Telomere-to-telomere genome assembly of the goose Anser cygnoides.

Our study presents the assembly of a high-quality Taihu goose genome at the Telomere-to-Telomere (T2T) level. By employing advanced sequencing technologies, including Pacific Biosciences HiFi reads, Oxford Nanopore long reads, Illumina short reads, and chromatin conformation capture (Hi-C), we achieved an exceptional assembly. The T2T assembly encompasses a total length of 1,197,991,206 bp, with contigs N50 reaching 33,928,929 bp and scaffold N50 attaining 81,007,908 bp. It consists of 73 scaffolds, including 38 autosomes and one pair of Z/W sex chromosomes. Importantly, 33 autosomes were assembled without any gap, resulting in a contiguous representation. Furthermore, gene annotation efforts identified 34,898 genes, including 436,162 RNA transcripts, encompassing 806,158 exons, 743,910 introns, 651,148 coding sequences (CDS), and 135,622 untranslated regions (UTR). The T2T-level chromosome-scale goose genome assembly provides a vital foundation for future genetic improvement and understanding the genetic mechanisms underlying important traits in geese.

Genome-wide selective signatures mining the candidate genes for egg laying in goose.

BACKGROUND: Improving the egg production of goose is a crucial goal of breeding, because genetics is the key factor affecting egg production. Thus, we sequenced the genomes of 55 Chinese indigenous geese from six breeds, which were divided into the high egg-laying group (ZE, HY, and SC) and low egg-laying group (ZD, LH, and ST). Based on the results of the inter-population selection signal analysis, we mined the selected genome regions in the high egg-laying germplasm population to identify the key candidate genes affecting the egg-laying traits. RESULTS: According to the whole-genome sequencing data, the average sequencing depth reached 11.75X. The genetic relationships among those six goose breeds coincided with the breed's geographical location. The six selective signal detection results revealed that the most selected regions were located on Chr2 and Chr12. In total, 12,051 single-nucleotide polymorphism (SNP) sites were selected in all six methods. Using the enrichment results of candidate genes, we detected some pathways involved in cell differentiation, proliferation, and female gonadal development that may cause differences in egg production. Examples of these pathways were the PI3K-Akt signaling pathway (IGF2, COMP, and FGFR4), animal organ morphogenesis (IGF2 and CDX4), and female gonad development (TGFB2). CONCLUSION: On analyzing the genetic background of six local goose breeds by using re-sequencing data, we found that the kinship was consistent with their geographic location. 107 egg-laying trait-associated candidate genes were mined through six selection signal analysis. Our study provides a critical reference for analyzing the molecular mechanism underlying differences in reproductive traits and molecular breeding of geese.

ACE2 negatively regulates the Warburg effect and suppresses hepatocellular carcinoma progression via reducing ROS-HIF1α activity.

Aerobic glycolysis has pleiotropic roles in the pathogenesis of hepatocellular carcinoma (HCC). Emerging studies revealed key promoters of aerobic glycolysis, however, little is known about its negative regulators in HCC. In this study, an integrative analysis identifies a repertoire of differentially expressed genes (DNASE1L3, SLC22A1, ACE2, CES3, CCL14, GYS2, ADH4, and CFHR3) that are inversely associated with the glycolytic phenotype in HCC. ACE2, a member of the rennin-angiotensin system, is revealed to be downregulated in HCC and predicts a poor prognosis. ACE2 overexpression significantly inhibits the glycolytic flux as evidenced by reduced glucose uptake, lactate release, extracellular acidification rate, and the expression of glycolytic genes. Opposite results are noticed in loss-of-function studies. Mechanistically, ACE2 metabolizes Ang II to Ang-(1-7), which activates Mas receptor and leads to the phosphorylation of Src homology 2-containing inositol phosphatase 2 (SHP-2). SHP2 activation further blocks reactive oxygen species (ROS)-HIF1α signaling. Addition of Ang-(1-7) or the antioxidant N-acetylcysteine compromises in vivo additive tumor growth and aerobic glycolysis induced by ACE2 knockdown. Moreover, growth advantages afforded by ACE2 knockdown are largely glycolysis-dependent. In clinical settings, a close link between ACE2 expression and HIF1α or the phosphorated level of SHP2 is found. Overexpression of ACE2 significantly retards tumor growth in patient-derived xenograft model. Collectively, our findings suggest that ACE2 is a negative glycolytic regulator, and targeting the ACE2/Ang-(1-7)/Mas receptor/ROS/HIF1α axis may be a promising therapeutic strategy for HCC treatment.

Long-term effects and benefits of Helicobacter pylori eradication on the gastric mucosa in older individuals.

