Inhibition of neutrophil extracellular trap formation ameliorates neuroinflammation and neuronal apoptosis via STING-dependent IRE1α/ASK1/JNK signaling pathway in mice with traumatic brain injury.

BACKGROUND: Neuroinflammation is one of the most important pathogeneses in secondary brain injury after traumatic brain injury (TBI). Neutrophil extracellular traps (NETs) forming neutrophils were found throughout the brain tissue of TBI patients and elevated plasma NET biomarkers correlated with worse outcomes. However, the biological function and underlying mechanisms of NETs in TBI-induced neural damage are not yet fully understood. Here, we used Cl-amidine, a selective inhibitor of NETs to investigate the role of NETs in neural damage after TBI. METHODS: Controlled cortical impact model was performed to establish TBI. Cl-amidine, 2'3'-cGAMP (an activator of stimulating Interferon genes (STING)), C-176 (a selective STING inhibitor), and Kira6 [a selectively phosphorylated inositol-requiring enzyme-1 alpha [IRE1α] inhibitor] were administrated to explore the mechanism by which NETs promote neuroinflammation and neuronal apoptosis after TBI. Peptidyl arginine deiminase 4 (PAD4), an essential enzyme for neutrophil extracellular trap formation, is overexpressed with adenoviruses in the cortex of mice 1 day before TBI. The short-term neurobehavior tests, magnetic resonance imaging (MRI), laser speckle contrast imaging (LSCI), Evans blue extravasation assay, Fluoro-Jade C (FJC), TUNEL, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative-PCR were performed in this study. RESULTS: Neutrophils form NETs presenting in the circulation and brain at 3 days after TBI. NETs inhibitor Cl-amidine treatment improved short-term neurological functions, reduced cerebral lesion volume, reduced brain edema, and restored cerebral blood flow (CBF) after TBI. In addition, Cl-amidine exerted neuroprotective effects by attenuating BBB disruption, inhibiting immune cell infiltration, and alleviating neuronal death after TBI. Moreover, Cl-amidine treatment inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization at 3 days after TBI. Mechanistically, STING ligand 2'3'-cGAMP abolished the neuroprotection of Cl-amidine via IRE1α/ASK1/JNK signaling pathway after TBI. Importantly, overexpression of PAD4 promotes neuroinflammation and neuronal death via the IRE1α/ASK1/JNK signaling pathway after TBI. However, STING inhibitor C-176 or IRE1α inhibitor Kira6 effectively abolished the neurodestructive effects of PAD4 overexpression after TBI. CONCLUSION: Altogether, we are the first to demonstrate that NETs inhibition with Cl-amidine ameliorated neuroinflammation, neuronal apoptosis, and neurological deficits via STING-dependent IRE1α/ASK1/JNK signaling pathway after TBI. Thus, Cl-amidine treatment may provide a promising therapeutic approach for the early management of TBI.

Osteochondroma of the pubic symphysis causing hematuria: a case report and literature review.

BACKGROUND: Osteochondroma is the most common benign bone neoplasm and is sometimes referred to as osteocartilaginous exostosis. The symptoms caused by osteochondroma are rare, especially the urogenital complications. Therefore, this tumour is sometimes misdiagnosed. CASE PRESENTATION: This report described a 70-year-old woman with hematuria who was initially misdiagnosed with a bladder tumour in the outpatient department by a urologist. However, during cystoscopy, we found that the mass did not resemble a bladder tumor. Multidisciplinary approach with careful analysis of the imaging data suggested the diagnosis of osteochondroma. Open surgical excision of the mass was done and histology confirmed the diagnosis of benign osteochondroma. After 6 months of follow-up, the patient was still asymptomatic. CONCLUSIONS: This case illustrates that hematuria is caused by not only urogenital disease but also osteochondroma. We present this case to draw the attention of clinicians to osteochondroma of the pubic symphysis.

CLIC4 abrogation promotes epithelial-mesenchymal transition in gastric cancer.

