Characterizing mobile element insertions in 5675 genomes.

Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36 699 non-reference MEIs constructed from 5675 genomes, comprising 2998 Chinese samples (∼26.2×, NyuWa) and 2677 samples from the 1000 Genomes Project (∼7.4×, 1KGP). We discovered that LINE-1 insertions were highly enriched in centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings.

Case report: a case report and literature analysis on intestinal tuberculosis intestinal perforation complicated by umbilical intestinal fistula and bladder ileal fistula.

BACKGROUND: Intestinal tuberculosis is a chronic and specific infection caused by Mycobacterium tuberculosis invading the intestine. Due to the nonspecific clinical presentation, it is stressed that intestinal perforation complicates umbilical intestinal fistula and bladder ileal fistula is very rare and extremely difficult to be diagnosed. It is significant to identify the disease and take urgent intervene in the early stage. CASE PRESENTATION: An 18-month-old boy patient presented with abdominal pain. Abdominal CT suggested abscess formation in the right lower abdomen and pelvis. The patient underwent resection of necrotic and stenotic intestinal segments with the creation of an ileostomy, cystostomy and vesicoureteral fistula repair for the presence of intestinal perforation complicated by vesicoureteral fistula and umbilical enterocutaneous fistula. Histopathology confirmed the intestinal tuberculosis. The patient was discharged successfully after 11 days post anti-tuberculosis treatment. CONCLUSION: Our case report here is a rare case of umbilical intestinal fistula with bladder ileal fistula secondary to intestinal perforation from intestinal tuberculosis. The purpose of this report is to make the surgical community aware of atypical presentations of intestinal tuberculosis. If our peers encounter the similar situation, they can be prepared for corresponding diagnosis and treatment.

ß-Cryptoxanthin Attenuates Cigarette-Smoke-Induced Lung Lesions in the Absence of Carotenoid Cleavage Enzymes (BCO1/BCO2) in Mice.

High dietary intake of ß-cryptoxanthin (BCX, an oxygenated provitamin A carotenoid) is associated with a lower risk of lung disease in smokers. BCX can be cleaved by ß-carotene-15,15'-oxygenase (BCO1) and ß-carotene-9',10'-oxygenase (BCO2) to produce retinol and apo-10'-carotenoids. We investigated whether BCX has protective effects against cigarette smoke (CS)-induced lung injury, dependent or independent of BCO1/BCO2 and their metabolites. Both BCO1-/-/BCO2-/- double knockout mice (DKO) and wild type (WT) littermates were supplemented with BCX 14 days and then exposed to CS for an additional 14 days. CS exposure significantly induced macrophage and neutrophil infiltration in the lung tissues of mice, regardless of genotypes, compared to the non-exposed littermates. BCX treatment significantly inhibited CS-induced inflammatory cell infiltration, hyperplasia in the bronchial epithelium, and enlarged alveolar airspaces in both WT and DKO mice, regardless of sex. The protective effects of BCX were associated with lower expression of IL-6, TNF-α, and matrix metalloproteinases-2 and -9. BCX treatment led to a significant increase in hepatic BCX levels in DKO mice, but not in WT mice, which had significant increase in hepatic retinol concentration. No apo-10'-carotenoids were detected in any of the groups. In vitro BCX, at comparable doses of 3-OH-ß-apo-10'-carotenal, was effective at inhibiting the lipopolysaccharide-induced inflammatory response in a human bronchial epithelial cell line. These data indicate that BCX can serve as an effective protective agent against CS-induced lung lesions in the absence of carotenoid cleavage enzymes.

NPInter v4.0: an integrated database of ncRNA interactions.

