15 %) were found except for urinary 6PPD-Q (86 %), which suggested the poor residue tendency of 6PPD and 6PPD-Q in blood. The low DFs also lead to no substantial association between two chemicals. Data analysis based on urinary 6PPD-Q showed a significant difference between males and females (p < 0.05). No significant correlation was found for other demographic factors (Body Mass Index (BMI), age, drinking, and smoking). The mean values of daily excretion (ng/kg bw/day) calculated using urinary 6PPD-Q for females and males were 7.381 ng/kg bw/day (female) and 3.360 ng/kg bw/day (male), and apparently female suffered higher daily exposure. Further analysis with daily excretion and ALT (alanine aminotransferase)/TSH (thyroid stimulating hormone)/ blood cell analysis indicators found a potential correlation with 6PPD-Q daily excretion and liver/immune functions. Considering this preliminary assessment, systematic research targeting the potential organs at relevant concentrations is required.

Phenotypic comparison and the potential antitumor function of immortalized bone marrow-derived macrophages (iBMDMs).

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.

Systemic immune-inflammation index is associated with cardiac complications following acute ischemic stroke: A retrospective single-center study.

BACKGROUND: Stroke-induced heart syndrome is a feared complication of ischemic stroke, that is commonly encountered and has a strong association with unfavorable prognosis. More research is needed to explore underlying mechanisms and inform clinical decision making. This study aims to explore the relationship between the early systemic immune-inflammation (SII) index and the cardiac complications after acute ischemic stroke. METHODS: Consecutive patients with acute ischemic stroke were prospectively collected from January 2020 to August 2022 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections or cancer on admission. SII index [(neutrophils × platelets/ lymphocytes)/1000] was calculated from laboratory data at admission. RESULTS: A total of 121 patients were included in our study, of which 24 (19.8 %) developed cardiac complications within 14 days following acute ischemic stroke. The SII level was found higher in patients with stroke-heart syndrome (p<.001), which was an independent predictor of stroke-heart syndrome (adjusted odds ratio 5.089, p=.002). CONCLUSION: New-onset cardiovascular complications diagnosed following a stroke are very common and are associated with early SII index.

SERS-electrochemical dual-mode detection of microRNA on same interface assisted by exonuclease III signal transformation.

Dual-mode sensing has attracted more attentions which provide more accurate and reliable approach of cancer-related biomarkers. Herein, we developed a novel SERS/electrochemical dual-mode biosensor for miRNA 21 detection based on Exo III-assisted signal transformation. Firstly, the Au NPs were deposited on electrode as SERS substrate and Mn3O4/S4(DNA signal strand) was modified on Au NPs/S5 by the DNA strands S5-S4 pairing principle as hydrogen peroxide catalyst, leading to an obviously high DPV electrical signal without Raman signal. Subsequently, the presence of miRNA 21 will activate the Mn3O4/S4 to be decomposed under exonuclease III-assisted process, then the S3' chains modified with Raman molecular Cy3(Cy3-S3') is continuously connected to the Au NPs/S5 by DNA stands S5-S3' pairing principle, leading to the Raman signal response and DPV signal reduction. The biosensor shows good linear calibration curves of both SERS and electrochemical sensing modes with the detection limit of 3.98 × 10-3 nM and 6.89 × 10-5 nM, respectively. This work finds an ingenious mode for dual detection of microRNA on a same interface, which opens a new strategy for SERS and electrochemical analysis.

Identification and Characterization of PrognosticMacrophage Subpopulations for HumanEsophagealCarcinoma.

