The value of toxicological analysis in acute poisoning patients with uncertain exposure histories:a retrospective and descriptive study from an institute of poisoning

BACKGROUND:In clinical practice,some patients might not be able or unwilling to provide a thorough history of medication and poison exposure.The aim of this study was to use toxicological analysis to examine the clinical characteristics of patients with acute poisoning whose exposure history was uncertain from a toxicological analysis perspective.METHODS:This was a retrospective and descriptive study from an institute of poisoning.Patient registration information and test reports spanning the period from April 1,2020 to March 31,2022,were obtained.Patients with uncertain exposure histories and who underwent toxicological analysis were included.Clinical manifestations and categories of toxics were analyzed.RESULTS:Among the 195 patients with positive toxicological analysis results,the main causes of uncertain exposure history was disturbance of consciousness(62.6%),unawareness(23.6%)and unwillingness or lack of cooperation(13.8%).The predominant clinical manifestations were disturbed consciousness(62.6%),followed by vomiting and nausea(14.4%)and liver function abnormalities(8.7%).A comparison of clinical manifestations between patients with positive and negative(n=99)toxicological analyses results revealed significantly different proportions of disturbances in consciousness(63%vs.21%),dizziness(1.5%vs.5.1%),multi-organ failure(1.5%vs.7.1%),and local pain(0 vs 4%).The main categories of substances involved were psychiatric medications(23.1%),sedatives(20.5%),insecticides(13.8%),and herbicides(12.8%).CONCLUSION:The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific,and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of such patients.

Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS

The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.

Biological functions and potential implications of circular RNAs

Circular RNAs(circRNAs) are characterized by a covalent closed-loop structure with an absence of both 5′ cap structure and 3′ polyadenylated tail. Numerous studies have found that circRNAs play an important role in various diseases and have a variety of biological regulatory mechanisms, including acting as microRNA sponges,interacting with proteins, modulating the expression of related genes and translating into peptides or proteins.CircRNAs have also been used as biomarkers for a number of diseases, which could improve clinical practice.This review summarizes the most recent advances in biogenesis and knowledge of the biological functions of circRNAs as well as the related bioinformatics databases. We specifically describe developments in understanding of circRNA functions in the field of environmental exposure-induced diseases. Finally, we focus on potential clinical implications of circRNAs to facilitate their clinical transformation into disease treatment.

circPVT1 promotes silica-induced epithelial-mesenchymal transition by modulating the miR-497-5p/TCF3 axis

Epithelial-mesenchymal transition(EMT)is a vital pathological feature of silica-induced pulmonary fibrosis.However,whether circRNA is involved in the process remains unclear.The present study aimed to investigate the role of circPVT1 in the silica-induced EMT and the underlying mechanisms.We found that an elevated expression of circPVT1 promoted EMT and enhanced the migratory capacity of silica-treated epithelial cells.The isolation of cytoplasmic and nuclear separation assay showed that circPVT1 was predominantly expressed in the cytoplasm.RNA immunoprecipitation assay and RNA pull-down experiment indicated that cytoplasmic-localized circPVT1 was capable of binding to miR-497-5p.Furthermore,we found that miR-497-5p attenuated the silica-induced EMT process by targeting transcription factor 3(TCF3),an E-cadherin transcriptional repressor,in the silica-treated epithelial cells.Collectively,these results reveal a novel role of the circPVT1/miR-497-5p/TCF3 axis in the silica-induced EMT process in lung epithelial cells.Once validated,this finding may provide a potential theoretical basis for the development of interventions and treatments for pulmonary fibrosis.

Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediated FAM227A expression

Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.

Optogenetics-induced activation of glutamate receptors improves memory function in mice with Alzheimer’s disease

Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.

