A Multi-Omics Study of Familial Lung Cancer: Microbiome and Host Gene Expression Patterns.

Background: Inherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology. The lung microbiome is getting rising attention in carcinogenesis. The present work sought to investigate the microbiome in lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution (IAP); and further, to compare host gene expression patterns with their microbiome for potential links. Methods: Tissue sample pairs (cancer and adjacent nonmalignant tissue) were used for 16S rRNA (microbiome) and RNA-seq (host gene expression). Subgroup microbiome diversities and their matched gene expression patterns were analyzed. Significantly enriched taxa were screened out, based on different clinicopathologic characteristics. Results: Our FLC microbiome seemed to be smaller, low-diversity, and inactive to change; we noted microbiome differences in gender, age, blood type, anatomy site, histology type, TNM stage as well as IAP and smoking conditions. We also found smoking and IAP dramatically decreased specific-OTU biodiversity, especially in normal lung tissue. Intriguingly, enriched microbes were in three categories: opportunistic pathogens, probiotics, and pollutant-detoxication microbes; this third category involved Sphingomonas, Sphingopyxis, etc. which help degrade pollutants, but may also cause epithelial damage and chronic inflammation. RNA-seq highlighted IL17, Ras, MAPK, and Notch pathways, which are associated with carcinogenesis and compromised immune system. Conclusions: The lung microbiome can play vital roles in carcinogenesis. FLC and IAP subjects were affected by fragile lung epithelium, vulnerable host-microbes equilibrium, and dysregulated immune surveillance and response. Our findings provided useful information to study the triple interplay among environmental carcinogens, population genetic background, and diversified lung microbiome.

Poly(lactic-co-glycolic acid)-Chitosan-Gelatin Composite Nanomaterials for the Treatment of Diabetic Foot Ulcer Wound Infection.

In this experiment, a solid carrier was prepared with PLGA, gelatin, and chitosan as the main raw materials, so that BMSCs could exert their repairing effect directly in the ulcer area under the stimulation of Klotho protein. We chose to use electrospun PLGA as the main technical means to provide suitable adhesion growth environment for BMSCs by preparing PLGA nanofibers. At the same time, PLGA nanofibers are also a controlled release material, so that Klotho protein can remain active, thereby achieving the purpose of stimulating BMSCs for a long time. Through the nano-scale porous structure provided on the surface of the PLGA film, BMSCs can adhere well to the surface of the material and continuously receive stimulation from the inner Klotho protein. We applied this composite to mice with diabetic ulcers, and verified the effects of Klotho protein and BMSCs on DFU healing in five groups of mice. From the results, the Klotho+BMSCs group achieved the best healing effect, followed by the Klotho group alone, while the other three groups had no significant difference in healing effects. It is proved that both Klotho and BMSCs can help the healing of diabetic ulcers, but BMSCs alone cannot survive in harsh environments, and it is difficult to play a normal repair role. The purpose of this study was to investigate the effect of Klotho protein on BMSCs and ECs under high glucose conditions, and to find a suitable carrier for planting BMSCs on it. At the same time, the material also has a certain sustained release function. We have concluded that Klotho protein can promote the proliferation and migration of BMSCs and ECs under high glucose conditions. When combined with electrospinning technology to prepare a protein that can release Klotho, it also provides a microstructure suitable for BMSCs adhesion, thereby ensuring that BMSCs can successfully survive. In the end, we artificial Klotho protein can promote angiogenesis in diabetic ulcer areas by protecting BMSCs and ECs, thereby promoting healing of ulcer areas.

Research on the Treatment of Diabetic Foot with Ulcer Based on Nano-Silver Antibacterial Dressing.

The incidence of diabetes has been increasing year by year. Long-term growth in blood sugar causes complications such as diabetic foot ulcer and infections, which will increase the difficulty of ulcer treatment. The diabetes brings great pain and heavy economic burden to patients and their families. In view of the above problems, a nano-silver antibacterial dressing is synthesized in this paper to control bacterial infection on the ulcer surface and promote wound healing. This paper describes the preparation process and morphological characterization of nano-silver antibacterial dressings. 100 patients were selected, which divided into two groups for comparative experiments. The conventional group used conventional vaseline dressing, and the control group was nano-silver antibacterial dressing. The ulcer surface healing time, the number of dressing changes, and the control of infection were analyzed separately, and statistical analysis was performed with SPSS19.0. The experimental results are as follows. The use of nano-silver antibacterial dressing can significantly reduce the incidence of infection in diabetic foot patients, which is helpful to reduce the number of dressing changes, shorten the healing time of ulcer, and accelerate the turnover rate. It helps to shorten the course of diabetic foot, and it is recommended to promote its clinical application.