AIMS: The aim of the present study was to investigate the relationship between the cellular ecosystem and the progression of esophageal carcinoma (ESCA) based on the evolution of macrophages and to analyze the potential of using macrophages as a new therapeutic approach in ESCA treatment. BACKGROUND: Macrophage-based immunotherapy could be used for treating ESCA patients, but its clinical application is limited by the intra-tumor heterogeneity of macrophages. OBJECTIVE: The objective of this study was to analyze the diversity, differentiation trajectory, and intercellular communication of macrophages in ESCA and its prognostic significance. METHODS: Single-cell RNA sequencing (scRNA-seq) data in the GSE154763 dataset were downloaded from Gene Expression Omnibus (GEO) to identify cell clusters and annotate cell types using the Seurat R package. The scRNA-seq profiles of macrophages were extracted, and cluster analysis was performed to identify macrophage subsets. The differentiation trajectories of macrophage subgroups were visualized employing Monocle2. Finally, ligand-receptor pairs and communication intensity among the classified subgroups were analyzed using CellChat. RESULTS: A total of 8 cell types were identified between ESCA tissues and paracancer tissues. The most abundant macrophages in ESCA tissues were further divided into 5 cell clusters. Compared with the normal tissues, the proportion of HSPA6+ macrophages in ESCA tissues increased the most, and the number of ligand-receptor pairs that mediated the communication of HSPA6+ macrophages with mast cells and monocytes also increased significantly. More importantly, a high proportion of HSPA6+ macrophages was inversely correlated with the survival outcomes for ESCA patients. CONCLUSIONS: This study analyzed the diversity, distribution and differentiation trajectory of macrophages in ESCA tissues at single-cell level and classified a prognostic macrophage subtype (HSPA6+ macrophages) of ESCA, providing a theoretical basis for macrophage-targeted therapy in ESCA.

Elevated of NDUFA4L2 expression in colon adenocarcinoma is correlated with an unfavorable prognosis and increased immune cell infiltration.

Background: Colon adenocarcinoma (COAD) is a prevalent malignancy worldwide, yet, its underlying pathogenesis and genetic characteristics are still unclear. Previous studies have suggested that NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) may affect tumor progression across various cancers. However, this effect on COAD has rarely been reported. Thus, this study investigated NDUFA4L2's prognostic and diagnostic relevance and explored its potential connection with immune cell infiltration in COAD. Methods: To achieve this, RNA sequencing data from Cancer Genome Atlas (TCGA) was analyzed to assess NDUFA4L2's prognostic value in COAD, and factors relevant to the prognosis of COAD, including NDUFA4L2, were scrutinized using Kaplan-Meier analyses as well as univariate and multivariate Cox regression. A nomogram model was created to project prognosis based on the results of multivariate Cox analysis. Furthermore, gene set enrichment analysis (GSEA) was employed to pinpoint key NDUFA4L2-related pathways, and single-sample GSEA (ssGSEA) on TCGA data was employed to investigate the connections of NDUFA4L2 with cancer immune infiltrations. Results: Our findings revealed significant associations of high NDUFA4L2 expression with poor overall survival, progression-free interval, and disease-specific survival of COAD patients. GSEA indicated close links of NDUFA4L2 with several signaling pathways implicated in tumorigenesis, including extracellular matrix receptor interaction, the intestinal immune network for immunoglobulin A production, natural killer (NK) cell-mediated cytotoxicity, pathways in cancer, cell adhesion molecules, mitogen-activated protein kinase signaling pathway, Hedgehog signaling pathway, transforming growth factor beta signaling pathway, and chemokine signaling pathway. Additionally, ssGSEA identified a positive link between increased NDUFA4L2 expression and higher infiltration degree of various immune cells, such as immature dendritic cells, macrophages, NK cells and dendritic cells. Conclusions: Collectively, our findings demonstrate the association of increased NDUFA4L2 expression with adverse prognosis and heightened immune cell infiltration in COAD patients.

M1 macrophage-related gene model for NSCLC immunotherapy response prediction.

