Thioclava litoralis sp. nov., a novel species of alphaproteobacterium, isolated from surface seawater.

A Gram-negative, aerobic, rod-shaped, non-motile bacterium, designated as FTW29T, was isolated from surface seawater sampled in Futian district, Shenzhen, China. Growth of strain FTW29T was observed at 15-42 ℃ (optimum, 28-30 ℃), pH 4.0-9.0 (optimum, pH 5.5-7.5) and in the presence of 0.5-10% NaCl (optimum, 3.0% NaCl). Strain FTW29T showed 95.0-96.8% 16 S rRNA gene sequence similarity to various type strains of the genera Thioclava, Sinirhodobacter, Rhodobacter, Haematobacter and Frigidibacter of the family Paracoccaceae, and its most closely related strains were Thioclava pacifica DSM 10,166T (96.8%) and Thioclava marina 11.10-0-13T (96.7%). The phylogenomic tree constructed on the bac120 gene set showed that strain FTW29T formed a clade with the genus Thioclava, with a bootstrap value of 100%. The evolutionary distance values between FTW29T and type strains of the genus Thioclava were 0.17-0.19, which are below the recommended standard (0.21-0.23) for defining a novel genus in the family Paracoccaceae. In strain FTW29T, the major fatty acids identified were summed feature 8 (C18:1ω7c) and C16:0, and the predominant respiratory quinones were ubiquinone-10 and ubiquinone-9. The composition of polar lipids in strain FTW29T included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, an unidentified aminolipid, two unidentified glycolipids and an unidentified lipid. The genome of strain FTW29T comprised one circle chromosome and six plasmids, with a G + C content of 61.4%. The average nucleotide identity, average amino acid identity, and digital DNA-DNA hybridization values between strain FTW29T and seven type strains of the genus Thioclava were 76.6-78.4%, 53.2-56.4% and 19.3-20.4%, respectively. Altogether, the phenotypic, phylogenetic and chemotaxonomic evidence illustrated in this study suggested that strain FTW29T represents a novel species of the genus Thioclava, with the proposed name Thioclava litoralis sp. nov. The type strain is FTW29T (= KCTC 82,841T = MCCC 1K08523T).

Microbulbifer bruguierae sp. nov., isolated from sediment of mangrove plant Bruguiera sexangula, and comparative genomic analyses of the genus Microbulbifer.

A Gram-negative, non-motile, strictly aerobic, rod-shaped bacterium, designated as H12T, was isolated from the sediments of mangrove plant Bruguiera sexangula taken from Dapeng district, Shenzhen, PR China. The pairwise 16S rRNA gene sequence analysis showed that strain H12T shared high identity levels with species of the genus Microbulbifer, with the highest similarity level of 98.5 % to M. pacificus SPO729T, followed by 98.1 % to M. donghaiensis CN85T. Phylogenetic analysis using core-genome sequences showed that strain H12T formed a cluster with type species of M. pacificus SPO729T and M. harenosus HB161719T. The complete genome of strain H12T was 4 481 396 bp in size and its DNA G+C content was 56.7 mol%. The average nucleotide identity and digital DNA-DNA hybridization values among strain H12T and type species of genus Microbulbifer were below the cut-off levels of 95-96 and 70 %, respectively. The predominant cellular fatty acids of strain H12T were iso-C15 : 0 (22.5 %) and C18 : 1 ω7c (13.9 %). Ubiquinone-8 was detected as the major respiratory quinone. The polar lipids of strain H12T comprised one phosphatidylglycerol, one phosphatidylethanolamine, one unidentified aminoglycophospholipid, one unidentified glycophospholipid, three unidentified glycolipids, two unidentified aminolipids, and one unidentified lipid. Based on polyphasic evidence, strain H12T represents a novel species of the genus Microbulbifer, for which the name Microbulbifer bruguierae sp. nov. is proposed. The type strain is H12T (=KCTC 92859T=MCCC 1K08451T). Comparative genomic analyses of strain H12T with strains of the genus Microbulbifer reveal its potential in degradation of pectin.

Cardiac-derived extracellular vesicles improve mitochondrial function to protect the heart against ischemia/reperfusion injury by delivering ATP5a1.

