The Effect of Algorithmic Recommendations on Female University Students’ Willingness to Engage in Romantic Behaviour

With algorithmic recommendations becoming an important way and means of information distribution, social media platforms are developing rapidly, and students in colleges and universities today have become the main audience for their information access. In this paper, through the application of TPB model in the intention to fall in love of young female groups in colleges and universities, four variables, namely attention, attitude, subjective norm and perceived behavioural control, were studied in depth, and a research model of factors influencing the relationship behaviour of young female groups was constructed based on the theoretical model of planned behaviour. According to the results, the factor of attention did not have a significant positive effect on relationship behaviour intentions, and behavioural attitudes, subjective norms and perceived behavioural control (PBC) had a significant positive effect on relationship behaviour intentions

LH level on the antagonist administration day as a predictor of the reproductive outcomes in women with normal ovarian function

IntroductionThe addition of antagonists is mainly based on estrogen level and follicle size, while LH level has not received sufficient attention.In this study, LH Level on the antagonist administration day was used as the main research objective to explore its relationship with laboratory indicators and pregnancy outcomes.Methods and AnalysisWe enrolled 854 patients with normal ovarian function undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) between May 2021 to May 2022 at the Reproductive Center of Shandong University of Traditional Chinese Medicine.We used the quartile method to group LH levels on the antagonist administration day. There were four groups: Q1 (0.53IU/L≤LH ≤ 1.89IU/L); Q2 (1.89IU/L<LH ≤ 3.01IU/L); Q3 (3.01IU/L<LH≤ 5.29 IU/L); Q4 (5.29IU/L<LH ≤ 8.72IU/L). A total of 452 fresh embryo transplantation cycles and 1726 Frozen embryo transplantation cycles were carried out.ResultThere were significant differences among the four groups in terms of total Gn dosage, E2, P and LH on trigger day, number of retrieved oocytes, number of 2PN embryos, number of blastocysts, Number of ET and fresh ETR.There is a significant correlation between LH on antagonist administration day and Basal LH Level,LH on trigger day,number of oocytes retrieved,number of 2PN embryos,number of blastocysts, number of ET.Using Fresh ETR,Fresh CPR,OHSS and Cumulative CPR as the criterion respectively, the optimal cut-off value for evaluating LH on antagonist administration day was 4.18IU/L,3.99IU/L,4.63IU/L,4.66IU/L.ConclusionThere was a significant positive correlation between LH on the antagonist administration day and number of oocytes retrieved,number of 2PN embryos,number of blastocysts.LH on the antagonist administration day could predict Fresh CPR,OHSS and Cumulative CPR to some extent

Higher Activity of the Inducible Nitric Oxide Synthase Contributes to Very Early Onset Inflammatory Bowel Disease

OBJECTIVES: The NOS2 gene encodes for the inducible nitric oxide synthase (iNOS), responsible for nitric oxide (NO) production, which contributes to antimicrobial and antipathogenic activities. Higher levels of both iNOS and NO-induced damage have been observed in inflammatory bowel disease (IBD) patients. NOS2 may have a role in a specific subset of IBD patients with severe and/or extensive colitis. Therefore, the aim of this study is to examine the role of NOS2 in such a subset, very early onset IBD (VEO-IBD). METHODS: Seventeen tag single nucleotide polymorphisms (SNPs) in the NOS2 gene were successfully genotyped in VEO-IBD patients. Genetic associations were replicated in an independent VEO-IBD cohort. Functional analysis for iNOS activity was performed on the most significantly associated functional variant. RESULTS: The NOS2 rs2297518 SNP was found to be associated in VEO-IBD in two independent cohorts. Upon combined analysis, a coding variant (S608L) showed the strongest association with VEO-IBD (Pcombined=1.13 × 10−6, OR (odds ratio)=3.398 (95% CI (confidence interval) 2.02–5.717)) as well as associations with VEO-Crohn's disease and VEO-ulcerative colitis (UC). This variant also showed an association with UC diagnosed between 11 and 17 years of age but not with adult-onset IBD (>17 years). B-cell lymphoblastoid cell lines genotyped for the risk variant as well as Henle-407 cells transfected with a plasmid construct with the risk variant showed higher NO production. Colonic biopsies of VEO-IBD patients showed higher immunohistochemical staining of nitrotyrosine, indicating more nitrosative stress and tissue damage. CONCLUSIONS: These studies suggest the importance of iNOS in genetic susceptibility to younger IBD presentation due to higher NO production

Highly potent multivalent VHH antibodies against Chikungunya isolated from an alpaca naïve phage display library