Patients diagnosed with non-small cell lung cancer (NSCLC) have a limited lifespan and exhibit poor immunotherapy outcomes. M1 macrophages have been found to be essential for antitumor immunity. This study aims to develop an immunotherapy response evaluation model for NSCLC patients based on transcription. RNA sequencing profiles of 254 advanced-stage NSCLC patients treated with immunotherapy are downloaded from the POPLAR and OAK projects. Immune cell infiltration in NSCLC patients is examined, and thereafter, different coexpressed genes are identified. Next, the impact of M1 macrophage-related genes on the prognosis of NSCLC patients is investigated. Six M1 macrophage coexpressed genes, namely, NKX2-1, CD8A , SFTA3, IL2RB, IDO1, and CXCL9, exhibit a strong association with the prognosis of NSCLC and serve as effective predictors for immunotherapy response. A response model is constructed using a Cox regression model and Lasso Cox regression analysis. The M1 genes are validated in our TD-FOREKNOW NSCLC clinical trial by RT-qPCR. The response model shows excellent immunotherapy response prediction and prognosis evaluation value in advanced-stage NSCLC. This model can effectively predict advanced NSCLC prognosis and aid in identifying patients who could benefit from customized immunotherapy as well as sensitive drugs.

PZR suppresses innate immune response to RNA viral infection by inhibiting MAVS activation in interferon signaling mediated by RIG-I and MDA5.

RNA viral infections seriously endanger human health. Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP2) suppresses innate immunity against influenza A virus, and pharmacological inhibition of SHP2 provokes hepatic innate immunity. SHP2 binds and catalyzes tyrosyl dephosphorylation of protein zero-related (PZR), but the regulatory effect of PZR on innate immune response to viral infection is unclear. In this study, the transcription and protein level of PZR in host cells were found to be decreased with RNA viral infection, and high level of PZR was uncovered to inhibit interferon (IFN) signaling mediated by RIG-I and MDA5. Through localizing in mitochondria, PZR targeted and interacted with MAVS (also known as IPS-1/VISA/Cardif), suppressing the aggregation and activation of MAVS. Specifically, Y263 residue in ITIM is critical for PZR to exert immunosuppression under RNA viral infection. Moreover, the recruited SHP2 by PZR that modified with tyrosine phosphorylation under RNA viral infection might inhibit phosphorylation activation of MAVS. In conclusion, PZR and SHP2 suppress innate immune response to RNA viral infection through inhibiting MAVS activation. This study reveals the regulatory mechanism of PZR-SHP2-MAVS signal axis on IFN signaling mediated by RIG-I and MDA5, which may provide new sight for developing antiviral drugs.

RNA 5-methylcytosine writer NSUN5 promotes hepatocellular carcinoma cell proliferation via a ZBED3-dependent mechanism.

Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer-related mortality worldwide. Nop2/Sun domain family member 5 (NSUN5), a conserved RNA 5-methylcytosine methyltransferase, is conventionally recognized as oncogenic. However, its role in HCC development remains unknown. In this study, we observed a remarkable upregulation of NSUN5 expression in both tumor tissues from patients with HCC, establishing a correlation with unfavorable clinical outcomes. NSUN5 knockdown and overexpression significantly inhibited and promoted HCC cell proliferation, respectively. Additionally, employing a combination of methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RIP-seq techniques, we identified zinc finger BED domain-containing protein 3 (ZBED3) as a novel downstream target of NSUN5. Additionally, we found that the overexpression of ZBED3 counteracted the tumor-suppressing effect of NSUN5 knockdown and simultaneously reversed the inhibition of the Wnt/ß-catenin signaling pathway. In summary, we elucidated the oncogenic role of NSUN5 in HCC development and identified the ZBED3/Wnt/ß-catenin signaling pathway as its downstream target. This study provides a novel therapeutic target for further development in HCC treatment.

Direct entry of micro(nano)plastics into human blood circulatory system by intravenous infusion.