BACKGROUND: Numerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently, we reported that EVs derived from ischemia-reperfusion heart exacerbate cardiac injury. However, the role of EVs from healthy heart tissue (heart-derived EVs, or cEVs) on myocardial ischemia-reperfusion (MI/R) injury remains unclear. RESULTS: Here, we demonstrated that intramyocardial administration of cEVs significantly enhanced cardiac function and reduced cardiac damage in murine MI/R injury models. cEVs treatment effectively inhibited ferroptosis and maintained mitochondrial homeostasis in cardiomyocytes subjected to ischemia-reperfusion injury. Further results revealed that cEVs can transfer ATP5a1 into cardiomyocytes, thereby suppressing mitochondrial ROS production, alleviating mitochondrial damage, and inhibiting cardiomyocyte ferroptosis. Knockdown of ATP5a1 abolished the protective effects of cEVs. Furthermore, we found that the majority of cEVs are derived from cardiomyocytes, and ATP5a1 in cEVs primarily originates from cardiomyocytes of the healthy murine heart. Moreover, we demonstrated that adipose-derived stem cells (ADSC)-derived EVs with ATP5a1 overexpression showed much better efficacy on the therapy of MI/R injury compared to control ADSC-derived EVs. CONCLUSIONS: These findings emphasized the protective role of cEVs in cardiac injury and highlighted the therapeutic potential of targeting ATP5a1 as an important approach for managing myocardial damage induced by MI/R injury.

Mendelian randomization analysis reveals causal relationships between gut microbiome and optic neuritis.

BACKGROUND: It is unclear whether gut microbiota (GM) affects the risk of optic neuritis (ON) through the "gut-brain" axis and the "gut-retina" axis. To examine the causal relationship between GM and ON, we conducted Mendelian randomization (MR) study. METHODS: Up to 18,340 samples of 24 population-based cohorts were included in genome-wide association study (GWAS) of 196 GM taxa. ON outcomes were selected from the FinnGen GWAS (951 ON cases and 307,092 controls). In addition, the GWAS based on UK Biobank (UKB) (105 ON cases and 456,243 controls) was used for further exploration. Inverse variance weighted (IVW) was carried out to estimate their effects on ON risk and the MR assumptions were evaluated in sensitivity analyses. RESULTS: Among the 196 GM taxa, the IVW results confirmed that Family -Peptococcaceae (P = 2.17 × 10-3), Genus- Hungatella (P = 4.57 × 10-3) and genus-Eubacterium_rectale_group (P = 0.02) were correlated with the risk of ON based on Finngen GWAS. Based on data from UKB, Genus- Eubacterium_hallii_group (P = 1.50 × 10-3) and Genus- Ruminococcaceae_UCG_002 (P = 0.02) were correlated with the risk of ON. At the phylum, class and order levels, no GM taxa were causally related to ON (P > 0.05). Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analysis confirmed the robustness of the MR results. CONCLUSION: Our MR findings support the causal effect of specific GM taxa on ON. GM may affect the risk of ON through the "gut-brain" axis and the "gut-retina" axis. However, further research is needed to confirm the relevant mechanism of the relationship between GM and ON.

TFEB attenuates hyperglycemia-induced retinal capillary endothelial cells injury via autophagy regulation.

Diabetic retinopathy is a common microvascular complication of diabetes mellitus. The maintenance of retinal capillary endothelial cell homeostasis requires a complete and unobtrusive flow of autophagy because it may help combat the inflammatory response, apoptosis, and oxidative stress damage of cells in diabetes mellitus. The transcription factor EB is a master regulator of autophagy and lysosomal biogenesis, but its role in diabetic retinopathy remains unknown. This study aimed to confirm the involvement of transcription factor EB in diabetic retinopathy and explore the role of transcription factor EB in hyperglycemia-linked endothelial injury in vitro. First, the expression levels, including the nuclear location of transcription factor EB and autophagy, were reduced in diabetic retinal tissues and high glucose-treated human retinal capillary endothelial cells. Subsequently, autophagy was mediated by transcription factor EB in vitro. Moreover, transcription factor EB overexpression reversed high glucose-induced autophagy inhibition and lysosomal dysfunction and protected human retinal capillary endothelial cells from inflammation, apoptosis, and oxidative stress damage caused by high glucose treatment. Additionally, under high-glucose stimulation, the autophagy inhibitor chloroquine attenuated transcription factor EB overexpression-mediated protection, and the autophagy agonist Torin1 rescued transcription factor EB knockdown-induced damage effects. Taken together, these results suggest that transcription factor EB is involved in the development of diabetic retinopathy. In addition, transcription factor EB protects human retinal capillary endothelial cells from high glucose-induced endothelial damage via autophagy.

