Community prevalence of carbapenemase-producing Gram-negative bacteria

Purpose: To raise awareness of carbapenemase-producing organisms, identify “at-risk” patients when admitted in a medical healthcare facility, and to outline effective infection prevention and control measures in order to halt the entry and spread of these organisms. Methods: A total of 1043 un-duplicated urine specimens of healthy volunteers who had no travel history or history of hospitalization were screened. The carbapenemase genotype of each imipenem-resistant strain was determined. Molecular typing and homology analysis of the main carbapenemase-producing strains were used to reveal the mode of transmission of resistance genes. Through transfer joint experiments, the potential risk of spread of carbapenemase genes was assessed. Results: A total of 19 carbapenemase-producing strains from 1,043 non-duplicated healthy volunteers (1.82 %) were identified. The main carbapenemase-producing organism was E. coli (42.1 %, 8/19). The main carbapenemase genotype of E. coli was blaKPC-2 (7 strains). Results from multi-locus sequence typing (MLST) indicated that 7 E. coli isolates belonged to ST-10, ST-101, ST-131, ST-405, ST-410 and ST-1193 and ST-2562. Homologous cluster analysis revealed that the sequence types among the 7 E. coli were high in diversity. The blaKPC-2 gene was successfully transferred from these isolates to 10.22-14 via conjugation. All recipient cells showed marked decreases in carbapenem sensitivity to imipenem (p < 0.05)). The degrees of conjugation were 2.10±0.12 ×10-4, 1.96±0.14×10-4, 2.72±0.18 ×10-4, 3.15±0.20 × 10-4, 2.92±0.23 ×10-4, 3.50±0.20 ×10-4 and 4.12±0.24 ×10-4 in recipient cells of TC7.23-51, TC8.9-42, TC8.15-11, TC8.23-59-3, TC8.23-83, TC9.08-47 and TC10.13-15, respectively. Conclusion: The findings demonstrate the pattern and features of carbapenemase-insensitive E. coli. The blaKPC-2 was the main community-prevalent gene of carbapenem-resistant E. coli. In view of increasing incidence of resistance to multi-drug therapy, surveillance of insensitivity to antibiotics is vital, especially urinary system infection due to carbapenem-insensitive E. coli

Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair.

Contrary to the long-held belief that DNA methylation of terminally differentiated cells is permanent and essentially immutable, post-mitotic neurons exhibit extensive DNA demethylation. The cellular function of active DNA demethylation in neurons, however, remains largely unknown. Tet family proteins oxidize 5-methylcytosine to initiate active DNA demethylation through the base-excision repair (BER) pathway. We found that synaptic activity bi-directionally regulates neuronal Tet3 expression. Functionally, knockdown of Tet or inhibition of BER in hippocampal neurons elevated excitatory glutamatergic synaptic transmission, whereas overexpressing Tet3 or Tet1 catalytic domain decreased it. Furthermore, dysregulation of Tet3 signaling prevented homeostatic synaptic plasticity. Mechanistically, Tet3 dictated neuronal surface GluR1 levels. RNA-seq analyses further revealed a pivotal role of Tet3 in regulating gene expression in response to global synaptic activity changes. Thus, Tet3 serves as a synaptic activity sensor to epigenetically regulate fundamental properties and meta-plasticity of neurons via active DNA demethylation

Prevalence and severity of anxiety and depression in Chinese patients with breast cancer: a systematic review and meta-analysis

ContextAnxiety/depression in breast cancer (BC) is common around the world, and Chinese BC patients should not be ignored. The prevalence of anxiety and depression among BC patients are various in different regions of China, but no clear summarization has been made.PurposeThis meta-analysis aimed to evaluate the prevalence and severity of anxiety and depression among breast cancer (BC) patients in China.MethodsA literature search on PubMed, Web of Science, Embase, CINAHL, Scopus, PsycINFO, Cochrane database library, CNKI, Wanfang, and SinoMed was conducted up to 29 December 2021. The effect size (ES) or standard mean difference (SMD) and the corresponding 95% confidence intervals (CIs) for the prevalence and severity of anxiety/depression were calculated using the STATA 12.0 software.ResultsA total of 63 identified studies were included, containing a total of 53,513 Chinese women confirmed breast cancer. The results showed a high pooled prevalence of anxiety (38%, 95% CI, 27–50%, I2 = 99.4%, p < 0.001) and depression (38%, 95% CI, 33–44%, I2 = 99.2%, p < 0.001) among Chinese BC patients. Moreover, both anxiety (SMD = 0.30, 95% CI, 0.08–0.53, I2 = 91.6%, p < 0.001) and depression (SMD = 0.25, 95% CI, −0.05–0.55, I2 = 95.3%, p < 0.001) in BC patients were more serious than those in healthy controls, but not significantly different from patients with other diseases. Specifically, among the six regions included, the prevalence of anxiety and depression were both the highest in Northeast China, obviously superior than the second-highest region.ConclusionThe study showed high levels of anxiety and depression among BC patients in China, especially those in the northeast. Clinicians and researchers should pay attention to the psychological problems of patients with breast cancer and regard it as one of the important prognostic outcomes of patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/index.php, PROSPERO: CRD42020151752

