Betaine delays age-related muscle loss by mitigating Mss51-induced impairment in mitochondrial respiration via Yin Yang1.

BACKGROUND: Mitochondrial dysfunction is one of the hallmarks of aging and a leading contributor to sarcopenia. Nutrients are essential for improving mitochondrial function and skeletal muscle health during the aging process. Betaine is a nutrient with potential muscle-preserving properties. However, whether and how betaine could regulate the mitochondria function in aging muscle are poorly understood. We aimed to explore the molecular target and underlying mechanism of betaine in attenuating the age-related mitochondrial dysfunction in skeletal muscle. METHODS: Young mice (YOU, 2 months), old mice (OLD, 15 months), and old mice with betaine treatment (BET, 15 months) were fed for 12 weeks. The effects of betaine on muscle mass, strength, function, and subcellular structure of muscle fibres were assessed. RNA sequencing (RNA-seq) was conducted to identify the molecular target of betaine. The impacts of betaine on mitochondrial-related molecules, superoxide accumulation, and oxidative respiration were examined using western blotting (WB), immunofluorescence (IF) and seahorse assay. The underlying mechanism of betaine regulation on the molecular target to maintain mitochondrial function was investigated by luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay. Adenoassociated virus transfection, succinate dehydrogenase staining (SDH), and energy expenditure assessment were performed on 20-month-old mice for validating the mechanism in vivo. RESULTS: Betaine intervention demonstrated anti-aging effects on the muscle mass (P = 0.017), strength (P = 0.010), and running distance (P = 0.013). Mitochondrial-related markers (ATP5a, Sdha, and Uqcrc2) were 1.1- to 1.5-fold higher in BET than OLD (all P ≤ 0.036) with less wasted mitochondrial vacuoles accumulating in sarcomere. Bioinformatic analysis from RNA-seq displayed pathways related to mitochondrial respiration activity was higher enriched in BET group (NES = -0.87, FDR = 0.10). The quantitative real time PCR (qRT-PCR) revealed betaine significantly reduced the expression of a novel mitochondrial regulator, Mss51 (-24.9%, P = 0.002). In C2C12 cells, betaine restored the Mss51-mediated suppression in mitochondrial respiration proteins (all P ≤ 0.041), attenuated oxygen consumption impairment, and superoxide accumulation (by 20.7%, P = 0.001). Mechanically, betaine attenuated aging-induced repression in Yy1 mRNA expression (BET vs. OLD: 2.06 vs. 1.02, P = 0.009). Yy1 transcriptionally suppressed Mss51 mRNA expression both in vitro and in vivo. This contributed to the preservation of mitochondrial respiration, improvement for energy expenditure (P = 0.008), and delay of muscle loss during aging process. CONCLUSIONS: Altogether, betaine transcriptionally represses Mss51 via Yy1, improving age-related mitochondrial respiration in skeletal muscle. These findings suggest betaine holds promise as a dietary supplement to delay skeletal muscle degeneration and improve age-related mitochondrial diseases.

Serum S-adenosylhomocysteine, rather than homocysteine, is associated with hepatocellular carcinoma survival: a prospective cohort study.

