Complete genome sequence analysis of Bacillus velezensis A5, a promising biocontrol agent from the Pacific Ocean.

Tobacco bacterial wilt (TBW) caused by Ralstonia solanacearum is a serious soil-borne disease, which seriously damages the growth of tobacco crops. Bacillus velezensis A5 was isolated from 3000 m deep-sea sediments of the Pacific Ocean, and was found to be antagonistic to TBW. Here, we report the complete genome sequence of strain A5, which has a 4,000,699-bp single circular chromosome with 3827 genes and a G + C content of 46.44%, 87 tRNAs, and 27 rRNAs. A total of 12 gene clusters were identified in the genome of strain A5, which were responsible for the biosynthesis of antibacterial compounds, including surfactin, bacillaene, fengycin, difficidin, bacillibactin, and bacilysin. Additionally, strain A5 was found to contain a series of genes related to the biosynthesis of carbohydrate-active enzymes and secreted proteins. Our results indicate that strain A5 can be considered a promising biocontrol agent against TBW in agricultural fields.

Discovery, Identification, and Mode of Action of Phenolics from Marine-Derived Fungus Aspergillus ustus as Antibacterial Wilt Agents.

The bacterial wilt caused by Ralstonia solanacearum seriously affects crop yield and safety and is difficult to control. Biological activity-guided screening led to the isolation of 11 phenolic compounds including three undescribed compounds (carnemycin H-I and stromemycin B) from the secondary metabolites of a marine-derived Aspergillus ustus. One new compound is an unusual phenolic dimer. Their structures were elucidated by comprehensive spectroscopic data and J-based configurational analysis. The antibacterial activities of the isolated compounds against R. solanacearum were evaluated. Compound 3 exhibited excellent inhibitory activity with an MIC value of 3 µg/mL, which was comparable to that of streptomycin sulfate. Additionally, 3 significantly changed the morphology and inhibited the activity of succinate dehydrogenase (SDH) to interfere with the growth of R. solanacearum. Molecular docking was conducted to clarify the potential mechanisms of compound 3 with SDH. Further in vivo experiments demonstrated that 3 could remarkably inhibit the occurrence of bacterial wilt on tomatoes.

Metabolic adaptations of Microbacterium sediminis YLB-01 in deep-sea high-pressure environments.

The deep-sea environment is an extremely difficult habitat for microorganisms to survive in due to its intense hydrostatic pressure. However, the mechanisms by which these organisms adapt to such extreme conditions remain poorly understood. In this study, we investigated the metabolic adaptations of Microbacterium sediminis YLB-01, a cold and stress-tolerant microorganism isolated from deep-sea sediments, in response to high-pressure conditions. YLB-01 cells were cultured at normal atmospheric pressure and 28 ℃ until they reached the stationary growth phase. Subsequently, the cells were exposed to either normal pressure or high pressure (30 MPa) at 4 ℃ for 7 days. Using NMR-based metabolomic and proteomic analyses of YLB-01 cells exposed to high-pressure conditions, we observed significant metabolic changes in several metabolic pathways, including amino acid, carbohydrate, and lipid metabolism. In particular, the high-pressure treatment stimulates cell division and triggers the accumulation of UDP-glucose, a critical factor in cell wall formation. This finding highlights the adaptive strategies used by YLB-01 cells to survive in the challenging high-pressure environments of the deep sea. Specifically, we discovered that YLB-01 cells regulate amino acid metabolism, promote carbohydrate metabolism, enhance cell wall synthesis, and improve cell membrane fluidity in response to high pressure. These adaptive mechanisms play essential roles in supporting the survival and growth of YLB-01 in high-pressure conditions. Our study offers valuable insights into the molecular mechanisms underlying the metabolic adaptation of deep-sea microorganisms to high-pressure environments. KEY POINTS: • NMR-based metabolomic and proteomic analyses were conducted on Microbacterium sediminis YLB-01 to investigate the significant alterations in several metabolic pathways in response to high-pressure treatment. • YLB-01 cells used adaptive strategies (such as regulated amino acid metabolism, promoted carbohydrate metabolism, enhanced cell wall synthesis, and improved cell membrane fluidity) to survive in the challenging high-pressure environment of the deep sea. • High-pressure treatment stimulated cell division and triggered the accumulation of UDP-glucose, a critical factor in cell wall formation, in Microbacterium sediminis YLB-01 cells.

