Pangenome analysis of the genus Herbiconiux and proposal of four new species associated with Chinese medicinal plants.

Five Gram-stain-positive, aerobic, non-motile actinobacterial strains designated as CPCC 205763T, CPCC 203386T, CPCC 205716T, CPCC 203406T, and CPCC 203407 were obtained from different ecosystems associated with four kinds of Chinese traditional medicinal plants. The 16S rRNA gene sequences of these five strains showed closely related to members of the genus Herbiconiux of the family Microbacteriaceae, with the highest similarities of 97.4-99.7% to the four validly named species of Herbiconiux. In the phylogenetic trees based on 16S rRNA gene sequences and the core genome, these isolates clustered into the clade of the genus Herbiconiux within the lineage of the family Microbacteriaceae. The overall genome relatedness indexes (values of ANI and dDDH) and the phenotypic properties (morphological, physiological and chemotaxonomic characteristics) of these isolates, readily supported to affiliate them to the genus Herbiconiux, representing four novel species, with the isolates CPCC 203406T and CPCC 203407 being classified in the same species. For which the names Herbiconiux aconitum sp. nov. (type strain CPCC 205763T = I19A-01430T = CGMCC 1.60067T), Herbiconiux daphne sp. nov. (type strain CPCC 203386T = I10A-01569T = DSM 24546T = KCTC 19839T), Herbiconiux gentiana sp. nov. (type strain CPCC 205716T = I21A-01427T = CGMCC 1.60064T), and Herbiconiux oxytropis sp. nov. (type strain CPCC 203406T = I10A-02268T = DSM 24549T = KCTC 19840T) were proposed, respectively. In the genomes of these five strains, the putative encoding genes for amidase, endoglucanase, phosphatase, and superoxidative dismutase were retrieved, which were classified as biosynthetic genes/gene-clusters regarding plant growth-promotion (PGP) functions. The positive results from IAA-producing, cellulose-degrading and anti-oxidation experiments further approved their potential PGP bio-functions. Pangenome analysis of the genus Herbiconiux supported the polyphasic taxonomy results and confirmed their bio-function potential.

NOX2 and NOX5 are increased in cardiac microvascular endothelium of deceased COVID-19 patients.

BACKGROUND: Cardiac injury and inflammation are common findings in COVID-19 patients. Autopsy studies have revealed cardiac microvascular endothelial damage and thrombosis in COVID-19 patients, indicative of microvascular dysfunction in which reactive oxygen species (ROS) may play a role. We explored whether the ROS producing proteins NOX2, NOX4 and NOX5 are involved in COVID-19-induced cardio-microvascular endothelial dysfunction. METHODS: Heart tissue were taken from the left (LV) and right (RV) ventricle of COVID-19 patients (n = 15) and the LV of controls (n = 14) at autopsy. The NOX2-, NOX4-, NOX5- and Nitrotyrosine (NT)-positive intramyocardial blood vessels fractions were quantitatively analyzed using immunohistochemistry. RESULTS: The LV NOX2+, NOX5+ and NT+ blood vessels fractions in COVID-19 patients were significantly higher than in controls. The fraction of NOX4+ blood vessels in COVID-19 patients was comparable with controls. In COVID-19 patients, the fractions of NOX2+, NOX5+ and NT+ vessels did not differ significantly between the LV and RV, and correlated positively between LV and RV in case of NOX5 (r = 0.710; p = 0.006). A negative correlation between NOX5 and NOX2 (r = -0.591; p = 0.029) and between NOX5 and disease time (r = -0.576; p = 0.034) was noted in the LV of COVID-19 patients. CONCLUSION: We show the induction of NOX2 and NOX5 in the cardiac microvascular endothelium in COVID-19 patients, which may contribute to the previously observed cardio-microvascular dysfunction in COVID-19 patients. The exact roles of these NOXes in pathogenesis of COVID-19 however remain to be elucidated.

Corrigendum: Pangenome analysis of the genus Herbiconiux and proposal of four new species associated with Chinese medicinal plants.

[This corrects the article DOI: 10.3389/fmicb.2023.1119226.].

