Fever of unknown origin (FUO) in children: a single-centre experience from Beijing, China.

OBJECTIVE: To date, there is no standard diagnostic practice to identify the underlying disease-causing mechanism for paediatric patients suffering from chronic fever without any specific diagnosis, which is one of the leading causes of death in paediatric patients. Therefore, we aimed this retrospective study to analyse medical records of paediatric patients with fever of unknown origin (FUO) to provide a preliminary basis for improving the diagnostic categories and facilitate the treatment outcomes. DESIGN: A retrospective study. SETTING: Beijing Children's Hospital. PARTICIPANTS: Clinical data were collected from 1288 children between 1 month and 18 years of age diagnosed with FUO at Beijing Children's Hospital between January 2010 and December 2017. INTERVENTIONS: According to the aetiological composition, age, duration of fever and laboratory examination results, the diagnostic strategies were analysed and formulated. PRIMARY AND SECONDARY OUTCOME MEASURES: The statistical analyses were carried out using SPSS V.24.0 platform along with the χ2 test and analysis of variance (p<0.05). RESULTS: The duration of fever ranged from 2 weeks to 2 years, with an average of 6 weeks. There were 656 cases (50.9%) of infectious diseases, 63 cases (4.9%) of non-infectious inflammatory diseases (NIIDs), 86 cases (6.7%) of neoplastic diseases, 343 cases (26.6%) caused by miscellaneous diseases and 140 cases (10.9%) were undiagnosed. With increasing age, the proportion of FUO from infectious diseases gradually decreased from 73.53% to 44.21%. NIID was more common in children over 3 years old, and neoplastic diseases mainly occurred from 1 to 6 years of age. Among miscellaneous diseases, the age distribution was mainly in school-aged children over 6 years. Respiratory tract infection was the most common cause of FUO in children, followed by bloodstream infections. Bacterial infection was the most common cause in children with less than 1 year old, while the virus was the main pathogen in children over 1 year old. CONCLUSIONS: The diagnosis of neoplastic diseases and miscellaneous diseases-related diseases still depends mainly on invasive examination. According to our clinical experience, the diagnostic process was formulated based on fever duration and the type of disease. This process can provide a guide for the diagnosis and treatment of paediatric FUO in the future.

Vagus nerve stimulation optimized cardiomyocyte phenotype, sarcomere organization and energy metabolism in infarcted heart through FoxO3A-VEGF signaling.

Vagus nerve stimulation (VNS) restores autonomic balance, suppresses inflammation action and minimizes cardiomyocyte injury. However, little knowledge is known about the VNS' role in cardiomyocyte phenotype, sarcomere organization, and energy metabolism of infarcted hearts. VNS in vivo and acetylcholine (ACh) in vitro optimized the levels of α/ß-MHC and α-Actinin positive sarcomere organization in cardiomyocytes while reducing F-actin assembly of cardiomyocytes. Consistently, ACh improved glucose uptake while decreasing lipid deposition in myocytes, correlating both with the increase of Glut4 and CPT1α and the decrease of PDK4 in infarcted hearts in vivo and myocytes in vitro, attributing to improvement in both glycolysis by VEGF-A and lipid uptake by VEGF-B in response to Ach. This led to increased ATP levels accompanied by the repaired mitochondrial function and the decreased oxygen consumption. Functionally, VNS improved the left ventricular performance. In contrast, ACh-m/nAChR inhibitor or knockdown of VEGF-A/B by shRNA powerfully abrogated these effects mediated by VNS. On mechanism, ACh decreased the levels of nuclear translocation of FoxO3A in myocytes due to phosphorylation of FoxO3A by activating AKT. FoxO3A overexpression or knockdown could reverse the specific effects of ACh on the expression of VEGF-A/B, α/ß-MHC, Glut4, and CPT1α, sarcomere organization, glucose uptake and ATP production. Taken together, VNS optimized cardiomyocytes sarcomere organization and energy metabolism to improve heart function of the infarcted heart during the process of delaying and/or blocking the switch from compensated hypertrophy to decompensated heart failure, which were associated with activation of both P13K/AKT-FoxO3A-VEGF-A/B signaling cascade.