Description and genomic characterization of Gallaecimonas kandeliae sp. nov., isolated from the sediments of mangrove plant Kandelia obovate.

The genus Gallaecimonas, proposed by Rodríguez-Blanco et al. (Int J Syst Evol Microbiol 60:504-509, 2010), is mainly isolated from marine environments. So far, only three species have been identified and characterized in this genus. In this study, a new Gallaecimonas strain named Q10T was isolated from the sediments of mangrove plant Kandelia obovate taken from Dapeng district, Shenzhen, China. Strain Q10T was a Gram-stain-negative, non-motile, strictly aerobic, rod-shaped bacterium, and grew with 0-8.0% (w/v) NaCl, at 10-45 °C and at pH 5.5-8.5. Phylogenetic analysis indicated that strain Q10T and the three Gallaecimonas species formed a clade in the tree, with 16S rRNA gene sequence similarities ranging from 96.0 to 97.0%. The major respiratory quinone is Q8. The polar lipids comprised aminolipid, aminophospholipid, diphosphatidylglycerol, glycolipid, phosphatidylethanolamine, phosphatidylglycerol, glycophospholipid and phospholipid. The predominant fatty acids are C16:0, C17:1ω8c, summed feature 3 (C16:1ω7c/C16:1ω6c), and iso-C16:0. The complete genome of strain Q10T is 3,836,841 bp with a G+C content of 62.6 mol%. The orthologous proteins analysis revealed 55 unique proteins in strain Q10T related to important biological processes, especially three frataxins related to iron-sulfur cluster assembly, which may play a pivotal role in environmental adaptability of this species. Based on polyphasic taxonomic data, strain Q10T is considered to represent a novel species within the genus Gallaecimonas, for which the name Gallaecimonas kandelia sp. nov. is proposed. The type strain is Q10T (=KCTC 92860T=MCCC 1K08421T). These results contribute to a better understanding of general features and taxonomy of the genus Gallaecimonas.

Internal limiting membrane peeling combined with mouse nerve growth factor injection for idiopathic macular hole.

