Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver.

BACKGROUND AND AIMS: An imbalance in lipid metabolism is the main cause of NAFLD. While the pathogenesis of lipid accumulation mediated by extrahepatic regulators has been extensively studied, the intrahepatic regulators modulating lipid homeostasis remain unclear. Previous studies have shown that systemic administration of IL-22 protects against NAFLD; however, the role of IL-22/IL22RA1 signaling in modulating hepatic lipid metabolism remains uncertain. APPROACH AND RESULTS: This study shows that hepatic IL22RA1 is vital in hepatic lipid regulation. IL22RA1 is downregulated in palmitic acid-treated mouse primary hepatocytes, as well as in the livers of NAFLD model mice and patients. Hepatocyte-specific Il22ra1 knockout mice display diet-induced hepatic steatosis, insulin resistance, impaired glucose tolerance, increased inflammation, and fibrosis compared with flox/flox mice. This is attributed to increased lipogenesis mediated by the accumulation of hepatic oxysterols, particularly 3 beta-hydroxy-5-cholestenoic acid (3ß HCA). Mechanistically, hepatic IL22RA1 deficiency facilitates 3ß HCA deposition through the activating transcription factor 3/oxysterol 7 alpha-hydroxylase axis. Notably, 3ß HCA facilitates lipogenesis in mouse primary hepatocytes and human liver organoids by activating liver X receptor-alpha signaling, but IL-22 treatment attenuates this effect. Additionally, restoring oxysterol 7 alpha-hydroxylase or silencing hepatic activating transcription factor 3 reduces both hepatic 3ß HCA and lipid contents in hepatocyte-specific Il22ra1 knockout mice. CONCLUSIONS: These findings indicate that IL22RA1 plays a crucial role in maintaining hepatic lipid homeostasis in an activating transcription factor 3/oxysterol 7 alpha-hydroxylase-dependent manner and establish a link between 3ß HCA and hepatic lipid homeostasis.

Variability in the relationship between light scattering and chlorophyll a concentration in oligotrophic tropical regions of the Western Pacific Ocean.

It is important to determine the relationship between the concentration of chlorophyll a (Chla) and the inherent optical properties (IOPs) of ocean water to develop optical models and algorithms that characterize the biogeochemical properties and estimate biological pumping and carbon flux in this environment. However, previous studies reported relatively large variations in the particulate backscattering coefficient (bbp(λ)) and Chla from more eutrophic high-latitude waters to clear oligotrophic waters, especially in oligotrophic oceanic areas where these two variables have little covariation. In this study, we examined the variability of bbp(λ) and Chla in the euphotic layer in oligotrophic areas of the tropical Western Pacific Ocean and determined the sources of these variations by reassessment of in-situ measurements and the biogeochemical-argo (BGC-Argo) database. Our findings identified covariation of bbp(λ) and Chla in the water column below the deep Chla maximum (DCM) layer, and indicated that there was no significant correlation relationship between bbp(λ) and Chla in the upper layer of the DCM. Particles smaller than 3.2 µm that were in the water column above the DCM layer had a large effect on the bbp(λ) in the vertical profile, but particles larger than 3.2 µm and smaller than 10 µm had the largest effect on the bbp(λ) in the water column below the DCM layer. The contribution of non-algal particles (NAPs) to backscattering is up to 50%, which occurs in the water depth of 50 m and not consistent with the distribution of Chla. Phytoplankton and NAPs were modeled as coated spheres and homogeneous spherical particles to simulate the bbp(λ) of the vertical profile by Aden-Kerker method and Mie theory, and the results also indicated that the backscattering caused by particles less than 20 µm were closer to the measured data when they were below and above the DCM layer, respectively. This relationship also reflects the bbp(λ) of particles in the upper water was significantly affected particle size, but bbp(λ) in the lower water was significantly affected by Chla concentration. This effect may have relationship with phytoplankton photoacclimation and the relationship of a phytoplankton biomass maximum with particle size distribution in the water column according to the previous relevant studies. These characteristics also had spatial and seasonal variations due to changes of Chla concentration at the surface and at different depths. There was mostly a linear relationship between Chla and bbp(700) during winter. During other seasons, the relationship between these two variables was better characterized by a power function (or a logarithmic function) in the lower layer of the DCM. The spatial and vertical relationships between the bbp(λ) and Chla and the corresponding variations in the types of particles described in this study provide parameters that can be used for accurate estimation of regional geochemical processes.

Cardiac-specific deletion of BRG1 ameliorates ventricular arrhythmia in mice with myocardial infarction.

