[Expression Levels and Regulation of Selenoprotein Genes in Patients With Coronavirus Disease 2019].

Objective To investigate the expression levels of selenoprotein genes in the patients with coronavirus disease 2019 (COVID-19) and the possible regulatory mechanisms.Methods The dataset GSE177477 was obtained from the Gene Expression Omnibus,consisting of a symptomatic group (n=11),an asymptomatic group (n=18),and a healthy control group (n=18).The dataset was preprocessed to screen the differentially expressed genes (DEG) related to COVID-19,and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analysis were performed for the DEGs.The protein-protein interaction network of DEGs was established,and multivariate Logistic regression was employed to analyze the effects of selenoprotein genes on the presence/absence of symptoms in the patients with COVID-19.Results Compared with the healthy control,the symptomatic COVID-19 patients presented up-regulated expression of GPX1,GPX4,GPX6,DIO2,TXNRD1,SELENOF,SELENOK,SELENOS,SELENOT,and SELENOW and down-regulated expression of TXNRD2 and SELENON (all P<0.05).The asymptomatic patients showcased up-regulated expression of GPX2,SELENOI,SELENOO,SELENOS,SELENOT,and SELENOW and down-regulated expression of SELP (all P<0.05).The results of multivariate Logistic regression analysis showed that the abnormally high expression of GPX1 (OR=0.067,95%CI=0.005-0.904,P=0.042) and SELENON (OR=56.663,95%CI=3.114-856.999,P=0.006) was the risk factor for symptomatic COVID-19,and the abnormally high expression of SELP was a risk factor for asymptomatic COVID-19 (OR=15.000,95%CI=2.537-88.701,P=0.003).Conclusions Selenoprotein genes with differential expression are involved in the regulation of COVID-19 development.The findings provide a new reference for the prevention and treatment of COVID-19.

ß-arrestin2 deficiency ameliorates S-100-induced autoimmune hepatitis in mice by inhibiting infiltration of monocyte-derived macrophage and attenuating hepatocyte apoptosis.

Autoimmune hepatitis (AIH) is a progressive hepatitis syndrome characterized by high transaminase levels, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Misdiagnosis or delayed treatment of AIH can lead to cirrhosis or liver failure, which poses a major risk to human health. ß-Arrestin2, a key scaffold protein for intracellular signaling pathways, has been found to be involved in many autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. However, whether ß-arrestin2 plays a role in AIH remains unknown. In the present study, S-100-induced AIH was established in both wild-type mice and ß-arrestin2 knockout (Arrb2 KO) mice, and the experiments identified that liver ß-arrestin2 expression was gradually increased, and positively correlated to serum ANA, ALT and AST levels during AIH progression. Furthermore, ß-arrestin2 deficiency ameliorated hepatic pathological damage, decreased serum autoantibody and inflammatory cytokine levels. ß-arrestin2 deficiency also inhibited hepatocyte apoptosis and prevented the infiltration of monocyte-derived macrophages into the damaged liver. In vitro experiments revealed that ß-arrestin2 knockdown suppressed the migration and differentiation of THP-1 cells, whereas ß-arrestin2 overexpression promoted the migration of THP-1 cells, which was regulated by the activation of the ERK and p38 MAPK pathways. In addition, ß-arrestin2 deficiency attenuated TNF-α-induced primary hepatocyte apoptosis by activating the Akt/GSK-3ß pathway. These results suggest that ß-arrestin2 deficiency ameliorates AIH by inhibiting the migration and differentiation of monocytes, decreasing the infiltration of monocyte-derived macrophages into the liver, thereby reducing inflammatory cytokines-induced hepatocytes apoptosis. Therefore, ß-arrestin2 may act as an effective therapeutic target for AIH.

[A Prediction Model for Human Immunodeficiency Virus Infection and Mother-to-Child Transmission Based on the Expression Levels of Selenoprotein Genes].

Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.

Pre-diagnostic dietary consumption of calcium and magnesium and calcium-to-magnesium intake ratio and ovarian cancer mortality: results from the ovarian cancer follow-up study (OOPS).