Chloride intracellular channel protein 4 (CLIC4) has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in 102 pairs of gastric adenocarcinomas by western blot and real-time PCR. Our data revealed that the expression of CLIC4 is reduced in GC tumor tissues compared with adjacent normal tissues. The expression levels of CLIC4 correlate inversely with the clinical stage of GC. CLIC4 expression is lowest in MKN45 cells, which have the highest tumorigenic potential and express the highest levels of cancer stem cell markers CD44 and OCT4, compared with N87 and AGS cells. Exogenous overexpression of CLIC4 downregulated the expression of CD44 and OCT4, and inhibited migration, invasion and epithelial-mesenchymal transition (EMT). Moreover, anchorage-independent growth of GC cells was decreased and the cells became more sensitive to 5-fluorouracil and etoposide treatment when CLIC4 was overexpressed. The ability of N87 cells to form tumors in nude mice was enhanced when CLIC4 was silenced. We, for the first time, demonstrate that CLIC4 suppresses tumor growth by inhibiting cancer cell stemness and EMT.

Regulation of ATP-binding cassette subfamily B member 1 by Snail contributes to chemoresistance in colorectal cancer.

Although accumulating evidence has indicated the intimate association between epithelial-mesenchymal transition (EMT) and acquired resistance to chemotherapy for colorectal cancer (CRC), the underlying mechanisms remain elusive. Herein, we reported that Snail, a crucial EMT controller, was upregulated in CRC tissues. Colorectal cancer cells overexpressing Snail were found to be more resistant to 5-fluorouracil (5-Fu). Mechanistic studies reveal that Snail could increase the expression of ATP-binding cassette subfamily B member 1 (ABCB1) rather than the other 23 chemoresistance-related genes. Additionally, knockdown of ABCB1 significantly attenuated Snail-induced 5-Fu resistance in CRC cells. Oxaliplatin increased Snail and ABCB1 expression in CRC cells. Snail and ABCB1 were upregulated in 5-Fu-resistant HCT-8 (HCT-8/5-Fu) cells and inhibition of Snail decreased ABCB1 in HCT-8/5-Fu cells. These results confirm the vital role played by ABCB1 in Snail-induced chemoresistance. Further investigation into the relevant molecular mechanism revealed Snail-mediated ABCB1 upregulation was independent of ß-catenin, STAT3, PXR, CAR and Foxo3a, which are commonly involved in modulating ABCB1 transcription. Instead, Snail upregulated ABCB1 transcription by directly binding to its promoter. Clinical analysis confirms that increased Snail expression correlated significantly with tumor size (P = .018), lymph node metastasis (P = .033), distant metastasis (P = .025), clinical stage grade (P = .024), and poor prognosis (P = .045) of CRC patients. Moreover, coexpression of Snail and ABCB1 was observed in CRC patients. Our study revealed that direct regulation of ABCB1 by Snail was critical for conferring chemoresistance in CRC cells. These findings unraveled the mechanisms underlying the association between EMT and chemoresistance, and provided potential targets for CRC clinical treatment.

Lipidomics reveal aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis.

1. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based lipidomics was employed to elucidate new mechanism of alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. 2. Multiple lipid components significantly increased in ANIT-induced intrahepatic cholestasis, including PC 16:0, 20:4, PC 16:0, 22:6, PC 16:0, 18:2, LPC 18:2, PC 18:2, LPC 18:1, PC 18:1, 14:0, SM 18:1, 16:0, oleoylcarnitine and palmitoylcarnitine. This alteration of lipid profile was induced by the changed expression of genes choline kinase (Chk) a, sphingomyelin phosphodiesterase (SMPD) and stearoyl-coenzyme A desaturase 1 (SCD1). 3. Knockout of aryl hydrocarbon receptor (Ahr) in mice can significantly reverse ANIT-induced intrahepatic cholestasis, as indicated by lowered ALT, AST and ALP activity, and liver histology. Aryl hydrocarbon receptor knockout significantly reversed ANIT-induced lipid metabolism alteration through regulating the expression of Chka. 4. In conclusion, this study demonstrated ANIT-induced lipid metabolism disruption might be the potential pathogenesis of ANIT-induced intrahepatic cholestasis in mice.

Runx1 promotes satellite cell proliferation during ischemia - Induced muscle regeneration.

RUNX1 is a transcription factor that is not expressed in uninjured muscles, but can be detected in denervated muscles, suggesting a role of RUNX1 in muscle's response to injury. However, the role of RUNX1 in muscle's response to ischemia has not been reported. Our study showed that Runx1 is up regulated in skeletal muscle during ischemia reperfusion induced injury. Over-expression of Runx1 in C2C12 cells inhibits myogenic differentiation, but promotes proliferation of myoblasts. Consistent with these findings, we found that Runx1 expression was decreased in differentiated satellite cells. Our results indicate that Runx1 regulates muscle regeneration by promoting proliferation of satellite cells.

