Comparison between models for detecting hepatocellular carcinoma in patients with chronic liver diseases of various etiologies: ASAP score versus GALAD score.

BACKGROUND: Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma (HCC). Based on age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II) with/without AFP-L3, ASAP and GALAD models are potential diagnostic panels. The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases (CLDs). METHODS: A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chinese hospitals. The etiologies of CLDs included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Using area under the receiver operating characteristic curve (AUC) values, the diagnostic performances of ASAP and GALAD models were compared to detect HCC among patients with various etiologies of CLDs. RESULTS: Among 248 HCC patients and 722 CLD controls, the ASAP model demonstrated the highest AUC (0.886) to detect HCC at any stage, outperforming the GALAD model (0.853, P = 0.001), as well as any individual biomarker (0.687-0.799, all P < 0.001). In the subgroup analysis of various CLDs etiologies, the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology. In addition, the ASAP model performed better in detecting early-stage (BCLC stage 0/A) HCC versus the GALAD model. CONCLUSIONS: Despite using one less laboratory variable (AFP-L3), the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various etiologies of CLDs-related HCC.

Monolithic 6 × 6 transmitter-router with simultaneous sub-nanosecond port and wavelength switching.

A monolithic 6 × 6 transmitter-router with both port and wavelength switching at sub-nanosecond speed is proposed and experimentally demonstrated. Based on an intra-cavity cyclic echelle diffraction grating router (EDGR) and semiconductor optical amplifier (SOA) arrays, each selectable output port can realize a selected multi-wavelength laser (MWL) output. The measurement results show that all 36 input-output combinations have a single-mode emission spectrum with a sidemode suppression ratio (SMSR) over 30 dB. Simultaneous switching of six laser wavelengths is achieved together with the switching of the output port by a single electrode selection. The switching time is less than 1 ns. It can offer a cost-effective solution to multi-wavelength multi-port optical transmitter-routers for fast distributed optical switching in datacenters and high-performance computers (HPCs).

Effects of different photoperiods on flower opening, flower closing and circadian expression of clock-related genes in Iris domestica and I. dichotoma.

The circadian clock can entrain to forced light-dark cycles by adjusting the phases and periods of flower opening and closing in ephemeral flowers. The responses of circadian rhythms to the same light conditions differ from species. However, the differences in internal genetic mechanisms underlying the different responses between species remain unclear. Iris domestica and I. dichotoma have ephemeral flowers and significantly divergent flower opening and closing times. The effects of different photoperiods (continuous darkness, 4L20D, 8L16D, 12L12D, 16L8D, 20L4D and continuous white light) on flower opening and closing, and expression patterns of seven genes (CRYPTOCHROME 1, PHYTOCHROME B, LATE ELONGATED HYPOCOTYL, PSEUDO RESPONSE REGULATOR 95, PHYTOCHROME INTERACTING FACTOR 4-like, SMUX AUXIN UP RNA 64-like and senescence-associated gene 39-like) involved in the circadian regulation of flower opening and closing were compared between I. domestica and I. dichotoma. Flower opening and closing in the two species exhibited circadian rhythms under continuous darkness (DD), but showed arrhythmia in continuous white light (LL). In the two species, keeping robust rhythms, strong synchronicity, rapid progressions of flower opening and closing and reaching full opening stage required a dark period longer than 4 h. In light-dark cycles with dark periods longer than 4 h, flower opening and closing times of the two species delayed with the delay of dawn, and the degree to which flower opening time varies with the time of dawn was greater in I. dichotoma than in I. domestica. The arrhythmia of flower opening and closing under 20L4D and LL would result from the arrhythmic output signals rather than arrhythmia of oscillators and photoreceptors. The different responses of the two species to the change of photoperiods would be caused by the transcriptional differences of genes in the output pathway of circadian clock system rather than in the input pathway or oscillators.

Transition from metabolically healthy to unhealth status associated with risk of carotid artery plaque in Chinese adults.

