An epigenome-wide association study of waist circumference in Chinese monozygotic twins.

OBJECTIVES: Central obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships. METHODS: A total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage. RESULTS: We identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites. CONCLUSIONS: Our research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms.

Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins.

Background: The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic relationship between genome-wide DNA methylation and handgrip strength (HGS) among Chinese monozygotic (MZ) twins. Methods: DNA methylation (DNAm) profiling was conducted in whole blood samples through Reduced Representation Bisulfite Sequencing method. Generalized estimating equation was applied to regress the DNAm of each CpG with HGS. The Genomic Regions Enrichment of Annotations Tool was used to perform enrichment analysis. Differentially methylated regions (DMRs) were detected using comb-p. Causal inference was performed using Inference about Causation through Examination of Familial Confounding method. Finally, we validated candidate CpGs in community residents. Results: We identified 25 CpGs reaching genome-wide significance level. These CpGs located in 9 genes, especially FBLN1, RXRA, and ABHD14B. Many enriched terms highlighted calcium channels, neuromuscular junctions, and skeletal muscle organ development. We identified 21 DMRs of HGS, with several DMRs within FBLN1, SLC30A8, CST3, and SOCS3. Causal inference indicated that the DNAm of 16 top CpGs within FBLN1, RXRA, ABHD14B, MFSD6, and TYW1B might influence HGS, while HGS influenced DNAm at two CpGs within FBLN1 and RXRA. In validation analysis, methylation levels of six CpGs mapped to FLBN1 and one CpG mapped to ABHD14B were negatively associated with HGS weakness in community population. Conclusion: Our study identified multiple DNAm variants potentially related to HGS, especially CpGs within FBLN1 and ABHD14B. These findings provide new clues to the epigenetic modification underlying muscle strength decline.

Mediation role of DNA methylation in association between handgrip strength and cognitive function in monozygotic twins.

Handgrip strength is a crucial indicator to monitor the change of cognitive function over time, but its mechanism still needs to be further explored. We sampled 59 monozygotic twin pairs to explore the potential mediating effect of DNA methylation (DNAm) on the association between handgrip strength and cognitive function. The initial step was the implementation of an epigenome-wide association analysis (EWAS) in the study participants, with the aim of identifying DNAm variations that are associated with handgrip strength. Following that, we conducted an assessment of the mediated effect of DNAm by the use of mediation analysis. In order to do an ontology enrichment study for CpGs, the GREAT program was used. There was a significant positive association between handgrip strength and cognitive function (ß = 0.194, P < 0.001). The association between handgrip strength and DNAm of 124 CpGs was found to be statistically significant at a significance level of P < 1 × 10-4. Fifteen differentially methylated regions (DMRs) related to handgrip strength were found in genes such as SNTG2, KLB, CDH11, and PANX2. Of the 124 CpGs, 4 within KRBA1, and TRAK1 mediated the association between handgrip strength and cognitive function: each 1 kg increase in handgrip strength was associated with a potential decrease of 0.050 points in cognitive function scores, mediated by modifications in DNAm. The parallel mediating effect of these 4 CpGs was -0.081. The presence of DNAm variation associated with handgrip strength may play a mediated role in the association between handgrip strength and cognitive function.

A New Network Structure for Speech Emotion Recognition Research.

Deep learning promotes the breakthrough of emotion recognition in many fields, especially speech emotion recognition (SER). As an important part of speech emotion recognition, the most relevant acoustic feature extraction has always attracted the attention of existing researchers. Aiming at the problem that the emotional information contained in the current speech signals is distributed dispersedly and cannot comprehensively integrate local and global information, this paper presents a network model based on a gated recurrent unit (GRU) and multi-head attention. We evaluate our proposed emotion model on the IEMOCAP and Emo-DB corpora. The experimental results show that the network model based on Bi-GRU and multi-head attention is significantly better than the traditional network model at detecting multiple evaluation indicators. At the same time, we also apply the model to a speech sentiment analysis task. On the CH-SIMS and MOSI datasets, the model shows excellent generalization performance.