Sequence analysis-based characterization and identification of neurovirulence-associated variants of 36 EV71 strains from China.

Enterovirus 71 (EV71) is the main pathogen of hand-foot-mouth disease (HFMD) and causes several neurological complications. As new strains of EV71 are constantly discovered, it is important to understand the genomic characteristics of the viruses and the mechanism of virulence. Herein, we isolated five strains of EV71 from HFMD patients with or without neurovirulence and sequenced their whole genomes. We then performed whole genome sequence analysis of totally 36 EV71 strains. The phylogenetic analysis of the VP1 region revealed all five isolated strains are clustered into C4a of C4 subgenotype. In addition, by comparing the complete genome sequences of 36 strains, 253 variable amino acid positions were found, 14 of which were identified to be associated with neurovirulence (P < 0.05). Moreover, a similar pattern of amino acid variants combination was identified in four strains without neurovirulence, indicating this type of variant pattern might be associated with avirulence. The strains with neurovirulence appeared to be distinguished from those without neurovirulence by the variants in VP1 and P2 regions, implying VP1 and P2 are the important regions associated with neurovirulence. Indeed, 3-D modeling of VP1 and P2 regions of non-neurovirulent and neurovirulent strains revealed that the different variants resulted in different protein structures and amino acid composition of ligand binding site, which might account for their difference in neurovirulence. In summary, our study reveals 14 variable amino acid positions of VP1, P2 and P3 regions are related to the virulence and that mutations in the capsid proteins of EV71 might contribute to neurovirulence.

Sodium butyrate increases P-gp expression in lung cancer by upregulation of STAT3 and mRNA stabilization of ABCB1.

As a new type of anticancer drug, the effect of histone deacetylase inhibitors (HDACIs) in cancer clinical therapy is disappointing owing to drug resistance. P-glycoprotein (P-gp) is clearly recognized as a multidrug resistance protein. However, the relationship between P-gp and sodium butyrate (SB), a kind of HDACIs, has not been investigated. In this study, we found that SB increased mRNA and protein expression of P-gp in lung cancer cells and the underlying mechanisms were elucidated. We found that SB treatment enhanced the mRNA and protein expression of STAT3 rather than that of ß-catenin, Foxo3a, PXR, or CAR, which were reported to directly regulate the transcription of ABCB1, a P-gp-encoding gene. Interestingly, inhibition of STAT3 expression obviously attenuated SB-increased P-gp expression in lung cancer cells, indicating that STAT3 played an important role in SB-mediated P-gp upregulation. Furthermore, we found that SB increased the mRNA stability of ABCB1. In summary, this study showed that SB increased P-gp expression by facilitating transcriptional activation and improving ABCB1 mRNA stability. This study indicated that we should pay more attention to HDACIs during cancer clinical therapy.

Plasma nesfatin-1 level is associated with severity of depression in Chinese depressive patients.

BACKGROUND: Nesfatin-1 plays a role in the regulation of emotional states like depression. The aim of this study was to investigate the plasma nesfatin-1levels in Chinese patients with depression and healthy subjects, and to determine the possible association between the plasma nesfatin-1 level and the severity of depression. METHODS: A total of 103 depressive patients and 32 healthy subjects were assessed. According to HAMD-17scores, 51, 18, and 34 patients were enrolled in the mild depression, moderate depression, and severe depression groups, respectively. Plasma nesfatin-1 levels were determined by the ELISA method. Differences between groups were compared and associations between plasma nesfatin-1 and other variables were analyzed. RESULTS: The plasma nesfatin-1 was significantly positively correlated with HAMD-17 score (r = 0.651). Compared with healthy controls (8.11 ± 3.31 ng/mL), the plasma nesfatin-1 level significantly increased in patients with mild depression (11.17 ± 3.58 ng/mL), with moderate depression (16.33 ± 8.78 ng/mL), and with severe depression (27.65 ± 8.26 ng/mL) respectively. Plasma nesfatin-1 level (Odds ratio [OR] = 1.269) was an independent indicator for severe depression by multivariate logistic regression analysis. CONCLUSION: The plasma nesfatin-1 level is positively correlated with the severity of depression. Plasma nesfatin-1 level may be a potential indicator for depression severity.

