Neural stem cell-conditioned medium ameliorates Aβ25–35-induced damage in SH-SY5Y cells by protecting mitochondrial function

Inhibition of amyloid β (Aβ)-induced mitochondrial damage is considered crucial for reducing the pathological damage in Alzheimer’s disease (AD). We evaluated the effect of neural stem cell-conditioned medium (NSC-CDM) on Aβ25–35-induced damage in SH-SY5Y cells. An in vitro model of AD was established by treating SH-SY5Y cells with 40 µM Aβ25–35 for 24 h. SH-SY5Y cells were divided into control, Aβ25–35 (40 µM), Aβ25–35 (40 µM) + NSC-CDM, and Aβ25–35 (40 µM) + neural stem cell-complete medium (NSC-CPM) groups. Cell viability was detected by CCK-8 assay. Apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) were detected by flow cytometry. Malondialdehyde content was detected by ELISA assay. Western blot analysis was used to detect cytochrome c release and apoptosis-related proteins. Transmission electron microscopy was used to observe mitochondrial morphology. Cell viability significantly decreased and apoptosis significantly increased in SH-SY5Y cells treated with Aβ25–35, and both effects were rescued by NSC-CDM. In addition, NSC-CDM reduced ROS production and significantly inhibited the reduction of MMP caused by Aβ25–35. Furthermore, NSC-CDM ameliorated Aβ25–35-induced reduction in Bcl-2 expression levels and increased the expression levels of cytochrome c, caspase-9, caspase-3, and Bax. Moreover, Aβ25–35 induced the destruction of mitochondrial ultrastructure and this effect was reversed by NSC-CDM. Collectively, our findings demonstrated the protective effect of NCS-CDM against Aβ25–35-induced SH-SY5Y cell damage and clarified the mechanism of action of Aβ25–35 in terms of mitochondrial maintenance and mitochondria-associated apoptosis signaling pathways, thus providing a theoretical basis for the development of novel anti-AD treatments

Syndemics of syphilis, HCV infection, and methamphetamine use along the east coast of China

An upsurge in club drug use has been observed in recent years in some cities of China, especially methamphetamine, which is quickly replacing heroin to become the most widespread drug across the nation. This study investigated the type of drugs used, syphilis and hepatitis C virus (HCV) infection and the correlates for syphilis, HCV and unprotected commercial sex behavior among drug users in two cities along the east coast of China. A cross-sectional survey conducted in 2010 provided demographics, sexual and drug use behaviors, HIV knowledge and the utilization of intervention services among drug users. Blood samples were tested for HIV, syphilis, and HCV infection. Of 805 eligible participants, 0.2% were infected with HIV, 3.7% with HCV, and 9.6% with syphilis. Of the participants, 96.6% were methamphetamine users, 11.9% reported ever having used ≥2 types of these drugs, and 11.4% reported ever injecting drugs. In the multivariable logistic regression analysis, participants infected with syphilis were more likely to be female (adjusted odds ratio (AOR)=2.8, 95% confidence interval (CI): 1.2-6.5), have ever had commercial sex in the past 12 months (AOR=2.0, 95% CI: 1.0-3.9), be infected with HCV (AOR=12.1, 95% CI: 4.1-20.3) and less likely to have ever had sex with regular partners in the past 12 months (AOR=0.2, 95% CI: 0.1-0.6). Participants infected with HCV were more likely to have ever injected drugs (AOR=2.7, 95% CI: 1.1-6.5) and be infected with syphilis (AOR=8.0, 95% CI: 3.5-18.0). Participants who had unprotected sex with commercial sex partners in the last sexual encounter were more likely to be female (AOR=2.9, 95% CI:1.7-4.9), have middle school or lower level education (AOR=3.4, 95% CI:2.0-5.5), never have received intervention in the last year (AOR=2.1, 95%CI:1.2-3.6) and be infected with syphilis (AOR=4.2, 95% CI:2.4-7.4). Methamphetamine is the predominant drug used among the drug users, the prevalence of syphilis and HCV infection are alarmingly high, and unprotected commercial sex was common among this group. The findings highlight the need for effective, multifaceted interventions addressing sexual and drug use-related risky behaviors among this group. Further research is needed to better understand the causal pathway of the syndemics.https://doi.org/10.1186/1471-2458-14-17

Multi-Depot Heterogeneous Vehicle Routing Optimization for Hazardous Materials Transportation