PURPOSE: Previous studies have indicated that dietary consumption of calcium (Ca), magnesium (Mg), and the Ca-to-Mg (Ca:Mg) ratio were associated with different health outcomes. However, no study has evaluated the association of pre-diagnostic Ca, Mg, and Ca:Mg ratio consumption with ovarian cancer (OC) survival. METHODS: The aforementioned associations were investigated in a cohort of 853 Chinese women diagnosed with OC between 2015 and 2020. A validated food frequency questionnaire was used to evaluate pre-diagnostic diet information. Deaths were recorded until March 31, 2021 via medical records and active follow-up. Cox proportional hazards model was applied to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 130 deaths were observed during a median follow-up of 37.2 months. After adjustment for potential confounders, pre-diagnostic Ca (HR< 600 vs. > 1000 = 1.45, 95% CI = 0.47-4.46, p for trend = 0.69) and Mg (HR< 250 vs. > 330 = 0.90, 95% CI = 0.39-2.08, p for trend = 0.77) intakes were found to be unrelated to OC survival, whereas a higher Ca:Mg intake ratio was significantly associated with worse survival (HR< 1.7 vs. > 2.5 = 2.72, 95% CI = 1.28-5.78, p for trend < 0.05). A significant result was also observed when treating the Ca:Mg ratio as a continuous variable (HR = 1.69, 95% CI = 1.12-2.55) for one-unit increment. CONCLUSION: Pre-diagnostic consumption of Ca and Mg was unrelated to OC survival, while a higher Ca:Mg intake ratio was strongly associated with worse survival among OC patients.

ß-Arrestin2 deficiency attenuates oxidative stress in mouse hepatic fibrosis through modulation of NOX4.

Hepatic fibrosis is a disease characterized by excessive deposition of extracellular matrix (ECM) in the liver. Activation of hepatic stellate cells (HSCs) is responsible for most of ECM production. Oxidative stress and reactive oxygen species (ROS) may be important factors leading to liver fibrosis. NADPH oxidase 4 (NOX4) is the main source of ROS in hepatic fibrosis, but the mechanism by which NOX4 regulates oxidative stress is not fully understood. ß-Arrestin2 is a multifunctional scaffold protein that regulates receptor endocytosis, signaling and trafficking. In this study, we investigated whether ß-arrestin2 regulated oxidative stress in hepatic fibrosis. Both ß-arrestin2 knockout (Arrb2 KO) mice and wild-type mice were intraperitoneally injected with carbon tetrachloride (CCl4) to induce hepatic fibrosis. Arrb2 KO mice showed significantly attenuated liver fibrosis, decreased ROS levels and NOX4 expression, and reduced collagen levels in their livers. In vitro, NOX4 knockdown significantly inhibited ROS production, and decreased expression of alpha-smooth muscle actin in angiotensin II-stimulated human HSC cell line LX-2. Through overexpression or depletion of ß-arrestin2 in LX-2 cells, we revealed that decreased ß-arrestin2 inhibited ROS levels and NOX4 expression, and reduced collagen production; it also inhibited activation of ERK and JNK signaling pathways. These results demonstrate that ß-arrestin2 deficiency protects against liver fibrosis by downregulating ROS production through NOX4. This effect appears to be mediated by ERK and JNK signaling pathways. Thus, targeted inhibition of ß-arrestin2 might reduce oxidative stress and inhibit the progression of liver fibrosis.

The identification of fish eggs of two species, the ovate sole Solea ovata and black porgy Acanthopagrus schlegelii.

Fish eggs of the ovate sole Solea ovata and black porgy Acanthopagrus schlegelii were identified through DNA barcoding of cytochrome c oxidase subunit I (COX1). Visual taxonomic features were achieved, and photographs of the eggs of both species at different developmental stages were reported for the first time. In addition, the dissolution of oil globules caused by ethanol as egg fixatives was observed. This result showed the importance of using formalin as egg fixatives in the case of morphometric analysis and the necessity of combining molecular and visual taxonomic method for morphological study.

Infertility and ovarian cancer risk: Evidence from nine prospective cohort studies.

Epidemiological studies have investigated the relationship between infertility and the risk of ovarian cancer (OC); however, the results have been inconsistent. We therefore conducted the first meta-analysis to update and quantify the aforementioned association based on prospective cohort studies. Studies were identified by searching PubMed, EMBASE and Web of Science databases up to January 8, 2020. We extracted data from the studies and performed quality assessments. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Publication bias, and subgroup, meta-regression and sensitivity analyses were also conducted. Nine prospective cohort studies with a total of 10 383 OC cases and 6 278 830 participants were included in the present study. The summary RR of the association between infertility and the risk of OC was 1.51 (95% CI: 1.35-1.69), with low heterogeneity. Positive associations were observed in most subgroup analyses stratified by predefined factors, including region, duration of follow-up, study quality, causes of infertility, invasiveness of OC, infertility treatment status and adjustment of potential confounding parameters. No significant publication bias was detected. Our findings suggest that infertility in women were associated with an increased risk of OC.

