Recommended urine culture is unsuitable for screening pregnant women for asymptomatic bacteriuria due to long turn-around time, unaffordability, and user-unfriendliness. The objective of this review was to evaluate the suitability of various tests for this purpose. A PubMed-based systematic review of published articles irrespective of year and language was done. Search terms included asymptomatic bacteriuria, screening test, urinary tract infection, and diagnostic test. Diagnostic accuracy studies conducted on human populations comparing tests with urine culture were included. One author extracted predefined data fields, including quality indicators, another validated it. Of 78 records, 25 studies describing 15 tests were included. All tests were rapid, seven were valid and two of them were affordable and easy-to-use. No test provided comprehensive identification with antibiotic susceptibility. Despite publication bias, no test was found suitable for screening asymptomatic bacteriuria antenatally and providing evidence-based prescription. Further research is needed to develop tests which suit this purpose.

Undernutrition among adolescents in tribal areas is an area of concern in India.

Laparoscopy has been widely used in general surgical procedures, but total laparoscopic pancreaticoduodenectomy (TLPD) is still a complex and challenging surgery that is only performed in a small number of patients at a few large academic medical centers. Although the safety and feasibility of TLPD have been established, few studies have compared it with open pancreaticoduodenectomy (OPD) with regard to perioperative and oncological outcomes. Therefore, we carried out a meta-analysis to evaluate whether TLPD is superior to OPD.

Smoking is the biggest risk factor for lung cancer. Smokers have a much higher chance of developing lung tumors with a worse survival rate; however, non-smokers also develop lung tumors. A number of questions remain including the underlying difference between smoker and non-smoker lung cancer patients and the involvement of genetic and epigenetic processes in tumor development. The present study analyzed the mutation data of 100 non-small cell lung cancer (NSCLC) patients, 12 non-smokers, 48 ex-smokers and 40 smokers, from Tracking Non-Small Cell Lung Cancer Evolution through Therapy Consortium. A total of 68 genes exhibited different mutation patterns across non-smokers, ex-smokers and smokers. A number of these 68 genes encode membrane proteins with biological regulation, metabolic process, and response to stimulus functions. For each group of patients, the top 10 most frequently mutated genes were selected and their oncogenetic tree inferred, which reflected how the genes evolve during tumor genesis. By comparing the oncogenetic trees of non-smokers and smokers, it was identified that in non-smokers, the mutation of epidermal growth factor receptor (EGFR) was an early genetic alteration event and EGFR was the key driver, but in smokers, the mutation of titin (TTN) was more important. Based on network analysis, TTN can interact with spectrin α erythrocytic 1 through calmodulin 2 and troponin C1. These genetic differences during tumorigenesis of non-smoker and smoker lung cancer patients provided novel insights into the effects of smoking on the evolutionary trajectory of non-small cell lung cancer and may prove helpful for targeted therapy of different lung cancer subtypes.

Atmospheric particulate matter with a diameter <2.5 µm (PM2.5) and pollution are worldwide environmental problems and may have negative effects on cardiovascular disease through the lung and gut. The dynamics of intestinal microflora in response to particulate pollutants is unclear. The present study investigated changes in the gut microbiota related to pollutant exposure using spontaneously hypertensive rats (SHR). DNA was extracted from fecal samples. Amplicon Generation and the quality control of PCR products were performed. PCR products was sequenced on an Illumina HiSeq 2500 platform. Data analysis included: operational taxonomic unit (OTU) clustering and species annotation, alpha diversity, beta diversity, principal coordinates analysis (PCoA), and the use of PICRUSt bioinformatics software. The microbial diversity of the SHR rats was inversely associated with exposure to pollutants. In terms of relative abundance, 24 bacterial genera and 2 genera in particular (Actinobacillus and Fusobacterium) significantly declined, and one genus (Treponema) increased. Moreover, pollutant exposure was associated with the accumulation of genes from the gut microbiota that are implicated in cardiovascular diseases. From the long-term exposure experiment, rats appeared to respond to pollutant injury. In conclusion, these results suggest that the effects of atmospheric pollutants on organisms are not limited to the respiratory tract, but also include the gastrointestinal tract. Pollutants are likely to influence the intestinal microbiota and promote the progression of cardiovascular disease.