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.

The effect of sodium bicarbonate on OHCA patients: A systematic review and meta-analysis of RCT and propensity score studies.

BACKGROUND: Evidence on the efficacy of sodium bicarbonate (SB) in out-of-hospital cardiac arrest (OHCA) is controversial and generally of low quality. A systematic review and meta-analysis was performed to evaluate the effect of SB in OHCA patients based on randomized controlled trial (RCT) and propensity score matching (PSM) cohort studies. METHODS: We searched the PubMed, Cochrane, and Embase databases for RCTs and PSM cohort studies from inception to July 15, 2023. We included studies involving adult (>16 years) no-trauma OHCA patients with clear comparisons between the Bicarbonate group and Control group. All studies reported our primary outcome of short-term survival rate included ROSC and survival to emergency department or hospital admission or secondary outcome of long-term survival rate included survival at hospital discharge and good neurologic survival at 1 month. Results were expressed as odds ratio (OR) with accompanying 95% confidence interval (CI). To reduce bias, we performed a subgroup analysis of RCTs and PSM cohort studies. Also, we performed sensitivity analysis to resolve the heterogeneity. RESULTS: Six studies (3 RCTs and 3 PSMs) comprising 21,402 patients were included. The primary outcome of this meta-analysis showed that short-term survival rate between the two groups was no difference (OR = 1.04; 95% CI, 0.98 to 1.12; P = 0.21; χ2 = 6.68; I2 = 25%). Secondary outcome demonstrated that long -term survival rate between the two groups was no difference (OR = 0.82; 95% CI, 0.50 to 1.34; P = 0.43; χ2 = 14.96; I2 = 80%). A sensitive analysis was performed by removing one study showed long-term survival rate of the Bicarbonate group was lower than that of the Control group. CONCLUSIONS: In patients with OHCA, sodium bicarbonate administration was associated neither with short-term survival rate nor with long-term survival rate, it may even worsen the long-term survival.

Value of variation of end-tidal carbon dioxide for predicting fluid responsiveness during the passive leg raising test in patients with mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: The ability of end-tidal carbon dioxide (ΔEtCO2) for predicting fluid responsiveness has been extensively studied with conflicting results. This meta-analysis aimed to explore the value of ΔEtCO2 for predicting fluid responsiveness during the passive leg raising (PLR) test in patients with mechanical ventilation. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to November 2021. The diagnostic odds ratio (DOR), sensitivity, and specificity were calculated. The summary receiver operating characteristic curve was estimated, and the area under the curve (AUROC) was calculated. Q test and I2 statistics were used for study heterogeneity and publication bias was assessed by Deeks' funnel plot asymmetry test. We performed meta-regression analysis for heterogeneity exploration and sensitivity analysis for the publication bias. RESULTS: Overall, six studies including 298 patients were included in this review, of whom 149 (50%) were fluid responsive. The cutoff values of ΔEtCO2 in four studies was 5%, one was 5.8% and the other one was an absolute increase 2 mmHg. Heterogeneity between studies was assessed with an overall Q = 4.098, I2 = 51%, and P = 0.064. The pooled sensitivity and specificity for the overall population were 0.79 (95% CI 0.72-0.85) and 0.90 (95% CI 0.77-0.96), respectively. The DOR was 35 (95% CI 12-107). The pooled AUROC was 0.81 (95% CI 0.77-0.84). On meta-regression analysis, the number of patients was sources of heterogeneity. The sensitivity analysis showed that the pooled DOR ranged from 21 to 140 and the pooled AUC ranged from 0.92 to 0.96 when one study was omitted. CONCLUSIONS: Though the limited number of studies included and study heterogeneity, our meta-analysis confirmed that the ΔEtCO2 performed moderately in predicting fluid responsiveness during the PLR test in patients with mechanical ventilation.

Scale-free resilience of real traffic jams.

The concept of resilience can be realized in natural and engineering systems, representing the ability of a system to adapt and recover from various disturbances. Although resilience is a critical property needed for understanding and managing the risks and collapses of transportation systems, an accepted and useful definition of resilience for urban traffic as well as its statistical property under perturbations are still missing. Here, we define city traffic resilience based on the spatiotemporal clusters of congestion in real traffic and find that the resilience follows a scale-free distribution in 2D city road networks and 1D highways with different exponents but similar exponents on different days and in different cities. The traffic resilience is also revealed to have a scaling relation between the cluster size of the spatiotemporal jam and its recovery duration independent of microscopic details. Our findings of universal traffic resilience can provide an indication toward better understanding and designing of these complex engineering systems under internal and external disturbances.