Shinella lacus sp. nov., a novel microcystin-degrading alphaproteobacterium containing the bla carbapenemase gene.

A Gram-stain-negative, rod-shaped, microcystin-degrading bacterium, designated as CPCC 100929T, was isolated from a fresh water reservoir in Sichuan Province, PR China. This isolate grew well at 4-37 °C and pH 6.0-8.0, with optimal growth at 28-32 °C and pH 7.0, respectively. The major cellular fatty acids were C18:1 ω7c/C18:1 ω6c, C16:0, C18:1 ω7c 11-methyl and C19:0 cyclo ω8c. The predominant respiratory quinone was Q-10. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine and phosphatidylcholine were detected in the polar lipids extraction. The 16S rRNA gene sequence of strain CPCC 100929T was closely related to those of members of the genus Shinella, with the highest similarity of 98.6 % to Shinella zoogloeoides DSM 287T and 97.4-98.4 % with other identified Shinella members. In the phylogenetic trees based on 16S rRNA gene sequences and the core-genes analysis, strain CPCC 100929T was included within the clade of the genus Shinella. The values of average nucleotide identity (81.4-86.7 %) and digital DNA-DNA hybridization (25.4-44.6 %) between strain CPCC 100929T and other Shinella species were all below the thresholds for bacterial species delineation, respectively. The genomic DNA G+C content of strain CPCC 100929T was 63.6 %. The genomic sequence analysis indicated that this species contained genes encoding peroxidase, bla carbapenemase and the key enzyme for microcystin bio degradation, as well as rich carbohydrate-active enzyme coding genes, which might endow the micro-organism with properties to adapt to diverse environments. Based on its phenotypic and genetic properties, we propose that strain CPCC 100929T (=T1A350T=KCTC 72957T) is the type strain of a novel species with the name Shinella lacus sp. nov.

Characterization of three Stenotrophomonas strains isolated from different ecosystems and proposal of Stenotrophomonas mori sp. nov. and Stenotrophomonas lacuserhaii sp. nov.

Stenotrophomonas spp. have primarily been reported as non-pathogenic, plant-probiotic bacteria, despite the presence of some opportunistic human pathogens in the genus. Here, three Gram-stain negative, rod-shaped, non-spore-forming bacteria, designated as strains CPCC 101365T, CPCC 101269T, and CPCC 101426 were isolated from surface-sterilized medicinal plant roots of a mulberry plant in Chuxiong of the Yunnan Province, freshwater from Erhai Lake in the Yunnan Province, and sandy soils in the Badain Jaran desert in Inner Mongolia Autonomous Region, China, respectively. The 16S rRNA gene sequences analysis of these isolates in comparison with sequences from the GenBank database indicated that they belong to the genus Stenotrophomonas, with nucleotide similarities of 96.52-99.92% to identified Stenotrophomonas members. Phylogenetic analysis based on 16S rRNA gene and genome sequences confirmed that the isolates are members of the genus Stenotrophomonas. Values for genomic average nucleotide identity (ANI; <95%) and digital DNA-DNA hybridization (dDDH; < 70%) indicated that strains CPCC 101365T and CPCC 101269T were well-differentiated from validly described Stenotrophomonas species, while strain CPCC 101426 shared high ANI (97.7%) and dDDH (78.3%) identity with its closest phylogenetic neighbor, Stenotrophomonas koreensis JCM 13256T. The three genomes were approximately 3.1-4.0 Mbp in size and their G + C content ranged in 66.2-70.2%, with values slightly differing between CPCC 101365T (3.4 Mbp; 70.2%), CPCC 101269T (4.0 Mbp; 66.4%), and CPCC 101426 (3.1 Mbp; 66.2%). Genes encoding enzymes involved in the biosynthesis of indole-3-acetic acid (IAA) and siderophores were identified in the genomes of the three isolates, suggesting that these strains might serve roles as plant-growth promoting microorganisms. The polar lipid fractions of the three isolates primarily comprised diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE). The predominant cellular fatty acid was iso-C15: 0, with moderate amounts of antesio-C15: 0, iso-C11: 0, iso C17: 1 É·9c/C16: 0 10-methyl, iso-C14: 0, and C16: 1 É·7c/C16: 1 É·6c. These results indicated that polyphasic characteristics of strains CPCC 101365T and CPCC 101269T differed from other identified Stenotrophomonas species and that strain CPCC 101426 was affiliated with the species Stenotrophomonas koreensis. Accordingly, two novel species of the genus Stenotrophomonas were consequently proposed, corresponding to Stenotrophomonas mori sp. nov. (type strain CPCC 101365T = DY006T = KCTC 82900T) and Stenotrophomonas lacuserhaii sp. nov. (type strain CPCC 101269T = K32T = KCTC 82901T). Highlights: Members of the genus Stenotrophomonas, and particularly Stenotrophomonas maltophilia, are opportunistic human pathogens, but not enough research has evaluated the identification of environmental Stenotrophomonas spp. However, most Stenotrophomonas spp. serves as plant-probiotic bacteria.In this study, we obtained and characterized three Stenotrophomonas strains from different ecosystems. Based on phenotypic differences, chemotaxonomic properties, ANI and dDDH identity values, and phylogenetic analyses, two novel Stenotrophomonas species are proposed for the strains identified here. The encoding genes related to plant-growth promotion in the genomes of the newly recovered Stenotrophomonas spp. were retrieved. Follow-on experiments confirmed that these strains produced the important plant hormone IAA. Thus, these Stenotrophomonas spp. could considerably contribute to shaping and maintaining ecological stability in plant-associated environments, particularly while acting as plant-probiotic microorganisms.