BACKGROUND: The current international consensus report indicated that all Helicobacter pylori (H. pylori)-positive patients should be treated. This study aimed to evaluate the long-term effects and benefits of H. pylori eradication on the gastric mucosa in the elderly population. METHODS: We performed a retrospective cohort study with 311 individuals aged ≥60 years, including 83 with persistent H. pylori infection (persistent group), 128 with successful H. pylori eradication (eradicated group), and 100 without H. pylori infection (control group). The results of endoscopy and mucosal histology were investigated at baseline and followed up for 5 and 10 years. RESULTS: In the 5 to 10-year follow-up, there was a significant difference in the atrophy score among the three groups (P < 0.001); however, no significant difference was observed in the intestinal metaplasia (IM) score (P > 0.05). There was no significant difference in the cumulative incidence of gastric neoplastic lesion (GNL) between the eradicated and persistent groups during the 5 to 10-year follow-up period (P > 0.05). The baseline IM score of patients with GNL was significantly higher than that of those without GNL in the eradicated and control groups (P < 0.05). In all patients with GNL, the mean interval time between baseline and diagnosis of GLN was more than 6 years. The severity of baseline mucosal IM (odds ratio: OR 3.092, 95% confidence interval [CI]: 1.690-5.655, P < 0.001) and H. pylori infection (OR: 2.413, 95%CI: 1.019-5.712, P = 0.045) significantly increased the risk for GNL. CONCLUSIONS: Older patients with a life expectancy of less than 5 to 10 years, especially those with moderate to severe gastric mucosal IM, may not benefit from the eradication of H. pylori to prevent gastric cancer.

Circadian Clock Genes in the Metabolism of Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a common disease, which is characterized by the accumulation of triglycerides in the hepatocytes without excess alcohol intake. Circadian rhythms can participate in lipid, glucose, and cholesterol metabolism and are closely related to metabolism seen in this disease. Circadian clock genes can modulate liver lipid metabolism. Desynchrony of circadian rhythms and the influences imparted by external environmental stimuli can increase morbidity. By contrast, synchronizing circadian rhythms can help to alleviate the metabolic disturbance seen in NAFLD. In this review, we have discussed the current research connections that exist between the circadian clock and the metabolism of NAFLD, and we have specifically focused on the key circadian clock genes, Bmal1, Clock, Rev-Erbs, Rors, Pers, Crys, Nocturnin, and DECs.

Long-term lifestyle interventions in middle-aged and elderly men with nonalcoholic fatty liver disease: a randomized controlled trial.

Nonalcoholic fatty liver disease (NAFLD), a metabolic disorder related to insulin resistance and metabolic syndrome, has become a public health concern. Currently, the principal therapeutic modalities targeting NAFLD are lifestyle interventions. However, the efficacy of long-term lifestyle interventions in managing NAFLD remains largely unexplored. This study aimed to evaluate the efficacy of long-term lifestyle interventions in middle-aged and elderly men with NAFLD. All 280 eligible patients were randomized to the control or test group. Patients in the test group received counseling on diet and exercise from 2 physicians every 3 months via a phone call. Patients in the control group received only counseling in annual checkups without regular intervention. After the 2-year periodic intervention, body weight, abdominal circumference, ALT, TCH, LDL-C and HDL-C decreased in the test group. Specifically, the fatty liver index (FLI) and NAFLD-fibrosis score (NAFLD-FS) reduced markedly in the test group. However, in the control group, there was only a significant decrease in LDL-C, HDL-C and NAFLD-FS (P < 0.001). The liver steatosis grade of the test group decreased significantly, while it increased in the control group. In NAFLD, long-term lifestyle interventions exert an anti-obesity effect and attenuate liver dysfunction and steatosis.

Effect of posture on (13)C-urea breath test in partial gastrectomy patients.

AIM: To investigate whether posture affects the accuracy of (13)C-urea breath test ((13)C-UBT) for Helicobacter pylori (H. pylori) detection in partial gastrectomy patients. METHODS: We studied 156 consecutive residual stomach patients, including 76 with H. pylori infection (infection group) and 80 without H. pylori infection (control group). H. pylori infection was confirmed if both the rapid urease test and histology were positive during gastroscopy. The two groups were divided into four subgroups according to patients' posture during the (13)C-UBT: subgroup A, sitting position; subgroup B, supine position; subgroup C, right lateral recumbent position; and subgroup D, left lateral recumbent position. Each subject underwent the following modified (13)C-UBT: 75 mg of (13)C-urea (powder) in 100 mL of citric acid solution was administered, and a mouth wash was performed immediately; breath samples were then collected at baseline and at 5-min intervals up to 30 min while the position was maintained. Seven breath samples were collected for each subject. The cutoff value was 2.0‰. RESULTS: The mean delta over baseline (DOB) values in the subgroups of the infection group were similar at 5 min (P > 0.05) and significantly higher than those in the corresponding control subgroups at all time points (P < 0.01). In the infection group, the mean DOB values in subgroup A were higher than those in other subgroups within 10 min and peaked at the 10-min point (12.4‰ ± 2.4‰). The values in subgroups B and C both reached their peaks at 15 min (B, 13.9‰ ± 1.5‰; C, 12.2‰ ± 1.7‰) and then decreased gradually until the 30-min point. In subgroup D, the value peaked at 20 min (14.7‰ ± 1.7‰). Significant differences were found between the values in subgroups D and B at both 25 min (t = 2.093, P = 0.043) and 30 min (t = 2.141, P = 0.039). At 30 min, the value in subgroup D was also significantly different from those in subgroups A and C (D vs C: t = 6.325, P = 0.000; D vs A: t = 5.912, P = 0.000). The mean DOB values of subjects with Billroth I anastomosis were higher than those of subjects with Billroth II anastomosis irrespectively of the detection time and posture (P > 0.05). CONCLUSION: Utilization of the left lateral recumbent position during the procedure and when collecting the last breath sample may improve the diagnostic accuracy of the (13)C-UBT in partial gastrectomy patients.

