Engineering zinc oxide hybrid selenium nanoparticles for synergetic anti-tuberculosis treatment by combining Mycobacterium tuberculosis killings and host cell immunological inhibition

IntroductionAs a deadly disease induced by Mycobacterium tuberculosis (Mtb), tuberculosis remains one of the top killers among infectious diseases. The low intracellular Mtb killing efficiency of current antibiotics introduced the long duration anti-TB therapy in clinic with strong side effects and increased drug-resistant mutants. Therefore, the exploration of novel anti-TB agents with potent anti-TB efficiency becomes one of the most urgent issues for TB therapies. MethodsHere, we firstly introduced a novel method for the preparation of zinc oxide-selenium nanoparticles (ZnO-Se NPs) by the hybridization of zinc oxide and selenium to combine the anti-TB activities of zinc oxide nanoparticles and selenium nanoparticles. We characterized the ZnO-Se NPs by dynamic laser light scattering and transmission electron microscopy, and then tested the inhibition effects of ZnO-Se NPs on extracellular Mtb by colony-forming units (CFU) counting, bacterial ATP analysis, bacterial membrane potential analysis and scanning electron microscopy imaging. We also analyzed the effects of ZnO-Se NPs on the ROS production, mitochondrial membrane potential, apoptosis, autophagy, polarization and PI3K/Akt/mTOR signaling pathway of Mtb infected THP-1 macrophages. At last, we also tested the effects of ZnO-Se NPs on intracellular Mtb in THP-1 cells by colony-forming units (CFU) counting. ResultsThe obtained spherical core-shell ZnO-Se NPs with average diameters of 90 nm showed strong killing effects against extracellular Mtb, including BCG and the virulent H37Rv, by disrupting the ATP production, increasing the intracellular ROS level and destroying the membrane structures. More importantly, ZnO-Se NPs could also inhibit intracellular Mtb growth by promoting M1 polarization to increase the production of antiseptic nitric oxide and also promote apoptosis and autophagy of Mtb infected macrophages by increasing the intracellular ROS, disrupting mitochondria membrane potential and inhibiting PI3K/Akt/mTOR signaling pathway. DiscussionThese ZnO-Se NPs with synergetic anti-TB efficiency by combining the Mtb killing effects and host cell immunological inhibition effects were expected to serve as novel anti-TB agents for the development of more effective anti-TB strategy

Research on control strategy of cascaded power electronic transformer based on capacitance minimization

Compared with the traditional power transformer, the cascaded PET has various functions, which integrates the functions of voltage conversion, high-frequency electrical isolation, flexible power flow control and AC/ DC power interface. In order to improve the transmission efficiency and power density of cascaded PET, it is necessary to reduce the voltage ripple of the DC sides in PET. The input stage and output stage of cascaded PET are modeled separately, and the ripple characteristics of DC side are analyzed. Compared with PI controller, PIR controller has higher gain at 100Hz is investigated. A coordinated control strategy of cascaded PET based on capacitance minimization is proposed. The input stage of PET is controlled by the traditional decoupling control method, and the output stage is controlled by phase-shift control method with PIR controller. The effectiveness and feasibility of the proposed strategy are verified by experiments. The results demonstrate that the voltage ripple can be reduced to 1/4 of the original. Within the boundary of the specified ripple, DC side capacitance can be reduced to 1/4 of the original

Orthostatic change in systolic blood pressure associated with cold pressor reflection and heart rate variability in the elderly

