Genetic Polymorphisms in CYP2E1: Association with Schizophrenia Susceptibility and Risperidone Response in the Chinese Han Population

CYP2E1 is a member of the cytochrome P450 superfamily, which is involved in the metabolism and activation of both endobiotics and xenobiotics. The genetic polymorphisms of CYP2E1 gene (Chromosome 10q26.3, Accession Number NC_000010.10) are reported to be related to the development of several mental diseases and to be involved in the clinical efficacy of some psychiatric medications. We investigated the possible association of CYP2E1 polymorphisms with susceptibility to schizophrenia in the Chinese Han Population as well as the relationship with response to risperidone in schizophrenia patients.In a case-control study, we identified 11 polymorphisms in the 5' flanking region of CYP2E1 in 228 schizophrenia patients and 384 healthy controls of Chinese Han origin. From among the cases, we chose 130 patients who had undergone 8 weeks of risperidone monotherapy to examine the relationship between their response to risperidone and CYP2E1 polymorphisms. Clinical efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS).Statistically significant differences in allele or genotype frequencies were found between cases and controls at rs8192766 (genotype p = 0.0048, permutation p = 0.0483) and rs2070673 (allele: p = 0.0018, permutation p = 0.0199, OR = 1.4528 95%CI = 1.1487-1.8374; genotype: p = 0.0020, permutation p = 0.0225). In addition, a GTCAC haplotype containing 5 SNPs (rs3813867, rs2031920, rs2031921, rs3813870 and rs2031922) was observed to be significantly associated with schizophrenia (p = 7.47E-12, permutation p<0.0001). However, no association was found between CYP2E1 polymorphisms/haplotypes and risperidone response.Our results suggest that CYP2E1 may be a potential risk gene for schizophrenia in the Chinese Han population. However, polymorphisms of the CYP2E1 gene may not contribute significantly to individual differences in the therapeutic efficacy of risperidone. Further studies in larger groups are warranted to confirm our results

Epidemiological and Genomic analysis of Vibrio parahaemolyticus isolated from imported travelers at the port of Shanghai, China (2017-2019)

Abstract Background Vibrio parahaemolyticus is the predominant etiological agent of seafood-associated foodborne illnesses on a global scale. It is essential to elucidate the mechanisms by which this pathogen disseminates. Given the existing research predominantly concentrates on localized outbreaks, there is a pressing necessity for a comprehensive investigation to capture strains of V. parahaemolyticus cross borders. Results This study examined the frequency and genetic attributes of imported V. parahaemolyticus strains among travelers entering Shanghai Port, China, between 2017 and 2019.Through the collection of 21 strains from diverse countries and regions, Southeast Asia was pinpointed as a significant source for the emergence of V. parahaemolyticus. Phylogenetic analysis revealed clear delineation between strains originating from human and environmental sources, emphasizing that underlying genome data of foodborne pathogens is essential for environmental monitoring, food safety and early diagnosis of diseases. Furthermore, our study identified the presence of virulence genes (tdh and tlh) and approximately 120 antibiotic resistance-related genes in the majority of isolates, highlighting their crucial involvement in the pathogenesis of V. parahaemolyticus. Conclusions This research enhanced our comprehension of the worldwide transmission of V. parahaemolyticus and its antimicrobial resistance patterns. The findings have important implications for public health interventions and antimicrobial stewardship strategies, underscoring the necessity for epidemiological surveillance of pathogen at international travel hubs

Multiplex, variant-tolerant, real-time RT-LAMP for SARS-CoV-2 detection using HFman probe

Viral evolution impacts diagnostic test performance through the emergence of variants with sequences affecting the efficiency of primer binding. Such variants that evade detection by nucleic acid-based tests are subject to selective pressure, enabling them to spread more efficiently. Here, we report a variant-tolerant diagnostic test for SARS-CoV-2 using a loop-mediated isothermal nucleic acid-based amplification (LAMP) assay containing high-fidelity DNA polymerase and a high-fidelity DNA polymerase-medicated probe (HFman probe). In addition to demonstrating a high tolerance to variable SARS-CoV-2 viral sequences, the mechanism also overcomes frequently observed limitations of LAMP assays arising from non-specific amplification within multiplexed reactions performed in a single “pot”. Results showed excellent clinical performance (sensitivity 94.5%, specificity 100%, n = 190) when compared directly to a commercial gold standard reverse transcription quantitative polymerase chain reaction assay for the extracted RNA from nasopharyngeal samples and the capability of detecting a wide range of sequences containing at least alpha and delta variants. To further validate the test with no sample processing, directly from nasopharyngeal swabs, we also detected SARS-CoV-2 in positive clinical samples (n = 49), opening up the possibility for the assay’s use in decentralized testing