BACKGROUND: The study was intended to confirm whether Pars Plana Vitrectomy (PPV) with Internal Limiting Membrane (ILM) peeling and intravitreal injection mouse Nerve Growth Factor(mNGF) was effective for the treatment of Idiopathic Macular Hole(IMH) by Optical Coherence Tomography Angiography(OCTA) and microperimetry. METHODS: A retrospective study was performed in adults' patients. A total of 44 eyes (March 2021-October 2021) with IMH who received surgical treatment in the Affiliated Eye Hospital of Nanchang University in Nanchang City, Jiangxi Province were selected. The subjects were treated using PPV combined with ILM peeling and intravitreal mNGF (combined group) or PPV combined with ILM peeling (placebo group). The Best Corrected Visual Acuity (BCVA), Optical Coherence Tomography Angiography (OCTA) and MP-3 microperimetry were carried out and observed at baseline, 1 week(1W), 1,3 and 6 months (1 M,3 M,6 M) postoperatively. RESULTS: The minimum diameter of MH were (568.650 ± 215.862)µm and (533.348 ± 228.836)µm in the Placebo and Combine group pre-operative. During the observation, the macular hole closure rate in the placebo group and combined group were 90% and 95.8% respectively and the difference was not statistically significant(p = 0.583). Compared to pre-surgery, the perimeter and circularity of Foveal Avascular Zone (FAZ) in the placebo group decreased at 1,3,6 M (p = 0.001, < 0.001, < 0.001) and 1W,1,6 M (p = 0.045,0.010, < 0.001) post-surgery respectively. And the perimeter and circularity of FAZ showed significant reduction in the combined group at 1,3,6 M (p = 0.005,0.004, < 0.001) and at each follow-up time point (all values of p < 0.001). The vascular density of SCP increased at 1W(p = 0.031) and 6 M(p = 0.007), the perfusion density of SCP was significantly improved at each follow-up time point (p = 0.028, 0.011, 0.046, 0.004) in the combined group. The BCVA in the combined group was more obvious than that in the placebo group at 1 M, 3 M and 6 M after operation (t1 = 2.248, p1 = 0.030; t3 = 3.546, p3 = 0.001; t6 = 3.054, p6 = 0.004). The changes of BCVA in the combined group was more conspicuous than that in the placebo group at each follow-up time point, and the difference was statistically significant (t1 = 2.206,p1 = 0.033;t2 = 2.54,p2 = 0.015;t3 = 3.546,p3 = 0.001;t6 = 3.124,p6 = 0.003).At 1 M, 3 M and 6 M, the MRS of 2° and 4° in the combined group was better than that in the placebo group(t = -2.429,-2.650,-3.510,-2.134,-2.820,-3.099 p = 0.020,0.011,0.001,0.039,0.007,0.004). During various time points, the MRS of 12°in the combined group was better than that in the placebo group, the difference was statistically significant (t = -3.151, -3.912, -4.521, -4.948, p1 = 0.003, < 0.001, < 0.001 < 0.001). The integrity of External Limiting Membrane (ELM) in combination group was better than that in placebo group at 6 M postoperative(p = 0.022) and that of Ellipsoid Zone(EZ) was preferable in the combined group at 3 M and 6 M after surgery(p = 0.012,0.004). Correlation analysis showed that the integrity of EZ was correlated with 12°MRS at 1 M, 3 M and 6 M after surgery(r = -0.318, -0.343,-0.322;p = 0.023,0.033, < 0.001). There was no correlation between postoperative ELM integrity and postoperative BCVA and 12°MRS(p > 0.05). CONCLUSIONS: Our results manifested that PPV combined with ILM peeling and intravitreal injection mNGF might be more effective for initial IMH. This method increased the blood flow, MRS and promoted the recovery of ELM and EZ in the macular and might improve the visual function of patients postoperatively.

Comparative genomic analysis provides insights into taxonomy and temperature adaption of Aeromonas salmonicida.

Aeromonas salmonicida has long been known as psychrophiles since it is mainly isolated from cold water fish, and recent reports have revealed the existence of mesophilic strains isolated from warm sources. However, the genetic differences between mesophilic and psychrophilic strains remain unclear due to few complete genomes of mesophilic strain are available. In this study, six A. salmonicida (2 mesophilic and 4 psychrophilic) were genome-sequenced, and comparative analyses of 25 A. salmonicida complete genomes were conducted. The ANI values and phylogenetic analysis revealed that 25 strains formed three independent clades, which were referred as typical psychrophilic, atypical psychrophilic and mesophilic groups. Comparative genomic analysis showed that two chromosomal gene clusters, related to lateral flagella and outer membrane proteins (A-layer and T2SS proteins), and insertion sequences (ISAs4, ISAs7 and ISAs29) were unique to the psychrophilic groups, while the complete MSH type IV pili were unique to the mesophilic group, all of which may be considered as lifestyle-related factors. The results of this study not only provide new insights into the classification, lifestyle adaption and pathogenic mechanism of different strains of A. salmonicida, but also contributes to the prevention and control of disease caused by psychrophilic and mesophilic A. salmonicida.

Diagnostic potential of a circulating miRNA model associated with therapeutic effect in heart failure.

Heart failure (HF), as the leading cause of death, is continuing to increase along with the aging of the general population all over the world. Identification of diagnostic biomarkers for early detection of HF is considered as the most effective way to reduce the risk and mortality. Herein, we collected plasma samples from HF patients (n = 40) before and after medical therapy to determine the change of circulating miRNAs through a quantitative real-time PCR (QRT-PCR)-based miRNA screening analysis. miR-30a-5p and miR-654-5p were identified as the most significantly changed miRNAs in the plasma of patients upon treatment. In consistence, miR-30a-5p showed upregulation and miR-654-5p showed downregulation in the circulation of 30 HF patients, compared to 15 normal controls in the training phase, from which a two-circulating miRNA model was developed for HF diagnosis. Next, we performed the model validation using an independent cohort including 50 HF patients and 30 controls. As high as 98.75% of sensitivity and 95.00% of specificity were achieved. A comparison between the miRNA model and NT-pro BNP in diagnostic accuracy of HF indicated an upward trend of the miRNA model. Moreover, change of the two miRNAs was further verified in association with the therapeutic effect of HF patients, in which miR-30a-5p showed decrease while miR-654-5p showed increase in the plasma of patients after LVAD implantation. In conclusion, the current study not only identified circulating miR-654-5p for the first time as a novel biomarker of HF, but also developed a novel 2-circulating miRNA model with promising potentials for diagnosis and prognosis of HF patients, and in association with therapeutic effects as well.

