Role of Clinical Features, Pathogenic and Etiological Characteristics of Community-acquired Pneumonia with Type 2 Diabetes Mellitus in Early Diagnosis.

OBJECTIVE: To study the etiological characteristics of community-acquired pneumonia (CAP) combined with type 2 diabetes (T2D), providing a reference for early clinical diagnosis and treatment of the disease. METHODS: We selected a total of 93 patients with CAP and analyzed their metagenomics nextgeneration sequencing (mNGS) data. The case group comprised 46 patients with combined CAP/T2D, and the control group comprised 47 patients without diabetes. We analyzed the pathogenic findings of the two groups. RESULTS: There were statistically significant differences in age between the two groups (P = 0.001). Leukocytes (P = 0.012), blood platelets (P = 0.034), fibrinogen (P = 0.037), D-dimer (P = 0.000), calcitonin ogen (P = 0.015), ultrasensitive C-reactive protein or C-reactive protein (CRP) (P = 0.000), serum amyloid A (P = 0.000), and erythrocyte sedimentation rate (P = 0.003) were higher in the case group than in the control group. Albumin was lower in the case group than in the control group. All differences were statistically significant. The infection rates of Klebsiella pneumoniae (P = 0.030), Pseudomonas aeruginosa (P = 0.043), and Candida albicans (P = 0.032) were significantly different between the two groups. CONCLUSION: Compared with those without diabetes, the infection rates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were higher in patients with combined CAP/T2D.

Clinical characteristics and pathogen analysis of bronchoalveolar lavage fluid in elderly patients with community-acquired pneumonia.

OBJECTIVE: To analyze the clinical characteristics and bronchoalveolar lavage fluid pathogens in elderly patients with community-acquired pneumonia (CAP). METHODS: This was a retrospective observational epidemiological study using that elderly cases diagnosed with community-acquired pneumonia receiving treatment at the Affiliated Hospital of North China University of Technology, Tangshan Hongci Hospital and Tangshan Fengnan District Hospital of Traditional Chinese Medicine. A total of 92 cases were divided into two groups according to age. There were 44 patients over 75-year-old and 48 patients between 65 and 74-year-old. RESULTS: Compared with the elderly 65 to 74-year-old, the elderly over 75-year-old with diabetes are more likely to suffer from CAP (35.42% vs. 63.64%, p = 0.007) and are more likely to have mixed infections (6.25% vs. 22.73%, p = 0.023) or larger lesions (45.83% vs. 68.18%, p = 0.031). Their hospital stays will also be extended (39.58% vs. 63.64%, p = 0.020), and the albumin level (37.51 ± 8.92 vs. 30.93 ± 6.58, p = 0.000), the neutrophils level (9.09(6.26-10.63) vs. 7.18(5.35-9.17),p = 0.026) is significantly lower and the d-dimer (505.42 ± 197.12 vs. 611.82 ± 195.85, p = 0.011), PCT (0.08 ± 0.04 vs. 0.12 ± 0.07, p = 0.001) levels are significantly higher. CONCLUSION: The clinical symptoms and signs of elderly CAP patients are not so typical, and the infection is more serious. Attention should therefore be paid to elderly patients. Hypoalbuminemia and high d-dimer can predict the prognosis of patients.

The De Novo Genome Sequencing of Silver Pheasant (Lophura nycthemera).

Silver pheasant (Lophura nycthemera) belongs to Phasianidae, Galliformes, which exhibits high subspecific differentiation. In this study, we assembled a novel genome based on 98.42 Gb of Illumina sequencing data and 30.20 Gb of PacBio sequencing data. The size of the final assembled genome was 1.01 Gb, with a contig N50 of 6.96 Mb. Illumina paired-end reads (94.96%) were remapped to the contigs. The assemble genome shows high completeness, with a complete BUSCO score of 92.35% using the avian data set. A total of 16,747 genes were predicted from the generated assembly, and 16,486 (98.44%) of the genes were annotated. The average length of genes, exons, and introns were 19,827.53, 233.69, and 1841.19 bp, respectively. Noncoding RNAs included 208 miRNAs, 40 rRNAs, and 264 tRNAs, and a total of 189 pseudogenes were identified; 116.31 Mb (11.47%) of the genome consisted of repeat sequences, with the greatest proportion of LINEs. This assembled genome provides a valuable reference genome for further studies on the evolutionary history and conversion genetics of L. nycthemera and the phylogenomics of the Galliformes lineage.