Understanding the pathways of human exposure to micro(nano)plastics (MNPs) is crucial for assessing their health impacts. Intravenous infusion can induce MNPs direct entry into the human blood, posing serious risks on human health, but remains unclear. Herein, we developed comprehensive analytical methods to detect polyvinyl chloride (PVC) MNPs down to 20 nm, and found about 0.52 µg equal to 105-1011 particles of PVC-MNPs released from intravenous infusion products (IVIPs) during each intravenous infusion of 250 mL injection. The released amounts of MNPs from IVIPs were dependent on the plastic materials, and the injection volume and composition. These findings indicated that the released MNPs should be directly introduced into the human blood circulatory system, causing serious impacts on human health. Our study reveals a previously ignored but important pathway of human exposure to MNPs, and calls for further research on the potential risks of these MNPs on human health.

Development and evaluation of a risk score model based on a WNT score gene-associated signature for predicting the clinical outcome and the tumour microenvironment of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is currently one of the most life-threatening diseases worldwide. However, the factors, genes, and processes involved in the mechanisms of HCC initiation, development, and metastasis remain to be identified.Methods: WNT signalling pathways may play important roles in cancer initiation and progression. Thus, it would be informative to construct a WNT signature-based gene model for the prognosis of HCC and the prediction of therapeutic efficacy. We curated genomic profiles for HCC from The Cancer Genome Atlas (TCGA) and divided them into training and internal validation datasets. We also used samples from GSE14520 and HCCDB18 as validation datasets and clustered them by ConsensusClusterPlus analysis. We applied WebGestaltR to the WNT score-associated differentially expressed genes (DEGs) and conducted a signalling pathway enrichment analysis. We assessed the tumour immune microenvironment with ESTIMATE, Microenvironment Cell Populations (MCP)-counter, single-sample gene set enrichment analysis (ssGSEA), and tumour immune dysfunction and exclusion (TIDE).Results: We performed a least absolute shrinkage and selection operator (LASSO) regression analysis to identify the prognosis-related hub genes, identified the risk and protective factor genes associated with HCC, classified them into two clusters, and found that Cluster 2 had a significantly better prognosis than Cluster 1. Moreover, the latter had advanced clinical features compared with the former. Uridine-cytosine kinase 1 (UCK1), myristoylated alanine-rich C-kinase substrate-like protein 1 (MARCKSL1), P-antigen family member 1 (PAGE1), and killer cell lectin-like receptor B1 (KLRB1) were detected and used to construct a simplified prognostic model for HCC. The high risk score subgroup showed a poorer prognosis than the low risk score subgroup, and the model assessed HCC prognosis consistently and effectively.Conclusions: The WNT score-related gene-based model designed and evaluated herein had strong prognostic and predictive ability for HCC and could, therefore, facilitate decision-making in the prognosis and therapeutic efficacy assessment of HCC.

Personal Exposure to Source-Specific Particulate Polycyclic Aromatic Hydrocarbons and Systemic Inflammation: A Cross-Sectional Study of Urban-Dwelling Older Adults in China.

Environmental exposure to ambient polycyclic aromatic hydrocarbons (PAHs) can disturb the immune response. However, the evidence on adverse health effects caused by exposure to PAHs emitted from specific sources among different vulnerable subpopulations is limited. In this cross-sectional study, we aimed to evaluate whether exposure to source-specific PAHs could increase systemic inflammation in older adults. The present study included community-dwelling older adults and collected filter samples of personal exposure to PM2.5 during the winter of 2011. Blood samples were collected after the PM2.5 sample collection. We analyzed PM2.5 bound PAHs and serum inflammatory cytokines (interleukin (IL)1ß, IL6, and tumor necrosis factor alpha levels. The Positive Matrix Factorization model was used to identify PAH sources. We used a linear regression model to assess the relative effects of source-specific PM2.5 bound PAHs on the levels of measured inflammatory cytokines. After controlling for confounders, exposure to PAHs emitted from biomass burning or diesel vehicle emission was significantly associated with increased serum inflammatory cytokines and systemic inflammation. These findings highlight the importance of considering exposure sources in epidemiological studies and controlling exposures to organic materials from specific sources.