Effect of exposure to ambient PM2.5 pollution on the risk of respiratory tract diseases： a meta-analysis of cohort studies

The International Agency for Research on Cancer and the World Health Organization have designated airborne particulates, including particulates of median aerodynamic diameter 〈 2.5 gm （PM2.5）, as Group 1 carcinogens. It has not been determined, however, whether exposure to ambient PM2.5 is associated with an increase in respiratory related diseases. This meta-analysis assessed the association between exposure to ambient fine particulate matter （PM2.5） and the risk of respiratory tract diseases, using relevant articles extracted from PubMed, Web of Science, and Embase. In results, of the 1,126 articles originally identified, 35 （3.1%） were included in this meta-analysis. PM2.5 was found to be associated with respiratory tract diseases. After subdivision by age group, respiratory tract disease, and continent, PM2.5 was strongly associated with respiratory tract diseases in children, in persons with cough, lower respiratory illness, and wheezing, and in individuals from North America, Europe, and Asia. The risk of respiratory tract diseases was greater for exposure to traffic-related than non-traffic-related air pollution. In children, the pooled relative risk （RR） represented significant increases in wheezing （8.2%）, cough （7.5%）, and lower respiratory illness （15.3%）. The pooled RRs in children were 1.091 （95%CI： 1.049, 1.135） for exposure to 〈 25 gg/m3 PM2.5, and 1.126 （95%CI： 1.067, l. 190） for exposure to 〉 25 gg/m3 PM2.5. In conclusion, exposure to ambient PM2.5 was significantly associated with the development of respiratory tract diseases, especially in children exposed to high concentrations of PM2.5.

Effects of extracellular vesicles from mesenchymal stem cells on oxygen-glucose deprivation/reperfusioninduced neuronal injury

BACKGROUND: Small extracellular vesicles (sEVs) from bone marrow mesenchymal stemcells (BMSCs) have shown therapeutic potential for cerebral ischemic diseases. However, themechanisms by which BMSC-derived sEVs (BMSC-sEVs) protect neurons against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we explored the neuroprotective effects ofBMSC-sEVs in the primary culture of rat cortical neurons exposed to oxygen-glucose deprivation andreperfusion (OGD/R) injury.METHODS: The primary cortical neuron OGD/R model was established to simulate the processof cerebral I/R in vitro. Based on this model, we examined whether the mechanism through whichBMSC-sEVs could rescue OGD/R-induced neuronal injury.RESULTS: BMSC-sEVs (20 μg/mL, 40 μg/mL) significantly decreased the reactive oxygenspecies (ROS) productions, and increased the activities of superoxide dismutase (SOD) and glutathioneperoxidase (GPx). Additionally, BMSC-sEVs prevented OGD/R-induced neuronal apoptosis in vivo, asindicated by increased cell viability, reduced lactate dehydrogenase (LDH) leakage, decreased terminaldeoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining-positivecells, down-regulated cleaved caspase-3, and up-regulated Bcl-2/Bax ratio. Furthermore, Westernblot and flow cytometry analysis indicated that BMSC-sEV treatment decreased the expression ofphosphorylated calcium/calmodulin-dependent kinase II (p-CaMK II)/CaMK II, suppressed the increaseof intracellular calcium concentration ([Ca2+]i) caused by OGD/R in neurons.CONCLUSIONS: These results demonstrate that BMSC-sEVs have signifi cant neuroprotectiveeff ects against OGD/R-induced cell injury by suppressing oxidative stress and apoptosis, and Ca2+/CaMK II signaling pathways may be involved in this process.

The preparation and application of N-terminal 57 amino acid protein of the follicle-stimulating hormone receptor as a candidate male contraceptive vaccine

Follicle-stimulating hormone receptor （FSHR）, which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein （FSHR-57aa） as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a（＋）-FSHR-57aa plasmid was constructed and expressed in Escherichia coil strain BL21 StarTM （DE3） and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 （16 weeks） after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.

Identification of the metabolites of polybrominated diphenyl ether 99 and its related cytochrome P450s