Molecular cloning, expression analysis and functional characterization of NEDD4 from Nile tilapia (Oreochromis niloticus).

Neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) was a member of HECT E3 ubiquitin ligases, which participated in various biological processes. In this study, a NEDD4 was identified and analyzed in Nile tilapia, Oreochromis niloticus (OnNEDD4) and its open reading frame was 2781 bp, encoding 926 amino acids. Three conserved structure features were found in OnNEDD4, including C2 domain, WW domains and HECT domain. OnNEDD4 was constitutively expressed in all examined tissues and the highest expression level was observed in thymus. After Streptococcus agalactiae stimulation, OnNEDD4 was significantly induced in several tissues, including thymus, intestine, blood and gill. Moreover, yeast two-hybrid assay shown OnNEDD4 could interact with extracellular region of OnCD40, but this interaction didn't affect the phagocytosis of monocytes/macrophages (MO/MΦ) to S. agalactiae and A. hydrophila. Taken together, the present study suggested that OnNEDD4 participate in CD40-mediated immune response excluding phagocytosis.

Characterization of TRAF2 in Nile tilapia: Expression profiles and the role in decreasing NF-κB pathway.

Mammals TRAF2 played a dual role in several immune signaling transduction processes. In this study, TRAF2 was cloned from Nile tilapia, Oreochromis niloticus, which named OnTRAF2. The open reading frame was 1797 bp, encoding 598 amino acids. Amino acid alignment and phylogenetic analysis indicated that OnTRAF2 showed relatively low identify with other teleost TRAF2 proteins, with the exception of TRAF2s from Epinephelus coioides. In healthy tilapia, OnTRAF2 was expressed widely in all the examined tissues, which had highest expression level in the brain. After Streptococcus agalactiae infection, the expression level of OnTRAF2 was increased significantly at different times in several organs, implying that OnTRAF2 may be involved in host defense against S. agalactiae infection. The result of subcellular localization showed that OnTRAF2 presented in cytoplasm and nucleus of HEK293T cells. Additionally, overexpression of OnTRAF2 significantly decreased the transcriptional activity of the NF-κB reporter in HEK293T cells, yeast two-hybrid results revealed that OnTRAF2 had no interaction with E3 ubiquitin ligase OnNEDD4. These results indicated that OnTRAF2 played important function during bacterial infection, and negatively mediated the immune signaling transduction in Nile tilapia, while the mechanism need further study.

Ubiquitin-like protein FAT10 promotes osteosarcoma growth by modifying the ubiquitination and degradation of YAP1.

Osteosarcoma is a common malignancy of the bone tissue. The rapid growth exhibited by this cancer is a primary challenge in its treatment. In many types of cancers, FAT10, a ubiquitin-like protein, is involved in several biological activities, especially cell proliferation. Herein, we demonstrate that FAT10 plays a vital role in tumorigenesis and is overexpressed in tumor tissues compared to its expression in adjacent normal tissues. Functional assays revealed that knockdown of FAT10 expression significantly repressed the proliferation of osteosarcoma in vitro and in vivo. Furthermore, our results indicate that FAT10 exhibits oncogenic functions by regulating the level of YAP1, a key protein of the Hippo/YAP signaling pathway, and a significant positive correlation exists between the levels of FAT10 and YAP1. Further analysis showed that FAT10-induced growth of osteosarcoma cells is dependent on YAP1. Mechanistically, FAT10 stabilizes YAP1 expression by regulating its ubiquitination and degradation. Taken together, our results link the two drivers of cell growth in osteosarcoma and reveal a novel pathway for FAT10 regulation. We provide new evidence for the biological and clinical significance of FAT10 as a potential biomarker for osteosarcoma.