Background: Impaired orthostatic blood pressure (BP) response is a frequent finding in the elderly. The goal of the study was to investigate the association of variability of supine-to-orthostatic BP with cold pressor reflection and heart rate variability in the elderly. Methods: From June 2010 to September 2013, 287 elderly aged ≥ 60 years were enrolled in Jinan area, China. The elderly were classified into lower (n = 96), intermediate (n = 95), and higher (n = 96) tertile groups according to the tertile of the percentage change of supine-to-orthostatic systolic BP. Results: There were significant increasing trends in systolic BP response to the CPT at 0 and 60 sec; the plasma levels of epinephrine, norepinephrine, and angiotensin II; and decreasing trends in DNN, SDNN index, and SDANN from the lower to the higher tertile group, and differences between any two groups were significant (P < .05). The percentage change of supine-to-orthostatic systolic BP was positively correlated with systolic BP response to CPT at 0 and 60 sec, VLF, epinephrine, norepinephrine, and angiotensin II (P < .001) and negatively correlated with SDNN, SDNN index, SDANN, rMSSD, pNN50, LF, and ratio of LF/HF (P < .001). The BP response to CPT, parameters of HRV, and the plasma levels of norepinephrine and angiotensin II were independently associated with the percentage change of supine-to-orthostatic systolic BP after adjustment for confounders. Conclusion: Aggressive variability of supine-to-orthostatic systolic BP might be significantly associated with the imbalance of sympathetic and parasympathetic activity, especially high sensitivity sympathetic response in the elderly. Abbreviations: BP: blood pressure; BMI: body mass index; CPT: cold pressor test; HRV: heart rate variability; SDNN: standard deviation of all normal-to-normal R-R intervals; SDNN index: mean of the standard deviations of all 5-min normal-to-normal R-R intervals of the entire recording; SDANN: standard deviation of the averages of normal-to-normal R-R intervals during all 5-min periods of the entire recording; rMSSD: square root of the mean squared differences between successive normal R-R intervals; pNN50: number of adjacent normal R-R intervals differing by more than 50 ms; VLF: very low frequency; LF: low frequency; HF: high frequency; TCHO: total cholesterol; HDL-c: high-density lipoprotein cholesterol; LDL-c: low-density lipoprotein cholesterol; FPG: fasting plasma glucose; SD: standard deviation

Rapid screening and determination of 11 new psychoactive substances by direct analysis in real time mass spectrometry and liquid chromatography/quadrupole time-of-flight mass spectrometry

RATIONALE: With the amounts and types of new psychoactive substances (NPSs) increasing rapidly in recent years, an excellent high-throughput method for the analysis of these compounds is urgently needed. In this article, a rapid screening method and a quantitative analysis method for 11 NPSs are described and compared, respectively. METHOD: A simple direct analysis in real time mass spectrometry (DART-MS) method was developed for the analysis of 11 NPSs including three categories of these substances present on the global market such as four cathinones, one phenylethylamine, and six synthetic cannabinoids. In order to analyze these compounds quantitatively with better accuracy and sensitivity, another rapid analytical method with a low limit of detection (LOD) was also developed using liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (LC/QTOFMS). RESULTS: The 11 NPSs could be determined within 0.5 min by DART-MS. Furthermore, they could also be separated and determined within 5 min by the LC/QTOFMS method. The two methods both showed good linearity with correlation coefficients (r(2)) higher than 0.99. The LODs for all these target NPSs by DART-MS and LC/QTOFMS ranged from 5 to 40 ng mL(-1) and 0.1 to 1 ng mL(-1), respectively. Confiscated samples, named as &quot;music vanilla&quot; and &quot;bath salt&quot;, and 11 spiked samples were firstly screened by DART-MS and then determined by LC/QTOFMS. CONCLUSIONS: The identification of NPSs in confiscated materials was successfully achieved, and the proposed analytical methodology could offer rapid screening and accurate analysis results. Copyright (C) 2016 John Wiley &amp; Sons, Ltd.SCI(E)CPCI-S(ISTP)[email protected],SI141-1463

The Use of Dental Patient-Reported Outcomes Among Randomized Controlled Trials in Orthodontics: A Methodological Study

