关键词： Prdm1   Blimp1   Bcl6   Gene expression   Cis-element   Reporter assay   Medaka  

摘要： Bcl6 and Prdm1 (Blimp1) are a pair of transcriptional factors that repressing each other in mammals. Prdm1 represses the expression of bcl6 by binding a cis-element of the bcl6 gene in mammals. The homologs of Bcl6 and Prdm1 have been identified in teleost fish. However, whether these two factors regulate each other in the same way in fish like that in mammals is not clear. In this study, the regulation of bcl6aa by Prdm1 was investigated in medaka. The mRNA of bcl6aa has three variants (bcl6aaX1-X3) at the 5 '-end by alternative splicing detected by RT-PCR. The three variants can be detected in adult tissues and developing embryos of medaka. Prdm1a and prdm1b are expressed in the tissues and embryos where and when bcl6aa is expressed. The expression of prdm1a was high while the expression of bcl6aa was low, and vice versa, detected in the spleen after stimulation with LPS or polyI:C. In vitro reporter assay indicated that bcl6aa could be directly repressed by both Prdm1a and Prdm1b in a dosage-dependent manner. After mutation of the key base, G, of all predicted binding sites in the core promoter region of bcl6aa, the repression by Prdm1a and/or Prdm1b disappeared. The binding site of Prdm1 in the bcl6aa gene is GAAAA(T/G). These results indicate that both Prdm1a and Prdm1b directly repress the expression of bcl6aa by binding their binding sites where the 5 '-G is critical in medaka fish.

关键词： clinical microbiology   teaching   engagement   online   in-person  

摘要： The COVID-19 (coronavirus disease 2019) pandemic has had significant impacts upon higher education teaching. Clinical microbiology teaching is primarily focused on a combination of practical skill development and didactic delivery of content. In the pandemic, the absence of in-person teaching has led to educators adapting in-person content for online platforms and delivery. This commentary covers alternative innovative and engaging teaching approaches to deliver clinical microbiology content during the COVID-19 *** teaching of clinical microbiology during COVID-19 pandemic to engage students.

关键词： 5-HT   IBS   IBS-C   serotonin transporter  

摘要： Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

摘要： INTRODUCTION: The increasing liver-related mortality calls for hepatic surveillance programs. To design them, factors selectively increasing liver-related vs overall mortality need to be identified. METHODS: We analyzed mortality data from 467,558 individuals recruited by the community-based UK Biobank. The mean follow-up was 11.4 years. Results: While all assessed genetic factors associated with increased liver-specific mortality, only homozygous TM6SF2 mutation and SERPINA1 mutation conferred elevated overall mortality. Among the environmental factors, obesity and metabolic syndrome disproportionately contributed to liver-related deaths. Discussion: Our data demonstrate an interplay between genetics and environment and provide a basis for hepatic surveillance programs.

关键词： Optical and Electronic Materials   Characterization and Evaluation of Materials  

摘要： In this paper, three different samples of spinel carbon@Sb2SnS4 (C@S) sulphide were successfully synthesized via simple hydrothermal technique using L-cysteine (L-cyst.), thioacetic acid (TAA) and thioacetamide (TAM) compounds as sulphur sources. Physical and surface characterizations for the synthesized sulphide powders, including X-ray diffraction (XRD), field emission electron microscope (FE-SEM), energy dispersive spectroscopy (EDS) and XPS techniques were carried out. The XRD results confirmed the formation of ternary sulphide Sb2SnS4 in the spinel cubic phase associated with graphite and minor phases of binary sulphides. The microstructure investigation of carbon-coated Sb2SnS4/TAA (C@S/TAA) revealed two-dimensional thin sheets collected as bundles that correspond to ternary sulphide phase, while small bright grains are related to the binary sulphides and oxides. Moreover, the existence of Sb3+ and Sn4+ was confirmed from the XPS double peaks of Sb3d and Sn3d orbitals. Galvanostatic cycling of the assembled cells indicated that C@S/TAA anode delivered the maximum discharge capacity of about 880 mA g(-1), while the C@S/L-cyst. cell possessed the lowest discharge capacity of about 772 mAh g(-1). Finally, the cell with C@S/TAA anode displayed the highest diffusion coefficient of Li+ ions and best rate capability performance due to the unique two-dimensional thin sheets-like morphology of Sb2SnS4 hybridized with carbon nanoplates.

摘要： INTRODUCTION: Patients with immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD) on immunosuppressive and biologic therapies were largely excluded from severe acute respiratory syndrome coronavirus-2 messenger RNA vaccine trials. METHODS: We evaluated adverse events (AE) after messenger RNA vaccination in 246 adults with IBD participating in a longitudinal vaccine registry. RESULTS: In general, AE frequency was similar to that reported in the general population. AEs were more common among younger patients and those with previous COVID-19. AEs were less common in individuals receiving advanced therapies with biologics or small-molecule inhibitors. DISCUSSION: Those with IBD and other immune-mediated inflammatory diseases can be reassured that the AE risk is likely not increased, and may be reduced, while on advanced therapies.