Diverse ortho-C(sp2)-H Functionalization of Benzaldehydes Using Transient Directing Groups.

Pd-catalyzed C-H functionalizations promoted by transient directing groups remain largely limited to C-H arylation only. Herein, we report a diverse set of ortho-C(sp2)-H functionalizations of benzaldehyde substrates using the transient directing group strategy. Without installing any auxiliary directing group, Pd(II)-catalyzed C-H arylation, chlorination, bromination, and Ir(III)-catalyzed amidation, could be achieved on benzaldehyde substrates. The transient directing groups formed in situ via imine linkage can override other coordinating functional groups capable of directing C-H activation or catalyst poisoning, significantly expanding the scope for metal-catalyzed C-H functionalization of benzaldehydes. The utility of this approach is demonstrated through multiple applications, including late-stage diversification of a drug analogue.

Prognostic Value of Expression of MicroRNAs in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: microRNAs are widely involved in a variety of life processes and considered as potential biomarkers of tumor prognosis. A growing number of studies have documented that miRNAs were associated with outcome in NSCLC patients and can act as a prognostic marker. However, existing studies concerning the relationship between miRNAs and outcome in NSCLC patients were contentious and dispersive. Therefore, a systematic metaanalysis to explore the prognostic value of miRNAs on NSCLC patients is urgently needed. METHODS: Electronic databases, including PubMed, EMBASE, and Web of Science were searched for all relevant articles. Only articles investigating the survival effect of microRNAs on NSCLC patients were included in this meta-analysis. Hazard ratios (HRs) with 95% confidence interval (CI) were extracted and pooled on overall survival (OS) and progression free survival (PFS)/disease-specific survival (DSS). RESULTS: 28 articles were finally included in the overall meta-analysis. The pooled results revealed that high expression miR-21 (HR = 2.82, 95% CI: 2.10 - 3.79), miR-200c (HR = 2.05, 95% CI: 1.36 - 3.07), and miR-125b (HR = 1.72, 95% CI: 1.30 - 2.28) were negatively associated with survival in NSCLC patients. Conversely, high expression miR-148b (HR = 0.37, 95% CI: 0.19 - 0.70), miR-365 (HR = 0.40, 95% CI: 0.27 - 0.59), miR-124 (HR = 0.29, 95% CI: 0.16 - 0.53), miR-32 (HR = 0.46, 95% CI: 0.33 - 0.65), miR-146a (HR = 0.35, 95% CI: 0.18 - 0.68), and miR-375 (HR = 0.66, 95% CI: 0.45 - 0.96) were significantly associated with better prognosis. Meanwhile, the expression of miR-93 (HR = 1.19, 95% CI: 0.38 - 3.69) and miR-126 (HR = 0.38, 95% CI: 0.12 - 1.16) showed no relationship with NSCLC prognosis. CONCLUSIONS: Our meta-analysis provided the evidence that miR-21, miR-200c, miR-125b, miR-148b, miR-365, miR-124, miR-32, miR-146a, and miR-375 can act as prognostic biomarkers in NSCLC.

Production of a therapeutic protein by fusing it with two fragments of the carboxyl-terminal peptide of human chorionic gonadotropin ß-subunit in Pichia pastoris.

OBJECTIVE: To produce a therapeutic protein (endostatin) by fusion with two fragments of the carboxyl-terminal peptide (CTP) of the human chorionic gonadotropin ß-subunit in Pichia pastoris. RESULTS: Two CTP sequences were fused to the C-terminal of human endostatin, and the fusion protein (endo-CTP) was expressed by P. pastoris. Endo-CTP inhibited proliferation of endothelial cells with an IC50 of 7 µg ml(-1), and 30 % of cells were annexin V-positive after treatment with 20 µg endo-CTP ml(-1) for 48 h. Migration of endothelial cells was inhibited by endo-CTP in a concentration-dependent manner. The half-life of endo-CTP in Sprague-Dawley rats was much longer than that of its commercial counterpart (Endostar). CONCLUSION: A long-acting endostatin can be produced using CTP technology.

Identification of minor chromosomal defects causing abnormal foetus and spontaneous abortions.