Noncoding RNAs (ncRNAs) play crucial regulatory roles in a variety of biological circuits. To document regulatory interactions between ncRNAs and biomolecules, we previously created the NPInter database (http://bigdata.ibp.ac.cn/npinter). Since the last version of NPInter was issued, a rapidly growing number of studies have reported novel interactions and accumulated numerous high-throughput interactome data. We have therefore updated NPInter to its fourth edition in which are integrated 600 000 new experimentally identified ncRNA interactions. ncRNA-DNA interactions derived from ChIRP-seq data and circular RNA interactions have been included in the database. Additionally, disease associations were annotated to the interacting molecules. The database website has also been redesigned with a more user-friendly interface and several additional functional modules. Overall, NPInter v4.0 now provides more comprehensive data and services for researchers working on ncRNAs and their interactions with other biomolecules.

Dietary ß-Cryptoxanthin Inhibits High-Refined Carbohydrate Diet-Induced Fatty Liver via Differential Protective Mechanisms Depending on Carotenoid Cleavage Enzymes in Male Mice.

BACKGROUND: ß-Cryptoxanthin (BCX), a provitamin A carotenoid shown to protect against nonalcoholic fatty liver disease (NAFLD), can be cleaved by ß-carotene-15,15'-oxygenase (BCO1) to generate vitamin A, and by ß-carotene-9',10'-oxygenase (BCO2) to produce bioactive apo-carotenoids. BCO1/BCO2 polymorphisms have been associated with variations in plasma carotenoid amounts in both humans and animals. OBJECTIVES: We investigated whether BCX feeding inhibits high refined-carbohydrate diet (HRCD)-induced NAFLD, dependent or independent of BCO1/BCO2. METHODS: Six-week-old male wild-type (WT) and BCO1-/-/BCO2-/- double knockout (DKO) mice were randomly fed HRCD (66.5% of energy from carbohydrate) with or without BCX (10 mg/kg diet) for 24 wk. Pathological and biochemical variables were analyzed in the liver and mesenteric adipose tissues (MATs). Data were analyzed by 2-factor ANOVA. RESULTS: Compared to their respective HRCD controls, BCX reduced hepatic steatosis severity by 33‒43% and hepatic total cholesterol by 43‒70% in both WT and DKO mice (P < 0.01). Hepatic concentrations of BCX, but not retinol and retinyl palmitate, were 33-fold higher in DKO mice than in WT mice (P < 0.001). BCX feeding increased the hepatic fatty acid oxidation protein peroxisome proliferator-activated receptor-α, and the cholesterol efflux gene ATP-binding cassette transporter5, and suppressed the lipogenesis gene acetyl-CoA carboxylase 1 (Acc1) in the MAT of WT mice but not DKO mice (P < 0.05). BCX feeding decreased the hepatic lipogenesis proteins ACC and stearoyl-CoA desaturase-1 (3-fold and 5-fold) and the cholesterol synthesis genes 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and HMG-CoA synthase 1 (2.7-fold and 1.8-fold) and increased the cholesterol catabolism gene cholesterol 7α-hydroxylase (1.9-fold) in the DKO but not WT mice (P < 0.05). BCX feeding increased hepatic protein sirtuin1 (2.5-fold) and AMP-activated protein kinase (9-fold) and decreased hepatic farnesoid X receptor protein (80%) and the inflammatory cytokine gene Il6 (6-fold) in the MAT of DKO mice but not WT mice (P < 0.05). CONCLUSION: BCX feeding mitigates HRCD-induced NAFLD in both WT and DKO mice through different mechanisms in the liver-MAT axis, depending on the presence or absence of BCO1/BCO2.

Metabolic and lifestyle risk factors for acute pancreatitis in Chinese adults: A prospective cohort study of 0.5 million people.