Depletion of ß-arrestin 2 protects against CCl4-induced liver injury in mice.

Acute liver injury can be caused by oxidative stress within a short period and is a common pathway to many liver diseases. The liver is vulnerable to reactive oxygen species (ROS) and free radical-mediated disorders. ß-arrestin2 was initially discovered to be a negative regulator of G protein-coupled receptor signaling. Recently, ß-arrestin2 has been found to act as a multifunctional adaptor protein and play new roles in regulating intracellular signaling networks. However, the role of ß-arrestin2 in the pathogenesis of acute liver injury is unclear. In this study, we hypothesize that ß-arrestin2 regulates acute liver injury via modulation of oxidative stress. ß-arrestin2 knockout mice were used to investigate the impacts of ß-arrestin2 on carbon tetrachloride (CCl4)-induced acute liver injury and oxidative stress. Results here suggested that ß-arrestin2 deficiency decreased serum activities of aminotransferase and alleviated liver injury induced by CCl4 injection as compared with wildtype mice. ß-arrestin2 knockout mice exhibited stronger tolerance in oxidative stress compared with wild-type mice, which was demonstrated by decreased ROS level and increased superoxide dismutase (SOD) and glutathione (GSH) in the liver. Furthermore, ß-arrestin2 deficiency significantly inhibited NOX4 (a major source of ROS) expression and the activation of the extracellular regulated kinase (ERK) and, c-Jun NH2-terminal kinase (JNK) pathways. These results suggest that ß-arrestin2 deficiency protects against CCl4-induced acute liver injury through attenuating oxidative damage and decreased ERK and JNK phosphorylation.

DL-3-n-butylphthalide alleviates vascular cognitive impairment by regulating endoplasmic reticulum stress and the Shh/Ptch1 signaling-pathway in rats.

BACKGROUND: DL-3-n-butylphthalide (NBP) has been approved to be effective in improving cognitive deficits. The aim of the current study was to determine whether NBP protects against cognitive deficits in a rat model of vascular dementia (VD) induced by chronic cerebral hypoperfusion (CCH) by regulating the sonic hedgehog (Shh)/patched1 (Ptch1) pathway and endoplasmic reticulum stress (ERS)-related markers. METHODS: Adult male Sprague-Dawley rats were subjected to permanent bilateral occlusion of the common carotid arteries (2VO) to established the model of VD. These rats were randomly divided into five groups: sham, model, NBP30 (30 mg/kg), NBP 60 (60 mg/kg), and NBP 120 (120 mg/kg) groups. The Morris water maze test was used to assess for cognitive function at 4 weeks after operation. RESULTS: NBP significantly alleviated spatial learning and memory impairment, and inhibited the loss of neurons in the CA1 region of the hippocampus. Western blot analysis and real-time quantitative polymerase chain reaction analysis revealed that plasticity-related synaptic markers and the Shh/Ptch1 pathway significantly increased in the NBP treated groups, while ERS-related markers decreased. CONCLUSION: The results of the current study prove that the Shh/Ptch1 pathway plays an essential role in the model of VD. NBP had protective effects on cognitive impairment induced by CCH. This mechanism was associated with ERS and the Shh/Ptch1 pathway. Meanwhile, the Shh/Ptch1 pathway and ERS may interact with each other.

The effects of isotope-labeled analogs on the LC-IDMS measurement by comparison of ESI responses and matrix effect of melamine, 13C3-melamine, 13C3+15N3-melamine, and 15N3-melamine.