CD40 induces an antimicrobial response against the intracellular pathogen Streptococcus agalactiae in Nile tilapia, Oreochromis niloticus.

Streptococcus agalactiae is a Gram-positive facultative intracellular bacterium that leads to severe economic loss of tilapia worldwide. Previous studies demonstrated that CD40 contributes to host protection against intracellular injection. In this study, CD40 was characterized from Nile tilapia (Oreochromis niloticus), named OnCD40. Sequence analysis showed that open reading frame of OnCD40 was 933 bp, containing a single peptide, a transmembrane domain and four cysteine-rich domains. The qRT-PCR revealed that OnCD40 was expressed in all examined tissues with the most abundant ones in spleen and thymus. After S. agalactiae stimulation, the expression of OnCD40 was significantly induced in most of the detected organs. Moreover, OnCD40-overexpressing fish elicited significant protection against subsequent S. agalactiae challenge; approximately 10000-fold fewer bacteria were detected in spleen of OnCD40-overexpressing fish in comparison with control fish. Thus, CD40 had protecting function in Nile tilapia against intracellular pathogens.

Nanocrystalline Li-Al-Mn-Si Foil as Reversible Li Host: Electronic Percolation and Electrochemical Cycling Stability.

When a metallic foil (Li metal or LixAl) with initial Li inventory (LiInv) is used as the anode in lithium-ion batteries, its metallurgical damage state in the presence of organic liquid electrolyte and cycling electrochemical potential is of great interest. While LixAl foil operates at a voltage that eliminates LiBCC dendrite, the state-of-health (SOH) of LixAl anode can still degrade quickly in full-cell cycling. To analyze the causes, we decompose SOH = SOHe × SOHi × LiInv, where SOHe is SOH of electronic percolation within the anode, SOHi is SOH of Li percolation from cathode to the anode interior, and LiInv is the amount of cyclable lithium in a full cell, all normalized such that 1 means perfectly healthy, and 0 means dead. Any of the three (SOHe, SOHi, LiInv) dropping to zero would mean death of the full cell. Considering the poor performance of pure Al foil due to rapid drop in LiInv, we employed a mechanical prelithiation (MP) method to make LiInv >1 initially. The chemomechanical shock from MP creates an ultrananocrystalline LiAl layer with grain size 10-30 nm on top of unreacted Al. We then monitor SOHe evolution of the anode foil by measuring the in-plane electronic conductance in situ. We find that small additions of Mn or Si into Al induce nanoprecipitates Zener pinning, and the resulting denser grain boundary (GB) network before MP significantly reduces foil porosity after MP, delays gross foil fracture, and improves SOHe in subsequent cycling. Microstructural analysis reveals that the refined grain size of foil before MP relieves stress and reduces the chance of forming electronically isolated dead grain cluster due to cracking and invasion of electrolyte and solid-electrolyte interphase (SEI). By maintaining good electronic percolation, binder-free LixAlMnSi anode demonstrates an order-of-magnitude more stable SOHe and better electrochemical cycling performance than LixAl anode.

Endothelial S1pr1 regulates pressure overload-induced cardiac remodelling through AKT-eNOS pathway.

Cardiac vascular microenvironment is crucial for cardiac remodelling during the process of heart failure. Sphingosine 1-phosphate (S1P) tightly regulates vascular homeostasis via its receptor, S1pr1. We therefore hypothesize that endothelial S1pr1 might be involved in pathological cardiac remodelling. In this study, heart failure was induced by transverse aortic constriction (TAC) operation. S1pr1 expression is significantly increased in microvascular endothelial cells (ECs) of post-TAC hearts. Endothelial-specific deletion of S1pr1 significantly aggravated cardiac dysfunction and deteriorated cardiac hypertrophy and fibrosis in myocardium. In vitro experiments demonstrated that S1P/S1pr1 praxis activated AKT/eNOS signalling pathway, leading to more production of nitric oxide (NO), which is an essential cardiac protective factor. Inhibition of AKT/eNOS pathway reversed the inhibitory effect of EC-S1pr1-overexpression on angiotensin II (AngII)-induced cardiomyocyte (CM) hypertrophy, as well as on TGF-ß-mediated cardiac fibroblast proliferation and transformation towards myofibroblasts. Finally, pharmacological activation of S1pr1 ameliorated TAC-induced cardiac hypertrophy and fibrosis, leading to an improvement in cardiac function. Together, our results suggest that EC-S1pr1 might prevent the development of pressure overload-induced heart failure via AKT/eNOS pathway, and thus pharmacological activation of S1pr1 or EC-targeting S1pr1-AKT-eNOS pathway could provide a future novel therapy to improve cardiac function during heart failure development.

