With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
To identify the critical genes and pathways that related to OP development in male AS patients, bioinformatic gene analysis and qRT-PCR validation were performed. SBNO2 and VPS13B were ...identified as the potential target for OP development, which may be valuable for the prevention of OP in male AS patients.
Introduction
Osteoporosis (OP) is common in men with ankylosing spondylitis (AS). The specific pathogenesis of OP in AS, however, is still unclear. The present study attempted to identify potential genes associated with the development of OP in males with AS.
Methods
Gene expression profiles were downloaded from the GSE73754 and GSE35959 datasets from the Gene Expression Omnibus (GEO). Data from OsteoporosAtlas were downloaded as a supplement. Differentially expressed genes (DEGs) were determined with the
limma
package. The overlapping DEGs between male AS-related genes and OP-related genes were determined. The DEGs were validated by qRT-PCR in the blood samples of males with AS. Weighted gene co-expression network analysis (WGCNA) was utilized to establish a co-expression network to identify the hub genes.
Results
A total of 17 overlapping DEGs were identified; 6 genes in 17 overlapping DEGs were verified as the essential genes in the pathogenesis of OP in male AS by qRT-PCR analysis. After WGCNA, the modules of MEblue (> 0.6) and MEred (> 0.8) were screened out by the correlation analysis and were determined to function mainly in MAPK signaling pathway and osteoclast differentiation. Analysis of the two modules revealed VPS13B and SBNO2 as key genes due to the high degree of correlation. Both genes play an important role in bone metabolism regulation in male AS. Two hub genes MYD88 in MEblue and NCK1 in MEred with high degree of connectivity were selected.
Conclusions
Gender-specific SBNO2 and VPS13B may be key genes involved in OP in male AS.
To assess the association between the elevation of plasma homocysteine (Hcy) level and long‐term levodopa (L‐dopa) therapy in idiopathic Parkinson's disease (PD). We performed a systematic literature ...review to recruit original studies published up to May 14, 2012. Studies enrolled should be controlled, with specific information of long‐term L‐dopa application and plasma Hcy in patients with PD. Effects were summarized using standardized mean differences (SMDs) or weighted mean differences (WMDs). Our search enrolled 22 eligible studies. Plasma Hcy levels were significantly higher in L‐dopa‐treated patients than those in healthy controls SMD 0.97; 95% confidence interval (CI) 0.80–1.14, P < 0.001, L‐dopa‐naïve patients with PD (SMD 0.99; 95% CI 0.54–1.44, P < 0.001), and untreated patients (SMD 0.52; 95% CI 0.18–0.86, P < 0.01). However, its levels in untreated patients with PD were not significantly higher than in healthy controls (SMD 0.24; 95% CI −0.03 to 0.51, P > 0.05). Patients with PD treated with L‐dopa plus catechol‐O‐methyltransferase inhibitor (COMT‐I) showed lower plasma Hcy concentrations compared with L‐dopa‐treated patients (WMD 4.62; 95% CI 2.89–6.35, P < 0.001). L‐dopa treatment is associated with the increase in plasma Hcy level in patients with PD. COMT‐I may attenuate L‐dopa‐induced elevation of Hcy level.
Growing evidence indicates that resistin-an obesity-related cytokine-is upregulated in breast cancer patients, yet its impact on breast cancer behavior remains to be ascertained. Similarly, Toll-like ...receptor 4 (TLR4) has been implicated in breast cancer progression, however, its clinically relevant endogenous ligand remains elusive. In this study, we observed that high serum resistin levels in breast cancer patients positively correlated with tumor stage, size and lymph node metastasis. These findings were replicated in animal models of breast cancer tumorigenesis and metastasis. Resistin was found to promote epithelial-mesenchymal transition and stemness in breast cancer cells-mechanisms critical to tumorigenesis and metastasis-through a TLR4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and negated by TLR4-specific antibody and antagonist. These findings provide clear evidence that resistin is a clinically relevant endogenous ligand for TLR4, which promotes tumor progression via TLR4/NF-κB/STAT3 signaling, providing insights into a novel therapeutic target in breast cancer.