This paper considers a multi-depot heterogeneous vehicle routing problem (MDHVRP) with time windows, which is very crucial for hazardous materials transportation. For this reason, we formalize this problem as a multi-objective MDHVRP optimization model, where the actual load dependent risk of hazardous materials transportation is considered. To solve the optimization problem, we propose a hybrid multi-objective evolutionary algorithm (HMOEA) and a two-stage algorithm (TSA). In addition, we verify the performance of the proposed algorithms by experiments on the modified Solomon’s VRPTW examples. In the experiment, it can be seen from the distribution of Pareto solution sets and the convergence distribution of IGD values that HMOEA is significantly superior to the other three algorithms in searching for Pareto solutions, as well as in the convergence and diversity of the algorithm. HMOEA and TSA were compared, and the minimum cost obtained by TSA was 13.38% lower than HMOEA, while the minimum risk was 81.69% higher than HMOEA. The advantages of each algorithm in finding solutions in reality were analyzed. A comparison was made between multi-depots heterogeneous VRP and multi-depots homogeneous VRP in the C101 instance, and the results showed that scheduling heterogeneous vehicles would reduce risk and cost

Production of highly efficient cellulase mixtures by genetically exploiting the potentials of Trichoderma reesei endogenous cellulases for hydrolysis of corncob residues

Abstract Background Trichoderma reesei is one of the most important fungi utilized for cellulase production. However, its cellulase system has been proven to be present in suboptimal ratio for deconstruction of lignocellulosic substrates. Although previous enzymatic optimization studies have acquired different types of in vitro synthetic mixtures for efficient lignocellulose hydrolysis, production of in vivo optimized cellulase mixtures by industrial strains remains one of the obstacles to reduce enzyme cost in the biofuels production from lignocellulosic biomass. Results In this study, we used a systematic genetic strategy based on the pyrG marker to overexpress the major cellulase components in a hypercellulolytic T. reesei strain and produce the highly efficient cellulase mixture for saccharification of corncob residues. We found that overexpression of CBH2 exhibited a 32-fold increase in the transcription level and a comparable protein level to CBH1, the most abundant secreted protein in T. reesei, but did not contribute much to the cellulolytic ability. However, when EG2 was overexpressed with a 46-fold increase in the transcription level and a comparable protein level to CBH2, the engineered strain QPE36 showed a 1.5-fold enhancement in the total cellulase activity (up to 5.8 U/mL FPA) and a significant promotion of saccharification efficiency towards differently pretreated corncob residues. To assist the following genetic manipulations, the marker pyrG was successfully excised by homologous recombination based on resistance to 5-FOA. Furthermore, BGL1 was overexpressed in the EG2 overexpression strain QE51 (pyrG-excised) and a 11.6-fold increase in BGL activity was obtained. The EG2–BGL1 double overexpression strain QEB4 displayed a remarkable enhancement of cellulolytic ability on pretreated corncob residues. Especially, a nearly complete cellulose conversion (94.2%) was found for the delignified corncob residues after 48 h enzymatic saccharification. Conclusions These results demonstrate that genetically exploiting the potentials of T. reesei endogenous cellulases to produce highly efficient cellulase mixtures is a powerful strategy to promote the saccharification efficiency, which will eventually facilitate cost reduction for lignocellulose-based biofuels

In Vitro and In Vivo Evaluation of Desogestrel-Loaded Poly(D,L-lactic Acid) Nanoparticles

The aim of this study was to explore the synthesis parameters of desogestrel-polylactic acid nanoparticles (DG-PLA-NPs), optimise the preparation technology, and elucidate the in vitro release characteristics. Considering encapsulation efficiency (EE) and drug loading as the main evaluation indexes, DG-PLA-NPs were prepared using the modified emulsion solvent diffusion method and single factor and orthogonal design tests were performed to investigate the influencing factors and optimise the preparation method. Morphology of the nanoparticles was observed using transmission electron microscopy (TEM), average particle diameter and distribution were determined using dynamic laser particle size analysis, and the EE and drug loading were measured using reversed-phase high-performance liquid chromatography. Among the eight factors, the drug-to-material ratio, water-to-organic phase ratio, and polyvinyl alcohol (PVA) concentration significantly affected the NP EE. In the optimised formulation, the PLA/DG ratio, PVA concentration, and oil-to-water phase ratio were 5, 0.5%, and 5, respectively. The DG-PLA-NPs prepared with the optimised formulation were round or spherical with an average diameter of 209 nm, 79.60% EE, and 6.81% drug loading capacity. The polydispersity index was 0.181, and the zeta potential was −27.37 mV. The in vitro releases of both DG and DG-PLA-NPs conformed to the Weibull equation. The DG-PLA-NPs released desogestrel rapidly in the early stages but slowly at later stages, indicating that compared to DG, the DG-PLA-NPs had obvious sustained-release effects. The DG-PLA-NPs prepared by the modified emulsion solvent diffusion method were small, simple to prepare, and had high drug loading with promising application prospects