OBJECTIVE: We aimed to evaluate the association between the shift of metabolic status and future risk of carotid artery plaque (CAP) in community-based Chinese adults. METHODS: The current study included 9836 Chinese adults (4085 males and 5751 females, mean age 35.8 years) with metabolically healthy status at baseline (2013). Metabolically healthy status was defined as no self-reported history of metabolic diseases and cancer, and normal blood pressure, fasting blood glucose, glycated hemoglobin A1c level, and lipid profiles. Metabolically unhealthy status was defined if any of the following metabolic abnormalities were confirmed twice during follow up: high blood pressure, impaired glucose regulation, high triglycerides, high total cholesterol, high low-density lipoprotein cholesterols, or low high-density lipoprotein cholesterols. The transition was confirmed if participants' metabolic status shifted from baseline healthy to unhealthy status during follow up (2014-2018). RESULTS: We have identified 133 incident cases of CAP during follow up. Compared to those who remained metabolically healthy, the transition to high blood pressure, high total cholesterol, and high low-density lipoprotein cholesterols, were associated with high risk of developing carotid artery plaque (Hazards ratios (HRs) ranged from 1.69 to 2.34; p < 0.05 for all). The transition to impaired glucose regulation, high total triglycerides, and low high-density lipoprotein cholesterols, were associated with high risk of carotid artery plaque only in participants with metabolically healthy overweight at baseline (HR ranged from 1.95 to 4.62; p < 0.05 for all). CONCLUSION: The transition from baseline metabolically healthy status to unhealth status was associated with high risk of incident CAP.

The change in kidney function was associated with carotid artery plaque in a community-based population: A cohort study.

BACKGROUND AND AIMS: We performed the current study to evaluate the association between dynamic change in estimated glomerular filtration rate (eGFR) and the risk of carotid artery plaque (CAP) in a community-based population. METHODS AND RESULTS: A total number of 37,093 Chinese adults (21,790 men and 15,303 women, aged 42.6 ± 11.6 years) free of chronic kidney diseases were enrolled. The change in eGFR was calculated based on two measurements in 2013 and 2014 (mean interval: 1.2 y). Participants were further classified into three groups based on the change in eGFR: fast-decrease (<-3.3%), stable (from -3.3% to 3.3%), and fast-increase (≥3.3%). CAP was annually assessed by ultrasound B model throughout the study (2013-2018). We have identified 1,624 new cases of CAP (16.0 per 1000 person-year) during follow up. Compared to participants with stable eGFR, participants in both fast-decrease and fast-increase groups were associated with 1.99 folds (HR = 1.99, 95% CI: 1.54, 2.57) and 3.15 folds (HR = 3.15, 95% CI: 2.38, 4.16) higher likelihood of developing CAP. The association between continuous change in eGFR and the risk of CAP demonstrate a "U" shape. Sensitivity analysis generated similar results with main analysis. CONCLUSIONS: Both fast decrease and increase in eGFR were associated with the risk of developing CAP in Chinese adults.

BMI, high-sensitivity C-reactive protein and the conversion from metabolically healthy to unhealthy phenotype in Chinese adults: a cohort study.

OBJECTIVE: We performed the cohort study to evaluate the association between BMI, high-sensitivity C-reactive protein (hs-CRP) and the conversion from metabolically healthy to unhealthy phenotype in Chinese adults. DESIGN: Metabolically healthy was defined as participants without history of metabolic diseases and with normal fasting blood glucose level, glycated Hb A1c level, blood pressure, lipid profile, serum uric acid level and liver ultrasonographic findings at baseline. Participants were either classified into normal weight (18·5 ≤ BMI < 24·0 kg/m2) and overweight (BMI ≥ 24·0 kg/m2) based on baseline BMI, or low (<1 mg/l) and high (≥1 mg/l) groups based on baseline hs-CRP. The conversion from metabolically healthy to unhealthy phenotype was deemed if any of the metabolic abnormalities had been confirmed twice or more during 5 years of follow-up. RESULTS: Included were 4855 (1942 men and 2913 women, aged 36·0 ± 8·9 years) metabolically healthy Chinese adults. We identified 1692 participants who converted to metabolically unhealthy phenotype during the follow-up. Compared with their counterparts, the adjusted hazards ratio of the conversion was 1·19 (95 % CI 1·07, 1·33) for participants with overweight, while it was 1·15 (95 % CI 1·03, 1·29) for those with high hs-CRP level (≥1 mg/l). Further adjustment of hs-CRP did not materially change the association between BMI and the conversion. However, the association between hs-CRP and the conversion was not significant after further adjustment of BMI. The sensitivity analysis generated similar results to main analysis. CONCLUSION: BMI was associated with the risk of the conversion from metabolically healthy to unhealthy status in Chinese adults.