BACKGROUND: Little prospective evidence exists about risk factors and prognosis of acute pancreatitis in China. We examined the associations of certain metabolic and lifestyle factors with risk of acute pancreatitis in Chinese adults. METHODS AND FINDINGS: The prospective China Kadoorie Biobank (CKB) recruited 512,891 adults aged 30 to 79 years from 5 urban and 5 rural areas between 25 June 2004 and 15 July 2008. During 9.2 years of follow-up (to 1 January 2015), 1,079 cases of acute pancreatitis were recorded. Cox regression was used to estimate adjusted hazard ratios (HRs) for acute pancreatitis associated with various metabolic and lifestyle factors among all or male (for smoking and alcohol drinking) participants. Overall, the mean waist circumference (WC) was 82.1 cm (SD 9.8) cm in men and 79.0 cm (SD 9.5) cm in women, 6% had diabetes, and 6% had gallbladder disease at baseline. WC was positively associated with risk of acute pancreatitis, with an adjusted HR of 1.35 (95% CI 1.27-1.43; p < 0.001) per 1-SD-higher WC. Individuals with diabetes or gallbladder disease had HRs of 1.34 (1.07-1.69; p = 0.01) and 2.42 (2.03-2.88; p < 0.001), respectively. Physical activity was inversely associated with risk of acute pancreatitis, with each 4 metabolic equivalent of task (MET) hours per day (MET-h/day) higher physical activity associated with an adjusted HR of 0.95 (0.91-0.99; p = 0.03). Compared with those without any metabolic risk factors (i.e., obesity, diabetes, gallbladder disease, and physical inactivity), the HRs of acute pancreatitis for those with 1, 2, or ≥3 risk factors were 1.61 (1.47-1.76), 2.36 (2.01-2.78), and 3.41 (2.46-4.72), respectively (p < 0.001). Among men, heavy alcohol drinkers (≥420 g/week) had an HR of 1.52 (1.11-2.09; p = 0.04, compared with abstainers), and current regular smokers had an HR of 1.45 (1.28-1.64; p = 0.02, compared with never smokers). Following a diagnosis of acute pancreatitis, there were higher risks of pancreatic cancer (HR = 8.26 [3.42-19.98]; p < 0.001; 13 pancreatic cancer cases) and death (1.53 [1.17-2.01]; p = 0.002; 89 deaths). Other diseases of the pancreas had similar risk factor profiles and prognosis to acute pancreatitis. The main study limitations are ascertainment of pancreatitis using hospital records and residual confounding. CONCLUSIONS: In this relatively lean Chinese population, several modifiable metabolic and lifestyle factors were associated with higher risks of acute pancreatitis, and individuals with acute pancreatitis had higher risks of pancreatic cancer and death.

Ablation of carotenoid cleavage enzymes (BCO1 and BCO2) induced hepatic steatosis by altering the farnesoid X receptor/miR-34a/sirtuin 1 pathway.

ß-Carotene-15, 15'-oxygenase (BCO1) and ß-carotene-9', 10'-oxygenase (BCO2) are essential enzymes in carotenoid metabolism. While BCO1/BCO2 polymorphisms have been associated with alterations to human and animal carotenoid levels, experimental studies have suggested that BCO1 and BCO2 may have specific physiological functions beyond the cleavage of carotenoids. In the present study, we investigated the effect of ablation of both BCO1/BCO2 in the development of non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism(s). BCO1/BCO2 double knock out (DKO) mice developed hepatic steatosis (8/8) and had significantly higher levels of hepatic and plasma triglyceride and total cholesterol compared to WT (0/8). Hepatic changes in the BCO1/BCO2 DKO mice were associated with significant: 1) increases in lipogenesis markers, and decreases in fatty acid ß-oxidation markers; 2) upregulation of cholesterol metabolism markers; 3) alterations to microRNAs related to TG accumulation and cholesterol metabolism; 4) increases in an hepatic oxidative stress marker (HO-1) but decreases in anti-oxidant enzymes; and 5) decreases in farnesoid X receptor (FXR), small heterodimer partner (SHP), and sirtuin 1 (SIRT1). The present study provided novel experimental evidence that BCO1 and BCO2 could play a significant role in maintaining normal hepatic lipid and cholesterol homeostasis, potentially through the regulation of the FXR/miR-34a/SIRT1 pathway.

Ex vivo liver resection and autotransplantation with cardiopulmonary bypass for hepatoblastoma in children: A case report.

