Machine learning to establish three sphingolipid metabolism genes signature to characterize the immune landscape and prognosis of patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Nevertheless, GC still lacks effective diagnosed and monitoring method and treating targets. This study used multi omics data to explore novel biomarkers and immune therapy targets around sphingolipids metabolism genes (SMGs). METHOD: LASSO regression analysis was performed to filter prognostic and differently expression SMGs among TCGA and GTEx data. Risk score model and Kaplan-Meier were built to validate the prognostic SMG signature and prognostic nomogram was further constructed. The biological functions of SMG signature were annotated via multi omics. The heterogeneity landscape of immune microenvironment in GC was explored. qRT-PCR was performed to validate the expression level of SMG signature. Competing endogenous RNA regulatory network was established to explore the molecular regulatory mechanisms. RESULT: 3-SMGs prognostic signature (GLA, LAMC1, TRAF2) and related nomogram were constructed combing several clinical characterizes. The expression difference and diagnostic value were validated by PCR data. Multi omics data reveals 3-SMG signature affects cell cycle and death via several signaling pathways to regulate GC progression. Overexpression of 3-SMG signature influenced various immune cell infiltration in GC microenvironment. RBP-SMGs-miRNA-mRNAs/lncRNAs regulatory network was built to annotate regulatory system. CONCLUSION: Upregulated 3-SMGs signature are excellent predictive diagnosed and prognostic biomarkers, providing a new perspective for future GC immunotherapy.

Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis.

BACKGROUND: Gastric cancer (GC) carries significant morbidity and mortality globally. An increasing number of studies have confirmed that circular RNA (circRNA) is tightly associated with the carcinogenesis and development of GC, especially acting as a competing endogenous RNA for miRNAs. OBJECTIVE: Our study aimed to construct the circRNA-miRNA-mRNA regulatory network and analyze the function and prognostic significance of the network using bioinformatics tools. METHODS: We first downloaded the GC expression profile from the Gene Expression Omnibus database and identified differentially expressed genes and differentially expressed circRNAs. Then, we predicted the miRNA-mRNA interaction pairs and constructed the circRNA-miRNA-mRNA regulatory network. Next, we established a protein-protein interaction network and analyzed the function of these networks. Finally, we primarily validated our results by comparison with The Cancer Genome Atlas cohort and by performing qRT-PCR. RESULTS: We screened the top 15 hub genes and 3 core modules. Functional analysis showed that in the upregulated circRNA network, 15 hub genes were correlated with extracellular matrix organization and interaction. The function of downregulated circRNAs converged on physiological functions, such as protein processing, energy metabolism and gastric acid secretion. We ascertained 3 prognostic and immune infiltration-related genes, COL12A1, COL5A2, and THBS1, and built a nomogram for clinical application. We validated the expression level and diagnostic performance of key prognostic differentially expressed genes. CONCLUSIONS: In conclusion, we constructed two circRNA-miRNA-mRNA regulatory networks and identified 3 prognostic and screening biomarkers, COL12A1, COL5A2, and THBS1. The ceRNA network and these genes could play important roles in GC development, diagnosis and prognosis.

The transcription factor MYB43 antagonizes with ICE1 to regulate freezing tolerance in Arabidopsis.

Previous discovering meticulously illustrates the post-translational modifications and protein stability regulation of ICE1 and their role in cold stress. However, the studies on the interaction of ICE1 with other transcription factors, and their function in modulation cold stress tolerance, as well as in the transition between cold stress and growth are largely insufficient. In this work, we found that maltose binding protein (MBP) 43 directly binds to the promoters of CBF genes to repress their expression, thereby negatively regulating freezing tolerance. Biochemical and genetic analyses showed that MYB43 interacts and antagonizes with ICE1 to regulate the expression of CBF genes and plant's freezing stress tolerance. PLEIOTROPIC REGULATORY LOCUS 1 (PRL1) accumulates under cold stress and promotes MYB43 protein degradation; however, when cold stress disappears, PRL1 restores normal protein levels, causing MYB43 protein to re-accumulate to normal levels. Furthermore, PRL1 positively regulates freezing tolerance by promoting degradation of MYB43 to attenuate its repression of CBF genes and antagonism with ICE1. Thus, our study reveals that MYB43 inhibits CBF genes expression under normal growth condition, while PRL1 promotes MYB43 protein degradation to attenuate its repression of CBF genes and antagonism with ICE1, and thereby to the precise modulation of plant cold stress responses.