Background Chikungunya virus (CHIKV) is a re-emerged mosquito-borne alphavirus that can cause musculoskeletal diseases, imposing a substantial threat to public health globally. High-affinity antibodies are need for diagnosis and treatment of CHIKV infections. As a potential diagnostic and therapeutic agent, the multivalent VHH antibodies is a promising tookit in nanomedicine. Here, we developed potent multivalent VHH antibodies from an alpaca naïve phage display library targeting the E2 glycoprotein of the CHIKV virus. Results In the present study, we generated 20 VHH antibodies using a naïve phage display library for binders to the CHIKV E2 glycoprotein. Of these, multivalent VHH antibodies Nb-2E8 and Nb-3C5 had specific high-affinity binding to E2 protein within the nanomolar range. The equilibrium dissociation constant (KD) was between 2.59–20.7 nM, which was 100-fold stronger than the monovalent antibodies’ affinity. Moreover, epitope mapping showed that Nb-2E8 and Nb-3C5 recognized different linear epitopes located on the E2 glycoprotein domain C and A, respectively. A facile protocol of sandwich ELISA was established using BiNb-2E8 as a capture antibody and HRP-conjugated BiNb-3C5 as a detection antibody. A good linear correlation was achieved between the OD450 value and the E2 protein concentration in the 5–1000 ng/mL range (r = 0.9864, P < 0.0001), indicating its potential for quantitative detection of the E2 protein. Conclusions Compared to monovalent antibodies, multivalent VHH antibodies Nb-2E8 and Nb-3C5 showed high affinity and are potential candidates for diagnostic applications to better detect CHIKV virions in sera. Graphical Abstrac

Novel CARMIL2 loss-of-function variants are associated with pediatric inflammatory bowel disease

CARMIL2 is required for CD28-mediated co-stimulation of NF-kappa B signaling in T cells and its deficiency has been associated with primary immunodeficiency and, recently, very early onset inflammatory bowel disease (IBD). Here we describe the identification of novel biallelic CARMIL2 variants in three patients presenting with pediatric-onset IBD and in one with autoimmune polyendocrine syndrome (APS). None manifested overt clinical signs of immunodeficiency before their diagnosis. The first patient presented with very early onset IBD. His brother was found homozygous for the same CARMIL2 null variant and diagnosed with APS. Two other IBD patients were found homozygous for a nonsense and a missense CARMIL2 variant, respectively, and they both experienced a complicated postoperative course marked by severe infections. Immunostaining of bowel biopsies showed reduced CARMIL2 expression in all the three patients with IBD. Western blot and immunofluorescence of transfected cells revealed an altered expression pattern of the missense variant. Our work expands the genotypic and phenotypic spectrum of CARMIL2 deficiency, which can present with either IBD or APS, aside from classic immunodeficiency manifestations. CARMIL2 should be included in the diagnostic work-up of patients with suspected monogenic IBD

Wheat Rhizosphere Metagenome Reveals Newfound Potential Soil Zn-Mobilizing Bacteria Contributing to Cultivars’ Variation in Grain Zn Concentration

An effective solution to global human zinc (Zn) deficiency is Zn biofortification of staple food crops, which has been hindered by the low available Zn in calcareous soils worldwide. Many culturable soil microbes have been reported to increase Zn availability in the laboratory, while the status of these microbes in fields and whether there are unculturable Zn-mobilizing microbes remain unexplored. Here, we use the culture-independent metagenomic sequencing to investigate the rhizosphere microbiome of three high-Zn (HZn) and three low-Zn (LZn) wheat cultivars in a field experiment with calcareous soils. The average grain Zn concentration of HZn was higher than the Zn biofortification target 40 mg kg–1, while that of LZn was lower than 40 mg kg–1. Metagenomic sequencing and analysis showed large microbiome difference between wheat rhizosphere and bulk soil but small difference between HZn and LZn. Most of the rhizosphere-enriched microbes in HZn and LZn were in common, including many of the previously reported soil Zn-mobilizing microbes. Notably, 30 of the 32 rhizosphere-enriched species exhibiting different abundances between HZn and LZn possess the functional genes involved in soil Zn mobilization, especially the synthesis and exudation of organic acids and siderophores. Most of the abundant potential Zn-mobilizing species were positively correlated with grain Zn concentration and formed a module with strong interspecies relations in the co-occurrence network of abundant rhizosphere-enriched microbes. The potential Zn-mobilizing species, especially Massilia and Pseudomonas, may contribute to the cultivars’ variation in grain Zn concentration, and they deserve further investigation in future studies on Zn biofortification

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development

Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer.

Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10- 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10- 4, replication P = 6.7 × 10- 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development