Overexpression of ERBB4 rejuvenates aged mesenchymal stem cells and enhances angiogenesis via PI3K/AKT and MAPK/ERK pathways.

The age-related functional exhaustion limits potential efficacy of mesenchymal stem cells (MSC) in treating cardiovascular disease. Therefore, rejuvenation of aged MSC in the elderly population is of great interest. We have previously reported that Erb-B2 receptor tyrosine kinase 4 ( ERBB4) plays a critical role in regulating MSC survival under hypoxia. The aim of this study was to investigate whether ERBB4 rejuvenates aged MSC and how ERBB4 enhances therapeutic efficacy of aged MSC in treating myocardial infarction (MI). Compared with vector aged MSC (aged-MSC), ERBB4-engineered aged MSC (ER4-aged-MSC) conferred resistance to oxidative stress-induced cell death and ameliorated the senescent phenotype in vitro. Four weeks after MI, the ER4-aged-MSC group exhibited enhanced blood vessel density, reduced cardiac remodeling and apoptosis with improved heart function compared with the aged-MSC group. Overexpression of ERBB4 caused an increase in phosphorylated v-akt murine thymoma viral oncogene homolog 1 (AKT), and phosphorylated ERK expression under hypoxia. ER4-aged-MSC secreted higher levels of angiopoietin, epithelial neutrophil activating peptide 78, VEGF, and fibroblast growth factor 2, and enhanced tube formation in HUVEC. The impact of ERBB4 on protein expression, proangiogenesis, cell behavior, and cytokine secretion was abolished by inhibiting PI3K/AKT and MAPK/ERK signaling pathway.-Liang, X., Ding, Y., Lin, F., Zhang, Y., Zhou, X., Meng, Q., Lu, X., Jiang, G., Zhu, H., Chen, Y., Lian, Q., Fan, H., Liu, Z. Overexpression of ERBB4 rejuvenates aged mesenchymal stem cells and enhances angiogenesis via PI3K/AKT and MAPK/ERK pathways.

Effects of Probiotics on Patients with Hypertension: a Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: This meta-analysis and systematic review was conducted to evaluate the effect of probiotics on blood pressure, body mass index (BMI), and blood glucose changes in patients with hypertension. RECENT FINDINGS: We searched the PubMed, Cochrane, Embase, and ProQuest databases using a combination of MeSH and free text, from the inception of these databases to 20 January 2020, with no language restrictions. The quantitative PEDro scale method was used to assess the quality of the included studies. We used the random effects models to estimate the outcomes, with heterogeneity among the studies assessed using Cochran's Q statistic. Fourteen included studies published between 2002 and 2019 were included in the meta-analysis, reporting results of 846 hypertension participants. A significant reduction in SBP by - 2.05 mmHg (95% CI - 3.87, -0.24, P = 0.03), DBP by - 1.26 mmHg (95% CI - 2.51, - 0.004, P = 0.047), BMI by - 1.03 (95% CI - 1.28, - 0.97, P < 0.01), and blood glucose by - 0.18 mmol/L (95% CI - 0.30 - 0.05, P = 0.007) was observed following probiotics intervention. Our meta-analysis showed a modest but a significant reduction in SBP and DBP in patients with hypertension, particularly in those with diabetes mellitus, following probiotic supplementation. This effect was associated with treatment duration, dosage, and the age of subject but was not associated with single or multiple strains usage. Additionally, probiotic supplement had a beneficial effect in reducing BMI and blood glucose.

A comprehensive model of N2O emissions in an anaerobic/oxygen-limited aerobic process under dynamic conditions.