S100B is required for maintaining an intermediate state with double-positive Sca-1+ progenitor and vascular smooth muscle cells during neointimal formation.

INTRODUCTION: Accumulation of vascular smooth muscle cells (VSMCs) within the neointimal region is a hallmark of atherosclerosis and vessel injury. Evidence has shown that Sca-1-positive (Sca-1+) progenitor cells residing in the vascular adventitia play a crucial role in VSMC assemblages and intimal lesions. However, the underlying mechanisms, especially in the circumstances of vascular injury, remain unknown. METHODS AND RESULTS: The neointimal formation model in rats was established by carotid artery balloon injury using a 2F-Forgaty catheter. Most Sca-1+ cells first appeared at the adventitia of the vascular wall. S100B expressions were highest within the adventitia on the first day after vessel injury. Along with the sequentially increasing trend of S100B expression in the intima, media, and adventitia, respectively, the numbers of Sca-1+ cells were prominently increased at the media or neointima during the time course of neointimal formation. Furthermore, the Sca-1+ cells were markedly increased in the tunica media on the third day of vessel injury, SDF-1α expressions were obviously increased, and SDF-1α levels and Sca-1+ cells were almost synchronously increased within the neointima on the seventh day of vessel injury. These effects could effectually be reversed by knockdown of S100B by shRNA, RAGE inhibitor (SPF-ZM1), or CXCR4 blocker (AMD3100), indicating that migration of Sca-1+ cells from the adventitia into the neointima was associated with S100B/RAGE and SDF-1α/CXCR4. More importantly, the intermediate state of double-positive Sca-1+ and α-SMA cells was first found in the neointima of injured arteries, which could be substantially abrogated by using shRNA for S100B or blockade of CXCR4. S100B dose-dependently regulated SDF-1α expressions in VSMCs by activating PI3K/AKT and NF-κB, which were markedly abolished by PI3K/AKT inhibitor wortmannin and enhanced by p65 blocker PDTC. Furthermore, S100B was involved in human umbilical cord-derived Sca-1+ progenitor cells' differentiation into VSMCs, especially in maintaining the intermediate state of double-positive Sca-1+ and α-SMA. CONCLUSIONS: S100B triggered neointimal formation in rat injured arteries by maintaining the intermediate state of double-positive Sca-1+ progenitor and VSMCs, which were associated with direct activation of RAGE by S100B and indirect induction of SDF-1α by activating PI3K/AKT and NF-κB.

A network meta-analysis protocol of adjuvant chemotherapy for unresectable patients with advanced gastric cancer.

BACKGROUND: The treatment methods about surgery, chemotherapy, and radiation therapy were recommended for gastric cancer (GC) patients by National Comprehensive Cancer Network (NCCN) guidelines. However, for the advanced gastric cancer patients or with metastatic lesions who have lost their chance of surgery, the current adjuvant chemotherapy treatments are still controversial. Therefore, this network meta-analysis is mainly to assess the relative efficacy of different adjuvant chemotherapy regimens for advanced gastric cancer (AGC). METHODS: In order to compare the relative efficacy among different adjuvant chemotherapy regimens for AGC patients, randomized controlled trials (RCTs) and non-RCTs were systematic searched in PubMed, Web of Science, Clinical Trials, Cochrane Library and Embase database. R-3.4.1 software will be used for data analysis. The risk of bias in RCTs and non-RCTs will be evaluated through the risk of bias tool from the Cochrane Handbook version 5.1.0 and non-randomized studies of interventions (ROBINS-I), respectively. RESULTS AND CONCLUSION: The results of this network meta-analysis will evaluate the relative effectiveness and rank the interventions among all chemotherapy methods for unresectable AGC patients, and provide more evidence-based guidance in clinical practice. PROTOCOL REGISTRATION NUMBER: CRD42018111835.

