Ribosome biogenesis protein Urb1 acts downstream of mTOR complex 1 to modulate digestive organ development in zebrafish

Ribosome biogenesis is essential for the cell growth and division. Disruptions in ribosome biogenesis result in developmental defects and a group of diseases, known as ribosomopathies. Here, we report a mutation in zebrafish urb1, which encodes an essential ribosome biogenesis protein. The urb1 cq31 mutant exhibits hypoplastic digestive organs, which is caused by impaired cell proliferation with the differentiation of digestive organ progenitors unaffected. Knockdown of mtor or raptor leads to similar hypoplastic phenotypes and reduced expression of urb1 in the digestive organs. Overexpression of Urb1 results in overgrowth of digestive organs, and can efficiently rescue the hypoplastic liver and pancreas in the mtor and raptor morphants. Reduced syntheses of free ribosomal subunits and impaired assembly of polysomes are observed in the urb1 mutant as well as in the mtor and raptor morphants, which can be rescued by the Urb1 overexpression. These data demonstrate that Urb1 plays an important role in governing ribosome biogenesis and protein synthesis downstream of mammalian/mechanistic target of rapamycin complex 1（mTORC1）, thus regulating the development of digestive organs. Our study indicates the requirement of hyperactive protein synthesis for the digestive organ development.

Effects of Dihydromyricetin Extracted from Ampelopsis grossedentata on Visceral Organ Indexes and Intestinal Digestive Enzyme Activities of Chickens

To provide a reference basis for reasonable development and utilization of Ampelopsis grossedentata resource and its application in production,we added 0.025%,0.05% and 0.1% dihydromyricetin（DMY）extracted from A.grossedentata into the basal diets of Yaoshan chickens,and studied the effects of DMY on visceral organ indexes and digestive enzyme activities of 40-day-old healthy Yaoshan chickens.Supplementation of DMY in basal diets influenced visceral organ weight,organ index,length and digestive enzyme activity of small intestine of chickens.Among them,0.05% DMY was the most appropriate volume for supplementation.Compared with control group（without DMY）,0.05% DMY reduced lung weight and index（P〉0.05）,significantly reduced liver weight（P〈0.05）,extremely reduced stomach weight and stomach index（P〈0.01）,increased activity of amylase in small intestine（P〉0.05）,significantly increased length of small intestine and activity of protease（P〈0.05）.Supplementation of 0.05% DMY reduced the visceral organ weight and organ index,enhanced digestion and absorption ability of gastrointestinal tract,thereby improving feed utilization rate and promoting the growth of chickens.

Repeatedly elevatedγ-glutamyltransferase levels are associated with an increased incidence of digestive cancers:A population-based cohort study

BACKGROUND The association between elevatedγ-glutamyltransferase(GGT)at a certain point and incident cancer has been suggested;however,no study has evaluated the association between repeatedly elevated GGT and cancer incidence.AIM To investigate the effects of repeatedly elevated GGT on the incidence of digestive cancers.METHODS Participants who had undergone health screening from 2009 to 2012 and 4 consecutive previous examinations were enrolled.GGT points were calculated as the number of times participants met the criteria of quartile 4 of GGT in four serial measurements(0-4 points).Multivariable Cox proportional hazard regression models were applied.RESULTS In total,3559109 participants were included;among them,43574 digestive cancers developed during a median of 6.8 years of follow-up.The incidence of total digestive cancers increased in a dose-response manner in men[adjusted hazard ratio(aHR)compared with those with 0 GGT points=1.28 and 95%confidence interval(CI)=1.24-1.33 in those with 1 point;aHR=1.40 and 95%CI=1.35-1.46 in those with 2 points;aHR=1.52 and 95%CI=1.46-1.58 in those with 3 points;aHR=1.88 and 95%CI=1.83-1.94 in those with 4 points;P for trend<0.001].This trend was more prominent in men than in women and those with healthy habits(no smoking,no alcohol consumption,and a low body mass index)than in those with unhealthy habits.CONCLUSION Repeatedly elevated GGT levels were associated with an increased risk of incident digestive cancer in a dose-responsive manner,particularly in men and those with healthy habits.Repeated GGT measurements may be a good biomarker of incident digestive cancer and could help physicians identify high-risk populations.