Metabolically healthy obesity is associated with longitudinal changes in high-density lipoprotein cholesterol in Chinese adults.

PURPOSE: Whether metabolically healthy obesity (MHO) is associated with longitudinal changes in high-density lipoprotein cholesterol (HDL-C) remains unclear. METHODS: MHO was defined as participants with overweight and obesity (BMI ≥ 24.0 kg/m2, n = 2921), free of history of metabolic diseases, and without abnormalities of blood pressure, fasting blood glucose, hemoglobin A1c, lipid profile, carotid artery and liver ultrasonographic findings at baseline. Metabolically healthy normal weight (MHN) was defined as participants with normal weight (BMI < 24.0 kg/m2, n = 9578) and without above-mentioned abnormalities. HDL-C, fasting blood glucose, hemoglobin A1c, and blood pressure were assessed annually. Glucose abnormality was considered if either FBG ≥ 5.6 mmol/L or HbA1c ≥ 5.7%; while, high blood pressure (HBP) was considered if either systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 80 mmHg during 5 years of follow-up. RESULTS: Compared with the MHN group, the adjusted mean difference in HDL-C change rate was - 0.005 mmol/L per year [95% confidence interval (CI) - 0.007, - 0.003] for MHO after adjustment for a series of potential confounders. Furthermore, transiting to abnormality of blood glucose, but not high blood pressure, was associated with lower cumulative average of HDL-C in MHN group, compared with those remained in metabolically healthy status. CONCLUSIONS: MHO and transiting from metabolically healthy to abnormality of blood glucose were associated with HDL-C in Chinese adults. LEVEL OF EVIDENCE: III, cohort study.

Alterations of gut microbiome in autoimmune hepatitis.

OBJECTIVE: The significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls. DESIGN: We performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy. RESULTS: The gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p<0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar, the most strongly disease-associated taxa (p=8.85E-8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites. CONCLUSION: Our study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.

To bloom once or more times: the reblooming mechanisms of Iris germanica revealed by transcriptome profiling.

BACKGROUND: The reblooming bearded iris (Iris germanica) can bloom twice a year, in spring and autumn. The extended ornamental period makes it more popular and brings additional commercial values. However, little is known about the reblooming mechanisms, making the breeding programs time-consuming and labor-wasting. Therefore, a comparative transcriptome profiling was conducted on once-bloomers and rebloomers from the same F1 generation on six development stages, and the candidate genes associated with reblooming were identified. RESULTS: A total of 100,391 unigenes were generated, the mean length being 785 bp. In the three comparisons (the floral initiation stage of spring flowering in once-bloomers (OB-T1) vs the floral initiation stage of spring flowering in rebloomers (RB-T1); RB-T1 vs the floral initiation stage of autumn flowering in rebloomers (RB-T5); OB-T1 vs RB-T5), a total of 690, 3515 and 2941 differentially expressed genes (DEGs) were annotated against the public databases, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis focused on the photoperiod response, the temperature insensitivity and the growth speed, to remove the redundant DEGs and figure out the candidate key genes. As a result, the following four genes, PHYTOCHROME A (PHYA), GIGANTEA (GI), SHORT VEGETATIVE PERIOD (SVP) and AUXIN RESPONSE FACTOR (ARF), were considered to be involved in the second floral initiation of the rebloomers. CONCLUSION: This research provides valuable information for the discovery of the reblooming-related genes. The insights into the molecular mechanisms of reblooming may accelerate the breeding of bearded iris and other perennials.

Reduction of mitochondria and up regulation of pyruvate dehydrogenase kinase 4 of skeletal muscle in patients with chronic kidney disease.