The mitogenome of common snipe, Gallinago gallinago gallinago Linnaeus, 1758 and evolutionary implications for the family Scolopacidae.

The mitochondrial genome (mitogenome) of Gallinago gallinago gallinago Linnaeus, 1758 was determined by the high-throughput data. The assembled mitogenome was 16,919 bp in length, with a 58.7% A + T content and GC skew of -0.3850. Among 13 PCGs, an unusual start codon (GTG) was identified for the COX1 gene, and incomplete stop codons (T-) were found in the COX3, ND2 and ND4 genes. The function of a cytosine insertion at site 174 in the ND3 gene and its phylogenetic significance are worthy of further scrutiny. In the control region (CR), thirteen 15-bp simple sequence repeats were found in G. g. gallinago. Phylogenetic analysis indicated that Gallinago was clustered at the basal position of the Scolopax clade and that the monophyly of Gallinago was also recovered. The mitogenome data of G. g. gallinago provides useful resources for further studying the evolution of Scolopacidae.

The first mitogenome of Lesser Whitethroat, Sylvia curruca blythi Ticehurst & Whistler, 1933 (Passeriformes: Sylviidae) and its phylogenetic implications for the genus Sylvia.

The complete mitogenome of the Lesser Whitethroat, Sylvia curruca blythi Ticehurst & Whistler, 1933 was determined, which belongs to Sylviidae, Passeriformes. The mitogenome had a length of 17,959 bp and consisted of 37 genes including 13 PCGs, 2 ribosomal RNAs (rRNA) genes, and 22 transfer RNAs (tRNA) genes. In addition, two control regions (CRs) were also existed in the mitogenome, with Sylvioidea typcial gene arrangement of cytb-trnT-CR1-trnP-nad6-trnE-CR2-trnF-rrnS. Phylogenetic analysis using 37 mitochondrial genes of 17 related species revealed that S. c. blythi had a closer relationship with S. crassirostris, and the monophyly of Sylvia was also recovered. The mitogenome data of S. c. blythi would provide useful resources for further studying the evolution of Sylvia and the subspecies taxonomic revision of S. curruca intraspecific.

Phragmunis a suppresses glioblastoma through the regulation of MCL1-FBXW7 by blocking ELK1-SRF complex-dependent transcription.

Glioblastoma (GBM) is a highly aggressive brain tumor. During screening work, we found a new compound named phragmunis A (PGA), which is derived from the fruitbody of Trogia venenata, exhibits a potential cytotoxic effect on patient-derived recurrent GBM cells and temozolomide (TMZ)-resistant cell lines. The present study was designed to investigate the potential molecular mechanism of the anti-glioma effects of PGA in vitro and in vivo. Studies investigating the mechanism revealed that PGA diminished the binding efficiency of ETS family of transcription factor (ELK1) and Serum response factor (SRF), and suppressed ELK1-SRF complex-dependent transcription, which decreased the transcriptional levels of downstream genes Early growth response protein 1 (EGR1)-Polycomb ring finger (BMI1), thus inducing the imbalanced regulation between Myeloid cell leukaemia-1 (MCL1) and F-Box and WD repeat domain containing 7 (FBXW7). Finally, orthotopic xenograft models were established to confirm the anti-glioma effect of PGA on tumour growth. We showed, for the first time, that the cytotoxic effects of PGA occurred by inducing MCL1 inhibition and FBXW7 activation by blocking ELK1-SRF complex-dependent transcription. The blockage of ELK1-mediated transcription resulted in the suppression of EGR1-BMI1, which led to the upregulation of FBXW7 expression and downregulation of MCL1. These findings suggested that PGA could be a therapeutic drug candidate for the treatment of recurrent GBM by targeting the ELK1-SRF complex.

Characterization of the complete mitogenomes of Baillon's Crake Porzana pusilla and phylogenetic analysis.