One hundred and thirty-six
bla
OXA-51
-negative strains were identified from 1,067
Acinetobacter calcoaceticus
–
A. baumannii
complex (ACB complex) isolates, which were collected during October 2010 ...to March 2013 from 15 general hospitals in 10 cities throughout Zhejiang Province, China. Seven of the 136
bla
OXA-51
-negative ACB complex isolates were New Delhi metallo-β-lactamase-1 (NDM-1)-positive, among which three were identified as
A. nosocomialis
and four were identified as
A. pittii
strains using 16S–23S rRNA gene intergenic spacer (ITS) sequencing and partial RNA polymerase β-subunit (
rpoB
) sequencing. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) analysis showed that the seven NDM-positive isolates belonged to three clonal strains with three novel sequence types (STs). Polymerase chain reaction (PCR) assays and DNA sequence analysis of the carbapenemase and other β-lactamase genes indicated that all the isolates harbored the
bla
NDM-1
gene, and that only one strain of
A. nosocomialis
isolates harbored both
bla
NDM-1
and
bla
OXA-23
. All of them were positive for
bla
ADC
, from which three novel
bla
ADC
genes (designated as
bla
ADC-69
,
bla
ADC-70
, and
bla
ADC-71
) were detected for the first time. The presence of
IS
Aba125 upstream of
bla
NDM-1
was identified through genetic environment analysis. Carbapenem resistance can be transferred from
A. nosocomialis
and
A. pittii
to
Escherichia coli
EC600 by the conjugation experiment. Plasmid analysis, DNA hybridization, and extraction experiments indicated that
bla
NDM-1
was located on a plasmid of approximately 50 kb. In conclusion, we characterized the dissemination of NDM-1-positive
A. pittii
strains in Zhejiang Province, China, and reported the NDM-producing
A. nosocomialis
for the first time.
Summary
Sugar‐sweetened beverages (SSBs) are the single largest source of added sugar and the top source of energy intake in the U.S. diet. In this review, we evaluate whether there is sufficient ...scientific evidence that decreasing SSB consumption will reduce the prevalence of obesity and its related diseases. Because prospective cohort studies address dietary determinants of long‐term weight gain and chronic diseases, whereas randomized clinical trials (RCTs) typically evaluate short‐term effects of specific interventions on weight change, both types of evidence are critical in evaluating causality. Findings from well‐powered prospective cohorts have consistently shown a significant association, established temporality and demonstrated a direct dose–response relationship between SSB consumption and long‐term weight gain and risk of type 2 diabetes (T2D). A recently published meta‐analysis of RCTs commissioned by the World Health Organization found that decreased intake of added sugars significantly reduced body weight (0.80 kg, 95% confidence interval CI 0.39–1.21; P < 0.001), whereas increased sugar intake led to a comparable weight increase (0.75 kg, 0.30–1.19; P = 0.001). A parallel meta‐analysis of cohort studies also found that higher intake of SSBs among children was associated with 55% (95% CI 32–82%) higher risk of being overweight or obese compared with those with lower intake. Another meta‐analysis of eight prospective cohort studies found that one to two servings per day of SSB intake was associated with a 26% (95% CI 12–41%) greater risk of developing T2D compared with occasional intake (less than one serving per month). Recently, two large RCTs with a high degree of compliance provided convincing data that reducing consumption of SSBs significantly decreases weight gain and adiposity in children and adolescents. Taken together, the evidence that decreasing SSBs will decrease the risk of obesity and related diseases such as T2D is compelling. Several additional issues warrant further discussion. First, prevention of long‐term weight gain through dietary changes such as limiting consumption of SSBs is more important than short‐term weight loss in reducing the prevalence of obesity in the population. This is due to the fact that once an individual becomes obese, it is difficult to lose weight and keep it off. Second, we should consider the totality of evidence rather than selective pieces of evidence (e.g. from short‐term RCTs only). Finally, while recognizing that the evidence of harm on health against SSBs is strong, we should avoid the trap of waiting for absolute proof before allowing public health action to be taken.