AIM: Muscle weakness is commonly among chronic kidney disease (CKD) patients. Muscle mitochondrial dysfunction and decreased pyruvate dehydrogenase (PDH) activity occur in CKD animals but have not been confirmed in humans, and changes in pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) expression have not been evaluated in CKD muscle. We presume that the reduction of muscle mitochondria and post-translational modification of PDH may cause muscle weakness in CKD patients. Herein, we explored changes in mitochondrial morphology, PDH expression and activity, and PDK/PDP expression in CKD patient muscle. METHODS: Twenty patients with stage 4-5 CKD (CKD group) and 24 volunteers (control group) were included. Clinical characteristics, biochemical information and handgrip strength (HGS) were determined. Skeletal muscle samples were collected from eight stage 5 CKD patients from CKD group. Other eight non-CKD surgical subjects' muscle samples were collected as control. PDH activity was determined using a PDH enzyme activity assay kit, and real-time PCR and western blotting analyses were performed to measure gene expression and protein levels, respectively. Transmission electron microscopy was used to study mitochondria morphology. RESULTS: CKD patients had lower HGS than non-CKD subjects, and HGS was correlated with gender, age, haemoglobin and albumin. Mitochondria were decreased in end-stage renal disease (ESRD) patients muscle. Mfn-1 expression and phospho-Drp1(S637)/Drp1 ratio were inhibited in the ESRD group, implicating dysfunctional mitochondrial dynamics. Muscle PDH activity and phospho-PDH(S293) were decreased in ESRD patient muscle, while PDK4 protein level was up regulated. CONCLUSION: Decreased mitochondria and PDH deficiency caused by up regulation of PDK 4 contribute to muscle dysfunction, and could be responsible for muscle weakness in CKD patients.

High-Sensitivity CRP (C-Reactive Protein) Is Associated With Incident Carotid Artery Plaque in Chinese Aged Adults.

Background and Purpose- CRP (C-reactive protein) is an inflammatory biomarker which predicts the risk of cardiovascular diseases. However, whether CRP is associated with carotid artery plaque (CAP) remains unclear. Methods- The current retrospective study was performed in 8229 Chinese aged adults (aged 65-99 years; 4677 men and 3552 women). hs-CRP (high-sensitivity CRP) concentrations were measured at baseline (2013), and further classified into 3 groups: low risk (<1.0 mg/L), intermediate risk (1.0-3.0 mg/L), and high risk (≥3.0 mg/L). Ultrasound B-mode imaging was repeatedly performed annually to detect CAP during 5-year follow-up (2013-2018). Potential confounders, including body mass index, blood pressure, fasting blood glucose, alanine transferase, aspartate transferase, alkaline phosphatase, gamma-glutamyl transferase, total bilirubin, direct bilirubin, blood urea nitrogen, creatinine, and uric acid, lipid profiles, were also collected at baseline. White blood cell was collected as well. We used a logistic regression model for the cross-sectional relation between CRP concentration and CAP status and proportional hazardous Cox model for prospective analyses. Results- Comparing to the low-risk group, the adjusted odds ratios for CAP was 1.66 (95% CI, 1.43-1.92) in the intermediate-risk group and 1.72 (95% CI, 1.39-2.13) in the high-risk group, after adjustment for potential confounders. We identified 512 incident CAP cases during 5-year follow-up. Each mg/L increase of hs-CRP was associated with a hazard ratio of 1.1 (95% CI, 1.03-1.17) to developing CAP. Sensitivity analysis generated similar results with prospective analyses after excluding participants with overweight and obesity, with elevated fasting blood glucose, LDL (low-density lipoprotein) cholesterol, and white blood cell. The association lost significant when we excluded participants with elevated blood pressure, however, few cases of CAP (n=41) was recruited in participants with normal blood pressure during follow-up. Conclusions- High hs-CRP concentration was associated with the high risk of developing CAP in Chinese aged adults.

A Novel Online Calculator Based on Serum Biomarkers to Detect Hepatocellular Carcinoma among Patients with Hepatitis B.