Differential effects of partial and complete loss of TREM2 on microglial injury response and tauopathy.

Alzheimer's disease (AD), the most common form of dementia, is characterized by the abnormal accumulation of amyloid plaques and hyperphosphorylated tau aggregates, as well as microgliosis. Hemizygous missense variants in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) are associated with elevated risk for developing late-onset AD. These variants are hypothesized to result in loss of function, mimicking TREM2 haploinsufficiency. However, the consequences of TREM2 haploinsufficiency on tau pathology and microglial function remain unknown. We report the effects of partial and complete loss of TREM2 on microglial function and tau-associated deficits. In vivo imaging revealed that microglia from aged TREM2-haploinsufficient mice show a greater impairment in their injury response compared with microglia from aged TREM2-KO mice. In transgenic mice expressing mutant human tau, TREM2 haploinsufficiency, but not complete loss of TREM2, increased tau pathology. In addition, whereas complete TREM2 deficiency protected against tau-mediated microglial activation and atrophy, TREM2 haploinsufficiency elevated expression of proinflammatory markers and exacerbated atrophy at a late stage of disease. The differential effects of partial and complete loss of TREM2 on microglial function and tau pathology provide important insights into the critical role of TREM2 in AD pathogenesis

PO-222 The Influence of Different Route Randomness on Energy Contributions of College Students' Badminton Running Practice with Change of Direction at Two Frequencies

Objective Badminton four-corner running practice with change of direction commonly includes fix route and random route. However, the study of the energy contributions characteristics of these two training methods was very limited. The aim of this study was to investigate the influence of different route randomness on energy contributions of college students' badminton running practice with change of direction at two frequencies.   Methods 15 college badminton player whom from Shanghai University of Sport (Male, N=15, 22.9±1.4 yrs, 175.7±6.0 cm, 68.0±6.4kg, badminton training experience 2.2±0.5 yrs) volunteered to perform one test for maximal oxygen uptake （VO2max） on treadmill and four field tests with two route randomness (fix route and random route, F and R ) and two frequencies (24 times per 1min and 24 times per 1min, H and L ) of change of direction. A portable spirometric system (K4b2, Cosmed, Italy) was utilized to measure the ventilator information during the test, and capillary blood was taken from earlobe and analyzed prior and post the tests. The energy contributions was calculated with the method based on the fast component of oxygen debt (WAla) , accumulated blood lactate (WLa) and VO2 (WAer)during the tests. Results Higher frequency significantly increased the energy contributions from the three pathways both with F and R (WAla:26.2±6.3 kJ vs. 39.5±12.6 kJ, WLa: 5.7±2.4kJ vs. 23.1±9.3 kJ, WAer: 27.1±6.5kJ vs. 33.3±5.7kJ, P<0.01), and significantly increased the WLa (F: 23.9±8.1% vs. 9.6±3.4%, P<0.01; R: 30.5±6.6% vs. 11.7±5.2%, P<0.01), whereas significantly reduced the WAer% (F: 35.2±6.5% vs. 46.0±8.5%, P<0.01; R: 35.7±5.4 % vs. 50.4±10.2%, P<0.01). The R significantly reduced the WLa% both in L (44.4±8.5% vs. 38.0±8.6% , P<0.05) and H (40.9±10.5% vs. 33.8±8.6%, P<0.05), significantly increased the WLa (23.1±9.3kJ vs. 28.9±7.3kJ, P<0.05) and WLa% (23.9±8.1% vs. 30.5±1.7%) in H. Conclusions The route randomness of badminton running practice with change of direction at two frequencies has different effects on the energy contributions. The R will reduce the stimulation to the WAla and increase the stimulation to the WLa ; the H will increase the intensity of the running with change of direction as a whole, and will reducing the stimulation to the WAer and increasing the stimulation to the WLa. It is recommended that the coaches can change the stimulation of the WLa by changing the frequency of the change of direction and the randomness of the route when design the badminton four-corner running practice with change of direction. &nbsp