Properties of Modestobacter deserti sp. nov., a Kind of Novel Phosphate-Solubilizing Actinobacteria Inhabited in the Desert Biological Soil Crusts.

Three Gram-stain-positive, aerobic, motile actinobacterial strains designated as CPCC 205119T, CPCC 205215, and CPCC 205251 were isolated from different biological soil crust samples collected from Tengger Desert, China. The 16S rRNA gene sequence comparison of these three strains showed they had almost identical 16S rRNA genes, which were closely related to members of the family Geodermatophilaceae, with the highest similarities of 96.3-97.3% to the species of Modestobacter. In the phylogenetic tree based on 16S rRNA gene sequences, these isolates clustered into a subclade next to the branch containing the species of Modestobacter lapidis and Modestobacter multiseptatus, within the lineage of the genus Modestobacter. The comparative genomic characteristics (values of ANI, dDDH, AAI, and POCP) and the phenotypic properties (morphological, physiological, and chemotaxonomic characteristics) of these isolates readily supported to affiliate them to the genus Modestobacter as a single separate species. For which, we proposed that the isolates CPCC 205119T, CPCC 205215, and CPCC 205251 represent a novel species of the genus Modestobacter as Modestobacter deserti sp. nov. CPCC 205119T (=I12A-02624=NBRC 113528T=KCTC 49201T) is the type strain. The genome of strain CPCC 205119T consisted of one chromosome (4,843,235bp) containing 4,424 coding genes, 48 tRNA genes, five rRNA genes, three other ncRNA genes, and 101 pseudogenes, with G+C content of 74.7%. The whole-genome sequences analysis indicated that this species contained alkaline phosphatase genes (phoA/phoD), phosphate transport-related genes (phoU, phnC, phnD, phnE, phoB, phoH, phoP, phoR, pitH, ppk, pstA, pstB, pstC, and pstS), trehalose-phosphate synthase gene (otsA), trehalose 6-phosphate phosphatase gene (otsB) and other encoding genes for the properties that help the microorganisms to adapt to harsh environmental conditions prevalent in deserts. Strains of this species could solubilize tricalcium phosphate [Ca3(PO4)2] and phytin, assimilate pyrophosphate, thiophosphate, dithiophosphate, phosphoenol pyruvate, 2-deoxy-d-glucose-6-phosphate, and cysteamine-S-phosphate.

Increased expression of LCN2 formed a positive feedback loop with activation of the ERK pathway in human kidney cells during kidney stone formation.