Prevalence of and prognosis for poor immunological recovery by virally suppressed and aged HIV-infected patients.

Background: Antiretroviral therapy (ART) prolongs lifespan and decreases mortality of HIV infected patients. However, many patients do not achieve optimal immune reconstitution. The influence of non-optimal immune recovery on non-AIDS related diseases is not well defined in aged HIV-infected patients receiving ART. Methods: A retrospective study was conducted at Tianjin Second People's Hospital, China to evaluate the association of an inadequate immunological response and non-AIDS diseases in HIV infected patients ≥60 years of age and virally suppressed for at least 2 years by ART. Results: The study included patients (n = 666) who initiated ART between August 2009 and December 2020. The prevalence of patients with an inadequate immunological response was 29.6%. The percentage of non-AIDS diseases such as hypertension, cardiovascular disease (CVD), diabetes, tumor, and chronic kidney disease (CKD) was 32.9, 9.9, 31, 4.1, and 13%, respectively. In addition to baseline CD4+ T cell counts, CVD and tumor were associated with poor immune reconstitution in aged Chinese HIV-1 infected patients. The adjusted odds ratios (95% confidence interval) were AOR 2.45 (95% CI: 1.22-4.93) and 3.06 (95% CI: 1.09-8.56, p = 0.03). Inadequate immunological response was associated with greater mortality (AOR: 2.83, 95% CI: 1.42-5.67, p = 0.003) in this cohort. Conclusion: These results tend to demonstrate appropriate drug selection at ART initiation and prevention of non-AIDS complications during ART decreased mortality of and an inadequate immunological response in aged HIV infected patients.

LncRNA MAFG-AS1 is involved in human cancer progression.

Long noncoding RNAs (lncRNAs) refer to a type of non-protein-coding transcript of more than 200 nucleotides. LncRNAs play fundamental roles in disease development and progression, and lncRNAs are dysregulated in many pathophysiological processes. Thus, lncRNAs may have potential value in clinical applications. The lncRNA, MAF BZIP Transcription Factor G (MAFG)-AS1, is dysregulated in several cancer, including breast cancer, lung cancer, liver cancer, bladder cancer, colorectal cancer, gastric cancer, esophagus cancer, prostate cancer, pancreatic cancer, ovarian cancer, and glioma. Altered MAFG-AS1 levels are also associated with diverse clinical characteristics and patient outcomes. Mechanistically, MAFG-AS1 mediates a variety of cellular processes via the regulation of target gene expression. Therefore, the diagnostic, prognostic, and therapeutic aspects of MAFG-AS1 have been widely explored. In this review, we discuss the expression, major roles, and molecular mechanisms of MAFG-AS1, the relationship between MAFG-AS1 and clinical features of diseases, and the clinical applications of MAFG-AS1.

Exploring the dual role of circRNA and PI3K/AKT pathway in tumors of the digestive system.

The interactions among circRNAs, the PI3K/AKT pathway, and their downstream effectors are intricately linked to their functional roles in tumorigenesis. Furthermore, the circRNAs/PI3K/AKT axis has been significantly implicated in the context of digestive system tumors. This axis is frequently abnormally activated in digestive cancers, including gastric cancer, colorectal cancer, pancreatic cancer, and others. Moreover, the overactivation of the circRNAs/PI3K/AKT axis promotes tumor cell proliferation, suppresses apoptosis, enhances invasive and metastatic capabilities, and contributes to drug resistance. In this regard, gaining crucial insights into the complex interaction between circRNAs and the PI3K/AKT pathway holds great potential for elucidating disease mechanisms, identifying diagnostic biomarkers, and designing targeted therapeutic interventions.

Heterogeneity characterization of hepatocellular carcinoma based on the sensitivity to 5-fluorouracil and development of a prognostic regression model.