In this paper, the effect of isotope-labeled analogs on the liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) measurement was evaluated based on the comparison research of electrospray ionization responses (ESI) and matrix effect of melamine, 13C3-melamine, 13C3+15N3-melamine, and 15N3-melamine. The isotope-labeled melamines had similar ionization efficiency with melamine in the electrospray ionization source, but the intensity of corresponding quantitative fragment ions had distinctive differences. Based on the density functional theory at the B3LYP/6-311+G** level, this phenomenon was explained very well. The rare cleavage pathways of melamine, which just could be exactly identified by 15N-labeled melamines, resulted in the difference of quantitative fragment ions between 15N-labeled melamines and melamine. The interaction of ESI response between melamine and isotope-labeled melamines was investigated using MRM monitor mode. 15N-labeled melamine had significant ion inter-suppression effect on melamine, while 13C-labeled melamine had little influence on melamine. Finally, the influence of different isotope-labeled melamines on the LC-IDMS result was evaluated using the IDMS correction factor (θ). Taking the determination of melamine in milk powder as an example, the matrix effects of different isotope-labeled melamines and melamine had notable difference and the impact of this difference on the measurement results depended on the concentrations of analyte and matrix solution. It was worth noting that 15N3-melamine exhibited significant ion suppression to melamine in matrix solution. The deviation of the results from IDMS method might reach 59% using 15N3-melamine as internal standard in special matrix solution. Graphical Abstract The comparison of ESI responses of melamine, 13C3-melamine, 13C3+15N3-melamine and 15N3-melamine.

Study on diffusion behavior of analyte in an electrospray ionization source.

RATIONALE: Diffusion of an analyte is one of the main determinants of reduced sensitivity in an electrospray ionization (ESI) source. In this work, the relative responses of compounds and their stable isotope-labeled (SIL) products in different injection modes were compared to investigate the diffusion behavior of analytes in ESI, without influence of other factors. METHODS: Chloramphenicol (CAP) and D5 -CAP as well as melamine (Mel) and (13) C3 -Mel were used to illustrate the diffusion behavior in different operation modes and different ion sources, by comparing their relative responses in infusion mode and flow injection analysis (FIA) mode under variable temperature. RESULTS: In infusion mode, sample solution was introduced by syringe, and formed a stable and continuous signal. While in FIA mode, because of the huge difference in volume between the sample solution and the mobile phase, it is assumed that analyte ionizes and transmits in the gaseous phase created by the mobile phase. Analytes formed different concentration distributions in the two injection modes. The relative responses of CAP and D5 -CAP increased from 0.81 to 0.98 when the temperature was increased from 300 °C to 650 °C in infusion mode and decreased from 1.37 to 1.17 with increasing temperature in FIA mode. The opposite trends of the two injection modes were also obtained in positive operation modes and ion sources with different configuration. CONCLUSIONS: Opposite variation tendencies of relative responses of model samples and their stable isotope-labeled products with temperature were observed for infusion and FIA injection modes, indicating different diffusion behaviors in the two injection modes. These results provide a theoretical basis for ion source designing and better understanding of the ESI mechanism. Copyright © 2016 John Wiley & Sons, Ltd.

[Research on Rapid Discrimination of Edible Oil by ATR Infrared Spectroscopy].

A rapid discrimination method of edible oils, KL-BP model, was proposed by attenuated total reflectance infrared spectroscopy. The model extracts the characteristic of classification from source data by KL and reduces data dimension at the same time. Then the neural network model is constructed by the new data which as the input of the model. 84 edible oil samples which include sesame oil, corn oil, canola oil, blend oil, sunflower oil, peanut oil, olive oil, soybean oil and tea seed oil, were collected and their infrared spectra determined using an ATR FT-IR spectrometer. In order to compare the method performance, principal component analysis (PCA) direct-classification model, KL direct-classification model, PLS-DA model, PCA-BP model and KL-BP model are constructed in this paper. The results show that the recognition rates of PCA, PCA-BP, KL, PLS-DA and KL-BP are 59.1%, 68.2%, 77.3%, 77.3% and 90.9% for discriminating the 9 kinds of edible oils, respectively. KL extracts the eigenvector which make the distance between different class and distance of every class ratio is the largest. So the method can get much more classify information than PCA. BP neural network can effectively enhance the classification ability and accuracy. Taking full of the advantages of KL in extracting more category information in dimension reducing and the features of BP neural network in self-learning, adaptive, nonlinear, the KL-BP method has the best classification ability and recognition accuracy and great importance for rapidly recognizing edible oil in practice.

Polyamidoamine dendrimer liposome-mediated survivin antisense oligonucleotide inhibits hepatic cancer cell proliferation by inducing apoptosis.