Complete genome sequence of Bacillus cereus Z4, a biocontrol agent against tobacco black shank, isolated from the Western Pacific Ocean.

Bacillus species have been considered as promising biological control agents due to their excellent antimicrobial ability. Bacillus cereus strain Z4 was isolated from 2000 m deep sea sediments of the Western Pacific Ocean, which possesses significant antifungal activity against Phytophthora nicotianae, the pathogenic fungus of tobacco black shank disease. To reveal the underlying antifungal genetic mechanisms, here, we report the complete genomic sequence of the strain Z4. The genome has one circular chromosome of 5,664,309 bp with a G + C content of 35.31%, 109 tRNAs, and 43 rRNAs. Genomic analysis identified 10 gene clusters related to the biosynthesis of biocontrol active compounds, including bacillibactin, petrobactin, fengycin, and molybdenum cofactor. Meanwhile, 6 gene clusters were responsible for the biosynthesis of metabolites with unknown functions. Strain Z4 also contains a large number of genes encoding carbohydrate-active enzymes and secreted proteins, respectively. The whole genomic analysis of Bacillus cereus Z4 may provide a valuable reference for elucidating its biocontrol mechanism against tobacco black shank.

Sodium-glucose cotransporter 2 inhibitor may not prevent atrial fibrillation in patients with heart failure: a systematic review.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) frequently coexist because of their similar pathological basis. However, whether sodium-glucose cotransporter 2 inhibitor (SGLT2i), a novel class of anti-HF medication, decreases the risk of AF in HF patients remains unclear. OBJECTIVES: The aim of this study was to assess the relationship between SGLT2i and AF in HF patients. METHODS: A meta-analysis of randomized controlled trails evaluating the effects of SGLT2i on AF in HF patients was performed. PubMed and ClinicalTrails.gov were searched for eligible studies until 27 November 2022. The risk of bias and quality of evidence were assessed through the Cochrane tool. Pooled risk ratio of AF for SGLT2i versus placebo in eligible studies was calculated. RESULTS: A total of 10 eligible RCTs examining 16,579 patients were included in the analysis. AF events occurred in 4.20% (348/8292) patients treated with SGLT2i, and in 4.57% (379/8287) patients treated with placebo. Meta-analysis showed that SGLT2i did not significantly reduce the risk of AF (RR 0.92; 95% CI 0.80-1.06; p = 0.23) in HF patients when compared to placebo. Similar results remained in the subgroup analyses, regardless of the type of SGLT2i, the type of HF, and the duration of follow-up. CONCLUSIONS: Current evidences showed that SGLT2i may have no preventive effects on the risk of AF in patients with HF. TRANSLATIONAL PERSPECTIVE: Despite HF being one of the most common heart diseases and conferring increased risk for AF, affective prevention of AF in HF patients is still unresolved. The present meta-analysis demonstrated that SGLT2i may have no preventive effects on reducing AF in patients with HF. How to effectively prevent and early detect the occurrence of AF is worth discussing.

Complete genome analysis of Bacillus subtilis TY-1 reveals its biocontrol potential against tobacco bacterial wilt.