Objective：To investigate the metabolites of polybrominated diphenyl ether 99（BDE-99）and its related cytochrome P450s in an in vitro system.Methods：Rat primary hepatocytes were isolated and treated with BDE-99 for 24-72 h.Metabolites were then extracted from the hepatocytes and media,and detected by GC/MS.Several mRNAs of metabolic enzymes were also extracted from the same cells and the gene expression levels were determined using quantitative real-time PCR.In addition,selected recombinant cytochrome P450s（CYPs） were expressed in a bacurovirus/sf9 system,and these were further used to explore the metabolism of BDE-99 in vitro.The parent depletion approach was used for screening the ability of CYPs to eliminate BDE-99.Results： A reductively debrominated metabolite,BDE-47,and three oxidative metabolites,2,4,5-tribromophenol,5-OH-BDE-47,and 5＇-OH-BDE-99,were identified from the BDE-99-treated rat hepatocytes,whereas no MeO metabolite was detected in the system.RT-PCR analysis showed that CYP 3A23/3A1,1A2,and 2B1/2 were induced by BDE-99.Furthermore,using the heterological expressed CYP proteins in in vitro BDE-99 metabolism experiments we found that CYP1A2 and CYP3A4 showed the highest metabolic efficiency for BDE-99,with the metabolic clearance rates of CYP1A2 and CYP3A4 being 30.3%and 27.7%,respectively.CYP1A1 and CYP2A6 displayed relatively low clearance rates,while CYP2E1 seemed not to be associated with the BDE-99 metabolism.Conclusions：In our in vitro rat primary hepatocyte metabolism system,four metabolites of BDE-99 were identified,and CYP3A4 and CYP1A2 were demonstrated to be involved in the BDE-99 metabolism.

Epigenetic regulation mechanism of ABCG2 induced drug-resistant phenotype

The aim of this study is to investigate epigenetic mechanism of ABCG2 induced drug-resistance.It is not only expatiate for drug-resistance regulation mechanism in all-round,but also to provide scientific experimental basis for selecting target to reverse its drug-resistance.Apply methylation-specific PCR(MSP) to have tested methylation of ABCG2 promoter region -359 to -353 specific positions in breast cancer tissues and paired adjacent tissue of 22 cases,and test their methylation positions with MSP products for sequencing;and adopt fluorescent quantitation RT-PCR to test expression level DNMT1,DNMT3A,DNMT3B and ABCG2;to make analysis on relationship between them with statistical spearman correlation.Specific positions of ABCG2 gene promoter region of 18 cases among the 22 cases with breast cancer(18/22,82%) existed high methylation(P<0.05),MSP products sequencing proved methylation of the specific position,and mRNA expression level was relative higher in remarkable positive correlation(P<0.05).ABCG2,DNMT1,DNMT3A,DNMT3B mRNA expression levels in breast cancer tissues were obviously higher than adjacent tissues(P<0.01),and DNMT3B expression level was obviously higher than DNMT1 and DNMT3A(P<0.01) in negative correlation with ABCG2 gene expression(P=0.001).-359 to -353 positions of promoter regions of ABCG2 gene existed high methylation capable to push expression of this gene in beast cancer tissue.DNMT3B is involved in expression regulation in ABCG2 gene,and provides new scientific basis for drug-resistance target as reverse ABCG2

A susceptibility locus rs7099208 is associated with non-obstructive azoospermia via reduction in the expression of FAM160B1

Non-obstructive azoospermia （NOA） is a severe defect in male reproductive health that occurs in 1% of adult men. In a previous study, we identified that rs7099208 is located within the last intron of FAM160B1 at 10q25.3. In this study, we analysed expression Quantitative Trait Loci （eQTL） of FAM16OB1, ABLIM1 and TRUB1, the three genes surrounding rs7099208. Only the expression level of FAM16OB1 was reduced for the homozygous alternate genotype （GG） of rs7099208, but not for the homozygous reference or heterozygous geno- types. FAM160B1 is predominantly expressed in human testes, where it is found in spermatocytes and round sper- matids. From 17 patients with NOA and five with obstructive azoospermia （OA）, immunohistochemistry revealed that expression of FAM160B1 is reduced, or undetectable in NOA patients, but not in OA cases or normal men. We conclude that rs7099208 is associated with NOA via a reduction in the expression of FAM160B1.