Chromosome-scale Genome assembly of the critically endangered White-eared Night-Heron (Gorsachius magnificus).

The White-eared Night-Heron (Gorsachius magnificus, G. magnificus) is a critically endangered heron that is very poorly known and only found in southern China and northern Vietnam, with an estimated population of 250 to 999 mature individuals. However, the lack of a reference genome has hindered the implementation of conservation management efforts. In this study, we present the first high-quality chromosome-scale reference genome, which was assembled by integrating PacBio long-reads sequencing, Illumina paired-end sequencing, and Hi-C technology. The genome has a total length of 1.176 Gb, with a scaffold N50 of 84.77 Mb and a contig N50 of 18.46 Mb. Utilizing Hi-C data, we anchored 99.89% of the scaffold sequences onto 29 pairs of chromosomes. Additionally, we identified 18,062 protein-coding genes in the genome, with 95.00% of which were functionally annotated. Notably, BUSCO assessment confirmed the presence of 97.2% of highly conserved Aves genes within the genome. This chromosome-level genome assembly and annotation will be valuable for future investigating the G. magnificus's evolutionary adaptation and conservation.

Co-methylation analyses identify CpGs associated with lipid traits in Chinese discordant monozygotic twins.

To control genetic background and early life milieu in genome-wide DNA methylation analysis for blood lipids, we recruited Chinese discordant monozygotic twins to explore the relationships between DNA methylations and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). 132 monozygotic (MZ) twins were included with discordant lipid levels and completed data. A linear mixed model was conducted in Epigenome-wide association study (EWAS). Generalized estimating equation model was for gene expression analysis. We conducted Weighted correlation network analysis (WGCNA) to build co-methylated interconnected network. Additional Qingdao citizens were recruited for validation. Inference about Causation through Examination of Familial Confounding (ICE FALCON) was used to infer the possible direction of these relationships. A total of 476 top CpGs reached suggestively significant level (P < 10-4), of which, 192 CpGs were significantly associated with TG (FDR < 0.05). They were used to build interconnected network and highlight crucial genes from WGCNA. Finally, four CpGs in GATA4 were validated as risk factors for TC; six CpGs at ITFG2-AS1 were negatively associated with TG; two CpGs in PLXND1 played protective roles in HDL-C. ICE FALCON indicated abnormal TC was regarded as the consequence of DNA methylation in CpGs at GATA4, rather than vice versa. Four CpGs in ITFG2-AS1 were both causes and consequences of modified TG levels. Our results indicated that DNA methylation levels of 12 CpGs in GATA4, ITFG2-AS1, and PLXND1 were relevant to TC, TG, and HDL-C, respectively, which might provide new epigenetic insights into potential clinical treatment of dyslipidemia.

Altered functional connectivity of the nucleus tractus solitarii in patients with chronic cough after lung surgery: an rs-fMRI study.

BACKGROUND: To explore the altered functional connectivity (FC) of the nucleus tractus solitarii (NTS) in patients with chronic cough after lung surgery using resting-state functional magnetic resonance imaging (rs-fMRI), and the association between abnormal FC and clinical scale scores. METHODS: A total of 22 patients with chronic cough after lung surgery and 22 healthy controls were included. Visual analog scale (VAS), Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC), and Hamilton anxiety rating scale (HAMA) scores were assessed, and rs-fMRI data were collected. The FC analysis was performed using the NTS as the seed point, and FC values with all voxels in the whole brain were calculated. A two-sample t-test was used to compare FC differences between the two groups. The FC values of brain regions with differences were extracted and correlated with clinical scale scores. RESULTS: In comparison to healthy controls, FC values in the NTS and anterior cingulate cortex(ACC) were reduced in patients with chronic cough after lung surgery (GRF correction, p-voxel < 0.005, p-cluster < 0.05) which were positively correlated with LCQ-MC scores (r = 0.534, p = 0.011), but with VAS (r = -0.500, p = 0.018), HAMA (r = -0.713, p < 0.001) scores were negatively correlated. CONCLUSIONS: Reduced FC of the NTS with ACC may be associated with cough hypersensitivity and may contribute to anxiety in patients with chronic cough after lung surgery.