Bacillus subtilis TY-1 was isolated from 2000 m-deep sea sediments of the Western Pacific Ocean, which was found to exhibit strong antagonistic activity against tobacco bacterial wilt caused by Ralstonia solanacearum. Here, we present the annotated complete genomic sequence of the strain Bacillus subtilis TY-1. The genome consists of a 4,030,869-bp circular chromosome with a G + C content of 43.88%, 86 tRNAs, and 30 rRNAs. Genomic analysis identified a large number of gene clusters involved in the biosynthesis of antibacterial metabolites, including lipopeptides(surfactin, bacillibactin, and fengycin) and polyketides(bacillaene). Meanwhile, numerous genes encoding carbohydrate-active enzymes and secreted proteins were found in TY-1. These findings suggest that Bacillus subtilis TY-1 appears to be a potential biocontrol agent against tobacco bacterial wilt in agricultural fields.

Sustained Upregulation of Endothelial Nox4 Mediates Retinal Vascular Pathology in Type 1 Diabetes.

NADPH oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in retinal endothelial cells (ECs) and is upregulated under hyperglycemic and hypoxic conditions. However, the role of endothelial Nox4 upregulation in long-term retinal blood vessel damage in diabetic retinopathy (DR) remains undefined. Here, we attempted to address this question using humanized EC-specific Nox4 transgenic (hNox4EC-Tg) and EC-specific Nox4 knockout (Nox4EC-KO) mouse models. Our results show that hNox4EC-Tg mice at age of 10-12 months exhibited increased tortuosity of retinal blood vessels, focal vascular leakage, and acellular capillary formation. In vitro study revealed enhanced apoptosis in brain microvascular ECs derived from hNox4EC-Tg mice, concomitant with increased mitochondrial ROS, elevated lipid peroxidation, decreased mitochondrial membrane potential, and reduced mitochondrial respiratory function. In contrast, EC-specific deletion of Nox4 decreased mitochondrial ROS generation, alleviated mitochondrial damage, reduced EC apoptosis, and protected the retina from acellular capillary formation and vascular hyperpermeability in a streptozotocin-induced diabetes mouse model. These findings suggest that sustained upregulation of Nox4 in the endothelium contributes to retinal vascular pathology in diabetes, at least in part, through impairing mitochondrial function. Normalization of Nox4 expression in ECs may provide a new approach for prevention of vascular injury in DR.

Proteomic Analysis of Retinal Mitochondria-Associated ER Membranes Identified Novel Proteins of Retinal Degeneration in Long-Term Diabetes.

The mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) is the physical contact site between the ER and the mitochondria and plays a vital role in the regulation of calcium signaling, bioenergetics, and inflammation. Disturbances in these processes and dysregulation of the ER and mitochondrial homeostasis contribute to the pathogenesis of diabetic retinopathy (DR). However, few studies have examined the impact of diabetes on the retinal MAM and its implication in DR pathogenesis. In the present study, we investigated the proteomic changes in retinal MAM from Long Evans rats with streptozotocin-induced long-term Type 1 diabetes. Furthermore, we performed in-depth bioinformatic analysis to identify key MAM proteins and pathways that are potentially implicated in retinal inflammation, angiogenesis, and neurodegeneration. A total of 2664 unique proteins were quantified using IonStar proteomics-pipeline in rat retinal MAM, among which 179 proteins showed significant changes in diabetes. Functional annotation revealed that the 179 proteins are involved in important biological processes such as cell survival, inflammatory response, and cellular maintenance, as well as multiple disease-relevant signaling pathways, e.g., integrin signaling, leukocyte extravasation, PPAR, PTEN, and RhoGDI signaling. Our study provides comprehensive information on MAM protein changes in diabetic retinas, which is helpful for understanding the mechanisms of metabolic dysfunction and retinal cell injury in DR.

Redistribution of adipose tissue is associated with left atrial remodeling and dysfunction in patients with atrial fibrillation.