A noninvasive model to predict liver histology for antiviral therapy decision in chronic hepatitis B with alanine aminotransferase < 2 upper limit of normal.

BACKGROUND: At present, most assessments of liver fibrosis staging mainly focus on non-invasive diagnostic methods. This study aims to construct a noninvasive model to predict liver histology for antiviral therapy in chronic hepatitis B (CHB) with alanine aminotransferase (ALT) < 2 times upper limit of normal (ULN). METHODS: We retrospectively analyzed 577 patients with CHB who received liver biopsy and whose ALT was less than 2 ULN. Then they were randomly divided into a training group and a validation group. Through logistic regression analysis, a novel predictive model was constructed in the training group to predict significant changes in liver histology [necro-inflammatory activity grade (G) ≥ 2 or fibrosis stage (S) ≥ 2] and then validated in the validation group. RESULTS: If liver biopsy showed moderate or severe inflammation or significant fibrosis, antiviral treatment was recommended. Aspartate aminotransferase (AST), anti-hepatitis B virus core antibody (anti-HBC) and glutamine transpeptidase (GGT) were identified as independent predictors for antiviral therapy, with area under the ROC curve (AUROC) of 0.649, 0.647 and 0.616, respectively. Our novel model index, which combined AST, anti- HBC and GGT with AUROC of 0.700 and 0.742 in training set and validation set. CONCLUSIONS: This study established a noninvasive model to predict liver histology for antiviral treatment decision in patients with CHB with ALT < 2 ULN, which can reduce the clinical needs of liver biopsy.

Response to crizotinib in a patient with MET-amplified hepatocellular carcinoma.

AIMS: Molecular profiling of hepatocellular carcinoma (HCC) has helped identify actionable genomic alterations that could guide therapeutic decision-making and clinical trial enrollment. However, in clinical practice, next-generation sequencing (NGS) is not extensively used in routine clinical care to identify patients with HCC who are likely to benefit from genome-directed targeted therapies. METHODS: Here, we describe the case of a 66-year-old man with advanced HCC. After rapid progression on transarterial chemoembolization, the tissue sample obtained from biopsy was subjected to NGS to verify whether precision therapy was an option. RESULTS: Our analysis revealed high MET amplification. The patient received crizotinib (250 mg, bid) and showed a remarkable response. CONCLUSIONS: Our case report suggests NGS could help identify patients with high MET amplification in HCC who were likely to benefit from MET inhibitors; moreover, this requires further investigation in clinical trials.

The effect of early vasopressin use on patients with septic shock: A systematic review and meta-analysis.

BACKGROUND: The effect of early vasopressin initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early start of vasopressin support within 6 h after the diagnosis on clinical outcomes in septic shock patients. METHODS: We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of February 2021. We included studies involving adult patients (> 16 years)with septic shock. All authors reported our primary outcome of short-term mortality and in the experimental group patients in the studies receiving vasopressin infusion within 6 h after diagnosis of septic shock and in the control group patients in the studies receiving no vasopressin infusion or vasopressin infusion 6 h after diagnosis of septic shock, clearly comparing with clinically relevant secondary outcomes(use of renal replacement therapy(RRT),new onset arrhythmias, ICU length of stay and length of hospitalization). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). RESULTS: Five studies including 788 patients were included. The primary outcome of this meta-analysis showed that short-term mortality between the two groups was no difference (odds ratio [OR] = 1.09; 95% CI, 0.8 to 1.48; P = 0.6; χ2 = 0.83; I2 = 0%). Secondary outcomes demonstrated that the use of RRT was less in the experimental group than that of the control group (OR = 0.63; 95% CI, 0.44 to 0.88; P = 0.007; χ2 = 3.15; I2 = 36%).The new onset arrhythmias between the two groups was no statistically significant difference (OR = 0.59; 95% CI, 0.31 to 1.1; P = 0.10; χ2 = 4.7; I2 = 36%). There was no statistically significant difference in the ICU length of stay(mean difference = 0.16; 95% CI, - 0.91 to 1.22; P = 0.77; χ2 = 6.08; I2 = 34%) and length of hospitalization (mean difference = -2.41; 95% CI, -6.61 to 1.78; P = 0.26; χ2 = 8.57; I2 = 53%) between the two groups. CONCLUSIONS: Early initiation of vasopressin in patients within 6 h of septic shock onset was not associated with decreased short-term mortality, new onset arrhythmias, shorter ICU length of stay and length of hospitalization, but can reduce the use of RRT. Further large-scale RCTs are still needed to evaluate the benefit of starting vasopressin in the early phase of septic shock.