Regulatory module WRKY33-ATL31-IRT1 mediates cadmium tolerance in Arabidopsis.

Cadmium (Cd) is one of the most dangerous environmental pollutants among heavy metals, and threatens food safety and human health by accumulating in plant sink tissues. Here, we report a novel regulatory cascade that profoundly influences Cd tolerance in Arabidopsis. Phenotypic analysis showed that an insertional knockdown mutation at the Arabidopsis Tóxicos en Levadura 31 (ATL31) locus resulted in hypersensitivity to Cd stress, most likely due to a significant increase in Cd accumulation. Consistently, ATL31-overexpressing lines exhibited enhanced Cd stress tolerance and reduced Cd accumulation. Further, IRON-REGULATED TRANSPORTER 1 (IRT1) was identified, and yeast two-hybrid, co-immunoprecipitation and bimolecular fluorescence complementation assays demonstrated its interaction with ATL31. Biochemical, molecular, and genetic analyses showed that IRT1 is targeted by ATL31 for ubiquitin-conjugated degradation in response to Cd stress. Intriguingly, transcription of ATL31 was strongly induced by Cd stress. In addition, transgenic and molecular analyses showed that WRKY33 directly activated the transcription of ATL31 in response to Cd stress and positively regulated Cd tolerance. Genetic analysis indicated that ATL31 acts upstream of IRT1 and downstream of WRKY33 to regulate Cd tolerance. Our study revealed that the WRKY33-ATL31-IRT1 module plays a crucial role in timely blocking Cd absorption to prevent metal toxicity in Arabidopsis.

SpyGlass in Diagnosis of Hepatocellular Carcinoma with Right Hepatic Duct Tumor Thrombus Hemorrhage: A Case Report.

Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.

MYB43 as a novel substrate for CRL4PRL1 E3 ligases negatively regulates cadmium tolerance through transcriptional inhibition of HMAs in Arabidopsis.

Controlled stability of proteins is a highly efficient mechanism to direct diverse processes in plants. A key regulatory system for protein stability is given by the CULLIN-RING E3 ligases (CRLs). In this work, MYB43 is identified as a novel target of a CUL4-DDB1-PRL1 (PLEIOTROPIC REGULATORY LOCUS 1)-RING E3 ligase (CRL4PRL1 E3 ligase). Its stability depends on the presence of PRL1, a WD40-containing protein functioning as a substrate receptor of the CRL4 E3 ligases. Genetic studies have indicated that MYB43 is a negative regulator of cadmium (Cd) tolerance in Arabidopsis by transcriptional inhibition of important Cd transporters (HMA2, HMA3 and HMA4), while PRL1 and CUL4 positively regulate Cd tolerance. Expression of CUL4 and PRL1 was enhanced in response to Cd stress, and PRL1 can interact with and target MYB43 for degradation depending on assembly of CRL4PRL1 E3 ligase, and consequently increase the expression of HMA2, HMA3 and HMA4 through attenuating the transcriptional inhibition. HMA2 and HMA4 are shown to transport cadmium ion (Cd2+ ) from the roots of plants to the shoots through the xylem, ultimately increasing the plants' tolerance to Cd stress.

Manipulation of the transcription factor SlNAC1 for improved tolerance to abiotic stress in tomato.

The tomato transcription factor SlNAC1 plays an important role in abiotic stress response and is fine-tuned at both transcriptional and posttranslational levels. The SlNAC1 gene is strongly induced by multiple abiotic stresses and the SlNAC1 protein is subjected to ubiquitin proteasome-mediated degradation. We found here that SlNAC1 possesses two distinct transactivation domains (TADs), TAD1 and TAD2. Significantly, the instability of SlNAC1 was attributed to the acidic amino acid-rich TAD1, in which the instability and transcriptional potential of TAD1 functionally overlapped; whereas the glutamine-rich TAD2 was stable and accounted for the abiotic stress signalling mediated by SlNAC1. Towards the goal of enhanced tolerance to abiotic stress in tomatoes, we manipulated SlNAC1 at both gene and protein levels: we generated a stable and functional SlNAC1 mutant SlNAC1∆191-270 by removing TAD1 and further engineered it to be stress-controllable by fusing the corresponding cDNA with the abiotic stress-inducible promoter ProStNAC1 . Transgenic tomato plants expressing the ProStNAC1 ::SlNAC1∆191-270 transgene did not display any undesired traits and exhibited enhanced tolerance to cold, drought and salt stresses. Taken together, our manipulation of the stress-related transcription factor via conditional expression of its derived stable and functional mutant provides a successful example for developing crops dynamically adapted to abiotic stress.