Influences of focusing conditions on optical poling in lithium niobate using a 1035 nm femtosecond fiber laser.

In this study, we demonstrate the optical induction of ferroelectric domain inversion on the -z surface of lithium niobate crystals using a 1035 nm femtosecond fiber laser. We investigate the effects of laser power and focusing parameters on domain morphology. The results revealed that domains exhibit an irregular random distribution at low power, whereas regularly arranged domains were formed near the crystal damage threshold. Furthermore, with sufficiently high power, lens focusing enables the fabrication of uniformly sized domains exceeding 100 µm. The results suggest potential applications for controlling domain morphology and the duty cycle, and fabricating ferroelectric functional devices.

Re-irradiation for local primary-recurrence esophageal squamous cell carcinoma treated with IMRT/VMAT.

PURPOSE: Local primary-recurrence of esophageal squamous cell carcinoma (ESCC) after definitive treatment has the potential for increasing overall survival with re-irradiation (Re-RT), especially with advanced technique. This study aimed to evaluate the efficacy and toxicities of Re-RT using intensity-modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) for local primary-recurrence of ESCC. MATERIALS AND METHODS: A total of 130 ESCC patients with local primary-recurrence from Xijing hospital between 2008 and 2021 were enrolled and 30 patients underwent IMRT/VMAT based salvage Re-RT. Cox regression analysis was used to analyze the prognostic factors for overall survival (OS) and after recurrence survival (ARS). The toxicities of 30 patients receiving Re-RT were also assessed. RESULTS: The median OS and ARS of the 130 recurrent patients were 21 months (1-164 months) and 6 months (1-142 months). The 1-, 2-, and 3-year OS rates were 81.5%, 39.2%, and 23.8%, respectively. Besides, the 1-, 2-, and 3-year ARS rates were 30.0%, 10%, and 6.2%. Multivariate analysis showed that Re-RT ± chemotherapy (p = 0.043) and chemotherapy alone (p < 0.001) and esophageal stents (p = 0.004) were independent prognostic factors for OS. The median OS of 30 patients treated with Re-RT were significantly better than that of 29 patients treated with chemotherapy (34.5 months vs. 22 months, p = 0.030). Among 30 ESCC patients treated with Re-RT, the median OS and ARS were 34.5 months (range 12-163 months) and 6 months (range 1-132 months), respectively. The recurrence-free interval (RFI) (> 12 months) and initial radiation dose (> 60 Gy) were significantly associated with improved OS. Radiation esophagitis (Grade 1-2) occurred in 16 patients and myelosuppression (Grade1-2) occurred in 10 patients. Grade 3 toxicities (radiation esophagitis and myelosuppression) were only 13.3%. There were no grade 4 toxicities. CONCLUSION: Our results demonstrated that IMRT/VMAT-based Re-RT was an effective therapeutic option for ESCC patients with local primary-recurrence compared with chemotherapy alone or without any treatment. Re-RT had improved OS but unfavorable ARS.

Identification of key DNA methylation changes on fasting plasma glucose: a genome-wide DNA methylation analysis in Chinese monozygotic twins.