Development of a negative pressure hood for isolation and transportation of individual patient with respiratory infectious disease.

The frequent and sudden occurrence of both known and unknown infectious diseases can cause global social panic. If the source of infection can be effectively controlled in the early stages of an outbreak, the spread of infectious diseases can be prevented. In view of this situation, this study developed for infectious or suspected infectious patients a negative pressure isolation hood which effectively achieves direct individual isolation during the early stages of disease outbreak, and facilitates long-distance transport. The hood body is made of flexible transparent polyvinyl chloride (PVC) material, and the combination of the hood material is airtight. The unique inflatable column support structure and the design of the inflatable neck sleeve effectively ensure both stiffness and air tightness of the hood body. The electrical exhaust system maintains a stable negative pressure environment inside the hood, and polluted air inside the hood can be purified by a high efficiency filter. Test results showed that the internal noise of the hood was 68 ± 1 dB (A), the air exhaust volume of the electric exhaust system was not <200 L/min, and the filtration efficiency of the filter to 0.3 µm particles was >99.99%, indicating that the hood achieved effective isolation protection for patients with respiration infectious diseases.

iTRAQ-coupled 2D LC/MS-MS analysis of CXCR7-transfected papillary thyroid carcinoma cells: A new insight into CXCR7 regulation of papillary thyroid carcinoma progression and identification of potential biomarkers.

Previous studies have demonstrated that C-X-C chemokine receptor type 7 (CXCR7) regulates papillary thyroid carcinoma (PTC) growth and metastasis; however, the molecular mechanisms underlying this regulation remain unclear. In the present study, the protein expression profiles of the PTC cell line GLAG-66 and GLAG-66 cells stably transfected with CXCR7 cDNA were analyzed and compared using isobaric tag for relative and absolute quantification-coupled two-dimensional liquid chromatography-tandem mass spectrometry. In total, 2,983 proteins were quantified and 130 proteins were identified to be differentially expressed, of which 87 were significantly upregulated and 43 were significantly downregulated. Gene Ontology enrichment analysis revealed that the differentially expressed proteins were primarily enriched in a number of biological processes, including metabolism-related processes, cellular component organization, transport, cellular development process and the immune response. The differentially expressed proteins identified included fibronectin 1, basigin, periplakin and serpin family B member 5, all of which are associated with cellular junctions and cancer progression. In addition, transgelin-2 and AHNAK nucleoprotein 2 were identified as potential novel biomarkers for the prognosis and treatment of PTC.

The chemokine receptor CXCR7 is a critical regulator for the tumorigenesis and development of papillary thyroid carcinoma by inducing angiogenesis in vitro and in vivo.

Papillary thyroid carcinoma (PTC) is a well-differentiated neoplasm, but it can transfer early to cervical lymph nodes. Accumulating evidences have confirmed the important roles of CXCR7 in tumor cell proliferation, invasion, metastasis, and angiogenesis. Our previous study demonstrated CXCR7 modulated proliferation, apoptosis, and invasion of PTC cells. In this study, we evaluated the effect of expression of CXCR7 in PTC cells on angiogenesis and whether its expression had an influence on the tumor growth of PTC in vivo. We evaluated the effect of CXCR7 on interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) secretion, angiogenesis, and tumor growth by ELISA, endothelial tube formation assay, and a xenograft tumor model in nude mice. Immunohistochemistry was used to assess expression of CD34 in tumor of mice. In vitro and in vivo studies in PTC cells suggested that the alteration of CXCR7 expression was correlated with angiogenesis and tumor growth. Moreover, CXCR7 mediated the expression of IL-8 and VEGF, which might be involved in the regulation of tumor angiogenesis. These findings suggest that CXCR7 affects the growth of PTC cells and participates in the tumorigenesis of PTC, probably through regulating angiogenesis by the proangiogenic VEGF or IL-8.

Gene expression profile analyze the molecular mechanism of CXCR7 regulating papillary thyroid carcinoma growth and metastasis.