The complete mitochondrial genome of the Baillon's Crake Porzana pusilla (Gruiformes: Rallidae) are sequenced and annotated, which contained 37 typical genes. The length of the complete mitochondrial genome is 16,966 bp (GenBank No. MW043485), with As, Ts, Cs, Gs, and AT content of the mitochondrial genome is 32.1, 23.2, 30.9, 13.8, and 55.3%, respectively. All protein-coding genes started with ATN except COX1 and ND5, which start with GTG, and all protein-coding genes end with a complete triplet codon (TAA, AGG, AGA, and TAG), except COX3, which ends with an incomplete T. The ND3 gene of P. pusilla with an extra C nucleotide in 174 site. Phylogenetic analysis revealed that the new sequenced species of P. pusilla was closer to the clade of Porzana fusca and Porzana paykullii, and all three Porzana are clustered into one branch.

Mitochondrial genome of captive Alpine musk deer, Moschus chrysogaster (Moschidae), and phylogenetic analyses with its coordinal species.

Alpine musk deer, Moschus chrysogaster, a solitary, primitive ungulate inhabiting high elevation areas (3000-4500 m) is an endangered species facing threat of extinction globally due to excessive hunting for its musk. In this study, we determined the complete mitochondrial genome of M. chrysogaster, which was 16,354 bp in length, and revealed the same gene order and genomic organization as typical Moschidae mitochondrial DNA. Start codons in 13 protein-coding genes (PCGs) were all typical ATGs except ATA for ND2 and ND3 and ATT for ND5. Stop codons were all typical types except an incomplete stop codon T for COX3, ND2, ND3, and ND4. Secondary structures in 22 transfer RNA genes all showed typical cloverleaf except tRNA-Ser (AGY), in which the dihydrouridine arm formed a simple loop. No repeat units were found in the control region. The topology structure indicated that M. cupreus was primitive and located at the root of the Moschidae clade. Phylogenetic reconstruction placed M. chrysogaster as a distinct lineage, closely related to the branch of M. leucogaster, M. berezovskii (wild) and predicted a sister relationship with M. moschiferus, M. anhuiensis, and M. berezovskii (captive). However, we suggested that the genetic resources of M. chrysogaster_JQ608470 should be further investigated.

Polydatin attenuates renal fibrosis in diabetic mice through regulating the Cx32-Nox4 signaling pathway.

We previously found that polydatin could attenuate renal oxidative stress in diabetic mice and improve renal fibrosis. Recent evidence shows that NADPH oxidase 4 (Nox4)-derived reactive oxygen species (ROS) contribute to inflammatory and fibrotic processes in diabetic kidneys. In this study we investigated whether polydatin attenuated renal fibrosis by regulating Nox4 in vitro and in vivo. In high glucose-treated rat glomerular mesangial cells, polydatin significantly decreased the protein levels of Nox4 by promoting its K48-linked polyubiquitination, thus inhibited the production of ROS, and eventually decreasing the expression of fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1), the main factors that exacerbate diabetic renal fibrosis. Overexpression of Nox4 abolished the inhibitory effects of polydatin on FN and ICAM-1 expression. In addition, the expression of Connexin32 (Cx32) was significantly decreased, which was restored by polydatin treatment. Cx32 interacted with Nox4 and reduced its protein levels. Knockdown of Cx32 abolished the inhibitory effects of polydatin on the expression of FN and ICAM-1. In the kidneys of streptozocin-induced diabetic mice, administration of polydatin (100 mg·kg-1·d-1, ig, 6 days a week for 12 weeks) increased Cx32 expression and reduced Nox4 expression, decreased renal oxidative stress levels and the expression of fibrotic factors, eventually attenuating renal injury and fibrosis. In conclusion, polydatin promotes K48-linked polyubiquitination and degradation of Nox4 by restoring Cx32 expression, thereby decreasing renal oxidative stress levels and ultimately ameliorating the pathological progress of diabetic renal fibrosis. Thus, polydatin reduces renal oxidative stress levels and attenuates diabetic renal fibrosis through regulating the Cx32-Nox4 signaling pathway.

Complete mitochondrial genome of Sellanucheza jaegeri Golovatch, 2013 by next generation sequencing (Polydesmida: Paradoxosomatidae) and phylogenetic analysis in Diplopoda.

The mitogenome of Sellanucheza jaegeri was 15,623 bp long, revealed the same gene order to that of typical Polydesmida. Both the tRNASer(AGN) and tRNASer(UCN) lacked the DHU arms. No tandem repeat was found in two control regions. Phylogenetic analysis indicated that Sphaerotheriida was so antiquity that divided out earlier than others. We supported that Polydesmida had a relatively systematic affinity between Julida and Playtdesmida, and suggested that the interordinal phylogenetic relationships within Diplopoda should be further investigated.