Antibiotic resistance status of helicobacter pylori strains isolated from initial eradication patients in Ningbo, China, from 2017 to 2021.

BACKGROUND: Resistance of Helicobacter pylori (H. pylori) to antibiotics is an evolving and dynamic process. Presence of antibiotic resistance impacts the success rate of initial eradication strategies in the clinic. AIM: To improve the success rate of initial eradication therapy and explore new antibiotic regimens, a large sample-based study utilizing antimicrobial susceptibility testing was performed. A total of 2508 H. pylori strains from patients subjected to initial eradication therapy were isolated, cultured, and tested for drug susceptibility from 2017 to 2021. The minimal inhibitory concentration (MIC) was recorded. H. pylori susceptibility profiles and its change trends from initial eradication patients were analyzed. The relationships between drug resistance, year of sample collection, age, and sex of patients were analyzed. RESULTS: The overall resistance rates were as follows: amoxicillin (9.25%), clarithromycin (38.48%), levofloxacin (42.86%), furazolidone (11.28%), doxycycline (8.56%), rifampicin (10.81%), tinidazole (74.32%), gatifloxacin (61.71%), tetracycline (0%), metronidazole (78.71%), ornidazole (97.87%), and fosfomycin (31.67%). Only 38.04% of the strains were pansusceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by those of mono resistance (29.90%), double resistance (24.96%), triple resistance (6.34%), and quadruple resistance (0.76%). Significant differences in the resistance rate and MIC were also observed in different age and sex groups. Time of collection and patient age and sex were associated with the distribution of antibiotic resistance. CONCLUSION: With the increasing resistance rate and multiple resistance of H. pylori to commonly used antibiotics, drug susceptibility testing is imperative to permit individualized therapy, and a regimen containing the combination of amoxicillin, furazolidone, tetracycline, doxycycline, or rifampicin is reasonable for initial empirical eradication therapy.

Effects of Exogenous α-Naphthaleneacetic Acid and 24-Epibrassinolide on Fruit Size and Assimilate Metabolism-Related Sugars and Enzyme Activities in Giant Pumpkin.

Size is the most important quality attribute of giant pumpkin fruit. Different concentrations and application frequencies of α-naphthaleneacetic acid (NAA) and 24-epibrassinolide (EBR) were sprayed on the leaves and fruits of giant pumpkin at different growth stages to determine their effects and the mechanism responsible for fruit size increase. NAA+EBR application improved source strength, and further analysis indicated that NAA+EBR markedly boosted net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr) and the expression level and activity of galactitol synthetase (GolS), raffinose synthetase (RS), and stachyose synthetase (STS), resulting in an increase in the synthesis of photoassimilate, especially stachyose. Concomitantly, NAA+EBR spray increased stachyose and sucrose contents throughout pumpkin fruit growth and the concentrations of glucose and fructose at 0 and 20 days post-anthesis (DPA) in peduncle phloem sap, implying that such treatment improved the efficiency of assimilate transport from the peduncle to the fruit. Furthermore, it improved the expression and activity of alkaline α-galactosidase (AGA), facilitating assimilate unloading, providing carbon skeletons and energy for fruit growth, and increasing fruit weight by more than 44.1%. Therefore, exogenous NAA and EBR increased source capacity, transportation efficiency, and sink strength, overall promoting the synthesis and distribution of photoassimilate, ultimately increasing fruit size.

Investigation on the effect of three isoflavones on the fibrillation of hen egg-white lysozyme.