BACKGROUND: Chromosomal abnormalities are the most common cause of recurrent abortions and miscarriages (RAM), but micro-variations on chromosomes causing RAM have never been previously studied. Single nucleotide polymorphisms (SNPs) are the single nucleotide variations frequently present at genome with the density of at least one common (>20% allele frequency) SNP per kilobase pair. It has already been reported that SNP array examination for chromosomal abnormalities has better performance than the conventional cytogenetic karyotyping. METHODS: We applied SNP array to detect the chromosomal defects in 80 placental villi and foetal tissues of abnormal foetus and spontaneous abortions. RESULTS: The analyses of data revealed that total 52.5% (42/80) cases were found to have chromosomal abnormalities. The trisomies were most commonly found 26/42 (61.9%) in current samples. Total 8/42 (19.1%) cases were found to have other structural aberrations including translocations in 2/8 (25%), duplications and deletions in 3/8 (37.5%) cases, respectively. SNP analysis also successfully detected triploidy 69,XXX and tetraploidy 92,XXXY. Total 12/80 cases were performed by cytogenetic karyotyping and results were compared with SNP data. Total 5/12 (41.7%) cases were found to have same findings with SNP data while results of 2/12 (16.7%) cases had partial similarity between both techniques. Four cases were declared as karyotypically normal (46,XY or 46,XX) by cytogenetic examination, but later on these four cases were found to have small chromosomal variation which could be the cause of RAM in women. CONCLUSION: Therefore, we conclude that use of a high-density SNP platform in diagnosis can give better understanding of molecular causes of pregnancy loss and foetal abnormalities.

Prospective Evaluation of a Transfusion Policy of RhD-Positive Red Blood Cells into DEL Patients in China.

BACKGROUND: The D antigen is highly immunogenic, requiring only a small quantity of transfused red blood cells (RBCs) to cause alloimmunization in D- immunocompetent recipients. DEL was reported arousing alloimmunization to true Rh- patients. Molecular studies of the RHD gene have revealed that DEL individuals retain a grossly intact RHD gene or have a portion of RHD in their genomes. Avoiding immunization with clinically important antibodies is a primary objective in transfusion medicine. METHODS: In order to determine whether pregnant DEL women carrying an RhD+ fetus are at risk of anti-D alloimmunization, 808 Rh- pregnant women with a history of gestations or parturitions who regularly visited hospitals for their prenatal anti-D screening and postpartum care from January 2011 to December 2012 were investigated. Samples were analyzed for DEL by PCR with specific primers, PCR-sequence-specific primers (PCR-SSP), reverse transcription-PCR (RT-PCR), PCRrestriction fragment length polymorphism (PCR-RFLP), and by gene sequencing to characterize different alleles. RESULTS: Among the 808 Rh- pregnant women of our sample, 178 (22.0%) were typed as DEL; 168 DEL samples were confirmed to have the RHD (1,227 G>A) allele, 8 DEL samples were characterized by one base mutation of the RHD (3G >A) allele, and the remaining two DEL samples were determined to carry RHD-CE(4-9)-D or RHD-CE(2-5)-D. The observation of allo-anti-D in two prominent D epitope loss cases confirmed the partial nature of these DEL phenotypes. CONCLUSIONS: In conclusion, evidence is provided that different DEL genotypes code either for partial or complete D antigen expression. It is suggested that the use of RhD+ RBCs in complete D antigen DEL patients does not induce adverse reaction.

Fish consumption and lung cancer risk: systematic review and meta-analysis.

There is evidence pointing to a possible role of diet on cancer etiology. Prior studies evaluating the relationship between fish consumption and lung cancer risk reported inconclusive results. The aim of this study was to achieve a comprehensive assessment of the relationship between fish consumption and lung cancer risk through systematic review and meta-analysis. Case control and cohort studies up to September 1, 2012 about fish consumption and lung cancer risk were confirmed by an online search. Separate relative risk (RR) or odds ratio (OR) estimates with 95% confidence interval (CI) of the relationship between lung cancer risk and fish consumption level from the included articles were combined by Stata11.0 software. Publication bias was evaluated by Egger's linear regression test and funnel plot. Twenty articles (17 case-control and 3 cohort studies) comprising 8799 cases of lung cancer and 17,072 noncases were included in the final analysis. The pooled results from all studies indicated that high fish consumption was significantly associated with a decreased risk of lung cancer (pooled RR: 0.79; 95% CI: 0.69-0.92). There was heterogeneity among the studies (I(2) = 73%, P < 0.05). Pooled RR in case control and cohort studies were 0.76 (95% CI: 0.63-0.91) and 0.95 (95% CI: 0.73-1.24), respectively. Omission of any single study had little effect on the combined risk estimates. This article had no publication bias. This study identifies a significant association between fish consumption and lung cancer, confirming a protective role of fish in lung cancer. More well-designed prospective studies are required to further verify the effect of fish consumption on lung cancer.