关键词： Polybrominated diphenyl ethers (PBDEs)   Decabromodiphenyl ethane (DBDPE)   House dust   Risk assessment   Hanoi urban area  

摘要： This study investigated the occurrence, distribution of several additive brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs) and some novel brominated flame retardants (NBFRs) in urban indoor dust collected from ten inner districts of Hanoi, Vietnam to assess the contamination status, emission sources, as well as their associated human exposure through indoor dust ingestion and health risks. Total concentrations of PBDEs and NBFRs in indoor dust samples ranged from 43 to 480 ng g(-1) (median 170 ng g(-1)) and from 56 to 2200 ng g(-1) (median 180 ng g(-1)), respectively. The most abundant PBDE congener in these dust samples was BDE-209 with concentrations ranging from 29 to 360 ng g(-1), accounting for 62.6-86.5% of total PBDE levels. Among the NBFRs analyzed, decabromodiphenyl ethane (DBDPE) was the predominant compound with a mean contribution of 98.6% total NBFR amounts. Significant concentrations of DBDPE were detected in all dust samples (median 180 ng g(-1), range 54-2200 ng g(-1)), due to DBDPE as a substitute for deca-BDE. Other NBFRs such as 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), pentabromoethylbenzene (PBEB) and 2,2',4,4',5,5'-hexabromobiphenyl (BB-153) were found at very low levels. Based on the measured BFR concentrations, daily intake doses (IDs) of PBDEs and NBFRs via dust ingestion at exposure scenarios using the median and 95(th) percentile levels for both adults and children were calculated for risk assessment. The results showed that the daily exposure doses via dust ingestion of all compounds, even in the high-exposure scenarios were also lower than their reference dose (RfD) values. The lifetime cancer risks (LTCR) were much lower than the threshold level (10(-6)), which indicated the acceptable health risks resulting from indoor BFRs exposure for urban residents in Hanoi.

关键词： LODDS   LNR   lymph node classification   colorectal cancer  

摘要： Simple Summary We compared the predictive and prognostic performance of different lymph node classification systems regarding overall survival in patients with colorectal cancer (CRC). Distinct lymph node ratio (LNR) and Log odds of positive lymph nodes (LODDS) classifications demonstrated prognostic superiority over the N category only in patients with Stage III CRC. Background: Lymph node ratio (LNR) and the Log odds of positive lymph nodes (LODDS) have been proposed as a new prognostic indicator in surgical oncology. Various studies have shown a superior discriminating power of LODDS over LNR and lymph node category (N) in diverse cancer entities, when examined as a continuous variable. However, for each of the classification systems various cut-off values have been defined, with the question of the most appropriate for patients with CRC still remaining open. The present study aimed to compare the predictive impact of different lymph node classification systems and to define the best cut-off values regarding accurate evaluation of overall survival in patients with resectable, non-metastatic colorectal cancer (CRC). Methods: CRC patients who underwent surgical resection from 1996 to 2018 were extracted from our medical data base. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 25 LNR and 26 LODDS classifications. Regression models were adjusted for age, sex, extent of the tumor, differentiation, tumor size and localization. Results: Our study group consisted of 654 consecutive patients with non-metastatic CRC. C-statistic revealed 2 LNR and 5 LODDS classifications that demonstrated superior prognostic performance in patients with UICC III CRC, compared to the N category. No clear advantage of one classification over another could be demonstrated in any other patient subgroup. Conclusions: Distinct LNR and LODDS classifications demonstrate a prognostic superiority over the N category only in patients

关键词： Rebuilding   Multispecies fisheries   Forgone yield   U   S   West Coast  

摘要： Rebuilding overfished stocks is central to fisheries policy, with the United States Magnuson-Stevens Act aligning with the United Nations Sustainable Development Goal 14.4 "to restore fish stocks in the shortest time feasible at least to levels that can produce maximum sustainable yield." In mixed stock fisheries, very low allowable catches for rebuilding stocks can lead to an inability to harvest abundant stocks. There are consequently trade-offs between the yield obtained during rebuilding and the rate of rebuilding. We retrospectively evaluate rebuilding plans in the US West Coast groundfish fishery to identify alternative harvest strategies that could have minimized adverse impacts to stakeholders while still achieving stock rebuilding targets. We use current assessments of 13 groundfish stocks to project spawning biomass and catch under various harvest policies. We estimate that an additional $886 million USD in ex-vessel revenue could have been obtained had an FMSY strategy permitting slower rebuilding rates been adopted. We also examined what catch limits would have been under a FMSY strategy using the information available at the time rebuilding plans were implemented. These alternative catch limits would have provided much greater fishing opportunity while still rebuilding the stocks. Our findings support those of the National Research Council, which in 2014 reported that rebuilding plans based on fishing mortality rates may be preferable to those focused on meeting strict rebuilding timelines.