Application of a Robotic Tele-Echography System for COVID-19 Pneumonia.

To date, coronavirus disease 2019 (COVID-19) has infected millions of people worldwide. Ultrasound plays an indispensable role in the diagnosis, monitoring, and follow-up of patients with COVID-19. In this study, we used a robotic tele-echography system based on a 5G communication network for remote diagnosis. The system has great potential for lung, heart, and vasculature information, medical staff protection, and resource sharing, can be a valuable tool for treating patients during the pandemic, and can be expected to expand to more specialized fields.

Unpaired Electron-Induced Wide-Range Light Absorption within Zn (or Cu) MOFs Containing Electron-Withdrawing Ligands: A Theoretical and Experimental Study.

In photocatalysis, it is of general interest to understand and design wide-range light-absorbing inorganic/organic hybrid materials with an excellent photo-induced intramolecular charge-transfer (ICT) effect. To verify the role of unpaired electrons in enhancing ICT within electron-withdrawing ligand-based metal-organic frameworks (MOFs), the molecular structure, density of states (DOS), and electronic structure of strong electron-deficient pyridine-diketopyrrolopyrrole (P-DPP)-based Zn (or Cu) MOFs were calculated in Gaussian package to validate the unpaired electron ICT. The electron spin resonance technique has detected the unpaired electrons for the coordination systems containing Zn-O or Cu-O clusters and P-DPP ligand on photoexcitation. The estimated band gaps from the DOS calculation for P-DPP-Cu and P-DPP-Zn are 1.4 and 2.4 eV, respectively, showing a good agreement with the experimental UV-vis optical spectra. The partial DOS, dipole moment, and frontier orbital analysis prove that the ICT should happen from Zn-O or Cu-O clusters to P-DPP ligands. This research may contribute to a comprehensive understanding of electron-withdrawing ligand-induced ICT within MOFs and shed light on the design of light-absorbing MOFs with excellent ICT or conductivity.

Thrombin cleavage of osteopontin controls activation of hepatic stellate cells and is essential for liver fibrogenesis.

Liver biopsy is the current reliable way of evaluating liver fibrosis. However, no specific sera biomarker could be applied in clinical diagnosis. As the pivotal role of osteopontin (OPN) reported in numerous liver diseases, thrombin-cleaved OPN (Thr-OPN) exposes an integrin-binding motif that promoted biological functions. Herein, we investigated the potential of Thr-OPN in liver fibrosis. Using patient samples, mouse models and hepatic stellate cells (HSCs), we analyzed the involvement of Thr-OPN in liver fibrosis. The result showed that, first, Thr-OPN level was significantly higher in patients with liver cirrhosis than that in patients with chronic hepatitis B and healthy controls. Thr-OPN level was positively correlated with liver fibrosis degree in clinical samples. Then in mouse models, it showed a similar correlation between hepatic Thr-OPN levels and liver fibrosis degree. Thr-OPN peptides exacerbated liver fibrosis in OPN-deficient mice, whereas the neutralization of Thr-OPN alleviated liver fibrosis in wild-type mice. Furthermore, when compared with full-length OPN (FL-OPN), Thr-OPN exhibited a greater ability to promote HSC activation, proliferation, and migration via mitogen-activated protein (MAP) kinase and nuclear factor (NF)-κB pathways. In conclusion, Thr-OPN, not FL-OPN, was critically involved in the exacerbation of liver fibrosis by α9 and α4 integrins via MAP kinase and NF-κB signaling pathway, thus representing a novel diagnostic biomarker and treatment target for liver cirrhosis.

Systemic air embolism in a fungal pneumonia patient with lung cavities formation and review of literature.

Systemic air embolism is a rare but potentially fatal complication related to many factors. The purpose of this article is to alert clinicians once patients occurs an abnormal neurological and cardiovascular status, following minor traumatic treatment, air embolism should be considered. A 20-year-old man who presented with fungal pneumonia with lung cavities formation was admitted to an intensive care unit (ICU) and received positive airway pressure ventilation. Four days later, the fungal pneumonia was improved, but the patient's blood pressure and arterial oxygen saturation deteriorated, so computed tomography (CT) scans were preformed to reevaluate him. The scans detected air embolism in the left atrium and ventricle, ascending aorta, aortic arch and its branches (right brachiocephalic, bilateral common carotid and right subclavian arteries), descending aorta and right coronary artery. A CT scan of the abdomen revealed air in the spleen, cauda pancreatic, superior mesenteric artery and right external iliac artery. The patient died two days later from multiple organ dysfunction. We suggest that vascular air embolism should be considered under mechanical ventilation when patients' neurologic and cardiovascular status deteriorates, and hyperbaric oxygen therapy should be conducted immediately.