BACKGROUND: Elevated fasting plasma glucose (FPG) levels can increase morbidity and mortality even when it is below the diagnostic threshold of type 2 diabetes mellitus (T2DM). We conducted a genome-wide DNA methylation analysis to detect DNA methylation (DNAm) variants potentially related to FPG in Chinese monozygotic twins. METHODS: Genome-wide DNA methylation profiling in whole blood of twins was performed using Reduced Representation Bisulfite Sequencing (RRBS), yielding 551,447 raw CpGs. Association between DNAm of single CpG and FPG was tested using a generalized estimation equation. Differentially methylated regions (DMRs) were identified using comb-P approach. ICE FALCON method was utilized to perform the causal inference. Candidate CpGs were quantified and validated using Sequenom MassARRAY platform in a community population. Weighted gene co-expression network analysis (WGCNA) was conducted using gene expression data from twins. RESULTS: The mean age of 52 twin pairs was 52 years (SD: 7). The relationship between DNAm of 142 CpGs and FPG reached the genome-wide significance level. Thirty-two DMRs within 24 genes were identified, including TLCD1, MRPS31P5, CASZ1, and CXADRP3. The causal relationship of top CpGs mapped to TLCD1, MZF1, PTPRN2, SLC6A18, ASTN2, IQCA1, GRIN1, and PDE2A genes with FPG were further identified using ICE FALCON method. Pathways potentially related to FPG were also identified, such as phospholipid-hydroperoxide glutathione peroxidase activity and mitogen-activated protein kinase p38 binding. Three CpGs mapped to SLC6A18 gene were validated in a community population, with a hypermethylated direction in diabetic patients. The expression levels of 18 genes (including SLC6A18 and TLCD1) were positively correlated with FPG levels. CONCLUSIONS: We detect many DNAm variants that may be associated with FPG in whole blood, particularly the loci within SLC6A18 gene. Our findings provide important reference for the epigenetic regulation of elevated FPG levels and diabetes.

Genetic and Environmental Correlation Analysis of Serum Creatinine Levels in Chinese Twins.

Almost all creatinine is excreted by the kidney in individuals. Serum creatinine concentration, a widely used renal function index in clinical practice, can be affected by both genetic and environmental factors, as evidenced by current research exploring the relationship between these factors and kidney function. However, few studies have explored the heritability of serum creatinine in Asian populations. Therefore, we explored the genetic and environmental factors that affect the serum creatinine level in Asian populations. Participants in this study came from the Qingdao Twin Registry in China, and 374 pairs of twins were included, of which 139 pairs were dizygotic twins, whose ages ranged from 40 to 80 years old, and the serum creatinine level ranged from 10 to 126 µmol/L. Structural equation models were constructed using Mx software to calculate heritability, with adjusted covariates being age, sex, and body mass index. The results of heritability analysis showed that ACE was the best fit model. Serum creatinine level is influenced by genetic and environmental factors. The result of heritability was 35.44%, and the influence of shared environmental factors accounted for 52.13%. This study provided the relevant basis for future research on genetic and environmental factors affecting serum creatinine levels in Asian populations.

Epigenome-wide association study in Chinese monozygotic twins identifies DNA methylation loci associated with blood pressure.

BACKGROUND: Hypertension is a crucial risk factor for developing cardiovascular disease and reducing life expectancy. We aimed to detect DNA methylation (DNAm) variants potentially related to systolic blood pressure (SBP) and diastolic blood pressure (DBP) by conducting epigenome-wide association studies in 60 and 59 Chinese monozygotic twin pairs, respectively. METHODS: Genome-wide DNA methylation profiling in whole blood of twins was performed using Reduced Representation Bisulfite Sequencing, yielding 551,447 raw CpGs. Association between DNAm of single CpG and blood pressure was tested by applying generalized estimation equation. Differentially methylated regions (DMRs) were identified by comb-P approach. Inference about Causation through Examination of Familial Confounding was utilized to perform the causal inference. Ontology enrichment analysis was performed using Genomic Regions Enrichment of Annotations Tool. Candidate CpGs were quantified using Sequenom MassARRAY platform in a community population. Weighted gene co-expression network analysis (WGCNA) was conducted using gene expression data. RESULTS: The median age of twins was 52 years (95% range 40, 66). For SBP, 31 top CpGs (p < 1 × 10-4) and 8 DMRs were identified, with several DMRs within NFATC1, CADM2, IRX1, COL5A1, and LRAT. For DBP, 43 top CpGs (p < 1 × 10-4) and 12 DMRs were identified, with several DMRs within WNT3A, CNOT10, and DAB2IP. Important pathways, such as Notch signaling pathway, p53 pathway by glucose deprivation, and Wnt signaling pathway, were significantly enriched for SBP and DBP. Causal inference analysis suggested that DNAm at top CpGs within NDE1, MYH11, SRRM1P2, and SMPD4 influenced SBP, while SBP influenced DNAm at CpGs within TNK2. DNAm at top CpGs within WNT3A influenced DBP, while DBP influenced DNAm at CpGs within GNA14. Three CpGs mapped to WNT3A and one CpG mapped to COL5A1 were validated in a community population, with a hypermethylated and hypomethylated direction in hypertension cases, respectively. Gene expression analysis by WGCNA further identified some common genes and enrichment terms. CONCLUSION: We detect many DNAm variants that may be associated with blood pressure in whole blood, particularly the loci within WNT3A and COL5A1. Our findings provide new clues to the epigenetic modification underlying hypertension pathogenesis.