Genome-Wide Identification of the B-Box Gene Family and Expression Analysis Suggests Their Potential Role in Photoperiod-Mediated β-Carotene Accumulation in the Endocarp of Cucumber (<i>Cucumis sativus</i> L.) Fruit

Carotenoids are indispensable to plants and essential for human nutrition and health. Carotenoid contents are strongly influenced by light through light-responsive genes such as B-Box (BBX) genes. BBX proteins, a class of zinc-finger transcription factors, mediate many light-signaling pathways, leading to the biosynthesis of important metabolites in plants. However, the identification of the BBX gene family and expression analysis in response to photoperiod-mediated carotenoid accumulation in cucumber remains unexplored. We performed a genome-wide study and determined the expression of cucumber BBX genes (hereafter referred to as CsaBBXs genes) in the endocarp of Xishuangbanna cucumber fruit (a special type of cucumber accumulating a high level of β-carotene in the endocarp) using an RNA-seq analysis of plants previously subjected to two photoperiodic conditions. Here, 26 BBX family genes were identified in the cucumber genome and named serially CsaBBX1 through CsaBBX26. We characterized CsaBBX genes in terms of their phylogenetic relationships, exon-intron structures, cis-acting elements, and syntenic relationships with Arabidopsis thaliana (L.) Heynh. RNA-seq analysis revealed a varied expression of CsaBBX genes under photoperiod treatment. The analysis of CsaBBXs genes revealed a strong positive correlation between CsaBBX17 and carotenoid biosynthetic pathway genes (phytoene synthase, ζ-carotene desaturase, lycopene ε-cyclase, β-carotene hydroxylase-1), thus suggesting its involvement in β-carotene biosynthesis. Additionally, nine CsaBBX genes (CsaBBX 4,5,7,9,11, 13,15,17 and 22) showed a significant positive correlation with β-carotene content. The selected CsaBBX genes were verified by qRT-PCR and confirmed the validity of RNA-seq data. The results of this study established the genome-wide analysis of the cucumber BBX family and provide a framework for understanding their biological role in carotenoid accumulation and photoperiodic responses. Further investigations of CsaBBX genes are vital since they are promising candidate genes for the functional analysis of carotenoid biosynthesis and can provide genetic tools for the molecular breeding of carotenoids in plants

Data_Sheet_1_Research on safety and compliance of imported microbial inoculants using high-throughput sequencing.docx

Microbial inoculants are widely used in wastewater treatment, soil remediation, and biological control. Safety and compliance for active constituents are considered to be the most important measures of imported microbial inoculants. Microbial inoculants composition was commonly identified by phenotypic culture, which is time-consuming and labor intense with occasionally false negative results provided, and can only be tested for specific species. High-throughput sequencing (HTS), known for its non-targeted detection of unknown species composition in samples, is suitable for composition consistency identification and biosafety analysis of imported microbial inoculants. In this study, the application of HTS for microflora distribution and resistance gene was verified in microbial inoculants for environmental protection and then applicated in imported microbial inoculants. Both Illumina- and Nanopore-based HTS methods identified the same dominant bacterial species successfully in the imported microbial inoculants. The main component of bacterial species was Bacillus subtilis, Bacillus amyloliquefaciens, Bacillus licheniformis, and Enterococcus faecium, and further confirmed with traditional methods. The antibiotic resistance genes Bacillus subtilis mprF, bcrA, blt, lmrB, rphB, tet(L), tmrB, vmlR, ykkC, and ykkD were detected in all samples. Our results indicated that HTS processes the application potential to identify the active ingredients of microbial inoculants. Therefore, rapid and accurate identification of the microbial compositions in microbial formulation products is of high importance for port biosafety supervision.</p

Estimated <i>CYP2E1</i> haplotype frequencies and p values among cases and controls.

<p>Only haplotypes with a frequency higher than 3% are listed.</p><p>OR: Odds ratio; CI: confidence interval.</p

Frequencies of estimated haplotypes and test statistics between responders and non-responders.

<p>Only haplotypes with a frequency higher than 3% are listed.</p><p>OR: Odds ratio; CI: confidence interval.</p

Pairwise polymorphisms LD analysis.

<p>Pairwise polymorphisms LD analysis.</p

Clinical characteristics and baseline demographics of schizophrenia patients treated with risperidone.

<p>Data are shown as mean±SD. BPRS: Brief Psychiatric Rating Scale. *Significant difference (p<0.05) between males and females.</p