Hemostatic function and transfusion efficacy of apheresis platelet concentrates treated with gamma irradiation in use for thrombocytopenic patients.

BACKGROUND: During the transfusion of blood components, the transfer of allogeneic donor white blood cells (WBCs) can mediate transfusion-associated graft-versus-host disease (TA-GVHD). To minimize the reaction, exposure of blood products to gamma irradiation is currently the standard of care. The aim of our study was to evaluate and compare hemostatic function, transfusion efficacy, and safety of gamma-irradiated single-donor apheresis platelet concentrates (PCs) and of conventional non-irradiated PCs in patients with chemotherapy-induced thrombocytopenia. METHODS: 20 double-dose single-donor leukoreduced PCs were split in two identical units; one was gamma-irradiated with 25 Gy (study arm A) and the other remains non-irradiated (study arm B). Both units were stored under equal conditions. Hematologic patients were randomly assigned to receive gamma-irradiated or conventional non-irradiated PCs. Hemostatic function was evaluated by thrombelastography (TEG). TEG measurements were taken pre transfusion and 1 and 24 h post transfusion. TEG profiles were measured, noting the time to initiate clotting (R), the angle of clot formation (α), and the maximum amplitude (clot strength (MA)). Whole blood samples were collected from these thrombocytopenic patients at 1 and 24 h for PLT count increments (CIs) and corrected count increments (CCIs) with assessments of transfusion efficacy. Time to next PLT transfusion, transfusion requirement of RBCs, active bleeding, and adverse events (AEs), were analyzed. RESULTS: No differences could be found in hemostatic function parameters (MA, R, and α) between study arms A and B (all p values > 0.096) pre transfusion as well as 1 and 24 h post transfusion. No differences between study arms A and B were observed for mean (± standard deviation (SD)) 1-hour CCI (12.83 ± 6.33 vs. 11.59 ± 5.97) and 24-hour CCI (6.56 ± 4.10 vs. 5.76 ± 4.05). Mean 1-hour CI and 24-hour CI were not significantly different in both study arms (p = 0.254 and p = 0.242 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2.4 vs. 2.2 days, p = 0.767). No differences could be found in transfusion requirement of red blood cells (p = 0.744) between both study arms. There were also no regarding bleeding, adverse events, and acute transfusion reaction(s). CONCLUSIONS: This study confirms safety of gamma-irradiated PCs for treatment thrombocytopenia. Hemostatic function, transfusion efficacy, bleeding, and safety of single-donor apheresis PCs treated with gamma irradiation versus untreated control PCs are comparable.

Emerging organophosphite and organophosphate esters in takeaway food and the implications for human exposure.

Takeaway food has become a prominent component of the diet in urban areas of China, especially for young people. Although dietary intake is a major pathway to contaminants for human exposure, studies on emerging organophosphite antioxidants (OPAs) and organophosphate esters (OPEs) in food are scarce. Here, we investigated four OPAs and 19 OPEs in takeaway foods (n = 99) and paired takeaway food packaging (n = 50) in China. AO168=O (mean: 14.9 ng/g ww), TPPO (mean: 1.05 ng/g ww), and TCIPP (mean: 0.579 ng/g ww) were dominant in the takeaway food. Some OPEs had significant correlations in takeaway food. Emerging OPAs and OPEs in takeaway food varied significantly depending on the packaging materials and food types. AO168 and AO168=O were widespread in the paired takeaway food packaging. The migration efficiencies of emerging OPAs and OPEs were low in takeaway food packaged in aluminum foil. Although the actual contamination of emerging OPAs and OPEs in takeaway food significantly differed from those of in food simulants migrated from paired takeaway food packaging, the results imply that food itself and takeaway food packaging are potential contamination sources of emerging OPAs and OPEs in takeaway food. The average estimated dietary intakes of emerging OPAs and OPEs were 465 ng/kg body weight (bw)/day and 91.9 ng/kg bw/day, respectively. The exposure risk of emerging OPAs and OPEs through takeaway food intake is low in China.

The Association between Diet-Exercise Patterns and Cirrhosis: A Cross-Sectional Study from NHANES 2017-March 2020.