Lujinxingia litoralis gen. nov., sp. nov. and Lujinxingia sediminis sp. nov., two new representatives in the order Bradymonadales.

In this study, two bacterial strains designated B210T and SEH01T, isolated from coastal sediment sampled in Weihai, PR China, were characterized using a polyphasic approach. Strains were Gram-stain-negative, facultative anaerobic, rod-shaped and motile. According to the results of phylogenetic analyses based on their 16S rRNA genes, these two strains should be classified under the order Bradymonadales and they both show <90 % sequence similarities with Bradymonas sediminis FA350T. Moreover, strain B210T showed 98.6 % sequence similarity to strain SEH01T. Genomic characteristics including average nucleotide identity and in silico DNA-DNA hybridization values clearly separated strain B210T from strain SEH01T. The sole quinone of these two strains was menaquinone MK-7, and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified lipid. Iso-C15 : 0 was the major fatty acid in both strains B210T and SEH01T, and iso-C14 : 0 3-OH was also a major fatty acid for strain SEH01T. Based on the polyphasic analysis, these two strains represent two novel species of a new genus within the family Bradymonadaceae. Consequently, the novel genus Lujinxingia gen. nov. is proposed, containing two new species Lujinxingia litoralis gen. nov. sp. nov. and Lujinxingia sediminis sp. nov., with strain B210T (=KCTC 42951T=CGMCC 1.16770T) and strain SEH01T (=KCTC 42950T=DSM 101859T) as the type strains, respectively.

VEGF-A and VEGF-B Coordinate the Arteriogenesis to Repair the Infarcted Heart with Vagus Nerve Stimulation.

BACKGROUND/AIMS: Vagus nerve stimulation (VNS) suppresses arrhythmic activity and minimizes cardiomyocyte injury. However, how VNS affects angiogenesis/arteriogenesis in infarcted hearts, is poorly understood. METHODS: Myocardial infarction (MI) was achieved by ligation of the left anterior descending coronary artery (LAD) in rats. 7 days after LAD, stainless-steel wires were looped around the left and right vagal nerve in the neck for vagus nerve stimulation (VNS). The vagal nerve was stimulated with regular pulses of 0.2ms duration at 20 Hz for 10 seconds every minute for 4 hours, and then ACh levels by ELISA in cardiac tissue and serum were evaluated for its release after VNS. Three and 14 days after VNS, Real-time PCR, immunostaining and western blot were respectively used to determine VEGF-A/B expressions and α-SMA- and CD31-postive vessels in VNS-hearts with pretreatment of α7-nAChR blocker mecamylamine (10 mg/kg, ip) or mACh-R blocker atropine (10 mg/kg, ip) for 1 hour. The coronary function and left ventricular performance were analyzed by Langendorff system and hemodynamic parameters in VNS-hearts with pretreatment of VEGF-A/B-knockdown or VEGFR blocker AMG706. Coronary arterial endothelial cells proliferation, migration and tube formation were evaluated for angiogenesis following the stimulation of VNS in coronary arterial smooth muscle cells (VSMCs). RESULTS: VNS has been shown to stimulate VEGF-A and VEGF-B expressions in coronary arterial smooth muscle cells (VSMCs) and endothelial cells (ECs) with an increase of α-SMA- and CD31-postive vessel number in infarcted hearts. The VNS-induced VEGF-A/B expressions and angiogenesis were abolished by m-AChR inhibitor atropine and α7-nAChR blocker mecamylamine in vivo. Interestingly, knockdown of VEGF-A by shRNA mainly reduced VNS-mediated formation of CD31+ microvessels. In contrast, knockdown of VEGF-B powerfully abrogated VNS-induced formation of α-SMA+ vessels. Consistently, VNS-induced VEGF-A showed a greater effect on EC tube formation as compared to VNS-induced VEGF-B. Moreover, VEGF-A promoted EC proliferation and VSMC migration while VEGF-B induced VSMC proliferation and EC migration in vitro. Mechanistically, vagal neurotransmitter acetylcholine stimulated VEGF-A/B expressions through m/nACh-R/PI3K/Akt/Sp1 pathway in EC. Functionally, VNS improved the coronary function and left ventricular performance. However, blockade of VEGF receptor by antagonist AMG706 or knockdown of VEGF-A or VEGF-B by shRNA significantly diminished the beneficial effects of VNS on ventricular performance. CONCLUSION: VNS promoted angiogenesis/arteriogenesis to repair the infracted heart through the synergistic effects of VEGF-A and VEGF-B.