Risk factors for de novo hepatitis B during solid cancer treatment

BACKGROUND Reactivation of hepatitis B virus(HBV)during anticancer treatment is a critical issue.When treating patients with solid tumors,it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen(HBsAg)-negative and hepatitis B core antibody(HBcAb)-positive patients,socalled de novo hepatitis B patients.The risk of de novo hepatitis B may vary based on different background factors.AIM To determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.METHODS This retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies(HBsAbs).The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements.Patient characteristics and disease and treatment information were investigated.HBV DNA measurements were performed using TaqMan polymerase chain reaction(PCR).To identify the risk factors associated with HBV DNA expression,the age,sex,original disease,pathology,treatment method,presence or absence of hepatitis C virus(HCV),and HBsAb and/or HBcAb titers of all subjects were investigated.In patients with HBV DNA,the time of appearance,presence of HBsAgs and HBsAbs at the time of appearance,and course of the subsequent fluctuations in virus levels were also investigated.RESULTS Among the 1040 patients,938 were HBcAb positive,and 102 were HBcAb negative and HBsAb positive.HBV DNA expression was observed before the onset of treatment in nine patients(0.9%)and after treatment in 35 patients(3.7%),all of whom were HBcAb positive.The HBV reactivation group showed significantly higher median HBcAb values[9.00(8.12-9.89)vs 7.22(7.02-7.43),P=0.0001]and significantly lower HBsAb values(14 vs 46,P=0.0342)than the group without reactivation.Notably,the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption(79.0%vs 58.7%,P=0.0051).A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation(multivariate analysis,P=0.0002 and P=0.0095).The group without HBsAbs tended to have a shorter time to reactivation(day 43 vs day 193),and the frequency of reactivation within 6 mo was significantly higher in this group(P=0.0459)than in the other group.CONCLUSION A high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.

Effect of Additional Feed Supplement Fermentation Shrimp Waste Extract on Digestibility in Sentul Chicken Growth Phase

This study aims to determine the effect of adding feed supplements of fermented shrimp waste extract in the ration on the digestibility of local chicken rations in the growth phase.The research was carried out in Jatinangor District as well as the Laboratory of Ruminant Animal Nutrition and Animal Feed Chemistry,Faculty of Animal Husbandry,Padjadjaran University,Sumedang.The method used in this study was experimental with a Complete Randomized Design(RAL).The data were analyzed by fingerprint test(ANOVA)with further tests using the Dunnet test.The object of this study consisted of 20 Sentul chickens raised from the age of 1 day to 12 weeks,divided into 5 treatments and 4 tests.The treatment consists of P0=Basal ration without the addition of feed supplement fermented shrimp waste extract,P1=Basal ration+0.5%feed supplement fermented shrimp waste extract,P2=Basal ration+1.0%feed supplement fermented shrimp waste extract,P3=Basal ration+1.5%feed supplement fermented shrimp waste extract,and P4=Basal ration+2.0%feed supplement fermented shrimp waste extract.The changes observed are the digestibility of dry matter,the digestibility of organic matter,and the digestibility of proteins.The results showed that the addition of feed supplements for fermented shrimp waste extract had a significantly different influence on the digestibility of dry matter,the digestibility of organic matter,and the digestibility of protein.This study concludes that the addition of a feed supplement of 2%fermented shrimp waste extract in the ration can produce a high ration digestibility value for Sentul chicken in the growth phase.

Ribosome Biogenesis Factor Bmsl-like Is Essential for Liver Development in Zebrafish

Ribosome biogenesis in the nucleolus requires numerous nucleolar proteins and small non-coding RNAs.Among them is ribosome biogenesis factor Bmsl,which is highly conserved from yeast to human.In yeast,Bmsl initiates ribosome biogenesis through recruiting Rcll to pre-ribosomes.However,little is known about the biological function of Bmsl in vertebrates.Here we report that Bmsl plays an essential role in zebrafish liver development.We identified a zebrafish bms1l^（sq163） mutant which carries a T to A mutation in the gene bmsl-like（bms1l）.This mutation results in L^（152） to Q^（152） substitution in a GTPase motif in Bmsll.Surprisingly,bmsll^（sq163） mutation confers hypoplasia specifically in the liver,exocrine pancreas and intestine after 3 days post-fertilization（dpf）.Consistent with the bmsll^（sq163） mutant phenotypes,whole-mount in situ hybridization（WISH） on wild type embryos showed that bmsll transcripts are abundant in the entire digestive tract and its accessory organs.Immunostaining for phospho-Histone 3（P-H3） and TUNEL assay revealed that impairment of hepatoblast proliferation rather than cell apoptosis is one of the consequences of bms1l（sq163） giving rise to an under-developed liver.Therefore,our findings demonstrate that Bmsll is necessary for zebrafish liver development.