Background: 5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug in clinical cancer treatment, including hepatocellular carcinoma (HCC). A correct understanding of the mechanisms leading to a low or lack of sensitivity of HCC to 5-FU-based treatment is a key element in the current personalized medical treatment. Methods: Weighted gene co-expression network analysis (WGCNA) was used to analyze the expression profiles of the cancer cell line from GDSC2 to identify 5-FU-related modules and hub genes. According to hub genes, HCC was classified and the machine learning model was developed by ConsensusClusterPlus and five different machine learning algorithms. Furthermore, we performed quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis on the genes in our model. Results: A total of 19 modules of the cancer cell line were divided by WGCNA, and the most negative correlation with 5-FU was the midnight blue module, from which 45 hub genes were identified. HCC was divided into three subgroups (C1, C2, and C3) with significant overall survival (OS) differences. OS of C1 was the shortest, which was characterized by a high clinical grade and later T stage and stage. OS of C3 was the longest. OS of C2 was between the two subtypes, and its immune infiltration was the lowest. Five out of 45 hub genes, namely, TOMM40L, SNRPA, ILF3, CPSF6, and NUP205, were filtered to develop a risk regression model as an independent prognostic indicator for HCC. The qRT-PCR results showed that TOMM40L, SNRPA, ILF3, CPSF6, and NUP205 were remarkably highly expressed in hepatocellular carcinoma. Conclusion: The HCC classification based on the sensitivity to 5-FU was in line with the prognostic differences observed in HCC and most of the genomic variation, immune infiltration, and heterogeneity of pathological pathways. The regression model related to 5-FU sensitivity may be of significance in individualized prognostic monitoring of HCC.

The Associations between Organophosphate Pesticides (OPs) and Respiratory Disease, Diabetes Mellitus, and Cardiovascular Disease: A Review and Meta-Analysis of Observational Studies.

Although some epidemiological studies have identified the associations between exposure to organophosphate pesticides (Ops) and respiratory diseases, diabetes mellitus (DM), and cardiovascular diseases (CVDs), controversial results still exist. In this review and meta-analysis, we aimed to investigate the overall pooled effect estimates and the possible mechanisms of the relationship between OP exposure and adverse health outcomes. In this study, Web of Science, PubMed, Embase, OVID, and the Cochrane Library were systematically searched until September 2022. Nineteen observational studies that focused on the general population or occupational populations examined the associations between OP exposure and respiratory diseases, DM, and CVD were included. Based on the overall pooled results, a significantly positive association was observed between OP exposure and respiratory diseases (OR: 1.12, 95% CI: 1.06-1.19). A significant link was also observed between various individual species of OP exposure and respiratory diseases, with an OR value of 1.11 (95% CI: 1.05-1.18). In particular, there was a significant association of OPs with wheezing and asthma, with OR values of 1.19 (95% CI: 1.08-1.31) and 1.13 (95% CI: 1.05-1.22), respectively. In addition, a significant association was also observed between OP exposure and DM (OR: 1.18, 95% CI: 1.07-1.29). However, no significant association was observed between OP exposure and CVD (OR: 1.00, 95% CI: 0.94-1.05). Exposure to OPs was associated with a significantly increased risk of respiratory diseases and DM, but there was no evidence of a significant association between OP exposure and CVD. Considering the moderate strength of the results, further evidence is needed to confirm these associations.

Recent advances in lignin antioxidant: Antioxidant mechanism, evaluation methods, influence factors and various applications.

Lignin, a by-product of processing lignocellulosic materials, has a polyphenolic structure and can be used as an antioxidant directly or synergistically with synthetic types of antioxidants, leading to different applications. Its antioxidant mechanism is mainly related to the production of ROS, but the details need to be further investigated. The antioxidant property of lignin is mainly related to the content of phenolic hydroxyl group, but methoxy, purity will also have an effect on it. In addition, different methods to detect the antioxidant properties of lignin have different advantages and disadvantages. In this paper, the antioxidant mechanism of lignin, the methods to determine the antioxidant activity and the progress of its application in various fields are reviewed. In addition, the current research on the antioxidant properties of lignin and the hot directions are provided, and an outlook on the research into the antioxidant properties of lignin is provided to broaden its potential application areas.