BACKGROUND: Emerging evidence suggested that S-adenosylhomocysteine (SAH) may be a better serum biomarker for cardiovascular disease than homocysteine (Hcy). However, the role of SAH in hepatocellular carcinoma (HCC) prognosis remains unclear. OBJECTIVES: We aimed to prospectively explore the relationships between serum SAH and related metabolites [Hcy, S-adenosylmethionine (SAM)] with HCC survival, and to evaluate the effect modifications by gene polymorphisms in one-carbon metabolism key enzymes. METHODS: We included 1080 newly diagnosed patients with HCC from the Guangdong Liver Cancer Cohort. Serum SAH, Hcy, and SAM were measured utilizing high-performance liquid chromatography-tandem mass spectrometry. Gene polymorphisms in one-carbon metabolism key enzymes were identified using kompetitive allele-specific polymerase chain reaction. Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariate Cox proportional hazards models. RESULTS: After a median follow-up of 3.6 y, 601 deaths occurred, with 552 (92%) attributed to HCC. Multivariable analysis revealed that patients in the highest quartile of serum SAH concentrations were significantly associated with worse survival compared with those in the lowest quartile, with HRs of 1.58 (95% CI: 1.19, 2.10; P-trend = 0.002) for LCSS and 1.54 (95% CI: 1.18, 2.02; P-trend = 0.001) for OS. There were no significant interactions between serum SAH concentrations and genetic variants of one-carbon metabolism key enzymes. No significant associations were found between serum Hcy, SAM concentrations, and SAM/SAH ratio with LCSS or OS. CONCLUSIONS: Higher serum SAH concentrations, rather than Hcy, were independently associated with worse survival in patients with HCC, regardless of the genetic variants of one-carbon metabolism key enzymes. These findings suggest that SAH may be a novel metabolism-related prognostic biomarker for HCC.

Vitamin D receptor gene polymorphisms, bioavailable 25-hydroxyvitamin D, and hepatocellular carcinoma survival.

BACKGROUND: Little is known about the role of vitamin D receptor polymorphisms and their interaction with vitamin D status in hepatocellular carcinoma (HCC) prognosis. METHODS: We evaluated the association of TaqI, BsmI, Cdx-2, and ApaI polymorphisms, individually and in combination, with liver cancer-specific (LCSS) and overall survival (OS) among 967 patients with newly diagnosed HCC. Subsequently, we examined whether these polymorphisms modified the association between serum bioavailable 25-hydroxyvitamin D (25OHD) concentrations and survival. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 1017 days, 393 deaths occurred, with 360 attributed to HCC. Having TaqI G allele (HRper allele = 1.30, 95% CI = 1.08 to 1.57) or BsmI T allele (HRper allele = 1.41, 95% CI = 1.01 to 1.99) was associated with worse LCSS. Carrying increasing numbers of protective alleles was associated with superior LCSS (HR6-8 vs 0-3 = 0.52, 95% CI = 0.34 to 0.80). The inverse association of bioavailable 25OHD with LCSS was statistically significant only in patients with TaqI AA (HRQuartile 4 vs Quartile 1 = 0.63, 95% CI = 0.44 to 0.92), BsmI CC (HRQuartile 4 vs Quartile 1 = 0.62, 95% CI = 0.44 to 0.88), and 6 to 8 protective alleles (HRQuartile 4 vs Quartile 1 = 0.45, 95% CI = 0.23 to 0.87). Similar associations were observed for OS. CONCLUSIONS: Patients carrying wild-type TaqI, BsmI, or more protective alleles had improved survival and might benefit from optimizing bioavailable 25OHD status.

Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 µg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1ß, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1ß. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

The Coulomb effect in nonsequential double ionization by counter-rotating two-color elliptical polarization fields.

Using a three-dimensional classical ensemble model, nonsequential double ionization (NSDI) of Ar atoms by counter-rotating two-color elliptical polarization (TCEP) fields is investigated. The major axes of the two elliptical fields are aligned in different directions. The relative alignment of the two elliptical fields strongly affects the waveform of the combined electric field and the ultrafast dynamics of NSDI in TCEP fields. Numerical results show that the correlated electron momentum distributions in the x direction evolve from a V-shaped structure near the axis to a distribution concentrated on the diagonal with the angle between the two elliptical major axes increasing. The asymmetry of the energy sharing between the two electrons during recollision results in the V-shaped structure in the correlated momentum spectrum. Back analysis indicates that the recollision times of a part of the trajectories move from the peak to the valley of the combined electric field with the angle between the two elliptical major axes increasing. Therefore, for the case of a larger angle between the two elliptical major axes, the electrons experience a longer time to escape away from the vicinity of the parent ion and thus the stronger Coulomb effect from the parent ion makes the momentum difference between two electrons small, which results in a distribution concentrated on the diagonal. This provides an effective avenue to control the electron ultrafast dynamics in NSDI.