Polyamidoamine dendrimer (PAMAM) is a new nanometer material, which can transfer the target genes to cells with high efficiency and lower toxicity. This study aims to evaluate antitumor effects of survivin antisense oligonucleotide (survivin-asODN) (carried by polyamidoamine dendrimer liposome) on hepatic cancer in nude mice. Hepatic cancer model was established by injecting SMMC-7721 cells subcutaneously into flanks of nude mice. Polyamidoamine dendrimer and liposome were mixed with survivin-asODN, respectively. The shape and size of complex were observed by transmission electron microscope, and zeta potential was measured by an analytical tool. Encapsulation efficiency and DNA loading level were determined by an ultraviolet spectrophotometer in centrifuging method. Expression of survivin in transplant tumor was measured by Western blotting. No significant difference appeared for diameter and envelopment ratio between PAMAM liposome-survivin-asODN and PAMAM-survivin-asODN (P > 0.05). Both zeta potential and transfection efficiency in PAMAM liposome-survivin-asODN were higher than that in PAMAM-survivin-asODN complex (P < 0.05). Expression of survivin protein and weight of tumors in transplanted tumors in PAMAM liposome-survivin-asODN group was less than that in PAMAM-survivin-asODN group (P < 0.05). Cell apoptosis rate in PAMAM liposome-survivin-asODN group was higher than that of PAMAM-survivin-asODN group (P < 0.05). In conclusion, polyamidoamine dendrimer liposome can deliver survivin-asODN into hepatic transplanted tumor cells effectively. Ployamidoamine dendrimer liposome-mediated survivin-asODN can inhibit hepatic cell proliferation by inducing apoptosis.

Generic and accurate prediction of retention times in liquid chromatography by post-projection calibration.

Retention time predictions from molecule structures in liquid chromatography (LC) are increasingly used in MS-based targeted and untargeted analyses, providing supplementary evidence for molecule annotation and reducing experimental measurements. Nevertheless, different LC setups (e.g., differences in gradient, column, and/or mobile phase) give rise to many prediction models that can only accurately predict retention times for a specific chromatographic method (CM). Here, a generic and accurate method is present to predict retention times across different CMs, by introducing the concept of post-projection calibration. This concept builds on the direct projections of retention times between different CMs and uses 35 external calibrants to eliminate the impact of LC setups on projection accuracy. Results showed that post-projection calibration consistently achieved a median projection error below 3.2% of the elution time. The ranking results of putative candidates reached similar levels among different CMs. This work opens up broad possibilities for coordinating retention times between different laboratories and developing extensive retention databases.

Peroxiredoxin III protein expression is associated with platinum resistance in epithelial ovarian cancer.

We investigated the association between peroxiredoxin III (PRX III) and chemotherapy resistance in ovarian cancer. Patient's specimens were taken at the time of surgery. Determination of resistance is based on whether first diagnosis of relapse occurred within 6 months after the cessation of chemotherapy. PRX III expression was immunohistochemically determined in paraffin-embedded specimens from platinum-resistant (Pt-resistant) and platinum-sensitive (Pt-sensitive) patients. The Pt-resistant group had significantly higher PRX III protein compared to the Pt-sensitive group. The two groups showed no significant differences in pathological classification and age, although they differed significantly in tissue differentiation and stage. PRX III protein was significantly higher in the Pt-resistant serous carcinomas, in moderately and poorly differentiated, and in stage III and IV ovarian cancer tissues compared to the Pt-sensitive group. PRX III may be associated with drug resistance in ovarian cancer.

[Screening of organophosphorus flame retardant residues in rice by QuEChERS-gas chromatography-quadrupole time-of-flight mass spectrometry].