A comprehensive model for nitrous oxide (N2O) emissions in an anaerobic/oxygen-limited aerobic (A/OLA) process is proposed here. This paper includes the following main innovations: (i) adding the phosphorus-accumulating organism (XPAO) denitrification pathway to the contribution of N2O emissions; (ii) considering the biological removal of organic matter and phosphorus and predicting the effect of influent phosphorus concentration on N2O emissions via an increase in the influent phosphorus concentration; and (iii) determining the effect of XPAO on N2O production in a simultaneous nitrification, denitrification and phosphorus removal (SNDPR) system by sensitivity analysis. The results suggested that the simulated data matched the measured data well. The predominant pathways of N2O emissions in the process of A/OLA were the ammonium-oxidizing bacterium (XAOB) denitrification pathway and the heterotrophic bacterium (XH) denitrification pathway, while the incomplete hydroxylamine (NH2OH) oxidation pathway and the XPAO denitrification pathway contributed less to N2O emissions. The metabolic activity of XPAO had a significant effect on N2O emissions, and increasing the influent phosphorus concentration was beneficial for reducing the release of N2O. This study is expected to provide a meaningful reference for reducing N2O emissions in wastewater treatment engineering.

Interferon alpha treatment leads to a high rate of hepatitis B surface antigen seroconversion in Chinese children with chronic hepatitis B.

Chronic hepatitis B virus (HBV) infection (CHB) in children remains a public health challenge despite significant success in programme is established to prevent mother-to-child transmission. In particular, CHB in Chinese children are mostly acquired through vertical transmission, which differs from the common infection route reported in other countries and regions. This situation has resulted in a high endemic prevalence of CHB in Chinese adults. Thus, successful treatment of children with CHB will prevent the development of advanced liver diseases in late adulthood. However, there is still no consensus on the clinical guideline to treat paediatric CHB. In this study, we evaluated the potential of interferon alpha (IFNa) treatment for Chinese children with CHB. A total of 41 patients with CHB aged 3-17 years were enrolled in this retrospective study: 21 patients were treated with pegylated (PEG)-IFNa and 20 patients without treatment served as the control group. The rates of HBV DNA suppression, hepatitis B e antigen (HBeAg) clearance and hepatitis B surface antigen (HBsAg) clearance were significantly higher in the PEG-IFNa treatment group than in the control group (P < 0.05 at 48 weeks). Unexpectedly, PEG-IFNa treatment achieved a high rate of HBsAb production, far exceeding the clinical outcome in documented PEG-IFNa-treated CHB adults. Further analysis revealed that younger children (3-6 years old) were more responsive to PEG-IFNa treatment with respect to achieving a protective level of HBsAb in a short treatment cycle than adolescents (10-17 years old). Overall, these results indicate that the immune system of children might have a preserved PEG-IFNa-mediated mechanism to completely control HBV, which can help to design new strategies to treat CHB patients.

Efficacy and Safety of Peginterferon Alfa-2a (40KD) in Children With Chronic Hepatitis B: The PEG-B-ACTIVE Study.

Children with chronic hepatitis B (CHB) represent an area of unmet medical need, attributed to increased lifetime risk of CHB sequelae and limited therapeutic options compared with adult CHB patients. The PEG-B-ACTIVE (NCT01519960) phase III study evaluated peginterferon (PegIFN) alfa-2a treatment in children aged 3 to <18 years with CHB. A total of 161 hepatitis B e antigen (HBeAg)-positive immune-active patients without advanced fibrosis (AF)/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with AF were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area (BSA) category, based on 180 µg/1.73 m2 . HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in Group A (25.7% vs. 6%; P = 0.0043), as were the rates of hepatitis B surface antigen (HBsAg) clearance (8.9% vs. 0%; P = 0.03), hepatitis B virus (HBV) DNA <2,000 IU/mL (28.7% vs. 2.0%; P < 0.001) or undetectable (16.8% vs. 2.0%; P = 0.0069), and alanine aminotransferase (ALT) normalization (51.5% vs. 12%; P < 0.001). Safety, including incidence of ALT flares and neutropenia, was comparable to the established PegIFN alfa-2a profile in HBV-infected adults or hepatitis C virus-infected children. Changes in growth parameters were minimal during treatment and comparable to those in untreated patients. Safety and efficacy outcomes in Group C were in line with Group A. Conclusion: PegIFN alfa-2a treatment of children in the immune-active phase of CHB was efficacious and well tolerated, and associated with higher incidence of HBsAg clearance than in adults. This represents an important advance to the treatment options for children with CHB.