Betaine attenuates age-related suppression in autophagy via Mettl21c/p97/VCP axis to delay muscle loss.

Age-related impairment of autophagy accelerates muscle loss and lead to sarcopenia. Betaine can delay muscle loss as a dietary methyl donor via increasing S-adenosyl-L-methionine (SAM, a crucial metabolite for autophagy regulation) in methionion cycle. However, whether betaine can regulate autophagy level to attenuate degeneration in aging muscle remains unclear. Herein, male C57BL/6J young mice (YOU, 2-month-old), old mice (OLD, 15-month-old), and 2%-betaine-treated old mice (BET, 15-month-old) were employed and raised for 12 weeks. All mice underwent body composition examination and grip strength test before being sacrificed. Betaine alleviated age-related decline in muscle mass and strength. Meanwhile, betaine preserved the expression autophagy markers (Atg5, Atg7, LC3-II, and Beclin1) both at transcriptional and translational level during the aging process. RNA-sequencing results generated from mice gastrocnemius muscle found Mettl21c, a SAM-dependent autophagy-regulating methyltransferase, was significantly higher expressed in BET and YOU group. Results were further validated by qPCR and western bloting. In vitro, C2C12 cells with or without Mettl21c RNA interference were treated different concentration of betaine (0 mM, 10 mM) under methionine-starved condition. Compared with control group, betaine upregulated autophagy markers expression and autophagy flux. By increasing the SAM level, betaine facilitated trimethylation of p97 (Mettl21c downstream effector) into valosin-containing protein (VCP). Increased VCP promoted autophagic turnover of cellular components, ATP production, and cell differentiation. Knock-down of Metthl21c dismissed improvements mentioned above. Collectively, betaine could enhance aged skeletal muscle autophagy level via Mettl21c/p97/VCP axis to delay muscle loss.

Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial.

PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 µg folic acid, 8 mg vitamin B6, 6.4 µg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (ß = -1.680, P = 0.004) and betaine (ß = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .

Dietary intake of one-carbon metabolism-related nutrients and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort.

Dietary intake of one-carbon metabolism-related nutrients has been linked to cancer-related outcomes, but their effects on hepatocellular carcinoma (HCC) mortality are still unknown. The objective was to assess whether pre-diagnostic dietary intakes of methionine, folate, Vitamin B6, Vitamin B12, riboflavin and niacin are associated with HCC survival in this prospective cohort study. In total, 905 newly diagnosed HCC patients were recruited in the Guangdong Liver Cancer Cohort study between September 2013 and April 2017. Dietary intake was assessed using a validated 79-item food frequency questionnaire. Cox proportional hazard regression models were utilized to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the overall and HCC-specific mortality. During a median of 791 days of follow-up, we documented 395 deaths, 353 (89%) of which resulted from HCC. The multivariate-adjusted HRs in the highest vs. the lowest quartile of methionine intake were 0.59 (95% CI: 0.42-0.80; P for trend = 0.001) for overall mortality and 0.68 (95% CI: 0.49-0.93; P for trend = 0.027) for HCC-specific mortality. However, no significant association of other micronutrients involved in one-carbon metabolism with HCC survival was observed. Our research suggests that a high level of methionine intake, but no other one-carbon metabolism-related nutrients, may improve survival in patients with newly diagnosed HCC.

Soy Food Intake Associated with Obesity and Hypertension in Children and Adolescents in Guangzhou, Southern China.