Protective effect of mesenchymal stem cell-derived exosomal treatment of hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury

BACKGROUND:Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury.Mesenchymal stem cell(MSC)transplantation is used to reduce tissue damage,but exosomes are more stable and highly conserved than MSCs.This study was conducted to investigate the therapeutic effects of MSC-derived exosomes(MSC-Exo)on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion(OGD/R),and to explore the underlying mechanisms.METHODS:Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment,with or without MSC-Exo treatment.Exosomal integration,cell viability,mitochondrial membrane potential,and generation of reactive oxygen species(ROS)were examined.Terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate nickend labeling(TUNEL)staining was performed to detect neuronal apoptosis.Moreover,mitochondrial function-associated gene expression,Nrf2 translocation,and expression of downstream antioxidant proteins were determined.RESULTS:MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation(P<0.05).The exosomes reduced OGD/R-induced Nrf2 translocation into the nucleus(2.14±0.65 vs.5.48±1.09,P<0.01)and increased the intracellular expression of antioxidative proteins,including superoxide dismutase and glutathione peroxidase(17.18±0.97 vs.14.40±0.62,and 20.65±2.23 vs.16.44±2.05,respectively;P<0.05 for both).OGD/R significantly impaired the mitochondrial membrane potential and modulated the expression of mitochondrial functionassociated genes,such as PINK,DJ1,LRRK2,Mfn-1,Mfn-2,and OPA1.The abovementioned changes were partially reversed by exosomal treatment of the hippocampal neurons.CONCLUSIONS:MSC-Exo treatment can alleviate OGD/R-induced oxidative stress and dysregulation of mitochondrial function-associated genes in hippocampal neurons.Therefore,MSCExo might be a potential therapeutic strategy to prevent OGD/R-induced neuronal injury.

Trichloroethylene Induces Biphasic Concentration-dependent Changes in Cell Proliferation and the Expression of SET-Associated Proteins in Human Hepatic L-02 Cells

Trichloroethylene （TCE） is a major pollutant that affects both occupational and general environments. The liver is an important target organ of TCEE. Substantial efforts and remarkable progress into understanding TCE cytotoxicity have been made in cultured liver cells. However, the molecular mechanisms by which TCE induces hepatotoxicity are not well understood. SET （also known as protein phosphatase 2A inhibitor, 12PP2A, or template-activating factor-I, TAF-D is a nuclear protein that regulates histone modification, gene transcription, DNA replication, nucleosome assembly,

Molecular epidemiology of DNA repair gene polymorphisms and head and neck cancer

Although tobacco and alcohol consumption are two common risk factors of head and neck cancer （HNC）, other specific etiologic causes, such as viral infection and genetic susceptibility factors, remain to be understood. Hu- man DNA is often damaged by numerous endogenous and exogenous mutagens or carcinogens, and genetic vari- ants in interaction with environmental exposure to these agents may explain interindividual differences in HNC risk. Single nucleotide polymorphisms （SNPs） in genes involved in the DNA damage-repair response are reported to be risk factors for various cancer types, including HNC. Here, we reviewed epidemiological studies that have assessed the associations between HNC risk and SNPs in DNA repair genes involved in base-excision repair, nucleotide-excision repair, mismatch repair, double-strand break repair and direct reversion repair pathways. We found, however, that only a few SNPs in DNA repair genes were found to be associated with significantly in- creased or decreased risk of HNC, and, in most cases, the effects were moderate, depending upon locus-locus in- teractions among the risk SNPs in the pathways. We believe that, in the presence of exposure, additional pathway- based analyses of DNA repair genes derived from genome-wide association studies （GWASs） in HNC are needed.

Association between exposure to particulate matter during pregnancy and birthweight:a systematic review and a metaanalysis of birth cohort studies

Studies of the associations between maternal exposure to particulate matter(PM) and risk of adverse effects on fetal growth are inconsistent and inconclusive. This question can be well answered by carefully designed birth cohort studies; however, so far the evidence from such studies has not come to the same conclusion. We sought to evaluate the association between maternal exposures to PM and low birthweight(LBW) enrolling 14 studies from 11 centers,and to explore the influence of trimester and exposure assessment methods on between-center heterogeneity in this association. Data were derived from PubMed, Embase, Google Scholar, CNKI, and WanFang database, references from relevant articles, and results from published studies until March 2017. Using a random-effects meta-analysis, we combined the coefficient and odds ratios(OR) of individual studies conducted among 14 birth cohort studies.Random-effect meta-analysis results suggested that a 17% and 6% increase in risk of LBW was relevant to a 10 μg/m^3 rise in PM_(2.5) and PM_(10) exposure concentrations at the 3 rd trimester(pooled odds ratios(OR), 1.17 and 1.06; 95%confidence interval(CI), 0.94-1.46 and 0.97-1.15, respectively), but the null value was included in our 95% CI. Our results showed that exposure to PM_(2.5) and PM_(10) during pregnancy has a positive relevance to LBW based on birth cohort studies. However, neither reached formal statistical significance. Negative impacts on outcomes of birth is implied by maternal exposure to PM. Further mechanistic researches are needed to explain the connection between PM pollution and LBW.