Some primary and secondary liver carcinomas cannot be resected using a conventional approach due to their size, location, or major vascular invasion. The aim of this study was to explore the application of ex vivo liver resection and autotransplantation for complicated HB in children. A 1.5-year-old girl with HB after repeated chemotherapy was analyzed. In this patient, tumor invasion includes the IV, V, and VIII liver segments, and thrombosis formed in the inferior vena cava and right atrium. It is difficult to obtain complete tumor resection using conventional hepatectomy. The patient was treated via ex vivo liver resection and autotransplantation, and tumor thrombus in the inferior vena cava and right atrium was removed via cardiopulmonary bypass. Operative methods and precautions were analyzed during and after the operation. The operation was completed successfully within 8 hours, and the liver's cold ischemia time was 190 minutes. The patient recuperated successfully, and the liver's function and AFP levels gradually tended to normalize 2 weeks after the operation. Ultrasonic examination revealed that the blood flow velocity of the hepatic vein, portal vein, and hepatic artery was good. The patient recovered and was discharged 3 weeks after the operation. Ex vivo liver resection and autotransplantation have great application value for complicated HB in children that is not suitable for conventional hepatic lobectomy.

Annular pancreas in China: 9 years' experience from a single center.

To summarize the clinical characteristics, diagnosis, treatment and prognosis among 152 children with annular pancreas (AP). A retrospective review of 152 patients with AP who were treated with surgical repair between January 2009 and August 2017 was performed at our pediatric surgical units. Presenting symptoms, birth weight, radiological findings, associated anomalies, the type of surgery performed were analyzed. (1) 152 patients were identified, out of which 82 were males, and 70 were females; (2) the average birth weight of children with AP was less than that of healthy newborns. The birth weights of 5.4% premature infants were less than 1500 g; the birth weight of 17% full-term infants, 69% premature infants and 50% post-term infants were less than 2500 g. (3) 100 (66%) patients presented symptoms during neonatal period and 43 (28%) patients had duodenal obstruction diagnosed by prenatal ultrasound scan. (4) All cases were managed surgically by open laparotomy, and all patients were duly discharged. AP most commonly presents symptoms in early neonatal period. Infants with AP are associated with a higher rate of low birth weight, and it was because swallowed amniotic fluid could not be absorbed and impaired insulin secretion caused by abnormal pancreas. Ultrasonography, abdominal plain film and upper gastrointestinal series (UGI) are helpful, but cannot make the diagnosis, and surgery is the only effective way to diagnose and treat AP.

Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.

Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8-10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF-κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK-induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF-κB and CYP2E1 in the liver and attenuated the NNK-induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen-associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen-induced pulmonary and hepatic injury.

Functional characteristics of reversibly immortalized hepatic progenitor cells derived from mouse embryonic liver.

BACKGROUND/AIMS: Liver is a vital organ and retains its regeneration capability throughout adulthood, which requires contributions from different cell populations, including liver precursors and intrahepatic stem cells. To overcome the mortality of hepatic progenitors (iHPs) in vitro, we aim to establish reversibly immortalized hepatic progenitor cells from mouse embryonic liver. METHODS AND RESULTS: Using retroviral system to stably express SV40 T antigen flanked with Cre/LoxP sites, we establish a repertoire of iHP clones with varied differentiation potential. The iHP cells maintain long-term proliferative activity and express varied levels of progenitor markers (Pou5f1/Oct4 and Dlk) and hepatocyte markers (AFP, Alb and ApoB). Five representative iHP clones express hepatic/pancreatic transcription factors HNF3α/Foxa1, HNF3ß/Foxa2, and HNF4α/MODY1. Dexamethasone is shown to promote the expression of hepatocyte markers AFP and TAT, along with ICG-uptake and glycogen storage functions in the iHP clones. Cre-mediated removal of SV40 T antigen reverses the proliferative activity of iHP cells. When iHP cells are subcutaneously implanted in athymic nude mice, no tumor formation is observed for up to 8 weeks. CONCLUSIONS: We demonstrate that the established iHP cells are stable, reversible, and non-tumorigenic hepatic progenitor-like cells, which should be valuable for studying liver organogenesis, metabolic regulations, and hepatic lineage-specific differentiation.