Objective: Adipose tissue is recognized as a crucial regulator of atrial fibrillation (AF). However, the effect of epicardial adipose tissue (EAT) on the pathophysiology of AF might be different from that of other adipose tissues. The purpose of this study was to explore the distribution features of different adipose tissues in AF patients and their relationships with left atrial (LA) remodeling and function. Methods: A total of 205 participants (including 112 AF and 93 non-AF patients) were recruited. Color doppler ultrasound was used to measure the thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue. Cardiac CT scan was performed to measure the mean thickness of EAT surrounding the whole heart (total-EAT) and specific regions, including left atrium (LA-EAT), left ventricle, right ventricle, interventricular groove, and atrioventricular groove. LA anatomical remodeling and function were measured by echocardiography, while electrical remodeling was evaluated by P-wave duration and dispersion using Electrocardiography (obtained after cardioversion or ablation in AF patients). Relationship between the thickness of different adipose tissues and LA remodeling and function was analyzed. Results: The thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue was similar between AF and non-AF patients, and had no or only weak association with LA remodeling and dysfunction. However, compared to non-AF participants, total-EAT thickness significantly increased in both paroxysmal and persistent AF patients (non-AF vs. paroxysmal AF vs. persistent AF: 6.31 ± 0.63 mm vs. 6.76 ± 0.79 mm vs. 7.01 ± 1.18 mm, P < 0.001), which was positively correlated with the LA size and P-wave duration and dispersion, and negatively correlated with LA ejection fraction and peak strain rate. More interestingly, EAT thickness in AF patients did not increase uniformly in different regions of the heart. Compared to EAT surrounding the other regions, LA-EAT was found to accumulate more greatly, and had a closer relationship to LA remodeling and dysfunction. Multivariate logistic regression analysis also showed that LA-EAT was significantly correlated with the presence of AF (OR = 4.781; 95% CI 2.589-8.831, P < 0.001). Conclusion: Rather than other adipose tissues, accumulation and redistribution of EAT, especially surrounding the LA, is associated with LA remodeling and dysfunction in AF patients.

Genomic analysis of Shewanella eurypsychrophilus YLB-09 reveals backgrounds related to its deep sea environment adaptation.

Shewanella eurypsychrophilus YLB-09 is a psychrophilic and piezotolerant bacterium that was isolated from 2699 m deep sea sediments of the Southwest Indian Ocean. The complete genome sequence of the strain Shewanella eurypsychrophilus YLB-09 was analyzed. The genome of Shewanella eurypsychrophilus YLB-09 contained one single circular chromosome 6,225,487 base pairs with a 43.6 mol% G + C content of 52 ribosomal RNA genes and 5124 protein-coding genes. YLB-09 has the largest number of genes related to energy production and conversion among 22 available complete genomes of Shewanella genus. Meanwhile， a large quantity of genes encoding flagellum/fimbrial-related proteins and two major secondary metabolic gene clusters were found in YLB-09. These data could provide insights into the mechanism of this strain in adapting to deep sea extreme environments.

Bacteroides ovatus-mediated CD27- MAIT cell activation is associated with obesity-related T2D progression.

Type 2 diabetes (T2D) is highly associated with obesity. However, the factors that drive the transition from excessive weight gain to glucose metabolism disruption are still uncertain and seem to revolve around systemic immune disorder. Mucosal-associated invariant T (MAIT) cells, which are innate-like T cells that recognize bacterial metabolites, have been reported to be altered in obese people and to lead to metabolic dysfunction during obesity. By studying the immunophenotypes of blood MAIT cells from a cross-sectional cohort of obese participants with/without T2D, we found an elevation in CD27-negative (CD27-) MAIT cells producing a high level of IL-17 under T2D obese conditions, which could be positively correlated with impaired glucose metabolism in obese people. We further explored microbial translocation caused by gut barrier dysfunction in obese people as a triggering factor of MAIT cell abnormalities. Specifically, accumulation of the bacterial strain Bacteroides ovatus in the peripheral blood drove IL-17-producing CD27- MAIT cell expansion and could be associated with T2D risk in obese individuals. Overall, these results suggest that an aberrant gut microbiota-immune axis in obese people may drive or exacerbate T2D. Importantly, CD27- MAIT cell subsets and Bacteroides ovatus could represent targets for novel interventional strategies. Our findings extend current knowledge regarding the clinical relevance of body mass index (BMI)-associated variation in circulating MAIT cells to reveal the role of these cells in obesity-related T2D progression and the underlying cellular mechanisms.