In order to understand the aging and processing of organic aerosols (OA), an intensive field campaign (Campaign of Air Pollution at Typical Coastal Areas IN Eastern China, CAPTAIN) was conducted ...March–April at a receptor site (a Changdao island) in central eastern China. Multiple fast aerosol and gas measurement instruments were used during the campaign, including a high resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) that was applied to measure mass concentrations and non-refractory chemical components of submicron particles (PM1nr). The average mass concentration of PM1(PM1nr+black carbon) was 47 ± 36 μg m−3 during the campaign and showed distinct variation, depending on back trajectories and their overlap with source regions. Organic aerosol (OA) is the largest component of PM1 (30%), followed by nitrate (28%), sulfate (19%), ammonium (15%), black carbon (6%), and chloride (3%). Four OA components were resolved by positive matrix factorization (PMF) of the high-resolution spectra, including low-volatility oxygenated organic aerosol (LV-OOA), semi-volatile oxygenated OA (SV-OOA), hydrocarbon-like OA (HOA) and a coal combustion OA (CCOA). The mass spectrum of CCOA had high abundance of fragments from polycyclic aromatic hydrocarbons (PAHs) (m/z 128, 152, 178, etc.). The average atomic ratio of oxygen to carbon in OA (O / C) at Changdao was 0.59, which is comparable to other field studies reported at locations downwind of large pollution sources, indicating the oxidized nature of most OA during the campaign. The evolution of OA elemental composition in the van Krevelen diagram (H / C vs. O / C) showed a slope of −0.63; however, the OA influenced by coal combustion exhibits a completely different evolution that appears dominated by physical mixing. The aging of organic aerosols vs. photochemical age was investigated. It was shown that OA / ΔCO, as well as LV-OOA / ΔCO and SV-OOA / ΔCO, positively correlated with photochemical age. LV-OOA accounted for 73% of the OA secondary formation (SOA) in the oldest plumes (photochemical age of 25 h). The kOH at Changdao, by assuming SOA formation and aging as a first-order process proportional to OH, was calculated to be 5.2 × 10−12 cm3 molec.−1 s−1, which is similar to those determined in recent studies of polluted air in other continents.
Sweet corn is one of the most important vegetables in the United States and Canada. Here, we present a de novo assembly of a sweet corn inbred line Ia453 with the mutated shrunken2-reference allele ...(Ia453-sh2). This mutation accumulates more sugar and is present in most commercial hybrids developed for the processing and fresh markets. The ten pseudochromosomes cover 92% of the total assembly and 99% of the estimated genome size, with a scaffold N50 of 222.2 Mb. This reference genome completely assembles the large structural variation that created the mutant sh2-R allele. Furthermore, comparative genomics analysis with six field corn genomes highlights differences in single-nucleotide polymorphisms, structural variations, and transposon composition. Phylogenetic analysis of 5,381 diverse maize and teosinte accessions reveals genetic relationships between sweet corn and other types of maize. Our results show evidence for a common origin in northern Mexico for modern sweet corn in the U.S. Finally, population genomic analysis identifies regions of the genome under selection and candidate genes associated with sweet corn traits, such as early flowering, endosperm composition, plant and tassel architecture, and kernel row number. Our study provides a high-quality reference-genome sequence to facilitate comparative genomics, functional studies, and genomic-assisted breeding for sweet corn.
Cutaneous leishmaniasis (CL) is a chronic skin infection caused by Leishmania parasites, causing single or multiple skin nodules and ulcers on the exposed body locations. Healing of lesions is ...followed by scar formation. Active and healed CL lesions may affect patient's health related quality of life (HRQL). The aim of this study was to determine whether the body location of the leishmaniasis lesions affects the HRQL of localized CL patients in Suriname. The HRQL of 163 patients with CL was assessed by Skindex-29 and EQ-5D/VAS questionnaires. Forty-six patients out of the total study population also participated in a qualitative anthropological study involving in depth interviews. All patients were allocated in 4 groups in the following hierarchy: head and face, upper limbs, lower limbs and trunk. Patients with lesions on the lower limbs had significantly higher Skindex-29 scores, indicating worse HRQL, in the symptom scale compared to lesions on head/face and trunk. The lower limb group was more likely to report problems in the dimensions self-care, mobility, daily activities and pain/discomfort of the EQ-5D. Little to no social stigma was reported in the in-depth interviews. The findings of this study indicate that Surinamese patients with CL lesions located on the lower limbs had more impairment in HRQL than on other body locations. Stigma related to CL seems to be virtually absent in Suriname.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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