Two-week triple therapy has a higher Helicobacter pylori eradication rate than 1-week therapy: A single-center randomized study.

BACKGROUND AND AIM: To evaluate a high effective and practical regimen for the eradication of Helicobacter pylori infection. PATIENTS AND METHODS: The 298 patients with H. pylori infection, diagnosed by biopsies performed during the endoscopy, were randomized into two groups. Group 1: Treated for one week with a combination of omeprazole, amoxicillin, and clarithromycin (OAC), named by OAC-1 group (n = 143); Group 2: OAC-2 group (n = 155) treated for two weeks with OAC. The OAC-1 group was treated with triple therapy of omeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg bid for 1 week. OAC-2 group was treated likewise, but for two weeks. A 13C-urea breath test was used to monitor H. pylori after four to eight weeks following therapy. RESULTS: The eradication of infection was 55% and 68% in the OAC-1 and OAC-2 groups, respectively. Moreover, the eradication rates in the two groups were 63% and 75%, respectively. Compared with the OAC-1 group, the efficacy of treatment in the OAC-2 group is significantly higher (P < 0.05). CONCLUSION: Two-week OAC regimen yields a higher eradication rate of H. pylori, which might be a practical regimen for the eradication of H. pylori.

Enteral nutrition before bowel preparation improves the safety of colonoscopy in the elderly.

BACKGROUND/AIMS: Adverse events during colonoscopy are more likely to occur in elderly. To avoid the adverse events without decreasing the bowel cleanliness is still an unsolved problem. The aim of this study was to determine the effect of enteral nutrition before colonoscopy in a randomized controlled trail. MATERIALS AND METHOD: A total of 108 patients over sixty-five years of age and indicated for colonoscopy were randomized into four groups. Group 1 received a solution of two packages of polyethylene glycol electrolyte powder dissolved in 2000 mL water. Group 2 received 500 mL of enteral nutrition plus polyethylene glycol of the same dosage as in group 1. Group 3 received 200 mL of 25% magnesium sulfate solution. Group 4 received 500 mL of enteral nutrition plus 25% magnesium sulfate solution of the same dosage as in group 3. The intestinal cleaning and various physiological indications were measured before, after bowel preparation, and during colonoscopy. RESULTS: No significant difference in the quality of colon cleansing was found among the four groups. The incidence of adverse effects in groups 2 and 4 was less than in groups 1 and 3. CONCLUSION: Additional enteral nutrition in elderly patients before bowel preparation did not affect the quality of colon cleansing. However, the process can significantly reduce the incidence of adverse effects.

Clinical research on liver reserve function by 13C-phenylalanine breath test in aged patients with chronic liver diseases.

BACKGROUND: The objective of this study was to investigate whether the 13C-phenylalanine breath test could be useful for the evaluation of hepatic function in elderly volunteers and patients with chronic hepatitis B and liver cirrhosis. METHODS: L-[1-13C] phenylalanine was administered orally at a dose of 100 mg to 55 elderly patients with liver cirrhosis, 30 patients with chronic hepatitis B and 38 elderly healthy subjects. The breath test was performed at 8 different time points (0, 10, 20, 30, 45, 60, 90, 120 min) to obtain the values of Delta over baseline, percentage 13CO2 exhalation rate and cumulative excretion (Cum). The relationships of the cumulative excretion with the 13C-%dose/h and blood biochemical parameters were investigated. RESULTS: The 13C-%dose/h at 20 min and 30 min combined with the cumulative excretion at 60 min and 120 min correlated with hepatic function tests, serum albumin, hemoglobin, platelet and Child-Pugh score. Prothrombin time, total and direct bilirubin were significantly increased, while serum albumin, hemoglobin and platelet, the cumulative excretion at 60 min and 120 min values decreased by degrees of intensity of the disease in Child-Pugh A, B, and C patients (P < 0.01). CONCLUSIONS: The 13C-phenylalanine breath test can be used as a non-invasive assay to evaluate hepatic function in elderly patients with liver cirrhosis. The 13C-%dose/h at 20 min, at 30 min and cumulative excretion at 60 min may be the key value for determination at a single time-point. 13C-phenylalanine breath test is safe and helpful in distinguishing different stages of hepatic dysfunction for elderly cirrhosis patients.