The associations between soy food intake and cardio-metabolic risk factors in children remain unclear due to limited evidence. We aim to explore soy food intake and its association with the risks of obesity and hypertension in Chinese children and adolescents. A total of 10,536 children and adolescents aged 7-18 years (5125 boys and 5411 girls) were enrolled in a cross-sectional study in Guangzhou City, southern China. Data on demographic characteristics and dietary consumption were collected using self-reported questionnaires, and anthropometric characteristics were measured. Obesity, abdominal obesity, and hypertension were defined using Chinese criteria for children and adolescents. A multiple logistic regression model was applied to estimate the association between soy food intake and obesity and hypertension. Roughly 39.5% of the participants consumed soy food more than three times per week. The mean amounts of liquid and solid soy food intake were 0.35 ± 0.54 cups/day and 0.46 ± 0.63 servings/day, respectively. The adjusted odds ratios (OR) of hypertension among those with high liquid soy food intake and a high frequency of all soy food intake (more than three times/week) were 0.79 (95% confidence interval (CI), 0.67-0.94), and 0.83 (95% CI, 0.70-0.97) compared to those with no intake. Additionally, the adjusted OR of obesity among those with high solid soy food intake and a high frequency of all soy food intake were 1.34 (95% CI, 1.09-1.63) and 1.30 (95% CI, 1.07-1.58), respectively. In conclusion, 39.5% of southern Chinese children and adolescents had high soy food intake (more than three times/week), which was significantly associated with a lower prevalence of hypertension and a greater prevalence of obesity.

High serum fibroblast growth factor 21 is associated with inferior hepatocellular carcinoma survival: A prospective cohort study.

BACKGROUND & AIMS: Epidemiological evidence linking fibroblast growth factor 21 (FGF21) with hepatocellular carcinoma (HCC) prognosis lacked. We aimed to evaluate the associations between serum FGF21 levels and HCC survival in a large prospective cohort. METHODS: 825 newly diagnosed, previously untreated HCC patients from the Guangdong Liver Cancer Cohort were enrolled between September 2013 and April 2017. Serum FGF21 levels were measured by ELISA. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Multivariable Cox proportional hazards models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with patients in the lowest tertile of serum FGF21 levels, patients in the highest tertile had inferior survival outcomes. HRs in the fully adjusted models were 1.44 (95% CI: 1.07, 1.94; P-trend  = .014) and 1.48 (95% CI: 1.12, 1.97; P-trend  = .002) for LCSS and OS, respectively. The associations were not significantly modified by selected metabolic disorder diseases or state such as arterial hypertension, diabetes, dyslipidemia, fatty liver, cirrhosis, and body mass index ≥25.0 kg/m2 , except for that stronger associations were observed in patients co-occurred more than three metabolic disorder diseases (P-interaction  = .046 for OS and .151 for LCSS), with an HR of 2.01 (95% CI: 1.04, 3.85; P-trend  = .009) for OS and 1.51 (95% CI: 0.73, 3.10; P-trend  = .195) for LCSS. CONCLUSIONS: Higher serum FGF21 levels were associated with worse survival in HCC patients, suggesting that serum FGF21 may be used as a novel metabolism-related prognostic biomarker for HCC.

Dietary protein and prognosis of hepatocellular carcinoma: a prospective cohort study.

Dietary protein has been linked with all-cause and cancer mortality. However, the relationship between dietary protein and the prognosis of hepatocellular carcinoma (HCC) is still unknown. The purpose of this study was to investigate whether dietary protein intake was related to HCC mortality using data from the Guangdong Liver Cancer Cohort (GLCC), a prospective cohort study of HCC survivors established at the Sun Yat-sen University Cancer Center. Dietary information one year before the diagnosis of HCC was obtained through a 79-item semi-quantitative food frequency questionnaire (FFQ). A total of 883 patients with newly diagnosed HCC who were recruited between September 2013 and April 2017 were included in this study. The hazard ratio (HR) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models. The multivariate-adjusted HRs in the highest vs. the lowest tertile of total protein intake were 0.68 (95% CI: 0.52-0.91, P-trend = 0.007) for all-cause mortality and 0.74 (95% CI: 0.55-0.99, P-trend = 0.040) for HCC-specific mortality. However, the associations of animal protein intake, plant protein intake, and animal-to-plant protein ratio with all-cause and HCC-specific mortality were not significant (all P-trend >0.05). Our research suggests that higher prediagnostic dietary intake of total protein was associated with reduced all-cause and HCC-specific mortality.