Thirty-five consecutive pediatric living donor liver transplantation: experiences and lessons learned from a single center.

BACKGROUND/AIMS: In the last 10 years, the early patient outcome of liver transplantation in children have significantly improved. Now the overall outcomes of pediatric LT are promising. METHODOLOGY: In this study, we review the outcome of all pediatric liver transplants performed at our center and analyze our experiences with pediatric liver transplant. Of the 34 liver transplant recipients, 26 were highly urgent (19.7%). RESULTS: Actuarial patient survival rates at 6, 12, and 36 months was 82.9%, 79.8% and 72.2%, respectively. Indications for liver transplant were biliary atresia (n = 22), Wilson's disease (n = 4), glycogen storage disease (n = 3), portal vein cavernous transformation (PVCT) (n = 3), fulminant liver failure (n = 1), and cryptogenic cirrhosis (n = 1). The main complications were surgical complications (including biliary complications, portal vein or arterial complications, intestinal perforation, postoperative bleeding, of which 20% required reoperation) and infections. Cyclosporine was the primary immunosuppressive agent used in 70.6% of patients, with a 26.5% incidence of acute allograft rejection within the first six months. One children underwent re-transplant as a result of hepatic artery thrombosis. Nine children died during followup. They were related to portal vein thrombosis (one), chronic rejection (one), sepsis (one), post-transplant lymphoproliferative disease (one) and so on. CONCLUSIONS: The overall outcomes of pediatric liver transplantation at our center are promising. Advances in post-transplant care and monitoring of the recipients, technical refinements enable these results.

Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma.

Osteosarcoma is a differentiation-deficient disease, and despite the unique advantages and great potential of differentiation therapy, there are only a few known differentiation inducers, and little research has been done on their targets. Cell differentiation is associated with an increase in mitochondrial content and activity. The metabolism of some tumor cells is characterized by impaired oxidative phosphorylation, as well as up-regulation of aerobic glycolysis and pentose phosphate pathways. Leucine-containing zipper and EF-hand transmembrane protein 1 (LETM1) is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression, as well as cancer cell stemness. We found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and function. Knockdown of LETM1 partially restored the mitochondrial structure and function, inhibited the pentose phosphate pathway, promoted oxidative phosphorylation, and led to osteogenic differentiation. It also inhibited spheroid cell formation, proliferation, migration, and invasion in an in vitro model. When LETM1 was knocked down in vivo, there was reduced tumor formation and lung metastasis. These data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells, and knockdown of LETM1 partially restores the mitochondrial structure and function, inhibits the pentose phosphate pathway, promotes oxidative phosphorylation, and increases osteogenic differentiation, thereby reducing malignant biological behavior of the cells.

The pre-Kasai procedure in living donor liver transplantation for children with biliary atresia.

BACKGROUND: Biliary atresia (BA) is a major cause of chronic cholestasis, a fatal disorder in infants. This study was undertaken to evaluate the safety and effectiveness of primary living donor liver transplantation (LDLT) in comparison with the traditional first-line treatment, the Kasai procedure. METHODS: We assessed 28 children with BA at age of less than two years (3-21.3 months) who had undergone LDLT in two hospitals in Southwest China during the period of 2008-2011. Eighteen children who had had primary LDLT were included in a primary LDLT group, and ten children who had undergone the Kasai operation in a pre-Kasai group. All patients were followed up after discharge from the hospital. The records of the BA patients and donors were reviewed. RESULTS: The time of follow-up ranged 12-44.5 months with a median of 31 months. The 30-day and 1-year survival rates were 85.7% and 78.6%, respectively. There was no significant difference in the 30-day or 1-year survival between the two groups (83.3% vs 90% and 77.8% vs 80%, P>0.05). The main cause of death was hepatic artery thrombosis. There were more patients with complications who required intensive medical care or re-operation in the pre-Kasai group (8, 80%) than in the primary LDLT group (9, 50%) (P=0.226). But no significant differences were observed in operating time (9.3 vs 8.9 hours, P=0.77), intraoperative blood loss (208.6 vs 197.0 mL, P=0.84) and blood transfusion (105.6 vs 100.0 mL, P=0.91) between the two groups. The durations of ICU and hospital stay in the primary LDLT group and pre-Kasai group were 180.4 vs 157.7 hours (P=0.18) and 27 vs 29 days (P=0.29), respectively. CONCLUSIONS: Primary LDLT is a safe and efficient management for young pediatric patients with BA. Compared with the outcome of LDLT for patients receiving a previous Kasai operation, a similar survival rate and a low rate of re-operation and intensive medical care for patients with BA can be obtained.