Risk factors for carbapenem-resistant K. pneumoniae bloodstream infection and predictors of mortality in Chinese paediatric patients.

BACKGROUND: Bloodstream infections (BSI) caused by carbapenem-resistant K. pneumoniae (CRKP) are associated with high rates of morbidity and mortality. Early identification of patients at highest risk is very important. The aim of this study was to describe the clinical characteristics and mortality of K. pneumoniae BSI and to identify risk factors associated with CRKP BSI among paediatric patients. METHODS: From January 2011 to December 2014, a retrospective case-control study was conducted at Beijing Children's Hospital, China. Risk factors for CRKP BSI and for K. pneumoniae BSI-related death were evaluated. Patients with BSI caused by K. pneumoniae were identified from the microbiology laboratory database. Data regarding demographic, microbiological and clinical characteristics, therapy and outcome were collected from the medical records. RESULTS: A total of 138 patients with K. pneumoniae BSI were enrolled, including 54 patients with CRKP BSI and 84 patients with carbapenem-susceptible K. pneumoniae (CSKP) BSI. Most of the BSI (114; 82.6%) were healthcare-associated, while the rest (24; 17.4%) were community-acquired. Hematologic malignancies (odds ratio (OR):4.712, [95% CI: 2.181-10.180], P <  0.001) and previous cephalosporin administration (OR: 3.427, [95% CI: 1.513-7.766], P = 0.003) were found to be associated with the development of CRKP BSI. 28-day mortality of K. pneumoniae BSI was 8.7%. Mechanical ventilation (OR:9.502, [95% CI: 2.098-43.033], P = 0.003), septic shock (OR:6.418, [95% CI: 1.342-30.686], P = 0.020), and isolation of CRKP (OR:9.171, [95% CI: 1.546-54.416], P = 0.015) were independent risk factors for 28-day mortality of K. pneumoniae BSI. CONCLUSION: Hematologic malignancies and previous cephalosporin administration were associated with the development of CRKP BSI, while mechanical ventilation, septic shock and CRKP infection were independent mortality predictors for K. pneumoniae BSI. More attention should be paid to CRKP BSI in the paediatric population.

Data on the involvement of Meox1 in balloon-injury-induced neointima formation of rats.

In the previous report, Meox1 was found to promote SMCs phenotypic modulation and injury-induced vascular remodeling by regulating the FAK-ERK1/2-autophagy signaling cascade (Wu et al., 2017) [1]. Here, we presented new original data on the involvement of Mesoderm/mesenchyme homeobox gene l (Meox1) in balloon-injury-induced neointima formation of rat. In rat carotid artery balloon injury model to induce vascular remodeling, Meox1 was induced in vascular smooth muscle cell (SMCs) of rat carotid arteries. Most proliferating cell nuclear antigen (PCNA)-positive cells also expressed Meox1. These data suggested that Meox1 may be involved in SMCs proliferation during injury-induced neointima formation. Furthermore, knocked down its expression in injured arteries by adenoviral delivery of Meox1 short hairpin RNA (shRNA) (shMeox1), neointima formation was significantly inhibited. Elastin staining also confirmed the reduction of neointima in Meox1 shRNA-transduced arteries. Moreover, knockdown of Meox1 decreased the collagen production/deposition that was significantly increased in neointima induced by balloon injury.

Bacillus marinisedimentorum sp. nov., isolated from marine sediment.