Changes in the levels of serum oxidative stress indexes, gastrointestinal hormones and inflammatory factors in children with different severity of reflux esophagitis (RE) were detected. Sixty child patients diagnosed with gastroesophageal reflux disease (GERD) via gastroscopy were selected and divided into non-erosive reflux disease group (NERD group, n=12) and RE group (n=48) according to whether there was esophageal mucosal injury. In RE group, the patients were further divided into grade I RE group (n=15), grade II RE group (n=18) and grade III RE group (n=15) based on the severity of mucosal injury. None of the child patients took PPI and domperidone within 2 weeks before enrollment. The content of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) in the esophageal mucosa was detected. The changes in the levels of serum vasoactive intestinal peptide (VIP), motilin, interleukin-1β (IL-1β), IL-8 and tumor necrosis factor-α (TNF-α) were determined. The DeMeester score was the highest in grade III RE group, followed by grade II RE group, grade I RE group and NERD group (P<0.05). The content of MDA in the esophageal mucosa was higher in RE group than that in NERD group, and the T-SOD activity declined with the increased severity of injury (P<0.05). In the three RE groups, the level of plasma VIP was significantly higher, while the motilin level was remarkably lower than those in NERD group (P<0.05). With the increased severity of disease, the expression levels of serum IL-1β, IL-8 and TNF-α in RE group were gradually raised (P<0.05). RE patients have strong oxidative stress and inflammatory response, an increased level of serum VIP, a regulator of gastrointestinal motility, and a decreased level of motilin. Controlling the changes in the above factors using effective treatment means can improve the development of GERD.

Breast cancer is the most common cancer in women worldwide, and the incidence and mortality rates are increasing every year. Dysregulation of microRNAs (miRNAs or miRs) is an important step in the initiation and development of breast cancer. Previous studies demonstrated that miR-205-5p is closely associated with occurrence and development of breast cancer; however, underlying mechanisms remain unclear. In the present study, reverse transcription-quantitative polymerase chain reaction assays were used to analyze miR-195-5p and endoplasmic reticulum protein 29 (ERp29) levels in breast cancer and matched normal tissues. Western blot analysis was performed to analyze ERp29 and heat shock protein 27 (HSP27) protein expression levels. Cell viability, flow cytometry and luciferase reporter assay were used to examine cell proliferation, apoptosis and direct miRNA-mRNA binding, respectively. The results revealed that miR-205-5p expression in breast cancer tissues and cell lines was decreased compared with normal tissues and a normal cell line. Overexpression of miR-205-5p significantly augmented cytotoxicity effects of gemcitabine treatment in MDA-MB-231 and BT549 cells. It was observed that miR-205-5p negatively regulated ERp29 expression in breast cancer cells. Dual luciferase assays confirmed that ERp29 was a target of miR-205-5p in breast cancer cells. Additionally, following the established gemcitabine-resistant MDA-MB-231 cells (MDA-MB-231/GEM), ERp29 and HSP27 expression was upregulated and miR-205-5p was downregulated compared with parental cells. Overexpression of miR-205-5p reversed gemcitabine resistance in MDA-MB-231/GEM cells. In conclusion, the present study indicated that miR-205-5p may inhibit gemcitabine resistance in breast cancer cells via inhibition of ERp29 expression.