Betaine Delayed Muscle Loss by Attenuating Samtor Complex Inhibition for mTORC1 Signaling Via Increasing SAM Level.

SCOPE: The muscle loss during aging results from the blunt of protein synthesis and poses threat to the elderly health. This study aims to investigate whether betaine affects muscle loss by improving protein synthesis. METHODS AND RESULTS: Male C57BL/6J mice are raised from age 12 or 15 months. Mice are fed with AIN-93M diet without or with 2% w/v betaine in distilled water as control group or betaine intervention group (Bet), respectively. Betaine supplementation to mice demonstrates better body composition, grip strength, and motor function. Muscle morphology upregulates expression of myogenic regulate factors, and elevates myosin heavy chain and also improves in Bet group. Betaine promotes muscle protein synthesis via tethering mammalian target of rapamycin complex1 protein kinase (mTORC1) on the lysosomal membrane thereby activating mTORC1 signaling. All these effects aforementioned are time-dependent (p < 0.05). Ultrahigh-performance liquid chromatography results show that betaine increases S-adenosyl-l-methionine (SAM) via methionine cycle. SAM sensor-Samtor-overexpression in C2C12 cells could displace mTORC1 from lysosome thereby inhibiting the mTORC1 signaling. Addition of betaine attenuates this inhibition by increasing SAM level and then disrupting interaction of Samtor complex. CONCLUSIONS: These observations indicate that betaine could promisingly promote protein synthesis to delay age-related muscle loss.

Association between dietary patterns and prognosis of hepatocellular carcinoma in the Guangdong liver cancer cohort study.

AIM: Adherence to dietary recommendations has been linked to a reduced risk of developing hepatocellular carcinoma (HCC) and dying of chronic liver disease. However, its role in the prognosis of HCC is still unclear. We prospectively investigated the association of two dietary quality indices, the Chinese Healthy Eating Index (CHEI) and the Healthy Eating Index-2015 (HEI-2015), with all-cause and HCC-specific mortality in a large prospective cohort of HCC survivors. METHODS: We included 887 patients with newly diagnosed, previously untreated HCC enrolled in the Guangdong Liver Cancer Cohort (GLCC) between September 2013 and April 2017 in the analysis. CHEI and HEI-2015 scores were calculated based on the dietary intake in the year before diagnosis of HCC. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for each index. RESULTS: During a median follow-up of 797 days, 389 deaths were identified, including 347 from HCC. Higher CHEI scores, reflecting favorable adherence to the 2016 Dietary Guidelines for Chinese, were associated with a lower risk of all-cause mortality (T3 vs. T1 : HR = 0.75, 95% CI: 0.58-0.98) and HCC-specific mortality (T3 vs. T1 : HR = 0.74, 95% CI: 0.56-0.98). Non-significant, inverse associations of HEI-2015 score with all-cause mortality (T3 vs. T1 : HR = 0.86, 95% CI: 0.67-1.11) and HCC-specific mortality (T3 vs. T1 : HR = 0.93, 95% CI: 0.71-1.21) were suggested. CONCLUSIONS: Our findings suggest that better adherence to the 2016 Dietary Guidelines for Chinese may reduce the risk of all-cause and HCC-specific mortality in patients with HCC.

Prediagnostic dietary intakes of vitamin A and ß-carotene are associated with hepatocellular-carcinoma survival.