A novel Gram-stain-positive, motile and facultatively anaerobic strain, designated NC2-31T, was isolated from sediment from the coast of Weihai, PR China. Optimal growth occurred at 37 °C, pH 7.5 and with 2.0-3.0 % (w/v) NaCl. MK-7 was the major respiratory quinone. Meso-diaminopimelic acid was a diagnostic diamino acid in the peptidoglycan. The major polar lipids of NC2-31T were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). The genomic DNA G+C content of the strain was 46.3 mol%. The predominant cellular fatty acids (>10.0 %) of NC2-31T were iso-C15 : 0 (18.9 %), anteiso-C15 : 0 (15.8 %), summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH) (15.3 %) and iso-C16 : 0 (10.3 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that NC2-31T should be classified as representing a member of the genus Bacillus. Based on data from the current polyphasic study, NC2-31T represents a novel species within the genus Bacillus, for which the name Bacillusmarinisedimentorum sp. nov. is proposed with type strain NC2-31T (=KCTC 33721T=MCCC 1K01239T).

Rhodosalinus sediminis gen. nov., sp. nov., isolated from marine saltern.

A novel Gram-stain-negative, moderately halophilic, motile, facultatively anaerobic and rod-shaped strain, designated WDN1C137T, was isolated from a marine saltern at Wendeng, PR China. Optimal growth occurred at 40 °C, pH 7.5 and with 7.0 % (w/v) NaCl. Q-10 was the sole respiratory quinone. The major cellular fatty acids (>10.0 %) in WDN1C137T were C18 : 1ω7c (46.2 %), cyclo C19 : 0ω8c (18.7 %) and C16 : 0 (12.3 %). The major polar lipids were phosphatidylglycerol, phosphoglycolipid, phosphatidylcholine, one unidentified glycolipid, one unidentified lipid, one unidentified aminolipid and two unidentified phospholipids. The genomic DNA G+C content was 70.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that WDN1C137T shared the highest similarity (94.5 %) to Roseivivax jejudonensis KCTC 42110T, followed by Roseivivax halodurans JCM 10272T (94.2 %) and Roseivivax roseus DSM 23042T (94.1 %). WDN1C137T formed a separate branch from the closely related genera Roseivivax, Loktanella, Paracoccus and Cribrihabitans within the family Rhodobacteraceae, which indicated that it represented a novel genus in the phylogenetic tree. On the basis of the data from the current polyphasic study, the isolate is proposed to represent a novel species of a novel genus within the family Rhodobacteraceae, with the name Rhodosalinus sediminis gen. nov., sp. nov. The type strain of the type species is WDN1C137T (=KCTC 52478T=MCCC 1H00170T).

Lentibacillus sediminis sp. nov., isolated from a marine saltern.

A novel, Gram-stain-positive, moderately halophilic, endospore-forming, motile, facultatively anaerobic and rod-shaped strain, designated 0W14T, was isolated from a marine saltern of Wendeng, China. Optimal growth occurred at 37 °C, pH 7.5 and with 6.0 % (w/v) NaCl. MK-7 was the sole respiratory quinone and the peptidoglycan type of 0W14T was A4ßl-Orn-d-Glu. The major cellular fatty acid (>10.0 %) in strain 0W14T was anteiso-C15 : 0. The polar lipid profile of strain 0W14T consisted of diphosphatidylglycerol, phosphatidylglycerol, two unknown glycolipids and four unknown phospholipids. The genomic DNA G+C content of the strain was 44.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 0W14T forms a phylogenetic lineage with members of the genus Lentibacillus within the family Bacillaceae. Based on data from the current polyphasic study, the isolate is proposed to represent a novel species of genus Lentibacillus, for which the name Lentibacillus sediminis sp. nov. is proposed. The type strain is 0W14T (=KCTC 33835T=MCCC 1H00171T).

S100B promotes injury-induced vascular remodeling through modulating smooth muscle phenotype.