An optimized method for Oil Red O staining with the salicylic acid ethanol solution.

Oil Red O (ORO) staining is a commonly used experimental technique to detect lipid content in cells or tissues. Freshly prepared ORO in 60% isopropanol is the most widely used method at present. However, isopropanol is volatile and harmful to the human body. It will also affect the interpretation of the results due to the formation of crystals and non-specific diffuse staining. In this paper, by screening and validation, we report a salicylic acid ethanol solution (containing 50% ethanol, 5%-10% salicylic acid) for the preparation of ORO solution, which has a better staining effect on lipid staining in cells and tissues, with a clean background and short dyeing time. What's more, this ORO solution is non-toxic, convenient to prepare, and can be stored for a long time. Therefore, it is reliable, easy to operate, and can be widely popularized and applied in laboratories.

Pyloric stenosis secondary to peptic ulcer disease in pediatric patients: A case report and review of the literature.

RATIONALE: Pediatric pyloric obstruction is a condition characterized by complete or incomplete obstruction of the distal stomach caused by obstructive lesions of the distal stomach, pyloric duct, or proximal duodenum. Congenital hypertrophic pyloric stenosis is the most common cause of pediatric pyloric obstruction, whereas acquired pyloric stenosis is comparatively rare, with peptic ulcer disease being the most common cause. PATIENT CONCERNS: We describe a case of a 5-year-old girl who had peptic ulcer disease and developed scarring pyloric stenosis. We also give comprehensive details of the diagnosis and course of treatment. DIAGNOSIS: Intraoperative findings revealed ulcerative, scarring pyloric obstruction. INTERVENTIONS: Conservative treatment failed and surgery was subsequently performed. OUTCOMES: No further vomiting symptoms occurred after surgery. And 3 months after surgery, the patient had gained weight on average and had no further complaints. LESSONS: Although scarring pediatric pyloric blockage due to peptic ulcer is less common, emphasis should be placed on rapid diagnosis by accurate gastroscopy, barium meal of the gastrointestinal tract, or ultrasonography. Depending on the patient's condition, conservative treatment or surgery should be chosen carefully selected.

Erratum: BMP4 augments the survival of hepatocellular carcinoma (HCC) cells under hypoxia and hypoglycemia conditions by promoting the glycolysis pathway.

[This corrects the article on p. 793 in vol. 11, PMID: 33791154.].

Arabidopsis RAP2.2 plays an important role in plant resistance to Botrytis cinerea and ethylene responses.

• Ethylene plays a crucial role in plant resistance to necrotrophic pathogens, in which ETHYLENE RESPONSE FACTORs (ERFs) are often involved. • Here, we evaluated the role of an ERF transcription factor, RELATED TO AP2 2 (RAP2.2), in Botrytis resistance and ethylene responses in Arabidopsis. We analyzed the resistance of transgenic plants overexpressing RAP2.2 and the T-DNA insertion mutant to Botrytis cinerea. We assessed its role in the ethylene signaling pathway by molecular and genetic approaches. • RAP2.2-overexpressing transgenic plants showed increased resistance to B. cinerea, whereas its T-DNA insertion mutant rap2.2-3 showed decreased resistance. Overexpression of RAP2.2 in ethylene insensitive 2 (ein2) and ein3 ein3-like 1 (eil1) mutants restored their resistance to B. cinerea. Both ethylene and Botrytis infection induced the expression of RAP2.2 and the induction was disrupted in ein2 and ein3 eil1 mutants. We identified rap2.12-1 as a T-DNA insertion mutant of RAP2.12, the closest homolog of RAP2.2. The hypocotyls of rap2.2-3 rap2.12-1 double mutants showed ethylene insensitivity. The constitutive triple response in constitutive triple response1 (ctr1) was partially released in the rap2.2-3 rap2.12-1 ctr1 triple mutants. • Our findings demonstrate that RAP2.2 functions as an important regulator in Botrytis resistance and ethylene responses.