Vitamin A and its precursor (ß-carotene) have been linked with cancer incidence and mortality. However, the relationship between vitamin A and the prognosis of hepatocellular-carcinoma (HCC) is still unknown. Therefore, we investigated whether dietary intakes of vitamin A, retinol, and ß-carotene were associated with survival in patients with HCC who participated in the Guangdong Liver Cancer Cohort (GLCC) study. Patients aged 18-80 years with a diagnosis of incident Primary Liver Cancer (PLC) were enrolled within one month of diagnosis prior to cancer treatment at the Sun Yat-sen University Cancer Center. Dietary information one year before diagnosis of HCC was obtained using a 79-item, validated semiquantitative food frequency questionnaire (FFQ). We restricted the present analysis to 877 HCC patients enrolled in the GLCC between September, 2013 and April, 2017 who had completed FFQ. Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for overall and HCC-specific survival. After a median follow-up of 797 days, 384 deaths were documented, 343 of which died from HCC. The multivariable-adjusted HRs (95% CI) of overall and HCC-specific survival for the highest versus the lowest quartile were 0.70 (0.53-0.94) and 0.68 (0.50-0.92) for vitamin A, and 0.72 (0.54-0.96) and 0.69 (0.51-0.94) for ß-carotene, respectively. However, no significant association of dietary retinol intakes with survival outcomes was observed. Our observations suggest that higher prediagnostic dietary intakes of vitamin A and ß-carotene were associated with improved overall and HCC-specific survival.

Identification of a lytic Pseudomonas aeruginosa phage depolymerase and its anti-biofilm effect and bactericidal contribution to serum.

Pseudomonas aeruginosa (P. aeruginosa) infection has imposed a great threat to patients with cystic fibrosis. With the emergence of multidrug-resistant P. aeruginosa, developing an alternative anti-microbial strategy is indispensable and more urgent than ever. In this study, a lytic P. aeruginosa phage was isolated from the sewage of a hospital, and one protein was predicted as the depolymerase-like protein by genomic sequence analysis, it includes two catalytic regions, the Pectate lyase_3 super family and Glycosyl hydrolase_28 super family. Further analysis demonstrated that recombinant depolymerase-like protein degraded P. aeruginosa exopolysaccharide and enhanced bactericidal activity mediated by serum in vitro. Additionally, this protein disrupted host bacterial biofilms. All of these results showed that the phage-derived depolymerase-like protein has the potential to be developed into an anti-microbial agent that targets P. aeruginosa.

Genome of Serratia nematodiphila MB307 offers unique insights into its diverse traits.

A pigment-producing species of Serratia was isolated from the rhizosphere of a heavy metal resistant Cannabis sativa plant growing in effluent-affected soil of Hattar Industrial Estate, Haripur, Pakistan. Here, we report the genome sequence of this bacterium, which has been identified as Serratia nematodiphila on the basis of whole genome comparison using the OrthoANI classification scheme. The bacterium exhibited diverse traits, including plant growth promotion, antimicrobial, bioremediation, and pollutant tolerance capabilities including metal tolerance, azo dye degradation, ibuprofen degradation, etc. Plant growth-promoting exoenzyme production as well as phosphate solubilisation properties were observed. Genes for phosphate solubilisation, siderophore production, and chitin destruction were identified in addition to other industrially important enzymes like nitrilase and lipase. Secondary metabolite producing apparatus for high value chemicals in the whole genome was also analysed. The number of antibiotic resistance genes was then profiled in silico, through a match with Antibiotic Resistant Gene and CAR database. This is the first report of a S. nematodiphila genome from a polluted environment. This could significantly contribute to the understanding of pollution tolerance, antibiotic resistance, association with nematodes, production of bio-pesticide, and their role in plant growth promotion.

Improved thermoelectric performance of solid solution Cu4Sn7.5S16 through isoelectronic substitution of Se for S.