S100B is a biomarker of nervous system injury, but it is unknown if it is also involved in vascular injury. In the present study, we investigated S100B function in vascular remodeling following injury. Balloon injury in rat carotid artery progressively induced neointima formation while increasing S100B expression in both neointimal vascular smooth muscle (VSMC) and serum along with an induction of proliferating cell nuclear antigen (PCNA). Knockdown of S100B by its shRNA delivered by adenoviral transduction attenuated the PCNA expression and neointimal hyperplasia in vivo and suppressed PDGF-BB-induced VSMC proliferation and migration in vitro. Conversely, overexpression of S100B promoted VSMC proliferation and migration. Mechanistically, S100B altered VSMC phenotype by decreasing the contractile protein expression, which appeared to be mediated by NF-κB activity. S100B induced NF-κB-p65 gene transcription, protein expression and nuclear translocation. Blockade of NF-κB activity by its inhibitor reversed S100B-mediated downregulation of VSMC contractile protein and increase in VSMC proliferation and migration. It appeared that S100B regulated NF-κB expression through, at least partially, the Receptor for Advanced Glycation End products (RAGE) because RAGE inhibitor attenuated S100B-mediated NF-κB promoter activity as well as VSMC proliferation. Most importantly, S100B secreted from VSMC impaired endothelial tube formation in vitro, and knockdown of S100B promoted re-endothelialization of injury-denuded arteries in vivo. These data indicated that S100B is a novel regulator for vascular remodeling following injury and may serve as a potential biomarker for vascular damage or drug target for treating proliferative vascular diseases.

[Small intestinal cavernous hemangioma causing chronic hemorrhage: a case report].

Small intestinal hemangioma is a rare condition that can be divided histologically into capillary, cavernous or mixed types, among which the cavernous type is the most common. Here we report a case of small intestinal cavernous hemangioma with chronic hemorrhage in 44-year-old man. The patient complained of weakness and dizziness for 2 years that aggravated 1 month before admission accompanied by intermittent melena. Laboratory tests suggest severe anemia, and computed tomography, gastroscopy and colonoscopy all revealed signs of anemia. Capsule endoscopy detected small intestinal erosions, bleeding lesions and prominent neoplasms. An exploratory laparotomy was performed, in which the segment of the jejunum with lesions was resected. Pathological examination of the resected jejunum identified the neoplasm as cavernous hemangioma of the small intestine, which was the cause of severe anemia.

Duodenal Bulb Adenocarcinoma Benefitted from Neoadjuvant Chemotherapy: A Case Report.

Duodenal bulb adenocarcinoma is an extremely rare malignancy in the alimentary tract which has a low incidence rate and nonspecific symptoms. It is difficult to diagnose early, and the misdiagnosis rate is high. CT, MRI, upper gastrointestinal endoscopy, and other advanced imaging modalities should be combined to make a comprehensive evaluation. The diagnostic confirmation of this tumor type mainly depends on the pathological examination. The combination of surgery with other treatment modalities is effective. A review of reports on duodenal bulb adenocarcinoma with chemotherapy revealed 6 cases since 1990. However, there are few reports on neoadjuvant chemotherapy for the disease. In this report, preoperative S-1 in combination with oxaliplatin neoadjuvant chemotherapy achieved a complete pathological response in the treatment of duodenal bulb adenocarcinoma. Neoadjuvant chemotherapy shows a better clinical efficacy in the treatment of duodenal bulb adenocarcinoma, but its value needs to be further verified.

Characteristics and outcomes of cryptococcal meningitis in HIV seronegative children in Beijing, China, 2002-2013.