Kidney stones are a common threat to the health of elderly patients with a high incidence of disease. However, the specific molecular mechanism of the formation of kidney stones has not been elucidated. Here, we combined signalling molecules with signalling pathways in a double positive circulation regulation model. In addition, we found that LCN2 plays a role in promoting kidney stones through regulation of the ERK signalling pathway and expression of other kidney stone-related genes. LCN2 expression was upregulated upon oxalate stimulation. P-ERK1/2 inhibition by U0126 in kidney epithelial cells resulted in decreased expression of LCN2. Furthermore, the upregulation of LCN2 not only depended on the activation of the ERK signalling pathway but also regulated the activation of the ERK signalling pathway. Importantly, upregulation of LCN2 not only caused kidney epithelial cell damage but also promoted the expression of other kidney stone-related genes. Our findings improved the understanding of LCN2 and might lead to the development of new therapeutic and prognostic markers for kidney stones.

Oncogenic Long Noncoding RNA DARS-AS1 in Childhood Acute Myeloid Leukemia by Binding to microRNA-425.

OBJECTIVE: Acute myeloid leukemia (AML) represents a hematological cancer. The aim of the investigation was to probe the regulatory relevance of long non-coding RNA (lncRNA) aspartyl-tRNA synthetase anti-sense 1 (DARS-AS1)/microRNA-425 (miR-425)/transforming growth factor-beta 1 (TGFB1) to the development of AML. METHODS: The DARS-AS1 expression in bone marrow tissues was first analyzed in healthy subjects and AML patients. Subsequently, AML cell lines with DARS-AS1 knockdown were constructed, followed by cell proliferation and apoptosis assays. Afterward, downstream miRNA of DARS-AS1 and target mRNA of the miRNA were analyzed by bioinformatics, and their binding relationships were verified. Functional rescue experiments were then implemented. Finally, activation of the Smad2/3 signaling in MV4-11 and BF-24 cells were detected by western blot. RESULTS: DARS-AS1 was overexpressed in bone marrow tissues of AML patients and cells, and DARS-AS1 knockdown suppressed the proliferation of AML cells and induced apoptosis. DARS-AS1 bound to and negatively correlated with miR-425. Further results suggested that TGFB1 might be a target gene of miR-425 and could promote Smad2/3 phosphorylation and nuclear translocation. Finally, DARS-AS1 depletion could diminish the tumor volume in vivo. CONCLUSION: All in all, we highlighted here that DARS-AS1 enhanced the expression of TGFB1 through binding to miR-425 to modulate AML progression via the Smad2/3 pathway, which might perform as a therapeutic target for AML.

Lethal Effect of Total Dissolved Gas-Supersaturated Water with Suspended Sediment on River Sturgeon (Acipenser dabryanus).

High total dissolved gas (TDG) levels and excessive suspended sediment (SS) concentrations pose serious threats to fish survival during flood season. However, little information is available on the effects of TDG supersaturation with varying SS concentrations on fish. In this study, laboratory experiments were performed to investigate the effects of TDG supersaturation with varying SS concentrations on five-month-old river sturgeons (Acipenser dabryanus). The test fish were exposed to combinations of SS concentrations (0, 200, 600 and 1,000 mg/L) and TDG levels (125, 130, 135 and 140%), and their mortality and median lethal time (LT50) were quantified. The fish showed abnormal behaviors (e.g., quick breathing, fast swimming and an agitated escape response) and symptoms of gas bubble disease (GBD). SS increased the mortality of river sturgeon exposed to TDG supersaturation. Furthermore, the LT50 values at 125% TDG were 4.47, 3.11, 3.07 and 2.68 h for the different SS concentrations (0, 200, 600 and 1,000 mg/L, respectively), representing a significant decrease in LT50 with increasing SS. However, at higher TDG levels (130-140%), there was no significant increase in LT50 with increasing SS. Therefore, river sturgeon showed weak tolerance of TDG-supersaturated water with SS.

Investigation into the expression levels of MAGEA6 in esophageal squamous cell carcinoma and esophageal adenocarcinoma tissues.