In this paper, the effects of three isoflavones including daidzein, genistein, and puerarin on fibrillation of hen egg-white lysozyme were investigated by various analytical methods. The results demonstrated that all isoflavones could effectively inhibit the fibrillogenesis of hen egg-white lysozyme and destabilized the preformed fibrils of hen egg-white lysozyme in a dose-dependent manner. To further understand the inhibition mechanism, molecular modeling was carried out. The docking results demonstrated that the isoflavones could bind to two key fibrogenic sites in hen egg-white lysozyme through van der Waals force, electrostatic forces, and hydrogen bonding, as well as σ-π stacking. By these means, isoflavones could not only obviously enhance the hydrophobicity of the binding sites, but also greatly stabilize the native state of HEWL, which was able to postpone the fibrosis process of hen egg-white lysozyme.

Analysis of clinical characteristics of severe pertussis in infants and children: a retrospective study.

BACKGROUND: The incidence of pertussis shows an increasing trend in recent years, but some clinicians often lack sufficient understanding of the clinical characteristics and risk factors for severe pertussis, and more effective measures should be taken to reduce the incidence and mortality of pertussis in young infants METHODS: A retrospective study was conducted, and 184 infants and children with pertussis who had been hospitalized in the Department of Pediatrics of Beijing Ditan Hospital affiliated with Capital Medical University from January 2016 to December 2017 were included. Clinical data of the patients were collected and the clinical characteristics were statistically analyzed RESULTS: Among the 184 patients, 41.85% were infants < 3 months of age, and 65.22% of the total patients were not vaccinated against pertussis. There were 22 critically ill children, among whom 4 died, and compared with mild cases, they had a higher proportion of children younger than 3 months of age and infants not vaccinated against pertussis (63.64% vs. 38.89% and 100% vs. 60.49%, respectively); a higher proportion of children with severe pneumonia (100% vs. 0%); higher leukocyte count(× 109/L , 35.80 ± 20.53 vs 19.41 ± 8.59); and a higher proportion of children with severe hyperleukocytosis (18.18% vs. 0%, respectively) (P<0.05) CONCLUSIONS: 1. Infants aged <3 months not vaccinated for pertussis appear more likely to become infected and have more severe disease. 2. Severe pneumonia and hyperleukocytosis are the main mechanisms underlying severe pertussis.

Mixed Transcriptome Analysis Revealed the Possible Interaction Mechanisms between Zizania latifolia and Ustilago esculenta Inducing Jiaobai Stem-Gall Formation.

The smut fungus Ustilago esculenta infects Zizania latifolia and induces stem expansion to form a unique vegetable named Jiaobai. Although previous studies have demonstrated that hormonal control is essential for triggering stem swelling, the role of hormones synthesized by Z. latifolia and U. esculenta and the underlying molecular mechanism are not yet clear. To study the mechanism that triggers swollen stem formation, we analyzed the gene expression pattern of both interacting organisms during the initial trigger of culm gall formation, at which time the infective hyphae also propagated extensively and penetrated host stem cells. Transcriptional analysis indicated that abundant genes involving fungal pathogenicity and plant resistance were reprogrammed to maintain the subtle balance between the parasite and host. In addition, the expression of genes involved in auxin biosynthesis of U. esculenta obviously decreased during stem swelling, while a large number of genes related to the synthesis, metabolism and signal transduction of hormones of the host plant were stimulated and showed specific expression patterns, particularly, the expression of ZlYUCCA9 (a flavin monooxygenase, the key enzyme in indole-3-acetic acid (IAA) biosynthesis pathway) increased significantly. Simultaneously, the content of IAA increased significantly, while the contents of cytokinin and gibberellin showed the opposite trend. We speculated that auxin produced by the host plant, rather than the fungus, triggers stem swelling. Furthermore, from the differently expressed genes, two candidate Cys2-His2 (C2H2) zinc finger proteins, GME3058_g and GME5963_g, were identified from U. esculenta, which may conduct fungus growth and infection at the initial stage of stem-gall formation.

Light-to-Moderate Alcohol Consumption Is Associated With Increased Risk of Type 2 Diabetes in Individuals With Nonalcoholic Fatty Liver Disease: A Nine-Year Cohort Study.