Objective: To identify and summarize the presence and characteristics of dental patient-reported outcomes (dPROs) and dental patient-reported outcome measures (dPROMs) within comparative observational studies published in 5 leading orthodontic journals.Methods: Electronic searching was performed to identify intervention (therapeutic or preventive) related comparative observational studies published in selected journals between 2015 and 2021. Two authors extracted the characteristics of each included study independently and in duplicate, and summarized the dPROs and dPROMs used in these studies. All dPROs were classified into 2 general types (oral health-related quality of life [OHRQoL] and others), while dPROMs were divided into 3 categories (single-item questionnaires, generic multiple-item questionnaires, and specific multiple-item questionnaires). In addition, dPROMs were examined if they evaluated the 4 dimensions of OHRQoL (Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact).Results: A total of 683 observational studies were eligible and included, of which 117 (17.1%) used dPROs and dPROMs. Seven different dPROs (OHRQoL, patients’ satisfaction with treatment, preferences, concerns, compliance, duration, and unwanted events) and 33 different dPROMs (including 8 single-item questionnaires, 11 generic multiple-item questionnaires, and 14 specific multiple-item questionnaires) were identified in these studies. OHRQoL was the most commonly used dPRO (92/117, 78.6%), while Oral Health Impact Profile 14 (OHIP-14) was the most frequently used dPROM (20/92, 21.7%). In terms of study design, cross-sectional studies had the highest proportion of dPRO usage (62/148, 41.9%), followed by cohort studies (63/505, 12.5%) and case-control studies (1/30, 3.3%).Conclusions: Only one-sixth of comparative observational studies published in leading orthodontic journals could reflect patients’ perspectives. Observational studies in orthodontics need to provide more patient-important information through the use of dPROs and dPROMs

Short term Load Forecasting Considering Demand Response under virtual power plant mode

In order to better manage demand response resources of user side and reduce short-term load forecasting error, a short-term load forecasting method considering demand response in virtual power plant mode is proposed. Firstly, the demand response mechanism of the virtual power plant is analyzed. Taking the maximum profit of the virtual power plant as the goal, considering the user’s energy consumption habits, self built photovoltaic, energy storage behavior and thermal electric coupling, the optimization model is established for each type of demand response resources. The CPLEX solver is called to solve the mixed integer linear programming problem after the model transformation, and the sub signals of each resource participating in the demand response are obtained. Then, based on this model, a long-term and short-term memory network model considering demand response signals is established to predict load power iteratively. At the same time, the long-term and short-term memory network model considering the demand response signals effectively makes up for the shortcomings of the traditional forecasting model without considering the demand response, and is more accurate in predicting the future trend of load change

MicroRNA-124 Regulates the Proliferation of Colorectal Cancer Cells by Targeting iASPP

MicroRNAs are a class of small, noncoding RNAs that function as critical regulators of gene expression by targeting mRNAs for translational repression or degradation. In this study, we demonstrate that expression of microRNA-124 (miR-124) is significantly downregulated in colorectal cancer tissues and cell lines, compared to the matched adjacent tissues. We identified and confirmed inhibitor of apoptosis-stimulating protein of p53 (iASPP) as a novel, direct target of miR-124 using target prediction algorithms and luciferase reporter gene assays. Overexpression of miR-124 suppressed iASPP protein expression, upregulated expression of the downstream signaling molecule nuclear factor-kappa B (NF-κB), and attenuated cell viability, proliferation, and colony formation in SW480 and HT-29 colorectal cancer cells in vitro. Forced overexpression of iASPP partly rescued the inhibitory effect of miR-124 on SW480 and HT29 cell proliferation. Taken together, these findings shed light on the role and mechanism of action of miR-124, indicate that the miR-124/iASPP axis can regulate the proliferation of colorectal cancer cells, and suggest that miR-124 may serve as a potential therapeutic target for colorectal cancer

Performance Analysis of Gas Turbine Using Hydrogen-Added Natural Gas

The off-design performance of gas turbine system is essential for a power plant. The present study developed an off-design simulation model to analyze a 4.5 MW level practical power gas turbine. The gas turbine was modelled on the basis of components models which are built with Simulink tools. Comparisons of different performance parameters at design point are performed to verify the simulation model. Off-design studies were performed on the gas turbine using hydrogen-added fuel to examine the effect of hydrogen ratio on key parameters, such as the power output, efficiency, exhaust temperature, etc. It has been shown that hydrogen-added natural gas fuels can improve gas turbine performance, as higher proportion of hydrogen leads to higher efficiency in some power output range. The study can provide a tool for performance analysis on natural gas/hydrogen fuel gas turbine