Esophageal carcinoma (EC) is the sixth most deadly of all cancers. It is among the most malignant cancers due to its highly aggressive nature and low survival rate. The incidence of EC is high in Asia, particularly in Southern areas including China, Iran and Japan. There is a large body of evidence to suggest an association between the melanoma antigen gene (MAGE) family and the initiation of cancer; however, there is no clear evidence to suggest an association between EC and MAGE. Discovery of the chemical and physiological processes relevant to the occurrence of EC is vital for clinicians to diagnose and treat this highly aggressive cancer. The present study focused on the association of EC with the expression of MAGE family member A6 (MAGEA6) at the mRNA and protein levels using gene chip, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. The expression of MAGEA6 in human esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) tissue samples were compared with those in paracancerous tissue. The result of the gene chip assay revealed that as the generation grew, there was a significant increase in MAGEA6 transcription in the esophageal epithelial cell line, SHEE Different ESC cell lines also exhibited a significantly higher transcription of MAGEA6 compared with the HaCaT cell line, as determined via reverse transcription-quantitative PCR. An higher positive rate of MAGEA6 expression in ESCC and EAC tissues was also revealed when compared with paracancerous tissues, as determined via immunohistochemistry. The results indicated that MAGEA6 is highly transcribed and expressed in the development of EC and may therefore serve as a novel biomarker for the diagnosis or treatment of EC.

Allorhizocola rhizosphaerae gen. nov., sp. nov., a new member of Micromonosporaceae isolated from rhizosphere soil of the plant Calligonum mongolicum.

The taxonomic position of an actinobacterium, designated CPCC 204380T, which was isolated from a rhizosphere soil sample of the plant Calligonum mongolicum collected from Xinjiang Province, China, was established using a polyphasic approach. Vegetative hyphae developed well and globose bodies formed from aged hyphae. Spore chains that differentiated from the vegetative hyphae contained non-motile rod-shaped spores. The peptidoglycan contained meso-diaminopimelic acid and 3-hydroxydiaminopimelic acid as the diagnostic amino acids. The acyl type of the peptidoglycan was glycolyl. Glucose, mannose, ribose and xylose were detected in whole-cell hydrolysates. The predominant menaquinone was MK-10(H8), followed by MK-10(H6) and MK-10(H4). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major fatty acids were iso-C15 : 0, iso-C16 : 0 and C17 : 1ω9c. The genomic G+C content was 64.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CPCC 204380T should be placed in the family Micromonosporaceae, in which it formed a distinct lineage next to the genera Rhizocola, Catellatospora, Catelliglobosispora, Hamadaea and Allocatelliglobosispora. It shared the highest 16S rRNA gene sequence similarities with Rhizocola hellebori K12-0602T (96.1 %), Catellatospora chokoriensis 2-25/1T (95.9 %), Catelliglobosispora koreensis DSM 44566T (95.9 %), Hamadaea tsunoensis DSM 44101T (95.3 %) and Allocatelliglobosispora scoriae Sco-B14 T (94.2 %), and less than 94.0 % sequence similarity with other validly described species. The combination of phylogenetic analysis and phenotypic characteristics supported the proposal of strain CPCC 204380T as representing a novel species of a new genus in the family Micromonosporaceae, for which the name Allorhizocola rhizosphaerae gen. nov., sp. nov. is proposed. CPCC 204380T (=DSM 102292T=KCTC 39746 T) is the type strain of the type species.

Simplicispira lacusdiani sp. nov., a novel betaproteobacterium isolated from a freshwater reservoir.