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients remains a challenge, especially in China. We sought to create an online calculator of serum biomarkers to detect HCC among patients with chronic hepatitis B (CHB). METHODS: Participants with HBV-HCC, CHB, HBV-related liver cirrhosis (HBV-LC), benign hepatic tumors, and healthy controls (HCs) were recruited at 11 Chinese hospitals. Potential serum HCC biomarkers, protein induced by vitamin K absence or antagonist-II (PIVKA-II), α-fetoprotein (AFP), lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and α-l-fucosidase (AFU) were evaluated in the pilot cohort. The calculator was built in the training cohort via logistic regression model and validated in the validation cohort. RESULTS: In the pilot study, PIVKA-II and AFP showed better diagnostic sensitivity and specificity compared with AFP-L3 and AFU and were chosen for further study. A combination of PIVKA-II and AFP demonstrated better diagnostic accuracy in differentiating patients with HBV-HCC from patients with CHB or HBV-LC than AFP or PIVKA-II alone [area under the curve (AUC), 0.922 (95% CI, 0.908-0.935), sensitivity 88.3% and specificity 85.1% for the training cohort; 0.902 (95% CI, 0.875-0.929), 87.8%, and 81.0%, respectively, for the validation cohort]. The nomogram including AFP, PIVKA-II, age, and sex performed well in predicting HBV-HCC with good calibration and discrimination [AUC, 0.941 (95% CI, 0.929-0.952)] and was validated in the validation cohort [AUC, 0.931 (95% CI, 0.909-0.953)]. CONCLUSIONS: Our results demonstrated that a web-based calculator including age, sex, AFP, and PIVKA-II accurately predicted the presence of HCC in patients with CHB. CLINICALTRIALSGOV IDENTIFIER: NCT03047603.

Prospective study of hemoglobin A1c and incident carotid artery plaque in Chinese adults without diabetes.

BACKGROUND: Diabetes has been reported to be associated with carotid artery plaque (CAP). However, it remains unclear whether hemoglobin A1c (HbA1c) level, a marker for long-term glycemic status, is associated with altered CAP risk in individuals with fasting blood glucose (FBG) concentrations below the current cutoff for diabetes. METHODS: Included were 16,863 Chinese adults (aged 18 years or more; 9855 men and 7008 women) with fasting blood glucose < 7.0 mmol/L at baseline (2013). Both HbA1c level and CAP (assessed via ultrasound B-mode imaging) were annually assessed during 2014-2018. All the participants were further classified into three groups based on baseline HbA1c level: ≤ 5.6%, 5.7-6.4%, and ≥ 6.5%. We used Cox proportional-hazards model to evaluate the association between HbA1c level and incident CAP, adjusting for a series of potential confounders. RESULTS: During 5 years of follow up, 3942 incident CAP cases were identified. Individuals with higher baseline HbA1c had higher future risk of CAP (p-trend < 0.001). In the full-adjusted model, each percent increase of HbA1c was associated with a 56% (HR = 1.56, 95% CI 1.37, 1.78) higher risk of CAP. Excluding participants with chronic inflammation, as assessed by high-sensitivity C-reactive protein and white blood cell, and those with FBG ≥ 5.6 mmol/L at baseline generated similar results. CONCLUSIONS: Elevated HbA1c level was associated with high risk of developing CAP in Chinese adults without FBG defined diabetes.

Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy.

OBJECTIVE: A close relationship between gut microbiota and some chronic liver disorders has recently been described. Herein, we systematically performed a comparative analysis of the gut microbiome in primary biliary cholangitis (PBC) and healthy controls. DESIGN: We first conducted a cross-sectional study of 60 ursodeoxycholic acid (UDCA) treatment-naïve patients with PBC and 80 matched healthy controls. Second, an independent cohort composed of 19 treatment-naïve patients and 34 controls was used to validate the results. Finally, a prospective study was performed in a subgroup of 37 patients with PBC who underwent analysis before and after 6 months of UDCA treatment. Faecal samples were collected, and microbiomes were analysed by 16S ribosomal RNA gene sequencing. RESULTS: A significant reduction of within-individual microbial diversity was noted in PBC (p=0.03). A signature defined by decreased abundance of four genera and increased abundance of eight genera strongly correlated with PBC (area under curve=0.86, 0.84 in exploration and validation data, respectively). Notably, the abundance of six PBC-associated genera was reversed after 6 months of UDCA treatment. In particular, Faecalibacterium, enriched in controls, was further decreased in gp210-positive than gp210-negative patients (p=0.002). Of interest was the finding that the increased capacity for the inferred pathway, bacterial invasion of epithelial cells in PBC, highly correlated with the abundance of bacteria belonging to Enterobacteriaceae. CONCLUSIONS: This study presents a comprehensive landscape of gut microbiota in PBC. Dysbiosis was found in the gut microbiome in PBC and partially relieved by UDCA. Our study suggests that gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC.