OBJECTIVE: This study explored the association between light-to-moderate alcohol consumption (LMAC) and risk of type 2 diabetes mellitus (T2DM) in individuals with nonalcoholic fatty liver disease (NAFLD). METHODS: A 9-year cohort study was performed among Chinese men who underwent their annual health checkups between 2009 and 2018. NAFLD was diagnosed based on abdominal ultrasound with exclusion of excess alcohol intake and other causes of liver disease. Logistic regression and Cox proportional regression analyses were applied to identify the risk of prevalent and incident T2DM. RESULTS: Of the 7,079 participants enrolled, 243 had T2DM at baseline and 630 developed T2DM during the 45,456 person-years follow-up. Both at the baseline and by the end of the follow-up, LMAC was associated with a decreased risk of prevalent T2DM in NAFLD-free participants but with a significantly increased risk in patients with NAFLD. LMAC was also associated with a decreased risk of incident T2DM in NAFLD-free participants. The adjusted hazard ratios (95% confidence interval) of incident T2DM were 0.224 (0.115-0.437) and 0.464 (0.303-0.710) for NAFLD-free light drinkers and NAFLD-free moderate drinkers, respectively. Nondrinking, light-drinking, and moderate-drinking patients with NAFLD all showed significantly increased risks of incident T2DM. Compared with NAFLD-free nondrinkers, the adjusted hazard ratios (95% confidence interval) of incident T2DM were 1.672 (1.336-2.092), 2.642 (1.958-3.565), and 2.687 (2.106-3.427) for nondrinking, light-drinking, and moderate-drinking patients with NAFLD, respectively. DISCUSSION: LMAC decreased the risks of prevalent and incident T2DM in NAFLD-free participants. LMAC, however, was associated with an increased risk of T2DM in patients with NAFLD (ClinicalTrials.gov number: NCT03847116).

A novel BSD domain-containing transcription factor controls vegetative growth, leaf senescence, and fruit quality in tomato.

BSD (mammalian BTF2-like transcription factors, synapse-associated proteins, and DOS2-like proteins) is a conserved domain that exists in a variety of organisms, but its function has not been well studied. Here, we identified a novel BSD domain-containing protein (SlBSD1) in tomato (Solanum lycopersicum). Biochemical and microscopy assays indicated that SlBSD1 is a functional transcription factor that is predominantly localized in the nucleus. Loss-of-function and overexpression analyses suggested that SlBSD1 is a novel regulator of vegetative growth and leaf senescence in tomato. SlBSD1-knockdown (-KD) plants exhibited retarded vegetative growth and precocious leaf senescence, whereas SlBSD1-overexpression (-OX) plants displayed the opposite phenotypes. The negative role of SlBSD1 in leaf senescence was also supported by RNA-seq analysis comparing leaf tissues from SlBSD1-KD and wild-type plants. In addition, contents of soluble solids were altered in fruits in the SlBSD1-KD and SlBSD1-OX plants. Taken together, our data suggest that the novel transcription factor SlBSD1 plays important roles in controlling fruit quality and other physiological processes in tomato, including vegetative growth and leaf senescence.

Ketorolac tromethamine pretreatment suppresses sufentanil-induced cough during general anesthesia induction: a prospective randomized controlled trial.