A Gram-stain-negative, motile, rod-shaped bacterium, designated CPCC 100842T, was isolated from a freshwater reservoir in south-west China. The 16S rRNA gene sequence comparison of strain CPCC 100842T with the available sequences in the GenBank database showed that the isolate was closely related to members of the family Comamonadaceae, with the highest similarities to Simplicispira metamorpha DSM 1837T (98.05 %), Simplicispira limi KCTC 12608T (97.86 %), Simplicispira psychrophila LMG 5408T (97.04 %) and Simplicispira piscis JCM 19291T (97.0 %). In the phylogenetic tree based on 16S rRNA gene sequences, strain CPCC 100842T formed a distinct phylogenetic subclade within the genus Simplicispira. The major cellular fatty acids were as C16 : 0 and summed feature 3 (C16 : 1 ω7c/C16 : 1ω6c). Q-8 was detected as the only respiratory quinone. Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, aminophospholipid and glycolipid were found in the polar lipid extraction. The genomic DNA G+C content was 67.4 mol%. The average nucleotide identity value was 80.4 % by comparing the draft genome sequences of strain CPCC 100842T and S. metamorpha DSM 1837T. The DNA-DNA hybridization result between strain CPCC 100842T and S. metamorpha DSM 1837T showed 37±3 % genomic relatedness. On the basis of the genotypic analysis and phenotypic characteristics, we propose that strain CPCC 100842T represents a novel species of the genus Simplicispira in the family Comamonadaceae with the name Simplicispira lacusdiani sp. nov. Strain CPCC 100842T (=KCTC 52093T=DSM 102231T) is the type strain of the species.

Polyplex Micelle with pH-Responsive PEG Detachment and Functional Tetraphenylene Incorporation to Promote Systemic Gene Expression.

Tetraphenylene (TPE), characterized as a lipophilic and aggregation-induced-emissive fluorophore, was used to incorporate into an electrostatic self-assembled polyethylenimine-poly(ethylene glycol) (PEI-PEG)/plasmid DNA (pDNA) complexed micelle. The hydrophobic character of TPE appeared to drive a higher degree of condensation of the pDNA payload, which consequently resulted in not only strengthened colloidal stability of the constructed polyplex micelle but also improved biocompatibility by virtue of the elevated PEG crowdedness owing to the TPE-induced collapse of pDNA. These beneficial consequences potentially permitted a larger number of polyplex micelles to be internalized into the cells. PEG segments were designed to enable selective detachment from polyplex micelles in acidic milieu, e.g., the tumor microenvironment, and intracellular endosome compartment, based on the strategic arrangement of acid-responsive cleavable linkage between PEG and PEI. Upon PEG detachment, the exposure of cationic PEI/TPE polyplex was allowed to directly interact with the cell membrane, endosome membrane, and charged intracellular species, thus promoting cell internalization, endosome escape, and the release of the pDNA payload. Of note, this association of cationic PEI/TPE polyplex with the endosomal membrane could be further facilitated with the aid of lipophilic TPE, thereby eliciting pronounced destabilization potency to the endosome membrane and exerting an endosomal escape function. Eventually, the proposed system of these facile strategies, including responsive PEG detachment and functional TPE incorporation, was proven to provide efficient gene expression in the targeted tumors with an appreciable safety profile via systemic administration.

Near-Infrared Triggered Upconversion Polymeric Nanoparticles Based on Aggregation-Induced Emission and Mitochondria Targeting for Photodynamic Cancer Therapy.

Photodynamic therapy (PDT) is an auspicious strategy for cancer therapy by yielding reactive oxygen species (ROS) under light irradiation. Here, we have developed near-infrared (NIR) triggered polymer encapsulated upconversion nanoparticles (UCNPs) based on aggregation-induced emission (AIE) characteristics and mitochondria target ability for PDT. The coated AIE polymer as a photosensitizer can be photoactivated by the up-converted energy of UCNPs upon 980 nm laser irradiation, which could generate ROS efficiently in mitochondria and induce cell apoptosis. Moreover, a "sheddable" poly(ethylene glycol) (PEG) layer was easily conjugated at the surface of NPs. The pH-responsive PEG layer shields the surface positive charges and shows stronger protein-resistance ability. In the acidic tumor environment, PEGylated NPs lose the PEG layer and show the mitochondria-targeting ability by responding to tumor acidity. A cytotoxicity study indicated that these NPs have good biocompatibility in the dark but exert severe cytotoxicity to cancer cells, with only 10% cell viability, upon being irradiated with an NIR laser. The AIE nanoparticles are a good candidate for effective mitochondria targeting photosensitizer for PDT.

Potentially functional variants in lncRNAs are associated with breast cancer risk in a Chinese population.