[Assessment of the health-related quality of life of patients with minimal hepatic encephalopathy].

OBJECTIVE: The Medical Outcome Study of 36-item Short-Form Health Survey (SF-36) is a well-validated generic questionnaire widely used to assess health-related quality of life (HRQOL), and the Chronic Liver Disease Questionnaire (CLDQ) is a specific HRQOL assessment designed for patients with liver diseases. The aim of our study is to evaluate the HRQOL based on SF-36 and CLDQ (Chinese version) in patients with chronic hepatitis B and liver cirrhosis, especially in the status of minimal hepatic encephalopathy (MHE). METHODS: The SF-36 and CLDQ were answered by 160 healthy volunteers, 20 patients with chronic hepatitis B and 106 patients with cirrhosis. HRQOL scores of the groups with different liver disease severities and with or without MHE were compared. The SF-36 includes one multi-item scale that assesses eight health categories: physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotion, and mental health. CLDQ assesses 6 categories: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry. RESULTS: Compared with the healthy controls, patients with chronic hepatitis B and liver cirrhosis at baseline had a lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increased severity of liver cirrhosis (based on the Child-Pugh score but with MHE or without) was associated with a decrease in most components, both in SF-36 and in CLDQ. However, patients with Child-Pugh B and C disease had similar HRQOL scores on both the SF-36 and CLDQ (P > 0.05), except role-physical and vitality on SF-36. There was a significant difference between patients with and without MHE on the SF-36 score (P < 0.01), and no significant difference (P > 0.05) on CLDQ scores except in abdominal symptoms. CONCLUSION: The Chinese version of SF-36 along with CLDQ are valid and reliable methods for testing MHE in patients with liver cirrhosis.

Assessment of health-related quality of life in Chinese patients with minimal hepatic encephalopathy.

AIM: To evaluate the health-related quality of life (HRQOL) based on the Chinese version of SF-36 and Chronic Liver Disease Questionnaire (CLDQ) in subjects with chronic hepatitis B, liver cirrhosis, including patients with minimal hepatic encephalopathy (MHE). METHODS: The SF-36 and CLDQ were administered to 160 healthy volunteers, 20 subjects with chronic hepatitis B and 106 patients with cirrhosis (33 cases exhibited MHE). HRQOL scores were compared among the different study groups. The SF-36 includes eight health concepts: physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotion, and mental health. Six domains of CLDQ were assessed: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry. RESULTS: Compared with healthy controls (96.9 +/- 4.5, 86.6 +/- 18.4, 90.1 +/- 12.5, 89.0 +/- 5.7, 87.5 +/- 4.3, 95.8 +/- 7.1, 88.5 +/- 15.9, 88.7 +/- 5.2 in SF-36 and 6.7 +/- 0.5, 6.1 +/- 0.6, 6.3 +/- 0.6, 6.5 +/- 0.5, 6.3 +/- 0.5, 6.8 +/- 0.4 in CLDQ), patients with chronic hepatitis B (86.3 +/- 11.0, 68.8 +/- 21.3, 78.9 +/- 14.4, 60.8 +/- 10.5, 70.8 +/- 8.6, 76.1 +/- 12.6, 50.0 +/- 22.9, 72.2 +/- 10.6 and 5.5 +/- 1.0, 4.5 +/- 1.0, 5.2 +/- 1.1, 5.3 +/- 0.9, 4.8 +/- 0.9, 4.9 +/- 1.0) and cirrhosis (52.8 +/- 17.4, 32.8 +/- 27.9, 61.6 +/- 18.9, 30.2 +/- 18.3, 47.9 +/- 20.1, 54.0 +/- 19.2, 28.9 +/- 26.1, 51.1 +/- 17.8 and 4.7 +/- 1.2, 3.9 +/- 1.2, 4.7 +/- 1.2, 4.7 +/- 1.3, 4.7 +/- 1.0, 4.4 +/- 1.1) had lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increasing severity of liver cirrhosis (based on the Child-Pugh score/presence or absence of MHE) was associated with a decrease in most components of SF-36 and CLDQ, especially SF-36. CONCLUSION: The Chinese version of SF-36 along with CLDQ is a valid and reliable method for testing MHE in patients with liver cirrhosis. Cirrhosis and MHE are associated with decreased HRQOL.