Monocyte to High-Density Lipoprotein Cholesterol Ratio Is Associated with Subclinical Left Cardiac Remodeling and Dysfunction in Type 2 Diabetes Mellitus.

Chronic inflammation is involved in the development of heart failure (HF) in type 2 diabetes mellitus (T2DM). However, reliable and easily accessible biomarker of subclinical left cardiac remodeling and dysfunction remains a challenge.Overall, 1020 patients with T2DM without overt HF were enrolled from May 2019 to April 2020. Monocyte to high-density lipoprotein ratio (MHR) was calculated by blood monocyte count divided by high-density lipoprotein cholesterol. Left cardiac structure and function were assessed using transthoracic echocardiography. Univariate and multivariate linear regression analyses were used to estimate the association of MHR (Lg transferred) with echocardiographic parameters. We found that septal wall thickness (SWT), left ventricular internal end-diastole dimension (LVIDd), and left ventricular mass index (LVMI) raised with increasing MHR (P = 0.002 for SWT, P < 0.001 for LVIDd, and P = 0.001 for LVMI). Declined trends were shown in ejection fraction (EF) (P = 0.016), E velocity (P = 0.037), E/A ratio (P = 0.009), and tissue Doppler e' (P < 0.001), and elevating trend was observed in E/e' (P < 0.001). In multivariate regression analysis, MHR (Lg transferred) was positively associated with LVIDd (ß = 0.031; P = 0.016), LVMI (ß = 0.073; P = 0.014), and E/e' (ß = 0.331; P < 0.001), whereas it was negatively associated with EF (ß = -0.086; P = 0.007), E/A (ß = -0.072; P = 0.009), and e' (ß = -0.332; P < 0.001).MHR could be a practical biomarker for indicating subclinical cardiac remodeling and dysfunction in T2DM, due to low cost and easy availability.

New Sorbicillinoids with Tea Pathogenic Fungus Inhibitory Effect from Marine-Derived Fungus Hypocrea jecorina H8.

Four new dimeric sorbicillinoids (1-3 and 5) and a new monomeric sorbicillinoid (4) as well as six known analogs (6-11) were purified from the fungal strain Hypocrea jecorina H8, which was obtained from mangrove sediment, and showed potent inhibitory activity against the tea pathogenic fungus Pestalotiopsis theae (P. theae). The planar structures of 1-5 were assigned by analyses of their UV, IR, HR-ESI-MS, and NMR spectroscopic data. All the compounds were evaluated for growth inhibition of tea pathogenic fungus P. theae. Compounds 5, 6, 8, 9, and 10 exhibited more potent inhibitory activities compared with the positive control hexaconazole with an ED50 of 24.25 ± 1.57 µg/mL. The ED50 values of compounds 5, 6, 8, 9, and 10 were 9.13 ± 1.25, 2.04 ± 1.24, 18.22 ± 1.29, 1.83 ± 1.37, and 4.68 ± 1.44 µg/mL, respectively. Additionally, the effects of these compounds on zebrafish embryo development were also evaluated. Except for compounds 5 and 8, which imparted toxic effects on zebrafish even at 0.625 µM, the other isolated compounds did not exhibit significant toxicity to zebrafish eggs, embryos, or larvae. Taken together, sorbicillinoid derivatives (6, 9, and 10) from H. jecorina H8 displayed low toxicity and high anti-tea pathogenic fungus potential.

The feasibility and safety of a simple method for coronary sinus blood sampling during catheter ablation of arrhythmias.