Organophosphorus flame retardants (OPFRs) have emerged as good alternatives to brominated flame retardants, the use of which is globally restricted. In this study, a screening method based on QuEChERS-gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q-TOF/MS) was established for the determination of 21 OPFRs in rice. First, full scan (scanning range, m/z 50-450) was performed with a mixed standard solution of the 21 OPFRs (0.1 µg/g) by GC-Q-TOF/MS. The fragmentation pathways of these OPFRs were then investigated to explore their cleavage fragments, the interrelationships among fragments, and the possible cleavage modes of alkylated, chlorinated, and aromatic OPFRs. The retention times, isotopic abundance ratios, and molecular formulas of the characteristic fragments as well as the exact mass of the compounds were obtained to establish a mass spectral library of the OPFRs. Rice samples were extracted and purified by the QuEChERS method, and 0.5% formate acetonitrile solution was used as the extraction solvent; 4 g of magnesium sulfate, 1 g of sodium chloride, 0.5 g of disodium hydrogen citrate, and 1 g of sodium citrate as the extraction-salt combination; and 50 mg of primary secondary amine (PSA), 50 mg of octadecylsilane (C18), and 150 mg of magnesium sulfate as the purification materials. The chromatographic separation of the 21 OPFRs was completed within 16 min under optimized temperature program conditions on the DB-5MS UI column. The screening parameters were optimized, and a full scan of the samples was performed under the following conditions: number of characteristic fragment ions ≥2; accurate mass window=±2×10-5 (±20 ppm); retention time deviation=±0.2 min, and ion abundance deviation<20%. The developed method was applied to the screening 21 OPFRs in the samples. The results indicated that the matrix interference was greatly reduced by decreasing the extraction accurate mass window, thereby improving the signal-to-noise ratio of the analytes. The targets were extracted from the matrix interference and background noise using deconvolution software, which improved the match between the target compounds and the mass spectral library. The detection rates of alkyl and aromatic OPFRs increased by 22% and 25%, respectively, when the spiking level was increased from 2 to 10 ng/g. Among the chlorinated OPFRs, only tris(2-chloroisopropyl) phosphate (TCIPP) was not detected at a spiking level of 2 ng/g, indicating that chlorinated OPFRs could be identified even at low concentrations. The characteristic ions of the detected compounds matched those of the home-made mass spectral library well, indicating that the practical application of the home-made mass spectral library. The established screening method was applied in the determination of OPFRs in rice samples from different regions in China. A total of 11 OPFRs were detected, among which trimethyl phosphate (TMP), tri-iso-butyl phosphate (TiBP), and tris(3,5-dimethylphenyl) phosphate (T35DMPP) had the highest detection rates. These results indicate that these three OPFRs are widely used and can easily come into contact with rice samples through various routes. Differences in the types of OPFRs detected in the actual samples may be related to the types of OPFRs produced in local factories. OPFRs can be detected in rice samples by the developed GC-Q-TOF/MS screening method, which is helpful for the identification of OPFRs in complex matrix samples.

Effect of Kangfuxiaomi suppository on pelvic inflammatory disease in rats.

Pelvic inflammatory disease (PID) is commonly encountered in gynecological practice. Kangfuxiaomi suppository, made from the compound extract of Periplaneta Americana, is a Traditional Chinese Medicine remedy widely used for the treatment of gynecological disorders. This study aimed to preliminarily explore the therapeutic effect of Kangfuxiaomi suppository in a rat model of PID established by chemical injury and pathogen infection. The key parameters assessed were vulvar inflammation score, vaginal + uterine organ index, and serum levels of interleukin (IL)- 8; tumor necrosis factor (TNF)-α; C-reactive protein (CRP); superoxide dismutase (SOD); and malondialdehyde (MDA). In addition, levels of IL-6, cyclooxygenase (COX)- 2, and IL-2 in cervical tissues as well as that of IL-1ß and prostaglandin E-2 (PGE2) in uterine tissues were measured. The expression levels of nuclear factor-kappa B (NF-κB) p65 and Toll-like receptor 4 (TLR4) in uterine tissues were detected by immunohistochemical method. After Kangfuxiaomi suppository treatment, the vulva inflammation score and histopathological score of PID rats showed a tendency to decrease. Serum IL-8, TNF-α, CRP, and MDA levels were reduced, while SOD levels were significantly increased. Levels of IL-6, IL-2, and COX-2 in cervical tissues were somewhat decreased, and PGE2 and IL-1ß levels in uterine tissue were significantly decreased. Moreover, the levels of NF-κB p65 and TLR4 protein expression were also decreased. These findings demonstrated the therapeutic effect of Kangfuxiaomi suppository in PID rats. The underlying mechanism may involve enhanced antioxidant capacity and decreased secretion of proinflammatory factors via the NF-κB/TLR4 signaling pathway.

Pre-diagnosis meat intake and cooking method and ovarian cancer survival: results from the Ovarian Cancer Follow-Up Study (OOPS).