Saturation of water reflectance in extremely turbid media based on field measurements, satellite data and bio-optical modelling.

Evidence of water reflectance saturation in extremely turbid media is highlighted based on both field measurements and satellite data corrected for atmospheric effects. This saturation is obvious in visible spectral bands, i.e., in the blue, green and even red spectral regions when the concentration of suspended particulate matter (SPM) reaches then exceeds 100 to 1000 g.m-3. The validity of several bio-optical semi-analytical models is assessed in the case of highly turbid waters, based on comparisons with outputs of the Hydrolight radiative transfer model. The most suitable models allow to reproduce the observed saturation and, by inversion, to retrieve information on the SPM mass-specific inherent optical properties.

Value of variation index of inferior vena cava diameter in predicting fluid responsiveness in patients with circulatory shock receiving mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Respiratory variations in the inferior vena cava diameter (ΔIVCD) have been studied extensively with respect to their value in predicting fluid responsiveness, but the results are conflicting. The aim of this meta-analysis was to explore the value of ΔIVCD for predicting fluid responsiveness in patients with circulatory shock receiving mechanical ventilation. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to June 2017. The diagnostic OR (DOR), sensitivity, and specificity were calculated. The summary ROC curve was estimated, and the area under the ROC curve (AUROC) was calculated. RESULTS: Overall, 603 patients were included in this review, 324 (53.7%) of whom were fluid-responsive. The cutoff values of ΔIVCD varied across studies, ranging from 8% to 21%. Heterogeneity between studies was assessed with an overall Q = 0.069, I2 = 0%, and P = 0.483. The pooled sensitivity and specificity for the overall population were 0.69 (95% CI, 0.51-0.83) and 0.80 (95% CI, 0.66-0.89), respectively. The DOR was 9.28 (95% CI, 2.33-36.98). AUROCs were reported in five studies. Overall, the pooled AUROC was 0.82 (95% CI, 0.79-0.85). CONCLUSIONS: The findings of this study suggest that the ΔIVCD performed moderately well in predicting fluid responsiveness in patients with circulatory shock receiving mechanical ventilation.

Evidence for an oxygen-depleted liquid outer core of the Earth.

On the basis of geophysical observations, cosmochemical constraints, and high-pressure experimental data, the Earth's liquid outer core consists of mainly liquid iron alloyed with about ten per cent (by weight) of light elements. Although the concentrations of the light elements are small, they nevertheless affect the Earth's core: its rate of cooling, the growth of the inner core, the dynamics of core convection, and the evolution of the geodynamo. Several light elements-including sulphur, oxygen, silicon, carbon and hydrogen-have been suggested, but the precise identity of the light elements in the Earth's core is still unclear. Oxygen has been proposed as a major light element in the core on the basis of cosmochemical arguments and chemical reactions during accretion. Its presence in the core has direct implications for Earth accretion conditions of oxidation state, pressure and temperature. Here we report new shockwave data in the Fe-S-O system that are directly applicable to the outer core. The data include both density and sound velocity measurements, which we compare with the observed density and velocity profiles of the liquid outer core. The results show that we can rule out oxygen as a major light element in the liquid outer core because adding oxygen into liquid iron would not reproduce simultaneously the observed density and sound velocity profiles of the outer core. An oxygen-depleted core would imply a more reduced environment during early Earth accretion.

Novosphingobium profundi sp. nov. isolated from a deep-sea seamount.