A20 reduces lipid storage and inflammation in hypertrophic adipocytes via p38 and Akt signaling.

Adipose tissue plays a vital role in the development of obesity and related disorders. Our previous study showed that A20, an ubiquitin-editing enzyme with anti-inflammation function, attenuated free fatty acids (FFAs)-induced lipid accumulation in nonalcoholic steatohepatitis. Here, we investigated A20 expression in adipose tissue of obese individuals and its effects on 3T3-L1 lipogenesis as well as the likely mechanisms underlying this process. By re-annotation of raw microarray data downloaded from Gene Expression Omnibus, we found that obese individuals showed significantly higher A20 mRNA levels in adipocytes. In vitro, A20 inhibited MCP-1 and IL-6 secretion in adipocytes. Forced expression of A20 resulted in decreased expression of key markers of lipogenesis and adipogenesis, such as sterol regulatory element binding protein 1c (SREBP-1c) and adipogenesis (aP2), leading to less lipids accumulation in differentiated 3T3-L1 cells. This process was concomitant with attenuated activation of p38 and Akt signaling. Our results suggest that A20 may have therapeutic potential for obesity and related diseases. The mechanisms involved the suppression of lipid storage and inflammation in adipocytes.

The European GWAS-identified risk SNP rs457717 within IQGAP2 is not associated with age-related hearing impairment in Han male Chinese population.

This study aimed to test the association between the European GWAS-identified risk IQGAP2 SNP rs457717 (A>G) and age-related hearing impairment (ARHI) in a Han male Chinese (HMC) population. A total of 2420 HMC subjects were divided into two groups [group 70+: >70 years (n = 1306), and group 70-: ≤70 years (n = 1114)]. The participants were categorised into case and control groups according to Z high scores for group 70- and the severity of hearing loss and different audiogram shapes identified by K-means cluster analysis for group 70+. The IQGAP2 tagSNP rs457717 was genotyped in accordance with the different ARHI phenotypes. The genotype distributions of IQGAP2 (AA/AG/GG) were not significantly different between the case and control groups (P = 0.613 for group 70-; P = 0.602 for group 70+). Compared with genotype AA, the ORs of genotypes AG and GG for ARHI were not significantly different following adjustment for other environmental risk factors. We demonstrated that the IQGAP2 TagSNP rs457717 (A/G) was not associated with ARHI in HMC individuals.

A causal analysis of the relationship between exposure to sunlight and colorectal cancer risk: A Mendelian randomization study.

Several observational studies have found that exposure to sunlight reduces the risk of colorectal cancer (CRC). However, sun exposure remains ambiguous in its relationship to CRC. We carried out a Mendelian randomization (MR) study to explore the potential associations between them. We examined the exposure to sunlight summary statistics of the UK Biobank Consortium using a 2-sample MR analysis. Using data from the FinnGen consortium, we derived summary statistics for CRC. We conducted our analysis with various methods, incorporating inverse variance weighted (IVW) along with 4 other approaches. A Cochran Q statistic was used to measure the heterogeneity of instrumental variables (IVs). We screened 133 single nucleotide polymorphisms (SNPs) (time spent outdoors in summer), 41 SNPs (time spent outdoors in winter), and 35 SNPs (frequency of solarium/sunlamp use) representing sunlight exposure for MR analysis. All selected SNPs had an F-statistic >20, indicating that IVs did not weakly bias the results. The summer outdoor activity trait exhibited significant heterogeneity (Cochran Q statistic = 183.795, P = .002 < 0.05), but we found no horizontal polymorphisms or significant heterogeneity for the other exposure traits. According to IVW estimates, no causal association exists between time spent outdoors in summer and CRC (Odds Ratio, OR = 0.735, 95% confidence interval, CI = 0.494-1.017, P = .128 > 0.017). No causal relationship existed between time spent outdoors in winter and CRC, as indicated by Bonferroni-corrected adjusted p-values. The OR was 0.877 with a 95% CI of 0.334-2.299, and the P value was .789, more significant than the significance threshold of 0.017. The solarium/sunlamp use frequency was not associated with CRC (OR = 1.567, 95%CI = 0.243-10.119, P = .637 > .017). Also, an IVW with random effects was applied to determine the causal relationship between summer outdoor time and CRC. No causal association between summer outdoor time and CRC was found (OR = 0.735, 95% CI = 0.494-1.017, P = .128 > .017). Additionally, 4 additional analyses yielded similar results. The findings of our study suggest that exposure to sunlight may reduce CRC risk, but the causal relationship remains unsolved. There is no evidence to suggest that exposure to sunlight prevents CRC. Randomized, controlled trials are needed to determine whether sunlight exposure protects against CRC.