Objectives: The relationships between pre-diagnosis meat intake and ovarian cancer (OC) survival were limited and controversial. To date, no study has taken account of cooking methods. Thus, we aimed to firstly clarify these associations based on the Ovarian Cancer Follow-Up Study. Methods: This prospective cohort study, including 853 OC patients between 2015 and 2020, was conducted to examine the aforementioned associations. All women completed a food frequency questionnaire. Deaths were ascertained up to March 31, 2021 via medical records and active follow-up. We used the Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During the median follow-up of 37.17 months, 130 women died. Pre-diagnosis fish and seafood intake was associated with better survival (HRT3 vs. T1 = 0.46, 95% CI = 0.26-0.82, p trend <0.05), whereas processed red meat (HR = 1.54, 95% CI = 1.04-2.26) and a high frequency of fried fish intake (HR = 1.49, 95% CI = 1.03-2.16) were associated with worse survival than consuming none. After considering the interaction of cooking methods, we found that compared with the lowest tertile of fish and seafood intake and almost no fried fish cooking, women with the highest tertile of intake and almost no fried fish cooking had better survival (HR = 0.35, 95% CI = 0.13-0.92). Additionally, compared with the lowest tertile of fish and seafood intake and almost no baked fish cooking, women with the lowest tertile of intake and consuming baked fish had worse survival (HR = 3.75, 95% CI = 1.53-9.15). Conclusions: Pre-diagnosis fish and seafood intake was associated with better OC survival, whereas processed red meat intake was associated with worse survival. Cooking methods, especially for fried or baked fish, may play interaction effects with fish intake on OC survival.

CP-25 exerts a protective effect against ConA-induced hepatitis via regulating inflammation and immune response.

Hepatitis is a complex multifactorial pathological disorder, which can eventually lead to liver failure and even potentially be life threatening. Paeoniflorin-6'-O-benzene sulfonate (CP-25) has proven to have critical anti-inflammatory effects in arthritis. However, the effects of CP-25 in the pathogenesis of hepatitis remains unclear. In this experiment, mice were intragastrically administered with CP-25 (25, 50 and 100 mg/kg), and then ConA (25 mg/kg) was intravenous injected to establish hepatitis model in vivo. CP-25 administration attenuated liver damage and decreased ALT and AST activities in mice with hepatitis. Besides, CP-25 modulated immune responses including down-regulated the proportions of activated CD4+, activated CD8+ T cells, and ratio of Th1/Th2 in ConA-injected mice. Furthermore, ConA-mediated production of reactive oxygen species (ROS), release of inflammatory cytokines including IFN-γ, TNF-α, activation of MAPK pathways and nuclear translocation of nuclear factor-kappaB (NF-κB) were significantly decreased in CP-25 administrated mice. In ConA-stimulated RAW264.7 cells, CP-25 suppressed inflammatory cytokines secretion and reduced ROS level, which were consistent with animal experiments. Otherwise, the data showed that CP-25 restrained phosphorylation of ERK, JNK and p38 MAPK pathways influenced by ROS, accompanied with inhibiting NF-κB nuclear translocation. In conclusion, our findings indicated that CP-25 protected against ConA-induced hepatitis may through modulating immune responses and attenuating ROS-mediated inflammation via the MAPK/NF-κB signaling pathway.

Association between pre-diagnostic dietary pattern and survival of ovarian cancer: Evidence from a prospective cohort study.

BACKGROUND: Evidence for a role of single nutrition or foods on ovarian cancer (OC) survival has been limited and inconclusive. Due to the potentially complex interactions in dietary, we applied dietary patterns to this study to firstly explore the relationship between the pre-diagnosis overall diet and OC survival. METHODS: The prospective cohort study was conducted among 853 OC patients aged 18-79 years during 2015-2020. Dietary intake was collected using a validated 111-item food frequency questionnaire. Deaths were obtained by medical records and cancer registry up to March 31, 2021. Cox proportional hazards regression models was used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of pre-diagnosis dietary patterns with overall survival (OS). RESULTS: Overall, during the follow-up period (median: 37.57 months, interquartile: 25.00-50.17 months), 130 (18.49%) OC patients died. Four dietary patterns were identified: healthy pattern, ethnic pattern, animal foods pattern, and sweet pattern. The highest tertile of the healthy pattern scores was related to better OS compared with the lowest tertile scores (HR = 0.54, 95% CI = 0.30-0.98, p trend <0.05), whereas OC patients with highest adherence to the animal foods pattern was associated with worse OS than those with the lowest adherence (HR = 1.90, 95% CI = 1.14-3.17, p trend <0.05). We found no significant associations between adherence to ethnic pattern and sweet pattern and OS of OC patients. CONCLUSION: Pre-diagnosis healthy patterns was associated with better OC survival, whereas animal pattern was associated with worse survival among OC survivals.