BACKGROUND: To detect genetic expression profile alterations after papillary thyroid carcinoma (PTC) cells transfected with chemokine receptor CXCR7 gene by gene microarray, and gain insights into molecular mechanisms of how CXCR7 regulating PTC growth and metastasis. METHODS: The Human OneArray microarray was used for a complete genome-wide transcript profiling of CXCR7 transfected PTCs (K1-CXCR7 cells), defined as experimental group. Non CXCR7 transfected PTCs (K1 cells) were used as control group. Differential analysis for per gene was performed with a random variance model and t test, p values were adjusted to control the false discovery rate. Gene ontology (GO) on differentially expressed genes to identify the biological processes in modulating the progression of papillary thyroid carcinoma. Pathway analysis was used to evaluate the signaling pathway that differentially expressed genes were involved in. In addition, quantitative real-time polymerase chain reaction (q-PCR) and Western blot were used to verify the top differentially expression genes. RESULTS: Comparative analysis revealed that the expression level of 1149 genes was changed in response to CXCR7 transfection. After unsupervised hierarchical clustering analysis, 270 differentially expressed genes were filtered, of them 156 genes were up-regulated whereas 114 genes were down-regulated in K1-CXCR7 cells. GO enrichment analysis revealed the differentially expressed genes were mainly involved in biopolymer metabolic process, signal transduction and protein metabolism. Pathway enrichment analysis revealed differentially expressed genes were mainly involved in ECM-receptor interaction, Focal adhesion, MAPK signaling pathway and Cytokine-cytokine receptor interaction pathway. More importantly, the expression level of genes closely associated with tumor growth and metastasis was altered significantly in K1-CXCR7 cells, including up-regulated genes FN1, COL1A1, COL4A1, PDGFRB, LTB, CXCL12, MMP-11, MT1-MMP and down-regulated genes ITGA7, and Notch-1. CONCLUSIONS: Gene expression profiling analysis of papillary thyroid carcinoma can further delineate the mechanistic insights on how CXCR7 regulating papillary thyroid carcinoma growth and metastasis. CXCR7 may regulate growth and metastasis of papillary thyroid carcinoma via the activation of PI3K/AKT pathway and its downstream NF-κB signaling, as well as the down-regulation of Notch signaling.

Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance.

The worldwide emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis threatens to make this disease incurable. Drug resistance mechanisms are only partially understood, and whether the current understanding of the genetic basis of drug resistance in M. tuberculosis is sufficiently comprehensive remains unclear. Here we sequenced and analyzed 161 isolates with a range of drug resistance profiles, discovering 72 new genes, 28 intergenic regions (IGRs), 11 nonsynonymous SNPs and 10 IGR SNPs with strong, consistent associations with drug resistance. On the basis of our examination of the dN/dS ratios of nonsynonymous to synonymous SNPs among the isolates, we suggest that the drug resistance-associated genes identified here likely contain essentially all the nonsynonymous SNPs that have arisen as a result of drug pressure in these isolates and should thus represent a near-complete set of drug resistance-associated genes for these isolates and antibiotics. Our work indicates that the genetic basis of drug resistance is more complex than previously anticipated and provides a strong foundation for elucidating unknown drug resistance mechanisms.

Draft genome sequences of two super-extensively drug-resistant isolates of Mycobacterium tuberculosis from China.

The prevalence of drug-resistance in Mycobacterium tuberculosis is already having a negative impact on the control of tuberculosis. We report the draft genome sequences of two super-extensively drug-resistant M. tuberculosis isolates from China, FJ05194 (lineage 2) and GuangZ0019 (lineage 4), and compare them with the H37Rv reference strain to identify possible sources of genetic variation associated with their extensive drug resistance. Our results suggest that their extensive drug resistance probably results from the stepwise accumulation of resistances to individual drugs.

Wavelet element method for lamellar gratings.

A wavelet element method is developed for analyzing lamellar diffraction gratings or grating stacks. The eigenmodes of the grating layers are accurately calculated by this method, and then the diffraction efficiencies of the gratings are calculated by the S-matrix algorithm. The method proposed in this paper consists in mapping each homogeneous layer to a wavelet element, and then matching them according to the boundary conditions between the layers. By this method the boundary conditions are satisfied rigorously and the Gibbs phenomenon in the Fourier modal method (FMM) can be avoided. The method performs better than the standard FMM for gratings involving metals. It can also be applied to analyze other discontinuous structures.

Genome Sequence of Enterobacter cancerogenus YZ1.

Enterobacter cancerogenus is usually known as an opportunistic human pathogen. Recently, it has attracted great attention for its capability to produce bioemulsifier, degrade xenobiotics, and resist alkalis and antibiotics. Here we report the complete genome of Enterobacter cancerogenus YZ1, isolated from a bran-feeding Coleoptera insect's frass.

Draft genome sequences of two Legionella dumoffii strains, TEX-KL and NY-23.

Legionella (Fluoribacter) dumoffii is one of the agents causing Legionnaires' disease. Here, we used Illumina second-generation sequencing technology to decipher for the first time the whole-genome sequences of two strains of this species, TEX-KL and NY-23. The assembly results for both strains consist of one chromosome and two plasmids.