BACKGROUND: Liver cirrhosis (LC) is one of the most significant causes of morbidity and mortality in patients with chronic liver disease worldwide. Nutrition may be an important component of primary prevention of chronic liver disease. Diet-exercise patterns frame the eating behaviors and exercise habits of people through statistical methods related to nutritional epidemiology, which can explore the relationship between living habits and diseases among diverse populations. The purpose of this study was to explore the association between diet-exercise patterns and cirrhosis, and provide guidance on preventive diets for liver patients. METHODS: This study identified diet-exercise patterns via clustering analysis of principal components and assessed their association with cirrhosis through the population samples of the National Health and Nutrition Examination Survey (NHANES) from 2017 to March 2020. RESULTS: We identified two diet-exercise patterns that were named the "prudent pattern" (consumption of various staple foods, eggs, meat, fruits and vegetables; less sedentary) and the "dangerous pattern" (higher consumption of desserts, nuts, milk, meat, alcoholic beverages; recreational activities). The t-test demonstrated a significant relationship between patterns and multiple foods. The simple logistic regression test showed a lower risk of cirrhosis in those in the "prudent pattern" (OR = 0.73, 95%CI = 0.59-0.93). CONCLUSIONS: Two diet-exercise patterns associated with cirrhosis were identified: "prudent pattern" and "dangerous pattern". The results of this study may be useful for suggesting preventive diets for people at risk of cirrhosis.

Contamination of dairy products with tris(2,4-di-tert-butylphenyl) phosphite and implications for human exposure.

Tris(2,4-di-tert-butylphenyl) phosphite (AO168), an organophosphite antioxidant, can be oxidized to tris(2,4-di-tert-butylphenyl) phosphate (AO168 = O) during the production, processing, and application of plastics. AO168 = O can be further transformed to bis(2,4-di-tert-butylphenyl) phosphate and 2,4-di-tert-butylphenol. Here, we discovered the contamination of AO168 and its transformation products in dairy products for the first time. More samples contained AO168 (mean concentration: 8.78 ng/g wet weight [ww]), bis(2,4-di-tert-butylphenyl) phosphate (mean:11.1 ng/g ww) and 2,4-di-tert-butylphenol (mean: 46.8 ng/g ww) than AO168 = O (mean: 40.2 ng/g ww). The concentrations of AO168 and its transformation products were significantly correlated, and differed with the packaging material and storage conditions of the product. Estimated daily intakes (EDIs) of AO168 and its transformation products were calculated. Although the overall dietary risks were below one, transformation products accounted for 96.7% of the total hazard quotients. The high-exposure EDIs of total AO168 were above the threshold of toxicological concern (300 ng/kg bw/day), and deserve continual monitoring.

Effects of short-term exposure to Pomacea canaliculata secretions on Limnodrilus hoffmeisteri and Propsilocerus akamusi: A study based on behavior, intestinal microbiota, and antioxidant system.

Pomacea canaliculata is one of the most notorious invasive aquatic snail, capable of influencing various aquatic organisms through their secretions. Limnodrilus hoffmeisteri and Propsilocerus akamusi are the most prevalent and powerful bioturbators in aquatic ecosystems. However, the mechanism of P. canaliculata's secretions affecting bioturbators remains unknown. This study aimed to investigate the effects of P. canaliculata's secretion on L. hoffmeisteri and P. akamusi. L. hoffmeisteri and P. akamusi were treated for 24 h with P. canaliculata and the native species Bellamya aeruginosa secretions at different densities (1 or 20). The migration numbers and aggregation rate of L. hoffmeisteri indicated that P. canaliculata secretion caused L. hoffmeisteri to become alert and migrate away from the nucleus community, resulting in poor population identification, especially at high concentrations. Moreover, the antioxidant enzymatic activity, lipid peroxidation, intestinal microbial diversity, and composition of the two bioturbators were analyzed. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration were elevated following P. canaliculata secretion treatment, indicating oxidative damage. Furthermore, the composition and diversity of intestinal microbiota of L. hoffmeisteri and P. akamusi were changed. The abundance of functional microbiota decreased, and pathogenic bacteria such as Aeromonas became dominant in the intestines of both bioturbators. The current research evaluates the effects of P. canaliculata secretion on the behavior, oxidative stress, and intestinal microbial composition and diversity of two bioturbators, providing new insights into the assessment of post-invaded ecosystems.