Functional characterization of two flowering repressors SHORT VEGETATIVE PHASE and TERMINAL FLOWER 1 in reblooming bearded Iris (Iris spp.).

Reblooming bearded iris (Iris spp.) could bloom in both spring and autumn, which has extended the ornamental periods. Our previous transcriptome analysis has indicated the possible regulatory role of SHORT VEGETATIVE PHASE (SVP) in reblooming of bearded iris. Moreover, it has been revealed that the mutations of TERMINAL FLOWER 1 (TFL1) led to the continuous-flowering phenotypes in rose (Rosa spp.) and strawberry (Fragaria spp.). In order to verify the functions of these two genes on reblooming in bearded iris, IgSVP and IgTFL1 were isolated and functionally characterized. All the overexpression Arabidopsis lines of IgSVP and IgTFL1 generated the late-flowering phenotypes, indicating their functions as flowering repressors. The ectopic expression of IgSVP and IgTFL1 also generated phenotypic changes on flowers, inflorescences and branch structures. Moreover, the protein-protein interaction was found between a homologue of IgSVP and the floral meristem identity gene APETALA 1. The expression profiling showed that IgSVP was expressed significantly lower in the rebloomers in the second floral initiation stage (T5) than those of the first one (T1) in both the once-bloomers and the rebloomers, suggesting the possible regulation of IgSVP on reblooming. However, the expression level of IgTFL1 in the rebloomers was significantly higher in T5 than that in T1. The functional characterization of the two important flowering repressors IgSVP and IgTFL1 could lay solid foundation for future molecular breeding of iris, for example, knocking out the key repressors by CRISPR/Cas9 system to extend the ornamental periods of bearded iris.

Association between non-alcoholic fatty liver disease and silent carotid plaque in Chinese aged population: a cross-sectional study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for carotid plaque in the general population; however, whether NAFLD is associated with carotid plaque in aged population remains unknown. This cross-sectional study was conducted to evaluate the association between NAFLD and carotid plaque in a Chinese aged population. METHODS: A total number of 12,990 Chinese aged adults (7,685 men and 5,305 women) were included. NAFLD was diagnosed based on the recommendation of Asia-Pacific Working Party on NAFLD and Chinese Association for the Study of Liver Disease and excessive alcohol consumption (weekly alcohol consumption ≤210 g in men and ≤140 g in women) was excluded. Carotid plaque was confirmed by ultrasonography. Potential confounders and biochemical findings were collected at baseline. Logistic regression model was employed to evaluate the association between NAFLD and carotid plaque. RESULTS: The prevalence of carotid plaque was significantly higher in aged participants with NAFLD than in those without NAFLD (22.4% vs. 16.3%, P<0.001). NAFLD is associated with carotid plaque [odd ratio (OR) =1.89, 95% confidence interval (CI): 1.59-2.24], after adjusting for age, gender, BMI, liver and kidney function, glucose level, lipid profiles, and white blood cell (WBC) count. The association between NAFLD and carotid plaque was attenuated when participants with elevated ALT (≥75 IU/L), a history of cardiovascular diseases (CVDs) and obesity were censored although the significant association remained. CONCLUSIONS: NAFLD is associated with carotid plaque in Chinese aged population.