Long non-coding RNAs (lncRNAs) participate in the development of breast cancer. Genetic variants in lncRNAs may be involved in their abnormal expressions and associated with cancer risk. In the present study, we performed RNA sequencing on five paired breast cancer tumor and adjacent non-cancerous tissues to obtain differentially expressed lncRNAs. We systematically selected potential regulatory variants of these lncRNAs and investigated the associations between these variants and breast cancer susceptibility in 1486 breast cancer cases and 1519 cancer-free controls in a Chinese population. Eleven lncRNAs were significantly differentially expressed between breast cancer tumor and normal tissues (false discovery rate (FDR) ≤0.05 and fold-change ≥2), including two known lncRNAs HOTAIR and UCA1. We subsequently genotyped 20 variants located on these lncRNAs and identified two variants (rs11471161 in AC104135.3 and rs3751232 in RP11-1060J15.4) associated with breast cancer risk. Logistic regression analysis indicated that the variant allele of rs11471161 was significantly associated with a decreased breast cancer risk (additive model: OR = 0.84, 95%CI = 0.74-0.94, P = 0.004), while the variant allele of rs3751232 showed an increased risk of breast cancer (additive model: OR = 1.20, 95%CI = 1.02-1.40, P = 0.027). Further co-expression analysis indicated that AC104135.3 associated with ERBB2, which promotes the development and progression of breast cancer through overexpression. Together, these results suggest that genetic variants rs11471161 and rs3751232 in AC104135.3, and RP11-1060J15.4, respectively, may influence the susceptibility to breast cancer in the Chinese population. Further functional evaluations and larger studies are warranted to validate these findings.

Low-power white light triggered AIE polymer nanoparticles with high ROS quantum yield for mitochondria-targeted and image-guided photodynamic therapy.

Photodynamic therapy (PDT) has received enormous attention due to its high specificity in eliminating the malignant tumor cells without interposing normal cells, as compared with chemotherapy. In this work, we fabricated mitochondria-targeted NPs using a new AIE cross-linked copolymer (PAIE-TPP) with far red/near-infrared (FR/NIR) subcellular bioimaging ability and a high reactive oxygen species (ROS) quantum yield of 77.9%. Such high efficiency ROS generation is desirable to increase the efficiency of PDT. The PAIE-TPP NPs possess great cytocompatibility but exert severe cytotoxicity to cancer cells with only 4% of cell viability under ultralow-power-intensity (10 mW cm-2) light irradiation. The AIE cross-linked copolymer NPs not only emit bright FR/NIR fluorescence for efficient in vitro subcellular-mitochondrial bioimaging but also generate high ROS for PDT.

A novel feature extraction approach for microarray data based on multi-algorithm fusion.

Feature extraction is one of the most important and effective method to reduce dimension in data mining, with emerging of high dimensional data such as microarray gene expression data. Feature extraction for gene selection, mainly serves two purposes. One is to identify certain disease-related genes. The other is to find a compact set of discriminative genes to build a pattern classifier with reduced complexity and improved generalization capabilities. Depending on the purpose of gene selection, two types of feature extraction algorithms including ranking-based feature extraction and set-based feature extraction are employed in microarray gene expression data analysis. In ranking-based feature extraction, features are evaluated on an individual basis, without considering inter-relationship between features in general, while set-based feature extraction evaluates features based on their role in a feature set by taking into account dependency between features. Just as learning methods, feature extraction has a problem in its generalization ability, which is robustness. However, the issue of robustness is often overlooked in feature extraction. In order to improve the accuracy and robustness of feature extraction for microarray data, a novel approach based on multi-algorithm fusion is proposed. By fusing different types of feature extraction algorithms to select the feature from the samples set, the proposed approach is able to improve feature extraction performance. The new approach is tested against gene expression dataset including Colon cancer data, CNS data, DLBCL data, and Leukemia data. The testing results show that the performance of this algorithm is better than existing solutions.

Vascular endothelial growth factor expression and pathological changes in the local tissue of facial hemangiomas following injections with pure alcohol.