Genetic and Environmental Influences on Serum Alanine Aminotransferase Level: A Chinese Twin Study.

An abnormal alanine aminotransferase (ALT) level is predictive of disease and all-cause mortality and may indicate liver injury. Using twin modeling, the genetic and environmental factors that affect human serum ALT levels have been well studied for the populations in the different countries, and the results showed moderate-to-high heritability. However, the heritability of ALT level has not been explored in Chinese population. Thus, we recruited 369 pairs of twins (233 monozygotic and 136 dizygotic) from the Qingdao Twin Registry in China with a median age of 50 years (40-80 years). Correlation analysis and a structural equation model (SEM) were conducted to evaluate the heritability of ALT level. The data for age, gender, body mass index and alcohol consumption were set as covariates. Intrapair correlation in monozygotic twins was 0.64 (95%CI [.56, .71]) and 0.42 (95% CI [.28, .55]) in dizygotic twins. The SEM analysis indicated that 65% (95% CI [57%, 71%]) of the variation in ALT levels can be explained by additive genetics and 35% (95% CI [29%, 44%]) of the variation is attributed to unique environmental factors or residuals. Shared environmental influences were not significant. In conclusion, serum ALT variations exhibited strong genetic effects. The variation could also be explained by unique environmental factors. However, shared environmental factors have a minor impact on the serum ALT level.

Mediation by DNA methylation on the association of BMI and serum uric acid in Chinese monozygotic twins.

Obesity is an established risk factor for hyperuricemia, but the mechanisms are only partially understood. We examined whether BMI-related DNA methylation (DNAm) variation would mediate the association of BMI with serum uric acid (SUA). We first conducted an epigenome-wide association analysis (EWAS) in 64 monozygotic twin pairs to detect BMI-related DNAm variation and then evaluated the mediated effect of DNAm using mediation analysis. Ontology enrichments analysis was performed for CpGs using GREAT tool. The genes where the candidate CpG mediators mapped were validated using gene expression data. BMI was positively associated with log10 transformed SUA level (ß = 0.01, P < 0.001). The association between BMI and DNAm of 138 CpGs reached P < 1 × 10-4 level. Twenty BMI-related differentially methylated regions within MAP2K2, POU4F2, AGAP2, MRGPRE, ADM5, and NKX1-1 were found. Of the 138 CpGs, 4 within VENTX (involved in cellular responses to stress pathway), SMOC2 (enable calcium ion binding), and FSCN2 (a member of fascin protein family) mediated the association between BMI and SUA, with a mediating effect of 0.002-µmol/L lower log10 transformed SUA levels and a proportion of 18.89 %-24.92 % negative mediating effect. BMI × DNAm interactions on SUA were observed for 2 CpGs within VENTX. The gene expression level of VENTX was also negatively associated with SUA level. BMI-related DNAm variation may partially mediate the association of BMI with SUA.

A genetic correlation and bivariate genome-wide association study of grip strength and depression.