Background: Coronary sinus (CS) blood sampling gives an insight into the localized pathophysiology of heart diseases. However, additional specifically-designed or modified catheters were needed in most previous studies, making the convenience of clinical application unsatisfactory. This study aimed to introduce a simple method for CS blood sampling without using additional catheters during catheter ablation (CA) of arrhythmias, and to investigate its feasibility and safety. Methods: A total of 119 patients undergoing CA were prospectively enrolled, including 25 with paroxysmal supraventricular tachycardia (PSVT), 30 with premature ventricular complexes (PVC), and 64 with atrial fibrillation (AF). Cannulation and sampling of CS was performed via the femoral vein using a conventional 8F SR0TM or 8.5F SL1TM introducer sheath (St. Jude Medical) guided by a 6F steerable diagnostic catheter (St. Jude Medical). The success rate and any suspicious complications were recorded. Untargeted liquid chromatograph-mass spectrometer (LC-MS)-based metabonomics of CS samples versus peripheral venous samples were also performed. Results: CS blood samples were successfully collected from 114 patients, with an overall success rate of 95.8%. Among patients with different arrhythmias, the success rates were similar, with 96.0% in PSVT, 96.7% in PVC, and 95.3% in AF (P=0.223). Adverse events occurred in four (3.4%) patients, including two patients with occasional atrial ectopic beats without causing any discomfort, and two patients with new-onset paroxysmal AF lasting for about 2 min. No serious complications were noted. Metabonomics analysis showed that CS samples provided a number of different metabolites (93 in PVST, 217 in PVC, and 109 in AF) versus peripheral samples. Conclusions: Our method for CS blood sampling during CA is feasible and safe, and can provide useful cardiometabolic information that is significantly different from a peripheral sample.

Transcriptomic Analysis Reveals that Changes in Gene Expression Contribute to Microbacterium sediminis YLB-01 Adaptation at Low Temperature Under High Hydrostatic Pressure.

Microbes living in extreme environments often adopt strategies for survival, however, only a few studies have examined the adaptive mechanism of deep-sea bacteria in in-situ environments. In this study, transcriptomic data of the deep-sea piezotolerant and psychrotolerant actinomycete Microbacterium sediminis YLB-01 under the conditions of NPNT (normal temperature and pressure: 28 °C, 0.1 MPa), HPNT (normal temperature and high pressure: 28 °C, 30 MPa), NPLT (low temperature and atmospheric pressure: 4 °C, 0.1 MPa) and HPLT (low temperature and high pressure: 4 °C, 30 MPa) were examined and compared. Transcriptome results showed that M. sediminis YLB-01 responds to deep-sea low temperature under high-pressure environments by upregulating the ABC transport system, DNA damage repair response, pentose phosphate pathway, amino acid metabolism and fatty acid metabolism, while down-regulating division, oxidative phosphorylation, the TCA cycle, pyruvate metabolism, ion transport and peptidoglycan biosynthesis. Seven key genes specifically expressed under HPLT conditions were screened, and these genes are present in many strains that are tolerant to low temperatures and high pressures. This study provides transcription level insights into the tolerance mechanisms of M. sediminis YLB-01 in a simulated deep-sea in situ environment.

Two new compounds from a mangrove sediment-derived fungus Penicillium polonicum H175.

Two new compounds, 6-acetyl-4-methoxy-3,5-dimethyl-2H-pyran-2-one (1) and (2E,4E)-5-((2S,3S,4R,5R)-3,4-dihydroxy-2,4,5-trimethyltetrahydrofuran-2-yl)-2,4-dimethylpenta-2,4-dienal (2), and 22 known compounds were identified from the mangrove-forest-derived fungus Penicillium polonicum H175. The structures of these compounds were elucidated by analysis of the high-resolution electrospray ionisation mass spectroscopy (HR-ESI-MS), 1 D and 2 D nuclear magnetic resonance (NMR) data. The hypoglycaemic effect of compounds was evaluated by the Tg (Ins: htBidTE-ON; LR) zebrafish model. Compound 3 (aspterric acid) exhibited a significant hypoglycaemic effect equivalent to the positive drug rosiglitazone (RSG) at 10 µmol/L.