The aim of the present study was to analyze the role of microRNA (miRNA)-21-5p in tongue squamous cell carcinoma (TSCC), predict the target gene of miR-21-5p and provide novel strategies for gene therapy in TSCC treatment. The expression levels of miRNA-21-5p in TSCC tissues were analyzed using reverse transcription quantitative polymerase chain reaction, and the effects of miRNA-21-5p on cell proliferation, invasion and apoptosis and the expression levels of target protein PDCD4 in the Cal 27 and SCC9 cell lines were determined. PI3K/AKT/Forkhead Box O1 (FOXO1) pathway-associated protein expression levels were evaluated by western blot analysis. miRNA-21-5p was consistently upregulated in TSCC tissues compared with normal tissues. Inhibition of miR-21-5p inhibited cell proliferation and invasion, and promoted cell apoptosis. A luciferase reporter assay confirmed that PDCD4 was the target of miR-21-5p. Inhibition of miRNA21-5p suppressed the PI3K/Akt/FOXO1 signaling pathway. The results from the present study indicated that miR-21-5p-targeting PDCD4 suppresses apoptosis in human TSCC cell lines. This anti-apoptotic effect was achieved by regulating the PI3K/Akt/FOXO1 signaling pathway. These data represent the basis for a promising novel strategy for the treatment of TSCC.

Improving the effects of radiotherapy, such as heavy ion radiation, is currently a research priority for oncotherapy. Long non-coding RNAs (lncRNAs) are a subtype of noncoding RNAs involved in the therapeutic response to tumor radiotherapy. However, little is known about the variations in lncRNAs that occur after heavy ion radiation therapy. In this study, we established two kinds of Agilent Human lncRNA arrays and examined the effects of heavy ion radiation and X-ray irradiation on HeLa cells. We compared the differences in lncRNA expression (>=2-fold changes) between cells treated with the two types of radiation and control cells and identified 504 lncRNAs and 285 mRNAs that were differentially expressed. Among these lncRNAs, TCONS-00009910 was the most highly up-regulated lncRNA, while NONHSAT060631 was the most down-regulated lncRNA in both groups. To validate these sequencing data, RT-PCR was performed, and similar findings were obtained. GO and KEGG pathway analyses were employed to probe the potential functions of the affected lncRNAs. Numerous lncRNAs were changed after radiation exposure, showing that they may have important functions in the response to tumour radiotherapy. The present findings may help to elucidate the mechanism by which lncRNAs affect the clinical responses of cancer to radiation and may provide potential diagnostic and therapeutic targets for cancer therapy.

Hepatocyte growth factor (HGF) expression is repressed in normal differentiated lung epithelial cells, but its expression is aberrantly upregulated in non-small cell lung cancer (NSCLC) and acts as a poor prognostic factor. The underlying molecular mechanisms of aberrant HGF expression are unclear. In this study, a novel differential methylation region located in the HGF promoter was identified, which was associated with aberrant HGF expression in NSCLC. The correlations of HGF promoter methylation detected by methylation specific PCR and HGF expression detected by immunohistochemistry with clinical outcomes were assessed in NSCLC patients. DNA methylation of the HGF promoter was correlated with the activation of HGF expression, which induced epithelial-mesenchymal transition, cell migration and invasion. According to the clinical correlation analysis in 63 NSCLC patients, those with high methylation were more likely to have stages III and IV (51.6% vs. 25.0%, P<0.05) and metastasis (57.5% vs. 16.7%, P<0.05) than patients with low methylation. In addition, compared with the protein marker of HGF expression, the DNA methylation marker of the HGF promoter had higher specificity for prognostic analysis of metastases in NSCLC. Our study indicated the regulatory mechanisms related to DNA methylation of the HGF promoter for HGF expression in NSCLC epithelial cells, and suggested that the DNA methylation signature of the HGF promoter could potentially be employed as a biomarker to improve the prognostic accuracy of NSCLC.