BACKGROUND: To observe the effect of pretreatment with ketorolac tromethamine on sufentanil-induced cough in general anesthesia patients. METHODS: A total of 102 patients were screened, and 90 patients were scheduled for elective surgery under general anesthesia. The 90 patients were randomly divided into two groups: the control group (C group) and the observation group (KT group). Five minutes before anesthesia induction, the observation group was given ketorolac tromethamine 0.5 mg/kg intravenously within 3 s, while the control group was given the same amount of normal saline intravenously. All patients were given a sufentanil bolus of 0.5 µg/kg (within 3 s) intravenously. One minute later, propofol 2.5 mg/kg and vecuronium 0.15 mg/kg were injected intravenously, and endotracheal intubation was guided by laryngoscopy. The number of coughs that occurred within 1 min after sufentanil injection was recorded. The mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2) were recorded at T0 (immediately before pretreatment), T1 (5 min after pretreatment), T2 (before intubation), T3 (1 min after intubation) and T4 (5 min after intubation). The incidence of adverse reactions, including nausea and vomiting, dizziness, drowsiness, delay of recovery, restlessness in the recovery period, respiratory depression and postoperative incision pain, was analyzed. RESULTS: Within 1 min after sufentanil injection, the incidence and severity of cough in the KT group was significantly lower than that in the C group (P <  0.05). At T0, T1, T2, T3 and T4, there were no significant differences in MAP, HR and SpO2 between the two groups (P >  0.05). There was no significant difference in the dosage of sufentanil, propofol, remifentanil and vecuronium, the incidence of nausea and vomiting, the delay of recovery, dizziness, drowsiness or respiratory depression between the two groups (P >  0.05). However, the incidence of restlessness and the number of patients with VAS scores > 3 in the KT group were significantly lower than those in the C group (P <  0.05). CONCLUSION: Pretreatment with intravenous ketorolac tromethamine can significantly reduce the incidence of sufentanil-induced cough during induction of general anesthesia, which can also significantly reduce postoperative incision pain and restlessness during the recovery period. TRIAL REGISTRATION: Chinese Clinical Trial Registry (registration number# ChiCTR2000030287 ; date of registration: 27/02/2020).

Functional analysis of the seven in absentia ubiquitin ligase family in tomato.

Seven in absentia (SINA) protein is one subgroup of ubiquitin ligases possessing an N-terminal cysteine-rich really interesting new gene (RING) domain, two zinc-finger motifs, and a C-terminal domain responsible for substrate-binding and dimerization. In tomato (Solanum lycopersicum), the SINA gene family has six members, and we characterize in this study all tomato SINA (SlSINA) genes and the gene products. Our results show that SlSINA genes are differentially regulated in leaf, bud, stem, flower, and root. All SlSINA proteins possess RING-dependent E3 ubiquitin ligase activity, exhibiting similar specificity towards the E2 ubiquitin-conjugating enzyme. SlSINA1/3/4/5/6 are localized in both cytoplasm and nucleus, whereas SlSINA2 is exclusively localized in the nucleus. Moreover, all SlSINAs can interact with each other for homo- or hetero-dimerization. The functionality of SlSINA proteins has been investigated. SlSINA4 plays a positive role in defense signalling, as manifested by elicitation of E3-dependent hypersensitive response-like cell death; the other SlSINAs are negative regulator and capable to suppress hypersensitive response cell death. Transgenic tomato plants overexpressing SlSINA2 exhibit pale-green leaf phenotype, suggesting SlSINA2 regulates chlorophyll level in plant cells, whereas transgenic tomato plants overexpressing SlSINA5 have altered floral structure with exserted stigma, implicating SlSINA5 plays a role in flower development.

Risk for the development of non-alcoholic fatty liver disease: A prospective study.

BACKGROUND AND AIM: Non-invasive assessment was widely used to identify the risk of non-alcoholic fatty liver disease (NAFLD) among individuals with increased metabolic risks. This study aimed to investigate the prospective relationship between ZJU index and the development of NAFLD in a Chinese population. METHODS: A cohort of 6310 initially NAFLD-free participants was enrolled in this prospective study. Abdominal ultrasound was used to diagnosis NAFLD. NAFLD incidence was calculated among participants with different baseline ZJU index quintiles. Cox proportional hazards regression analyses were conducted to calculate the risks for incident NAFLD. RESULTS: During 37 705 person-year follow-ups, 1071 incident NAFLD cases were identified. The baseline ZJU index was linear and positively correlated with NAFLD incidence. The incidence was 5.53, 11.75, 23.77, 43.28, and 85.60 cases per 1000 person-year follow-up for participants with baseline ZJU index in quintiles 1-5, respectively. Compared with participants with baseline ZJU index in quintile 1, the hazard ratios (95% confidence interval) for incident NAFLD were 2.092 (1.458-3.002), 4.094 (2.942-5.698), 7.095 (5.167-9.742), and 13.191 (9.684-17.968) for participants with baseline ZJU index in quintiles 2-5, respectively. Further analysis found that the changes of ZJU index during follow-up was also independently associated with risk for incident NAFLD. CONCLUSIONS: Baseline ZJU index and absolute ZJU index changes independently predicts the risk for incident NAFLD in Chinese population.