Association of the Monocyte-to-High-Density Lipoprotein Cholesterol Ratio With Diabetic Retinopathy.

Background: Chronic inflammation in type 2 diabetes mellitus (T2DM) is an essential contributor to the development of diabetic retinopathy (DR). The monocyte-to-high-density lipoprotein cholesterol (HDL-C) ratio (MHR) is a novel and simple measure related to inflammatory and oxidative stress status. However, little is known regarding the role of the MHR in evaluating the development of DR. Methods: A total of 771 patients with T2DM and 607 healthy controls were enrolled in this cross-sectional study. MHR determination and eye examination were performed. The association of MHR with the prevalence of DR in T2DM patients was analyzed. Results: The MHR in patients with DR was significantly higher than that in both non-DR diabetic patients (P < 0.05) and healthy controls (P < 0.01). No significance was observed in the MHR of different DR severity grades. Moreover, the MHR was similar between patients with non-macular oedema and those with macular oedema. Logistic regression analysis demonstrated that MHR was independently associated with the prevalence of DR in diabetic patients [odds ratio (OR) = 1.438, 95% confidence interval (CI): 1.249-1.655, P < 0.01]. After additional stratification by HbA1c level and diabetic duration, the MHR was still independently associated with the prevalence of DR. Conclusions: Our study suggests that the MHR can be used as a marker to indicate the prevalence of DR in patients with T2DM.

Characterization of two novel psychrophilic and piezotolerant strains, Shewanella psychropiezotolerans sp. nov. and Shewanella eurypsychrophilus sp. nov, adapted to an extreme deep-sea environment.

Three marine bacterial strains designated YLB-06T, YLB-08T and YLB-09 were isolated under high hydrostatic pressure from deep-sea sediment samples collected from the Southwest Indian Ocean. They were Gram-stain-negative, oxidase- and catalase-positive, facultative anaerobic and motile. In addition, the strains were capable of growing at 0-20 °C (optimum 4-10 °C) and 0.1-40 MPa (optimum 0.1 MPa), were psychrophiles and piezotolerant, and could use trimethylamine N-oxide (TMAO), DMSO, elemental sulfur and insoluble Fe (III) as terminal electron acceptors during anaerobic growth. Strain YLB-06T could also use nitrate, and strains YLB-08T and YLB-09 could use nitrite as a terminal electron acceptor. Phylogenetic tree analyses based on 16S rRNA gene sequences and 400 optimized universal marker sequences indicated that the strains belonged to the genus Shewanella. The 16S rRNA gene highest similarity, together with the estimated ANI and DDH values for these strains with their related type strains, were below the respective thresholds for species differentiation. The ANI and DDH values between YLB-08T and YLB-09 were 99.9% and 91.8%, respectively, implying that they should belong to the same genospecies. The YLB-06T genome had duplicated genes, and multiple movement modalities, attachment modalities, biofilm synthesis systems, intercellular interactions and a strong antioxidant system, which were all beneficial for survival in an extreme deep-sea environment. The G + C contents of strains YLB-06T, YLB-08T and YLB-09 were 45.1, 43.5 and 43.6 mol%, respectively. Based on polyphasic taxonomic properties, two novel psychropiezotolerant species are proposed, Shewanella psychropiezotolerans sp. nov. with YLB-06T (=MCCC 1A12715T = KCTC 62907T) and S. eurypsychrophilus sp. nov with YLB-08T (=MCCC 1A12718T = KCTC 62909T) as type strains.

Inhaled Beta2-Agonists Increase In-Hospital Mortality in ICU Patients with Heart Failure.