Apo-10'-lycopenoic acid, a lycopene metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice.

Lycopene has been shown to be beneficial in protecting against high-fat diet-induced fatty liver. The recent demonstration that lycopene can be converted by carotene 9',10'-oxygenase into a biologically active metabolite, ALA, led us to propose that the function of lycopene can be mediated by ALA. In the present study, male ob/ob mice were fed a liquid high-fat diet (60% energy from fat) with ALA supplementation (ALA group, 240 µg · kg body weight(-1) · d(-1)) or without ALA supplementation as the control (C group) for 16 wk. Steatosis, SIRT1 expression and activity, genes involved in lipid metabolism, and ALA concentrations in the livers of mice were examined. The results showed that ALA supplementation resulted in a significant accumulation of ALA in the liver and markedly decreased the steatosis in the ALA group without altering body and liver weights compared to the C group. The mRNA and protein levels of hepatic SIRT1 were higher in the ALA group compared to the C group. SIRT1 activity also was higher in the ALA group, as indicated by the lower levels of acetylated forkhead box class O1 protein levels. In addition, the mRNA level of acetyl CoA carboxylase 1 was significantly lower in the ALA group than in the C group. Because SIRT1 plays a key role in lipid homeostasis, the present study suggests that the lycopene metabolite, ALA, protects against the development of steatosis in ob/ob mice by upregulating SIRT1 gene expression and activity.

Risk Factors of Recurrent Appendiceal Abscess after Initial Non-Surgical Treatment without Drainage of Children with Appendiceal Abscess: A Single Center Retrospective Review.

Background: Exploration of the risk factors of recurrent appendiceal abscess after initial non-surgical treatment without drainage in children with appendiceal abscess. Patients and Methods: The medical records of all children diagnosed with appendiceal abscess and who were treated conservatively in the Children's Hospital of Chongqing Medical University from June 2012 to June 2020 were collected. The collected cases were divided into the recurrent group and the non-recurrent group, and all clinical indicators were compared. Logistic regression analysis was used to determine the risk factors for recurrent appendiceal abscess in children. Results: One hundred twenty-four patients were included and among them, 62 (50.0%) had clinical manifestations of recurrent appendiceal abscess (the recurrent group) and five patients (8%) suffered several instances of recurrence. Duration of intravenous antibiotic agents (odds ratio [OR], 0.905; 95% confidence interval [CI], 0.820-1.000) was independently associated with the recurrence of appendiceal abscess. The risk of recurrence was increased in children with the white blood cell (WBC) count at discharge greater than 8 × 109/L (OR, 2.702; 95% CI,1.172-6.231), the ratio of mass size to body surface area (BSA) at discharge greater than 4.255 (OR, 1.369; 95% CI, 1.104-1.697), and without continuous oral antibiotic agents after discharge (OR, 3.111; 95% CI, 1.240-7. 802). Conclusions: Interval appendectomy is recommended for children with WBC count at discharge greater than 8 × 109/L, and the ratio of mass size to BSA at discharge greater than 4.255, because they are more likely to develop recurrent appendiceal abscess after initial conservative treatment. The duration of intravenous antibiotic agents is an independent factor of the recurrence of appendiceal abscess, and a longer course of intravenous antibiotic agents is strongly associated with a reduced risk of recurrence. Continued oral antibiotic agents after discharge can effectively reduce the risk of recurrence of appendiceal abscesses.