Integrin β4 (ITGB4) has been reported to be involved in carcinomas. Currently, ITGB4 has been characterized in colon cancer, however, its clinical significance is not very clear. In the present study, we utilized the large public datasets from NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and collected clinical samples in our center to investigate the transcriptional expressions of ITGB4 in colon cancer, and then explored the associations of ITGB4 with clinicopathological features and overall survival. The statistical analyses suggested that ITGB4 mRNA expressions were up-regulated significantly in colon cancer. High ITGB4 expression was observed to be associated with elder onset age, proximal tumor location, and high microsatellite instability (MSH) status. Further, Kaplan-Meier curves and univariate analysis demonstrated high ITGB4 expression was significantly associated with unfavorable overall survival in colon cancer (HR=1.292, 95%CI=1.084-1.540, P=0.004). And significant association was also found after adjusting the confounding factors including age, gender, and stage (adjusted HR=1.254, 95%CI=1.050-1.497, P=0.012). The annotation of ITGB4 co-expressed genes suggested the pathways including cell growth, positive regulation of cell migration, and apoptotic signaling might be involved in the potential mechanisms of ITGB4 in colon cancer development. The molecular regulation mechanism of ITGB4 ectopic expression in colon cancer was also explored and the results indicated that ITGB4 might be up-regulated by the transcription factor FOSL1 (FOS like 1, AP-1 Transcription Factor Subunit) and its promoter hypomethylation. Our results revealed that ITGB4 might be a therapeutic target and prognosis marker for individual therapy of colon cancer.

As an indispensable factor in preventing the recirculation of tissue lymphocytes to the lymphatic and blood systems, the integrin CD103 has enabled the characterization of lymphocyte populations in non-lymphoid tissues and organs. However, the expression, distribution, and clinical significance of CD103+ tumor-infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) remain unclear. In the present study, we included tumor and adjacent non-tumor tissue specimens from 198 patients with ESCC who had undergone surgical resection. Immunohistochemistry and immunofluorescence were used to detect CD103+ TIL distribution, as well as the co-expression of CD103 and T cell markers and functional molecules. Kaplan-Meier analysis and the Cox proportional hazards model were used to estimate the prognostic value of CD103+ TILs. The results showed that CD103+ TILs were predominantly located in adjacent non-tumor tissues compared with tumor tissues (P < 0.0001). Immunofluorescence double staining revealed that CD8+ T cells, but not CD4+ T cells, comprised the majority of CD103-expressing cells. Most of these CD103-expressing cells co-expressed CTLA-4 and granzyme B rather than the exhaustion marker PD-1. High density of intratumoral CD103+ TIL is associated with longer overall survival (OS) and disease-free survival (DFS) in both the internal (OS, P = 0.0004 and DFS, P = 0.0002) and external (OS, P = 0.038 and DFS, P = 0.12) cohorts. Multivariate Cox analysis showed the density of CD103+ TILs was an independent positive prognostic factor for OS (hazards ratio [HR] = 0.406; P = 0.0003 in the internal cohort; HR = 0.328, P = 0.01, in the external cohort) and DFS (HR = 0.385; P = 0.0002 in the internal cohort; HR = 0.270, P = 0.003, in the external cohort). Our findings indicate that CD103+ TILs might play an important role in the tumor microenvironment, and intratumoral CD103+ TILs could serve as a promising prognostic marker in ESCC.

Although the inactivation of BRM plays oncogenic roles in tumorigenesis, regulation mechanism is rarely studied in clear cell renal cell carcinoma (RCC). Thus, we aimed to investigate the mechanism of BRM inactivation and explore the tumor suppressing roles of BRM in the development of clear cell RCC. We verified that hypermethylation of the BRM promoter was correlated with decreased expression of BRM by multi-omics analysis based on the TCGA database. This result was further confirmed in our own tumor tissues. Moreover, BRM inhibited the ability of proliferation and invasion of RCC cells in vitro. Consistent with this, BRM overexpressing virtually inhibited the xenograft tumor growth of ACHN cells in vivo. Finally we found that BRM promoted cell apoptosis and cellular cycle arrest in G2/M. In conclusion, our study confirms that the hypermethylation of BRM promoters plays oncogenic roles by the transcription inhibition of BRM in RCC, and the tumor suppressor gene BRM inhibits RCC cell vitality in vitro and in vivo.