Nighttime snacking is associated with risk of obesity and hyperglycemia in adults:a cross-sectional survey from Chinese adult teachers

Relationship between nighttime snack and human health conditions remains unclear. In this paper, we analyzed the association of frequency of nighttime snacking with obesity, hyperlipidemia and hyperglycemia using a Chinese teacher cohort. The Chinese teacher study contains 22,176 of the general adult population operated on in 2015.Information of nighttime snacking frequency was acquired by questionnaire. Overweight and obesity outcome were assessed by body mass index（BMI）, and hypertension; hyperlipidemia and hyperglycemia were self-reported.Associations between nighttime snacking consumption and outcomes were performed with multivariat regression and further stratification analyses. We found a significant association（OR 2.11, 95% CI 1.24, 3.62; P for trend 〈0.001）between most frequent nighttime snacking and hyperglycemia. A remarkable association was also observed between most frequent consumption of nighttime snack and obesity（OR 3.10, 95% CI 1.63, 5.89; P for trend〈0.001）. The present results provide epidemiological evidence that consumption of nighttime snack was associated with obesity and hyperglycemia in Chinese adult teachers. However, the underlying mechanisms still need further investigation.

Pre-evaluation of humoral immune response of Bactrian camels by the quantification of Th2 cytokines using real-time PCR

With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations,it is demanding to develop an easy-to-handle evaluation method of their humoral immune response before proceeding with immunization of foreign antigens that may be toxic to camels.In this study,we quantitatively determined the expression levels of T-helper 2(Th2) cytokines in peripheral blood lymphocytes obtained from Bactrian camels by real-time PCR.The recorded kinetic profiles resulting from the immunization of ovalbumin(OVA) indicated that after immunization,Th2 cytokines including interleukin(IL) families such as IL-4,IL-10,and IL-13 in the camels were up-regulated by a factor of 1.78,3.15,and 1.22,respectively,which was validated by traditional enzyme-linked immunosorbent assay(ELISA) methods.Unlike ELISA which requires specific enzyme-labeled antibodies,this established method based on the minimal amount of blood samples holds an advantage in the preliminary evaluation of camel humoral immune response with desirable precision,which is meaningful for biomedical explorations of camel-derived antibodies.

Alternative polyadenylation-related genetic variants contribute to bladder cancer risk

Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.

CoFe_(2)O_(4) decorated graphene/C_(18)-functionalized mesoporous silica nanocomposites prepared for magnetic enrichment and electrochemical detection of promethazine in beef

Promethazine(PHZ)is used as a sedative in veterinary medicine,and its residue can threaten the health of human.The electrochemical detection of PHZ is suitable method for application in the field.However,the traditional electroanalysis is difficult to perform directly in meat samples due to matrix interference.This work integrates magnetic solid-phase extraction and differential pulse voltammetry for highly sensitive and selective determination of PHZ in beef and beef liver for the first time.CoFe_(2)O_(4)/graphene coated with C_(18)-functionalized mesoporous silica(MG@mSiO_(2)-C_(18))is synthesized as dispersed magnetic adsorbent to extract PHZ.Magnetic glassy carbon electrode modified with nitrogen-doped hollow carbon microspheres(HCM)attracts the MG@mSiO_(2)-C_(18)with PHZ,and directly detects the PHZ without elution procedure.MG@mSiO_(2)-C_(18)can separate PHZ to avoid the interference of impurities on following detection,and also concentrate PHZ on magnetic electrode.Additionally,the electrode modification with HCM can amplify the electrochemical signal of PHZ.Finally,the integrated PHZ determination method exhibits a wide linear range from 0.08μmol/L to 300μmol/L with a low limit of detection of 9.8 nmol/L.The beef sample analysis presents excellent recovery,demonstrating that this protocol is promising for the rapid and onsite detection of PHZ in real meat samples。