Mitochondrial genomes of three Tetrigoidea species and phylogeny of Tetrigoidea.

The mitochondrial genomes (mitogenomes) of Formosatettix qinlingensis, Coptotettix longjiangensis and Thoradonta obtusilobata (Orthoptera: Caelifera: Tetrigoidea) were sequenced in this study, and almost the entire mitogenomes of these species were determined. The mitogenome sequences obtained for the three species were 15,180, 14,495 and 14,538 bp in length, respectively, and each sequence included 13 protein-coding genes (PCGs), partial sequences of rRNA genes (rRNAs), tRNA genes (tRNAs) and a A + T-rich region. The order and orientation of the gene arrangement pattern were identical to that of most Tetrigoidea species. Some conserved spacer sequences between trnS(UCN) and nad1 were useful to identify Tetrigoidea and Acridoidea. The Ka/Ks value of atp8 between Trachytettix bufo and other four Tetrigoidea species indicated that some varied sites in this gene might be related with the evolution of T. bufo. The three Tetrigoidea species were compared with other Caelifera. At the superfamily level, conserved sequences were observed in intergenic spacers, which can be used for superfamily level identification between Tetrigoidea and Acridoidea. Furthermore, a phylogenomic analysis was conducted based on the concatenated data sets from mitogenome sequences of 24 species of Orthoptera in the superorders Caelifera and Ensifera. Both maximum likelihood and bayesian inference analyses strongly supported Acridoidea and Tetrigoidea as forming monophyletic groups. The relationships among six Tetrigoidea species were (((((Tetrix japonica, Alulatettix yunnanensis), Formosatettix qinlingensis), Coptotettix longjiangensis), Trachytettix bufo), Thoradonta obtusilobata).

Data on taxonomic status and phylogenetic relationship of tits.

The data in this paper are related to the research article entitled "Taxonomic status and phylogenetic relationship of tits based on mitogenomes and nuclear segments" (X.J. Li et al., 2016) [1]. The mitochondrial genomes and nuclear segments of tits were sequenced to analyze mitochondrial characteristics and phylogeny. In the data, the analyzed results are presented. The data holds the resulting files of mitochondrial characteristics, heterogeneity, best schemes, and trees.

Characterization of the mitogenomes for two sympatric breeding species in Recurvirostridae (Charadriiformes) and their phylogenetic implications.

Recurvirostridae is a family of Charadriiformes that displays an amazing amount of characterization at evolutionary level. The mitogenomes of Himantopus himantopus and Recurvirostra avosetta are 17,378 bp and 16,856 bp in size, respectively. Both two mitogenomes reveal the same gene order and genomic organization to that of typical avian mtDNA. The first conserved block with two interrupted poly-C and four long terminal repeats with 140 bp are present in H. himantopus control region. Phylogenetic analysis indicated that Recurvirostridae (H. himantopus and R. avosetta) has the closest relationship with Haematopodidae. We supported that Stercorariidea is a sister group to (Alcidae (Laridae, Sternidae)), and suggested that the status of Larus vegae should be further investigated.

The mitogenomes of Gelochelidon nilotica and Sterna hirundo (Charadriiformes, Sternidae) and their phylogenetic implications.

Gelochelidon nilotica and Sterna hirundo are two sympatric breeding species. The mitogenomes of G. nilotica and S. hirundo are 16,748 bp and 16,707 bp in size. Both two mitogenomes reveal the same gene order and genomic organization to that of typical avian mtDNA. The first conserved blocks with a interrupted poly-C are present in the two species control regions, but not existed in S. albifrons. Seventeen and 11 simple sequence repeats are found in G. nilotica and S. hirundo, respectively. Phylogenetic analysis indicated that Sternidae has the closest relationship with Laridae. We supported that Stercorariidea is a sister group to (Alcidae (Laridae, Sternidae)), G. nilotica is genetically most related to S. hirundo (all belonged to Black cap species), but distant with S. albifrons (White blaze species) in kinship, and suggested that the status of Larus vegae should be further investigated.

Complete mitochondrial genome of Francolinus pintadeanus (Galliformes: Phasianidae).