Knowledge of the structure of interfacial water molecules at electrified solid materials is the first step toward a better understanding of important processes at such surfaces, in, e.g., electrochemistry, atmospheric chemistry, and membrane biophysics. As graphene is an interesting material with multiple potential applications such as in transistors or sensors, we specifically investigate the graphene-water interface. We use sum-frequency generation spectroscopy to investigate the pH- and potential-dependence of the interfacial water structure in contact with a chemical vapor deposited (CVD) grown graphene surface. Our results show that the SFG signal from the interfacial water molecules at the graphene layer is dominated by the underlying substrate and that there are water molecules between the graphene and the (hydrophilic) supporting substrate.

In this contribution, we report on the thin-film synthesis of a thermoresponsive polymer onto another polymer used as an enteric coating in drug applications. In particular, we deposit cross-linked poly(N-vinylcaprolactam) (pNVCL) thin films by initiated chemical vapor deposition (iCVD) onto spin-coated Eudragit (EUD) layers. Already upon iCVD synthesis, the layered structure starts to form wrinkles at a minimum iCVD thickness of 30 nm. By changing the EUD layer thickness and the amount of cross-linking used during iCVD, the morphology of the wrinkles is demonstrated to be readily tunable. Laterally, the double-layer structures vary in morphology from being ultrasmooth to exhibiting up to a 3.5 μm wrinkle wavelength. The surface roughness and, thus, the wrinkles' height can be tailored from below 1 nm up to 100 nm. From the resulting wavelength of wrinkles, an estimation of the elastic modulus of pNVCL proves its tunability over a wide range of values thanks to the iCVD process. This study elucidates an uncomplicated way to tune the wrinkles' morphology and, thus, the surface area of a system that can be employed in drug delivery applications. Hence, an enteric coating of EUD together with an iCVD-synthesized thermoresponsive thin film is proposed as a promising composite encapsulation layer to outperform established systems in terms of tunability of the response to multiple external stimuli.

Background: Hilsa shad ( Tenualosa ilisha), a widely distributed migratory fish, contributes substantially to the economy of Bangladesh. The harvest of hilsa from inland waters has been fluctuating due to anthropological and climate change-induced degradation of the riverine habitats.  The whole genome sequence of this valuable fish could provide genomic tools for sustainable harvest, conservation and productivity cycle maintenance. Here, we report the first draft genome of  T. ilisha from the Bay of Bengal, the largest reservoir of the migratory fish. Methods: A live specimen of T. ilisha was collected from the Bay of Bengal. The whole genome sequencing was performed by the Illumina HiSeqX platform (2 × 150 paired end configuration). We assembled the short reads using SOAPdenovo2 genome assembler and predicted protein coding genes by AUGUSTUS. The completeness of the T. ilisha genome assembly was evaluated by BUSCO (Benchmarking Universal Single Copy Orthologs). We identified single nucleotide polymorphisms (SNPs) by calling them directly from unassembled sequence reads using discoSnp++. Results: We assembled the draft genome of 710.28 Mb having an N50 scaffold length of 64157 bp and GC content of 42.95%. A total of 37,450 protein coding genes were predicted of which 29,339 (78.34%) were annotated with other vertebrate genomes. We also identified 792,939 isolated SNPs with transversion:transition ratio of 1:1.8. The BUSCO evaluation showed 78.1% completeness of this genome. Conclusions: The genomic data generated in this study could be used as a reference to identify genes associated with physiological and ecological adaptations, population connectivity, and migration behaviour of this biologically and economically important anadromous fish species of the Clupeidae family.