The aim of the present study was to investigate the association between the formation of hemangioma and the expression of vascular endothelial growth factor (VEGF) following local injections of pure alcohol in patients exhibiting hemangioma. Ten healthy subjects (control group) and 10 hemangioma patients (treatment group) were included in the study population, with the hemangioma patients receiving one injection of pure alcohol. The VEGF levels were evaluated in the treatment and control group subjects prior to and following the injection using enzyme-linked immunosorbent assay; furthermore, local tissue was excised to perform pathological analysis one week after the injections. The VEGF levels of the healthy group were identified to be significantly lower when compared with those of the treatment group prior to the injections (P<0.01) and one week after the injections (P<0.01), however, were not significantly different when compared with the treatment group one month after the injections (P>0.01). Therefore, serum VEGF concentrations in the peripheral blood may be a clinical indicator of the efficacy of clinical treatment and aid with determination of the prognosis.

Activation of microtubule dynamics increases neuronal growth via the nerve growth factor (NGF)- and Gαs-mediated signaling pathways.

Signals that activate the G protein Gαs and promote neuronal differentiation evoke Gαs internalization in rat pheochromocytoma (PC12) cells. These agents also significantly increase Gαs association with microtubules, resulting in an increase in microtubule dynamics because of the activation of tubulin GTPase by Gαs. To determine the function of Gαs/microtubule association in neuronal development, we used real-time trafficking of a GFP-Gαs fusion protein. GFP-Gαs concentrates at the distal end of the neurites in differentiated living PC12 cells as well as in cultured hippocampal neurons. Gαs translocates to specialized membrane compartments at tips of growing neurites. A dominant-negative Gα chimera that interferes with Gαs binding to tubulin and activation of tubulin GTPase attenuates neurite elongation and neurite number both in PC12 cells and primary hippocampal neurons. This effect is greatest on differentiation induced by activated Gαs. Together, these data suggest that activated Gαs translocates from the plasma membrane and, through interaction with tubulin/microtubules in the cytosol, is important for neurite formation, development, and outgrowth. Characterization of neuronal G protein dynamics and their contribution to microtubule dynamics is important for understanding the molecular mechanisms by which G protein-coupled receptor signaling orchestrates neuronal growth and differentiation.

Study of TNF-α, IL-1ß and LPS levels in the gingival crevicular fluid of a rat model of diabetes mellitus and periodontitis.

OBJECTIVE: In this study, we sought to investigate the dynamic changes in the levels of TNF-α, IL-1ß and LPS in the gingival crevicular fluid (GCF) in a rat model of diabetes mellitus (DM) and periodontitis (PD). Additionally, we evaluated alveolar bone loss and the histopathological response associated with experimental diabetes mellitus and experimental periodontitis. METHODS: DM and PD were induced together in 15 rats (group 1) by streptozotocin injection and ligature induction. Periodontitis alone was produced by ligature induction in 15 rats (group 2), diabetes alone was produced by streptozotocin injection in 15 rats (group 3), and fifteen systemically and periodontally healthy rats were used as controls (group 4). The gingival TNF-α, IL-1ß and LPS levels were measured by using ELISA method. Periodontal destruction was assessed by measuring the alveolar bone loss. Periodontal inflammation was quantified by histopathological grading in H&E stained samples. RESULTS: Higher levels of TNF-α, IL1-ß and LPS, increased alveolar bone loss and more serve histopathology were found in group 1 compared with group 2, group 3 and group 4 (p< 0.05). The quantities of TNF-α, IL1-ß and LPS, the amount of alveolar bone loss and the severity of the histopathological finding were greater in group 2 than group 3 and group 4 (p< 0.05). Group 3 demonstrated higher levels of TNF-α, IL1-ß and LPS, increased alveolar bone loss and more serve histopathology than group 4 (p< 0.05). Statistically significant differences were noted between all of the groups. CONCLUSIONS: These data indicate that DM may lead to enhanced TNF-α, IL1-ß and LPS production in the periodontal tissues. The resorption values of alveolar bone and the histological inflammation were more severe in rats with periodontitis and diabetes mellitus than in those with periodontitis alone, diabetes mellitus alone and control rats. Our findings are consistent with the hypothesis that hyperglycemia contributes to the heightened inflammatory response associated with periodontitis.