Effect of silybin on the fibrillation of hen egg-white lysozyme.

In this study, the fibrillation of hen egg-white lysozyme (HEWL) in the absence and presence of different concentrations of silybin was studied by thioflavin T spectroscopy, Congo red binding assays, 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence assay, circular dichroism, and transmission electron microscopy. The experimental results indicated that not only the fibrillation of HEWL at high temperature (65°C) and low pH (pH = 2.0) could be inhibited effectively by silybin but also the inhibition of HEWL by silybin followed a dose-dependent manner. Molecular docking studies indicated that 2 possible binding modes could be found in the interaction between silybin and HEWL via van der Waals forces and electrostatic forces as well as hydrogen bonding. One of these 2 conformations was directly entered into the cavity of HEWL (binding site I); the other was bound to the surface of HEWL (binding site II). In this way, silybin could not only increase the hydrophobicity of the cavity or the surface of HEWL but also influence the microenvironment of the binding site, which was able to stabilize the structure of HEWL and delay the process of HEWL fibrosis.

Serum apoB levels independently predict the development of non-alcoholic fatty liver disease: A 7-year prospective study.

BACKGROUND & AIMS: Cross-sectional studies have shown that apolipoprotein B (apoB) is positively associated with the prevalence of non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the prospective relationship between the serum apoB levels and the development of NAFLD in a Chinese population. METHODS: A cohort of 7077 initially NAFLD-free participants was enrolled in this prospectively study. The incidence of NAFLD was calculated among participants with different baseline serum apoB quintiles. Cox proportional hazards regression analyses were conducted to calculate the risks for incident NAFLD. RESULTS: During 41 555 person-year follow-ups, 1139 incident NAFLD cases were identified. The baseline apoB levels were linear and positively correlated with NAFLD incidence. The incidence was 16.99, 22.63, 24.73, 37.51 and 42.77 per 1000 person-year follow-up for participants with baseline apoB levels in quintiles 1-5, respectively. Compared with participants with baseline apoB levels in quintile 1, the hazard ratios (95% confidence interval) for incident NAFLD were 1.353 (1.100-1.663), 1.482 (1.207-1.820), 2.232 (1.832-2.720) and 2.543 (2.082-3.106) for participants with baseline apoB levels in quintile 2-5, respectively. The hazard ratios were attenuated but remained statistically significant after adjusting for age, gender, body mass index and variables associated with metabolic syndrome. CONCLUSION: Elevated serum apoB levels independently predict an increased risk for incident NAFLD.

Tomato MBD5, a methyl CpG binding domain protein, physically interacting with UV-damaged DNA binding protein-1, functions in multiple processes.

In tomato (Solanum lycopersicum), high pigment mutations (hp-1 and hp-2) were mapped to genes encoding UV-damaged DNA binding protein 1 (DDB1) and de-etiolated-1 (DET1), respectively. Here we characterized a tomato methyl-CpG-binding domain protein SlMBD5 identified by yeast two-hybrid screening using SlDDB1 as a bait. Yeast two-hybrid assay demonstrated that the physical interaction of SlMBD5 with SlDDB1 is mediated by the C-termini of SlMBD5 and the ß-propeller-C (BPC) of SlDDB1. Co-immunoprecipitation analyses revealed that SlMBD5 associates with SlDDB1-interacting partners including SlDET1, SlCUL4, SlRBX1a and SlRBX1b in vivo. SlMBD5 was shown to target to nucleus and dimerizes via its MBD motif. Electrophoresis mobility shift analysis suggested that the MBD of SlMBD5 specifically binds to methylated CpG dinucleotides but not to methylated CpHpG or CpHpH dinucleotides. SlMBD5 expressed in protoplast is capable of activating transcription of CG islands, whereas CUL4/DDB1 antagonizes this effect. Overexpressing SlMBD5 resulted in diverse developmental alterations including darker green fruits with increased plastid level and elevated pigmentation, as well as enhanced expression of SlGLK2, a key regulator of plastid biogenesis. Taken together, we hypothesize that the physical interaction of SlMBD5 with the CUL4-DDB1-DET1 complex component may affect its binding activity to methylated DNA and subsequently attenuate its transcription activation of downstream genes.