Pathogen-associated Molecular Patterns (PAMPs) are highly conserved structural motifs that are recognized by Pathogen Recognition receptors (PRRs) to initiate immune responses. Infection by these pathogens and the immune response to PAMPS such as lipopolysaccharide (LPS), Peptidoglycan (PGN), bacterial oligodeoxynucleotides [CpG oligodeoxynucleotides 2006 (CpG ODN2006) and CpG oligodeoxynucleotides 2216 (CpG ODN2216)], and viral RNA Polyinosinic-Polycytidylic Acid (Poly I:C), are associated with infectious and metabolic diseases in animals impacting health and production. It is established that PAMPs mediate the production of cytokines by binding to PRRs such as Toll-like receptors (TLR) on immune cells. Galectins (Gal) are carbohydrate-binding proteins that when expressed play essential roles in the resolution of infectious and metabolic diseases. Thus it is important to determine if the expression of galectin gene (LGALS) and Gal secretion in blood are affected by exposure to LPS and PGN, PolyI:C and bacterial CpG ODNs. LPS increased transcription of LGALS4 and 12 (2.5 and 2.02 folds respectively) and decreased secretion of Gal 4 (p < 0.05). PGN increased transcription of LGALS-1, -2, -3, -4, -7, and -12 (3.0, 2.3, 2.0, 4.1, 3.3, and 2.4 folds respectively) and secretion of Gal-8 and Gal-9 (p < 0.05). Poly I:C tended to increase the transcription of LGALS1, LGALS4, and LGALS8 (1.78, 1.88, and 1.73 folds respectively). Secretion of Gal-1, -3, -8 and nine were significantly increased in treated samples compared to control (p < 0.05). CpG ODN2006 did not cause any significant fold changes in LGALS transcription (FC < 2) but increased secretion of Gal-1, and-3 (p < 0.05) in plasma compared to control. Gal-4 was however reduced in plasma (p < 0.05). CpG ODN2216 increased transcription of LGALS1 and LGALS3 (3.8 and 1.6 folds respectively), but reduced LGALS2, LGALS4, LGALS7, and LGALS12 (-1.9, -2.0, -2.0 and; -2.7 folds respectively). Secretion of Gal-2 and -3 in plasma was increased compared to control (p < 0.05). Gal-4 secretion was reduced in plasma (p < 0.05). The results demonstrate that PAMPs differentially modulate galectin transcription and translation of galectins in cow blood.

To evaluate selective apoptosis of Y79 retinoblastoma versus ARPE-19 retinal pigment epithelial cells by using different doses of dextran-coated iron oxide nanoparticles (DCIONs) in a magnetic hyperthermia paradigm.

PyroGlu-Leu is present in certain food protein hydrolysates and traditional Japanese fermented foods. Our previous study demonstrated that the oral administration of pyroGlu-Leu (0.1 mg/kg body weight) attenuates dysbiosis in mice with experimental colitis. The objective of this study was to elucidate why such a low dose of pyroGlu-Leu attenuates dysbiosis in different animal models. High fat diet extensively increased the ratio of Firmicutes/Bacteroidetes in feces of rats compared to control diet. Oral administration of pyroGlu-Leu (1 mg/kg body weight) significantly attenuated high fat diet-induced dysbiosis. By focusing on the production of intestinal antimicrobial peptides, we found that pyroGlu-Leu significantly increased the level of 4962 Da peptides, which identified as the propeptide of rattusin or defensin alpha 9, in ileum. We also observed increased tryptic fragment peptides from rattusin in the lumen. Here, we report that orally administered pyroGlu-Leu attenuates dysbiosis by increasing in the host antimicrobial peptide, rattusin.

Reperfusion of patients after myocardial infarction (heart attack) triggers cardiac inflammation that leads to infarct expansion and heart failure (HF). We previously showed that the circadian mechanism is a critical regulator of reperfusion injury. However, whether pharmacological targeting using circadian medicine limits reperfusion injury and protects against HF is unknown. Here, we show that short-term targeting of the circadian driver REV-ERB with SR9009 benefits long-term cardiac repair post-myocardial ischemia reperfusion in mice. Gain and loss of function studies demonstrate specificity of targeting REV-ERB in mice. Treatment for just one day abates the cardiac NLRP3 inflammasome, decreasing immunocyte recruitment, and thereby allowing the vulnerable infarct to heal. Therapy is given in vivo, after reperfusion, and promotes efficient repair. This study presents downregulation of the cardiac inflammasome in fibroblasts as a cellular target of SR9009, inviting more targeted therapeutic investigations in the future.