Grip strength is an important biomarker reflecting muscle strength, and depression is a psychiatric disorder all over the world. Several studies found a significant inverse association between grip strength and depression, and there is also evidence for common physiological mechanisms between them. We used twin data from Qingdao, China to calculate genetic correlations, and we performed a bivariate GWAS to explore potential SNPs, genes, and pathways in common between grip strength and depression. 139 pairs of Dizygotic twins were used for bivariate GWAS. VEAGSE2 and PASCAL software were used for gene-based analysis and pathway enrichment analysis, respectively. And the resulting SNPs were subjected to eQTL analysis and pleiotropy analysis. The genetic correlation coefficient between grip strength and depression was -0.41 (-0.96, -0.15). In SNP-based analysis, 7 SNPs exceeded the genome-wide significance level (P<5×10-8) and a total of 336 SNPs reached the level of suggestive significance (P<1×10-5). Gene-based analysis and pathway-based analysis identified genes and pathways related to muscle strength and the nervous system. The results of eQTL analysis were mainly enriched in tissues such as the brain, thyroid, and skeletal muscle. Pleiotropy analysis shows that 9 of the 15 top SNPs were associated with both grip strength and depression. In conclusion, this bivariate GWAS identified potentially common pleiotropic SNPs, genes, and pathways in grip strength and depression.

Multivariate genome-wide association study of depression, cognition, and memory phenotypes and validation analysis identify 12 cross-ethnic variants.

To date, little is known about the pleiotropic genetic variants among depression, cognition, and memory. The current research aimed to identify the potential pleiotropic single nucleotide polymorphisms (SNPs), genes, and pathways of the three phenotypes by conducting a multivariate genome-wide association study and an additional pleiotropy analysis among Chinese individuals and further validate the top variants in the UK Biobank (UKB). In the discovery phase, the participants were 139 pairs of dizygotic twins from the Qingdao Twins Registry. The genome-wide efficient mixed-model analysis identified 164 SNPs reaching suggestive significance (P < 1 × 10-5). Among them, rs3967317 (P = 1.21 × 10-8) exceeded the genome-wide significance level (P < 5 × 10-8) and was also demonstrated to be associated with depression and memory in pleiotropy analysis, followed by rs9863698, rs3967316, and rs9261381 (P = 7.80 × 10-8-5.68 × 10-7), which were associated with all three phenotypes. After imputation, a total of 457 SNPs reached suggestive significance. The top SNP chr6:24597173 was located in the KIAA0319 gene, which had biased expression in brain tissues. Genes and pathways related to metabolism, immunity, and neuronal systems demonstrated nominal significance (P < 0.05) in gene-based and pathway enrichment analyses. In the validation phase, 12 of the abovementioned SNPs reached the nominal significance level (P < 0.05) in the UKB. Among them, three SNPs were located in the KIAA0319 gene, and four SNPs were identified as significant expression quantitative trait loci in brain tissues. These findings may provide evidence for pleiotropic variants among depression, cognition, and memory and clues for further exploring the shared genetic pathogenesis of depression with Alzheimer's disease.

Potential genetic biomarkers are found to be associated with both cognitive function and blood pressure: A bivariate genome-wide association analysis.

A bivariate genome-wide association study was conducted in 137 pairs of twins to explore the shared genetic loci between cognition and blood pressure (BP). Before SNPs imputation, rs72815554 is significantly (P < 5 × 10-8) associated with the cognition-pulse pressure (PP) phenotype, while after imputation, 4 and 9 SNPs are significantly associated with the cognition-SBP phenotype, and cognition-PP phenotype, respectively, including rs72815554. There existed SNPs with highly linkage disequilibrium (LD) of rs10998339, rs72815554, rs11665292, and rs10823231. Besides, rs10998347, rs12153038, and rs10998295 had higher RegulomeDB scores and are located in the transcription factors binding regions. Rs7574283 and rs58113664 are located in the super-enhancer regions which are expressed highly in the adrenal gland, artery, atrial tissue, brain, nerves, etc. There are 1108, 1154, 1071, and 1102 genes associated with cognition-SBP, cognition-DBP, cognition-PP, and cognition-mean arterial pressure (MAP) phenotypes at the suggestive significant association level (P < 0.05), respectively. Furthermore, 641, 630, 900, and 555 pathways are associated with cognition-SBP, cognition-DBP, cognition-PP, and cognition-MAP phenotypes at the suggestive significant association level (P < 0.05), respectively.

Application of artificial intelligence in a real-world research for predicting the risk of liver metastasis in T1 colorectal cancer.