BACKGROUND: Data regarding HIV-seronegative pediatric patients with cryptococcal meningitis (CM) have been very limited. METHODS: We retrospectively reviewed non-HIV-infected in patients with CM from January 2002 through December 2013 in Beijing Children's Hospital. Records of the all patients were obtained and compared. RESULTS: The 34 children had a median age of 5.6 years. Most of the patients were male (67.6 %). Only 23.5 % of the cases had identifiable underlying diseases. The sensitivity of the CSF cryptococcal antigen, India ink smear and CSF culture in our study were 81.5, 85.3 and 82.4 %, respectively. And the sensitivity of combinations of these tests was 91.2 %. Out of the 34 patients, 16 (47.1 %) had other organs involvement in addition to the brain. The main abnormal features via magnetic resonance imaging (MRI) were Virchow-Robin space dilatation (44.4 %), hydrocephalus (38.9 %), gelatinous pseudocysts (33.3 %), brain atrophy (33.3 %), meningeal enhancement (27.8 %) and local lesions (27.8 %). In total, 64.7 % of the patients were successfully treated at discharge, whereas treatment failed in 35.3 % of the patients. CONCLUSIONS: Cryptococcal meningitis is an infrequent disease with a high fatality rate in children in China. The majority of patients were apparently healthy. Clinicians should consider cryptococcal infection as a potential pathogen of pediatric meningitis. Cryptococcal antigen, India ink smear and culture tests are recommended for diagnosis.

Wenzhouxiangella sediminis sp. nov., isolated from coastal sediment.

A novel Gram-stain-negative, non-spore-forming, non-motile, facultatively anaerobic, rod-shaped strain, designated XDB06T, was isolated from coastal sediment of Xiaoshi Island, Weihai, China. Optimal growth occurred at 37 °C, pH 7.5 and with 4.0 % (w/v) NaCl. Q-8 was the sole respiratory quinone. The major cellular fatty acids in strain XDB06T were iso-C15 : 0 and iso-C16 : 0. The polar lipids of strain XDB06T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified glycolipids and four unidentified phospholipids. The genomic DNA G+C content of the strain was 65.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain XDB06T clusters within the genus Wenzhouxiangella and is most closely related to Wenzhouxiangella. marina MCCC 1K00261T, with a 16S rRNA gene sequence similarity of 96.50 %. Based on data from the current polyphasic study, strain XDB06T represents a novel species of the genus Wenzhouxiangella, for which the name Wenzhouxiangella sediminis sp. nov. is proposed. The type strain is XDB06T (=KCTC 52041T=MCCC 1K02285T).

Marinicrinis sediminis gen. nov., sp. nov., isolated from marine sediment.

Novel Gram-stain-variable, bent rods or long filaments that were endospore-forming, facultatively anaerobic, oxidase- and catalase-negative, and designated strain NC2-42T, were isolated from sediment on the coast of Weihai, China. Optimal growth occurred at 37 °C, pH 7.5 and with 2-3 % (w/v) NaCl. MK-7 was the sole respiratory quinone and meso-diaminopimelic acid was a diagnostic diamino acid in the peptidoglycan. The polar lipid profile of this novel isolate consisted of phosphatidylglycerol, phosphatidylethanolamine, an unknown phospholipid, an unknown phosphoaminolipid, two unknown glycolipids and an unknown lipid. The major cellular fatty acids in strain NC2-42T were anteiso-C15 : 0, iso-C16 : 0 and C16 : 0. The G+C content of the genomic DNA of strain NC2-42T was 58.11 mol% (HPLC). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain NC2-42T showed the highest similarity (92.32 %) to Paenibacillus profundus within the family Paenibacillaceae. Based on data from this taxonomic study using a polyphasic approach, the isolate is proposed to represent a novel species of a new genus within the family Paenibacillaceae, with the name Marinicrinis sediminis gen. nov., sp. nov. The type strain of the type species is NC2-42T (=KCTC 33676T=MCCC 1K01238T).

Marinagarivorans algicola gen. nov., sp. nov., isolated from marine algae.