Cu-Sn-S family of compounds have been considered as very competitive thermoelectric candidates in recent years due to their abundance and eco-friendliness. The first-principles calculation reveals that the density of states (DOS) increases in the vicinity of the Fermi level (Ef) upon an incorporation of Se in the Cu4Sn7.5S16-xSe x (x = 0-2.0) system, which indicates the occurrence of resonant states. Besides, the formation of Cu(Sn)-Se network upon the occupation of Se in S site reduces the Debye temperature from 395 K for Cu4Sn7S16 (x = 0) to 180.8 K for Cu4Sn7.5S16-xSe x (x = 1.0). Although the point defects mainly impact the phonon scattering, an electron-phonon interaction also bears significance in the increase in phonon scattering and the further reducion of lattice thermal conductivity at high temperatures. As a consequence, the resultant TE figure of merit (ZT) reaches 0.5 at 873 K, which is 25% higher compared to 0.4 for Cu4Sn7.5S16.

Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin.

Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health 1 . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) 2-10 . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.

Genome sequencing and analysis of Alcaligenes faecalis subsp. phenolicus MB207.

Bacteria within the genus Alcaligenes, exhibit diverse properties but remain largely unexplored at genome scale. To shed light on the genome structure, heterogeneity and traits of Alcaligenes species, the genome of a tannery effluent isolated Alcaligenes faecalis subsp. phenolicus MB207 was sequenced and assembled. The genome was compared to the whole genome sequences of genus Alcaligenes present in the National Centre for Biotechnology Information database. Core, pan and species specific gene sequences i.e. singletons were identified. Members of this genus did not portray exceptional genetic heterogeneity or conservation and out of 5,166 protein coding genes from pooled genome dataset, 2429 (47.01%) contributed to the core, 1193 (23.09%) to singletons and 1544 (29.88%) to accessory genome. Secondary metabolite forming apparatus, antibiotic production and resistance was also profiled. Alcaligenes faecalis subsp. phenolicus MB207 genome consisted of a copious amount of bioremediation genes i.e. metal tolerance and xenobiotic degrading genes. This study marks this strain as a prospective eco-friendly bacterium with numerous benefits for the environment related research. Availability of the whole genome sequence heralds an opportunity for researchers to explore enzymes and apparatus for sustainable environmental clean-up as well as important compounds/substance production.

Csseverin inhibits apoptosis through mitochondria-mediated pathways triggered by Ca2 + dyshomeostasis in hepatocarcinoma PLC cells.

BACKGROUND: Numerous experimental and epidemiological studies have demonstrated a link between Clonorchis sinensis (C. sinensis) infestation and cholangiocarcinoma (CCA) as well as hepatocellular carcinoma (HCC). The underlying molecular mechanism involved in the malignancy of CCA and HCC has not yet been addressed. Csseverin, a component of the excretory/secretory products of C. sinensis (CsESPs), was confirmed to cause obvious apoptotic inhibition in the human HCC cell line PLC. However, the antiapoptotic mechanism is unclear. In the present study, we investigated the cellular features of the antiapoptotic mechanism upon transfection of the Csseverin gene. METHODS: In the present study, we evaluated the effects of Csseverin gene overexpression on the apoptosis of PLC cells using an Annexin PE/7-AAD assay. Western blotting was applied to quantify the activation of caspase-3 and caspase-9, the mitochondrial translocation of Bax and the release of Cyt c upon Csseverin overexpression in PLC cells. Laser scanning confocal microscopy was used to analyze the changes of intracellular calcium. Fluorescence assay and immunofluorescence assays were performed to observe the changes of the mitochondrial permeability transition pore (MPTP). RESULTS: The overexpression of Csseverin in PLC cells showed apoptosis resistance after the induction of apoptosis. Additionally, the activation of caspase-3 and caspase-9 was specifically weakened in Csseverin overexpression PLC cells. The overexpression of Csseverin reduced the increase in intracellular free Ca2+, thereby inhibiting MPTP opening in PLC cells. Moreover, Bax mitochondrial translocation and the subsequent release of Cyt c were downregulated in apoptotic Csseverin overexpression PLC cells. CONCLUSIONS: The present findings suggest that Csseverin, a component of CsESPs, confers protection from human HCC cell apoptosis via the inactivation of membranous Ca2+ channels. Csseverin might be involved in the process of HCC through C. sinensis infestation in affected patients.