LIM-domain binding protein 2 was down-regulated by miRNA-96-5p inhibited the proliferation, invasion and metastasis of lung cancer H1299 cells

  Objectives: Lung cancer was one of the most common malignancies around the world. It has great significance in to search for the mechanism of occurrence and development of lung cancer. LIM Domain Binding protein 2 (LDB2) belongs to the LIM-domain binding family, it can be used as a binding protein that combined with other transcription factors to form the transcription complex for regulating the expression of target genes. The expression of microRNA-96-5p (miR-96-5p) has been investigated in various tumors. The aim of this study is to investigate the potential role of LDB2 and miR-96-5p in lung cancer. Methods: Real-time quantitative PCR was applied to detect the expression of LDB2 and miR-96-5p. The proliferation, invasion, and metastasis of H1299 cells were analyzed by CCK8, transwell, and wound healing assay after LDB2 or miR-96-5p transfection. Luciferase activities assay and western blot were used to reveal the targeted regulation between LDB2 and miR-96-5p. Results: Here the authors found LDB2 was down-regulated in lung cancer tissues and negatively correlated with miR-96-5p expression, it could promote or inhibit the proliferation, invasion and metastasis of H1299 cells after LDB2 knockdown or overexpression and regulate the expression of cyclinD1, MMP9, Bcl-2, and Bax via ERK1/2 signaling pathway. Furthermore, miR-96-5p exerted its function by directly binding to 3′-UTR of LDB2 and regulating expression of LDB2. miR-96-5p could promote the proliferation, invasion, and metastasis of H1299 cells. Conclusion: These findings demonstrate that LDB2 can act as a new regulator to inhibit cell proliferation, invasion, and metastasis via the ERK1/2 signaling pathway, and miR-96-5p may be a potential promising molecular by targeting LDB2 in lung cancer

Characterization and optimization of heroin hapten-BSA conjugates: method development for the synthesis of reproducible hapten-based vaccines

A potential new treatment for drug addiction is immunization with vaccines that induce antibodies that can abrogate the addictive effects of the drug of abuse. One of the challenges in the development of a vaccine against drugs of abuse is the availability of an optimum procedure that gives reproducible and high yielding hapten-protein conjugates. In this study, a heroin/morphine surrogate hapten (MorHap) was coupled to bovine serum albumin (BSA) using maleimide-thiol chemistry. MorHap-BSA conjugates with 3, 5, 10, 15, 22, 28, and 34 haptens were obtained using different linker and hapten ratios. Using this optimized procedure, MorHap-BSA conjugates were synthesized with highly reproducible results and in high yields. The number of haptens attached to BSA was compared by 2,4,6-trinitrobenzenesulfonic acid (TNBS) assay, modified Ellman’s test and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Among the three methods, MALDI-TOF MS discriminated subtle differences in hapten density. The effect of hapten density on enzyme-linked immunosorbent assay (ELISA) performance was evaluated with seven MorHap-BSA conjugates of varying hapten densities, which were used as coating antigens. The highest antibody binding was obtained with MorHap-BSA conjugates containing 3–5 haptens. This is the first report that rigorously analyzes, optimizes and characterizes the conjugation of haptens to proteins that can be used for vaccines against drugs of abuse. The effect of hapten density on the ELISA detection of antibodies against haptens demonstrates the importance of careful characterization of the hapten density by the analytical techniques described. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00216-014-8035-x) contains supplementary material, which is available to authorized users

Aerobic Anoxygenic Phototrophic Bacteria Promote the Development of Biological Soil Crusts

Chlorophyll-containing oxygenic photoautotrophs have been well known to play a fundamental role in the development of biological soil crusts (BSCs) by harvesting solar radiations and providing fixed carbon to the BSCs ecosystems. Although the same functions can be theoretically fulfilled by the widespread bacteriochlorophyll-harboring aerobic anoxygenic phototrophic bacteria (AAnPB), whether AAnPB play a role in the formation of BSCs and how important they are to this process remain largely unknown. To address these questions, we set up a microcosm system with surface sands of the Hopq desert in northern China and observed the significant effects of near-infrared illumination on the development of BSCs. Compared to near-infrared or red light alone, the combined use of near-infrared and red lights for illumination greatly increased the thickness of BSCs, their organic matter contents and the microalgae abundance by 24.0, 103.7, and 1447.6%, respectively. These changes were attributed to the increasing abundance of AAnPB that can absorb near-infrared radiations. Our data suggest that AAnPB is a long-overlooked driver in promoting the development of BSCs in drylands

Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy

Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.Peer reviewe