Photobiomodulation reduces neuropathic pain after spinal cord injury by downregulating CXCL10 expression.

BACKGROUND: Many studies have recently highlighted the role of photobiomodulation (PBM) in neuropathic pain (NP) relief after spinal cord injury (SCI), suggesting that it may be an effective way to relieve NP after SCI. However, the underlying mechanisms remain unclear. This study aimed to determine the potential mechanisms of PBM in NP relief after SCI. METHODS: We performed systematic observations and investigated the mechanism of PBM intervention in NP in rats after SCI. Using transcriptome sequencing, we screened CXCL10 as a possible target molecule for PBM intervention and validated the results in rat tissues using reverse transcription-polymerase chain reaction and western blotting. Using immunofluorescence co-labeling, astrocytes and microglia were identified as the cells responsible for CXCL10 expression. The involvement of the NF-κB pathway in CXCL10 expression was verified using inhibitor pyrrolidine dithiocarbamate (PDTC) and agonist phorbol-12-myristate-13-acetate (PMA), which were further validated by an in vivo injection experiment. RESULTS: Here, we demonstrated that PBM therapy led to an improvement in NP relative behaviors post-SCI, inhibited the activation of microglia and astrocytes, and decreased the expression level of CXCL10 in glial cells, which was accompanied by mediation of the NF-κB signaling pathway. Photobiomodulation inhibit the activation of the NF-κB pathway and reduce downstream CXCL10 expression. The NF-κB pathway inhibitor PDTC had the same effect as PBM on improving pain in animals with SCI, and the NF-κB pathway promoter PMA could reverse the beneficial effect of PBM. CONCLUSIONS: Our results provide new insights into the mechanisms by which PBM alleviates NP after SCI. We demonstrated that PBM significantly inhibited the activation of microglia and astrocytes and decreased the expression level of CXCL10. These effects appear to be related to the NF-κB signaling pathway. Taken together, our study provides evidence that PBM could be a potentially effective therapy for NP after SCI, CXCL10 and NF-kB signaling pathways might be critical factors in pain relief mediated by PBM after SCI.

Systematic review and meta-analysis of breast cancer risks in relation to 2,3,7,8-tetrachlorodibenzo-p-dioxin and per- and polyfluoroalkyl substances.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals that may cause breast cancer. However, there lacks consistent research on the association between TCDD, PFAS exposure, and breast cancer. To this end, a meta-analysis was carried out in this review to explore the relationship between these two endocrine disruptors and breast cancer. Relevant literature was searched from 5 databases: Medline, Scopus, Embase, PubMed, and Web of Science. Odds ratios (OR) with 95% confidence intervals (CIs) were pooled by fixed-effects and random-effects meta-analysis models. A total of 17 publications were finally included for quantitative evaluation. Meta-analysis showed that TCDD (OR = 1.00, 95% CI = 0.89-1.12, I2 = 39.3%, P = 0.144), PFOA (OR = 1.07, 95% CI = 0.84-1.38, I2 = 85.9%, P < 0.001), PFOS (OR = 1.01, 95% CI = 0.95-1.08, I2 = 65.7%, P < 0.001), PFNA (OR = 0.89, 95% CI = 0.67-1.19, I2 = 74.4%, P < 0.001), and PFHxS (OR = 0.90, 95% CI = 0.72-1.13, I2 = 74%, P < 0.001) were not significantly correlated with breast cancer. Internal exposure, however, showed a significant positive correlation between TCDD and BC (OR = 2.85, 95% CI = 1.23-6.59, I2 = 0.0%, P = 0.882). No statistically significant association between TCDD, PFAS exposure, and breast cancer was observed in this meta-analysis.