BACKGROUND: Liver is the most common metastatic site of colorectal cancer (CRC) and liver metastasis (LM) determines subsequent treatment as well as prognosis of patients, especially in T1 patients. T1 CRC patients with LM are recommended to adopt surgery and systematic treatments rather than endoscopic therapy alone. Nevertheless, there is still no effective model to predict the risk of LM in T1 CRC patients. Hence, we aim to construct an accurate predictive model and an easy-to-use tool clinically. METHODS: We integrated two independent CRC cohorts from Surveillance Epidemiology and End Results database (SEER, training dataset) and Xijing hospital (testing dataset). Artificial intelligence (AI) and machine learning (ML) methods were adopted to establish the predictive model. RESULTS: A total of 16,785 and 326 T1 CRC patients from SEER database and Xijing hospital were incorporated respectively into the study. Every single ML model demonstrated great predictive capability, with an area under the curve (AUC) close to 0.95 and a stacking bagging model displaying the best performance (AUC = 0.9631). Expectedly, the stacking model exhibited a favorable discriminative ability and precisely screened out all eight LM cases from 326 T1 patients in the outer validation cohort. In the subgroup analysis, the stacking model also demonstrated a splendid predictive ability for patients with tumor size ranging from one to50mm (AUC = 0.956). CONCLUSION: We successfully established an innovative and convenient AI model for predicting LM in T1 CRC patients, which was further verified in the external dataset. Ultimately, we designed a novel and easy-to-use decision tree, which only incorporated four fundamental parameters and could be successfully applied in clinical practice.

Effects of dietary supplementation with multispecies probiotics on intestinal epithelial development and growth performance of neonatal calves challenged with Escherichia coli K99.

BACKGROUND: Probiotics exhibit antibiotic properties and are capable of treating certain bacterial infections, including diarrhea. Therefore, the aim of this study is to investigate the effects of dietary supplementation with multispecies probiotic (MSP) on diarrhea, average daily gain (ADG) and intestinal development of neonatal calves challenged with Escherichia coli K99. RESULTS: Thirty-six neonatal Holstein calves were randomly assigned to three treatment groups. After E. coli K99 challenge, calves in the control (C) and MSP treatment groups had significantly higher ADG and feed efficiency, and significantly lower fecal scores than those of calves in the diarrhea (D) group. The mean time of diarrhea resolution was 4.5 and 3.1 days for calves in the D and MSP treatment groups, respectively. Furthermore, the structures of the various segments (duodenum, jejunum and ileum) of the small intestine of the calves, activities of several small intestinal enzymes, and expression of several energy metabolism-related genes in the small intestine segments were significantly affected by MSP treatments. CONCLUSION: Dietary supplementation of MSP had a positive effect in treating calf diarrhea; it improved ADG and feed efficiency and promoted development of the small intestine. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Basal ganglia-orbitofrontal circuits are associated with prospective memory deficits in Wilson's disease.

Degenerative changes in the basal ganglia (BG) are thought to contribute to neurological symptoms in Wilson's disease (WD). However, very little is known about whether and how the BG have an influence on prospective memory (PM) by interacting with the cerebral cortex. Here, we employed structural magnetic resonance imaging to systematically examine the effect of volume atrophy of BG on cortical thickness and to evaluate the relationships between cortical thickness of regions associated with BG atrophy and PM performance in WD. Cortical thickness atrophy in the left temporal pole and medial frontal gyrus are not related to degenerative changes in BG. Cortical thickness in the left superior frontal gyrus and right orbitofrontal gyrus (ORB) have stronger correlations with volume atrophy of the left accumbens, pallidum, and putamen in WD when compared with healthy controls. Furthermore, the cortical thickness of the right ORB is not only significantly correlated with PM performance but can also distinguish the severity of PM impairment in WD. Additionally, the middle cingulate cortex was related to volume atrophy of the accumbens, and its cortical thickness has a significant positive correlation with event-based PM. Together, these findings highlight that BG-orbitofrontal circuits may serve as neural biomarkers of PM and provide implications for the neural mechanisms underlying cognitive impairment in WD.