The impact of beta2-agonists (B2As) on heart failure (HF) remains controversial. This study aimed to investigate whether inhaled B2As increased in-hospital mortality in ICU patients with HF.The Multiparameter Intelligent Monitoring in Intensive Care III database was initially searched to identify adult patients (≥ 18 years old) with HF in ICU. Then, patients using or not using inhaled B2As were matched using propensity score matching on a 1:1 basis to control for baseline confounders. In-hospital mortality was compared between the two groups, and logistic regression analysis was performed to assess the association between B2As and in-hospital mortality.The initial search retrieved 2345 eligible patients with HF from the database. After propensity score matching, 705 pairs of patients were included in the final analysis. Patients using B2As had markedly higher in-hospital mortality than those not using B2As (4.68% versus 2.27%; P = 0.013). In the multivariate logistic regression analysis, B2A use (odd ratios (OR), 2.471; 95% confidence interval (CI), 1.289-4.734; P = 0.006), stroke (OR, 4.581; 95% CI, 1.621-12.948; P = 0.004), and simplified acute physiology score II (SAPS-II) scores (OR, 1.090; 95% CI, 1.064-1.116; P < 0.001) were significantly associated with increased risk of in-hospital mortality, whereas renin angiotensin system inhibitor use (OR, 0.396; 95% CI, 0.202-0.778; P = 0.007) was significantly associated with decreased risk of in-hospital mortality. Subgroup analysis further indicated that the association between B2A use and mortality was significant only in patients with HF without chronic pulmonary disease (OR, 2.427; 95% CI, 1.351-4.362; P = 0.003), but not in those with chronic pulmonary disease (OR, 2.094; 95% CI, 0.582-7.537; P = 0.258).In ICU patients with HF but without chronic pulmonary disease, the use of inhaled B2As is associated with increased in-hospital mortality.

High-Normal Serum Thyrotropin Levels Increased the Risk of Non-Alcoholic Fatty Liver Disease in Euthyroid Subjects with Type 2 Diabetes.

PURPOSE: The aim of this study was to investigate the association between high-normal thyrotropin (TSH) levels and the prevalence of non-alcoholic fatty liver disease (NAFLD) in euthyroid patients with T2DM. METHODS: A total of 2289 euthyroid adults with T2DM were included in this cross-sectional study conducted at the Third Affiliated Hospital of Sun Yat-sen University from January 2016 to December 2018. NAFLD was diagnosed by abdominal ultrasound. Thyroid function parameters, including the levels of TSH, free triiodothyronine (FT3) and free thyroxine (FT4), were analyzed. The patients were stratified by quartiles (Q1-4) of TSH levels. Multivariate logistic regression models were used to evaluate the association between the quartiles of TSH levels and the risk of NAFLD in euthyroid adults with T2DM. RESULTS: There were 940 (41.1%) euthyroid adults with T2DM who were diagnosed with NAFLD. The subjects were divided according to the thyroid function parameter quartiles. The prevalence of NAFLD increased with increasing TSH level quartiles (Q1 to Q4: 34.8%, 37.5%, 44.9% and 47.0%, P<0.01) but not with increasing FT3 or FT4 level quartiles. In the multivariate logistic regression model, compared with the lowest TSH level quartile (Q1), the highest TSH level quartile (Q4) (OR=1.610, 95% CI=1.131-2.289, P=0.008) was independently associated with an increased risk of NAFLD in euthyroid adults with T2DM after adjusting for multiple confounders. After additional stratification by the level of glycosylated haemoglobin (HbA1c) and body mass index (BMI), the highest TSH level quartile was still independently associated with an increased risk of NAFLD in euthyroid patients with T2DM who had an HbA1c level≥7% or a BMI<28 kg/m2. CONCLUSION: High-normal serum TSH levels are significantly associated with the presence of NAFLD in T2DM patients with euthyroid function, which provide novel insight for treating NAFLD.