Two novel agar-degrading, Gram-stain-negative, motile, heterotrophic, facultatively anaerobic and pale yellow-pigmented bacterial strains, designated Z1T and JL1, were isolated from marine algae Gelidium amansii (Lamouroux) and Gracilaria verrucosa, respectively. Growth of the isolates was optimal at 28-30 °C, pH 7.0-7.5 and with 2-3 % (w/v) NaCl. Both strains contained Q-8 as the sole respiratory quinone. The major cellular fatty acids in strain Z1T were C18 : 1ω7c, C16 : 0 and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH). The predominant polar lipids in strain Z1T were phosphatidylethanolamine, phosphatidylglycerol and an aminolipid. The genomic DNA G+C content of both strains was 45.1 mol%. Strains Z1T and JL1 were closely related, with 99.9 % 16S rRNA gene sequence similarity. The average nucleotide identity (ANI) value between strains Z1T and JL1 was 99.3 %. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains Z1T and JL1 form a distinct phyletic line within the class Gammaproteobacteria, with less than 92.3 % similarity to their closest relatives. Based on data from the current polyphasic study, the isolates are proposed to belong to a novel species of a new genus designated Marinagarivorans algicola gen. nov., sp. nov. The type strain of the type species is Z1T ( = ATCC BAA-2617T = CICC 10859T).

PEP-1-SOD1 fusion proteins block cardiac myofibroblast activation and angiotensin II-induced collagen production.

BACKGROUND: Oxidative stress is closely associated with cardiac fibrosis. However, the effect of copper, zinc-superoxide dismutase (SOD1) as a therapeutic agent is limited due to the insufficient transduction. This study was aimed to investigate the effect of PEP-1-SOD1 fusion protein on angiotensin II (ANG II)-induced collagen metabolism in rat cardiac myofibroblasts (MCFs). METHODS: MCFs were pretreated with SOD1 or PEP-1-SOD1 fusion protein for 2 h followed by incubation with ANG II for 24 h. Cell proliferation was measured by Cell Counting Kit-8. Superoxide anion productions were detected by both fluorescent microscopy and Flow Cytometry. MMP-1 and TIMP-1 were determined by ELISA. Intracellular MDA content and SOD activity were examined by commercial assay kits. Protein expression was analyzed by western blotting. RESULTS: PEP-1-SOD1 fusion protein efficiently transduced into MCF, scavenged intracellular O2 (-), decreased intracellular MDA content, increased SOD activity, suppressed ANG II-induced proliferation, reduced expression of TGF-ß1, α-SMA, collagen type I and III, restored MMP-1 secretion, and attenuated TIMP-1 secretion. CONCLUSION: PEP-1-SOD1 suppressed MCF proliferation and differentiation and reduced production of collagen type I and III. Therefore, PEP-1-SOD1 fusion protein may be a potential novel therapeutic agent for cardiac fibrosis.

4-Hydroxynonenal promotes growth and angiogenesis of breast cancer cells through HIF-1α stabilization.

4-Hydroxynonenal (4-HNE) is a stable end product of lipid peroxidation, which has been shown to play an important role in cell signal transduction, while increasing cell growth and differentiation. 4-HNE could inhibit phosphatase and tensin homolog (PTEN) activity in hepatocytes and increased levels have been found in human invasive breast cancer. Here we report that 4-HNE increased the cell growth of breast cancer cells as revealed by colony formation assay. Moreover, vascular endothelial growth factor (VEGF) expression was elevated, while protein levels of hypoxia inducible factor 1 alpha (HIF-1α) were up-regulated. Sirtuin-3 (SIRT3), a major mitochondria NAD+-dependent deacetylase, is reported to destabilize HIF-1α. Here, 4-HNE could inhibit the deacetylase activity of SIRT3 by thiol-specific modification. We further demonstrated that the regulation by 4-HNE of levels of HIF-1α and VEGF depends on SIRT3. Consistent with this, 4-HNE could not increase the cell growth in SIRT3 knockdown breast cancer cells. Additionally, 4-HNE promoted angiogenesis and invasion of breast cancer cells in a SIRT3-dependent manner. In conclusion, we propose that 4-HNE promotes growth, invasion and angiogenesis of breast cancer cells through the SIRT3-HIF-1α-VEGF axis.