The complete mitochondrial genome (mitogenome) of Francolinus pintadeanus, consisting of 16,693 bp, was determined and analyzed. It displayed as typical genome organization as other Galliformes mitogenomes: 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and one control region. The phylogenetic relationships of 25 Phasianidae species and three Odontophoridae species as outgroup using maximum likelihood and Bayesian inference methods based on a concatenated dataset from mitogenomes were analyzed. The results reveal that F. pintadeanus had a close relationship with Gallus gallus gallus/Bambusicola thoracica, then this clade formed a sister group with Pavo muticus/Argusianus argus.

Predicting essential genes and synthetic lethality via influence propagation in signaling pathways of cancer cell fates.

A major goal of personalized anti-cancer therapy is to increase the drug effects while reducing the side effects as much as possible. A novel therapeutic strategy called synthetic lethality (SL) provides a great opportunity to achieve this goal. SL arises if mutations of both genes lead to cell death while mutation of either single gene does not. Hence, the SL partner of a gene mutated only in cancer cells could be a promising drug target, and the identification of SL pairs of genes is of great significance in pharmaceutical industry. In this paper, we propose a hybridized method to predict SL pairs of genes. We combine a data-driven model with knowledge of signalling pathways to simulate the influence of single gene knock-down and double genes knock-down to cell death. A pair of genes is considered as an SL candidate when double knock-down increases the probability of cell death significantly, but single knock-down does not. The single gene knock-down is confirmed according to the human essential genes database. Our validation against literatures shows that the predicted SL candidates agree well with wet-lab experiments. A few novel reliable SL candidates are also predicted by our model.

Syn-lethality: an integrative knowledge base of synthetic lethality towards discovery of selective anticancer therapies.

Synthetic lethality (SL) is a novel strategy for anticancer therapies, whereby mutations of two genes will kill a cell but mutation of a single gene will not. Therefore, a cancer-specific mutation combined with a drug-induced mutation, if they have SL interactions, will selectively kill cancer cells. While numerous SL interactions have been identified in yeast, only a few have been known in human. There is a pressing need to systematically discover and understand SL interactions specific to human cancer. In this paper, we present Syn-Lethality, the first integrative knowledge base of SL that is dedicated to human cancer. It integrates experimentally discovered and verified human SL gene pairs into a network, associated with annotations of gene function, pathway, and molecular mechanisms. It also includes yeast SL genes from high-throughput screenings which are mapped to orthologous human genes. Such an integrative knowledge base, organized as a relational database with user interface for searching and network visualization, will greatly expedite the discovery of novel anticancer drug targets based on synthetic lethality interactions. The database can be downloaded as a stand-alone Java application.

Evolutionary inspirations for drug discovery.

Conceptual innovations are needed to address the challenge of 'more investments, fewer drugs' in the pharmaceutical industry. Since the publication of The Origin of Species by Charles Darwin 150 years ago, evolution has been a central concept in biology. In this article, we show that evolutionary concepts are also helpful to streamline the drug-discovery pipeline through facilitating the discovery of targets and drug candidates. Furthermore, the antioxidant paradox can be addressed by an evolutionary methodology. Through examining the evolved biological roles of natural polyphenols (which dominate current antioxidant drug discovery), we reveal that polyphenols (particularly flavonoids) are not evolved for scavenging free radicals. This finding provides new clues to understanding why the strong in vitro antioxidant activities of polyphenols cannot be translated into in vivo effects. Polyphenols have evolved a superior ability to bind various proteins, so we also argue that they are good starting points for multi-target drugs.

Chemoinformatics approaches for traditional Chinese medicine research and case application in anticancer drug discovery.

Traditional Chinese Medicine (TCM), which has been used for thousands of years to treat diseases, provides unique theoretical and practical methodologies for disease control. With the increasing accumulation of TCM data, it is imperative to study and analyze these resources with modern technologies and to elucidate the molecular mechanisms of TCM therapy. However, the philosophy, framework and technique of TCM are quite different from those of Western medicine, which causes complications when attempting to design modern drug treatments based on TCM. To meet this challenge, some basic chemoinformatics techniques, including molecular similarity searching, virtual screening and inverse docking, have been utilized in an attempt to gain a deeper understanding of TCM and to accelerate the TCM-based drug discovery. Recent progress on the use of chemoinformatics in TCM research will be discussed and an example of the preliminary application of chemoinformatics methods in anticancer drug design will be provided.