A marine bacterial strain, F72T, was isolated from a solitary scleractinian coral, collected in Yap seamounts in the Pacific Ocean. Strain F72T is a Gram-negative, light-yellow-pigmented, motile, rod-shaped bacterium. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain F72T is related to the genus Novosphingobium and has high 16S rRNA gene sequence similarities with the type strains of Novosphingobium pentaromativorans US6-1T (97.7 %), Novosphingobium panipatense SM16T (97.6 %), Novosphingobium mathurense SM117T (97.2 %) and Novosphingobium barchaimii LL02T (97.1 %). Ubiquinone Q-10 was detected as the dominant quinone. The predominant cellular fatty acids were C18:1ω7c and C17:1ω6c. The genomic DNA G+C content of strain F72T was 63.4 mol %. The polar lipids profile contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, sphingoglycolipid and one uncharacterized lipid. Strain F72T shared DNA relatedness of 25 % with N. pentaromativorans JCM 12182T, 31 % with N. panipatense DSM 22890T, 21 % with N. mathurense DSM 23374T and 26 % with N. barchaimii DSM 25411T. Combined data from phenotypic, phylogenetic and DNA-DNA relatedness studies demonstrated that the strain F72T is a representative of a novel species of the genus Novosphingobium, for which we propose the name Novosphingobium profundi sp. nov. (type strain F72T = KACC 18566T = CGMCC 1.15390T).

Toward Biomarker Development in Large Clinical Cohorts: An Integrated High-Throughput 96-Well-Plate-Based Sample Preparation Workflow for Versatile Downstream Proteomic Analyses.

We describe a cheap, robust, fast, high-throughput, and flexible proteomic sample processing method based on a regular 96-well plate by acetone precipitation under low centrifuge speed (96PACS), which enables predigestion processing of 96 samples within 2 h. Tested on a complex Huh-7 total lysate, 96PACS produced comparable proteome coverage and even showed better reproducibility than FASP. Quantitative performance of 96PACS was further tested using data-independent acquisition and parallel reaction monitoring quantitation in a set of 6 benchmark samples consisting of 6 serial dilutions of BSA spiked in complex E. coli proteome background. The protocol was also successfully modified for automation and was validated in a comparative label-free proteomic study to develop serum markers for early detection of liver fibrosis and necroinflammation in patients chronically infected with hepatitis B virus.

MyoD promotes porcine PPARγ gene expression through an E-box and a MyoD-binding site in the PPARγ promoter region.

Peroxisome proliferator-activated receptor γ (PPARγ) is a key transcription factor in adipogenesis and can be regulated by adipogenesis-related factors. However, little information is available regarding its regulation by myogenic factors. In this study, we found that over-expression of MyoD enhanced porcine adipocyte differentiation and up-regulated PPARγ expression, whereas small interfering RNA against MyoD significantly attenuated porcine adipocyte differentiation and inhibited PPARγ expression. The MyoD-binding sites in the PPARγ promoter region at -412 to -396 and -155 to -150 were identified by promoter deletion analysis and site-directed mutagenesis. Electrophoretic mobility shift assays and chromatin immunoprecipitation further showed that these two regions are MyoD-binding sites, both in vitro and in vivo, indicating that MyoD directly interacts with the porcine PPARγ promoter. Thus, our results demonstrate that an Enhancer box and a binding site for a cooperative co-activator of MyoD are present in the promoter region of porcine PPARγ; furthermore, MyoD up-regulates PPARγ expression and promotes porcine adipocyte differentiation.

Pseudoalteromonas profundi sp. nov., isolated from a deep-sea seamount.

A Gram-stain-negative, rod-shaped, strictly aerobic, motile bacterial strain, designated TP162T, was isolated from a seamount near the Yap Trench in the tropical western Pacific. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain TP162T was related to the genus Pseudoalteromonas and had highest 16S rRNA gene sequence similarities with the type strains Pseudoalteromonas shioyasakiensis SE3T (98.2 %), Pseudoalteromonas lipolytica LMEB 39T (97.7 %), Pseudoalteromonas arabiensis k53T (97.4 %) and Pseudoalteromonas aliena KMM 3562T (97.2 %). The predominant cellular fatty acids were summed feature 3 (composed of iso-C15 : 0 2-OH and/or C16 : 1ω7c), C17 : 1ω8c and C16 : 0. The quinone system for strain TP162T comprised predominantly ubiquinone-8, and the polar lipid profile contained phosphatidylethanolamine, phosphatidylglycerol, one unidentified phospholipid and four unidentified lipids. The genomic DNA G+C content of strain TP162T was 46.7 mol%. Strain TP162T shared 28 % DNA-DNA relatedness with P.shioyasakiensis JCM 18891T, 21 % with P. lipolytica JCM 15903T, 35 % with P.arabiensis JCM 17292T and 18 % with P.aliena LMG 22059T. Combined data from phenotypic, chemotaxonomic, phylogenetic and DNA-DNA relatedness studies demonstrated that strain TP162T is a representative of a novel species of the genus Pseudoalteromonas, for which we propose the name Pseudoalteromonas profundi sp. nov. (type strain TP162T=KACC 18554T=CGMCC 1.15394T).