POV-based molecular catalysts for highly efficient esterification of alcohols with aldehydes as acylating agents

The selective oxidative esterification of aldehydes with alcohols to the corresponding esters has been one of the hot spots in scientific research and industrial synthesis. However, the application of precious metal catalytic systems is limited by their complicated synthetic steps and high cost. Thus a highly efficient, green, recyclable selective synthesis method of esters catalyzed by POV(polyoxovanadate)-based molecular catalysts has been developed in this paper. The results show that supramolecular interaction between POV and 1,3-dibenzylimidazolium bromide (Act2Im) can efficiently convert alcohols and aldehydes to the corresponding esters in high yield under much milder conditions. Mechanistic insight is also provided based on the control experiments, single crystal X-ray diffraction and cyclic voltammetry studies

Sedimentary environment and shale gas exploration potential of Qiongzhusi Formation in the upslope area: A case study on Well W-207, Weiyuan area, Sichuan Basin

To deeply analyze the thalassochemical conditions and organic matter enrichment mechanism during the Early Cambrian (541-509 Ma)and actively evaluate the potential of shale gas resources of the Lower Cambrian Qiongzhusi Formation(Fm) in the southwestern Sichuan Basin, based on the analysis of the petrology, organic geochemistry, element characteristics, pore structure and adsorption capacity of Qiongzhusi Formation, Well W-207, Weiyuan area, this study has discussed the Early Cambrian paleo-ocean environment, organic matter enrichment control factors and gas-bearing properties of shale gas in the upslope area of the Upper Yangtze Platform. Sedimentary cycle shows that multiple interactive conversioncycles of deep-water continental shelf and shallow-water continental shelf are developed during the fine-grained deposition period of Qiongzhusi Formation under the control of eustasy. In particular, the slope turbidite (fan) and gravity flow sediments indicate that shallow-water continental shelf facies are dominant, and the wells in the upslope of the Weiyuan area are not in deep-water for a long time, with the sedimentary thickness of organic-rich black shale limited. Organic geochemistry evidence indicates that the organic matter of Qiongzhusi Formation in Well W-207 is mainly Type-Ⅰ kerogen, with a high degree of thermal evolution, fewer residual hydrocarbons and a low hydrocarbon generation capacity. The redox parameters indicate that the marine environment on the upslope has a medium restrictive degree, and there is a certain degree of upwelling. The seawater has experienced the transformation process of "anoxic-oxidation-anoxic-secondary oxidation- oxidation". Therefore, the paleo-ocean productivity level in the upslope area is generally low, with an obvious downward trend from bottom to top. The pore structure and nitrogen adsorption curve show that the reservoirs of the Qiongzhusi Formation are mainly complex and irregular slit pores. The methane adsorption capacity is positively correlated with TOC but negatively correlated with temperature, indicating that the high-pressure and high-temperature conditions generally faced by the Qiongzhusi Fm are not suitable for methane adsorption. As a result, the geological conditions of shale gas for Qiongzhusi Fm in the upslope area are complex. With high exploration risk, this study suggests that the resource evaluation direction should change to the intracratonic sag (downslope area), which is characterized by deep-water continental shelf facies

Alcohol Use, Stigmatizing/Discriminatory Attitudes, and HIV High-Risk Sexual Behaviors among Men Who Have Sex with Men in China

Objective. This research was conducted to assess the correlates of alcohol consumption and HIV/AIDS-related stigmatizing and discriminatory attitudes among men who have sex with men (MSM) in Shandong province, China. Methods. A cross-sectional survey provided demographics, sexual behaviors, illicit drug use, alcohol consumptions, and service utilization. Results. Of 1,230 participants, 82.8% were single, 85.7% aged <35 years, 47.2% had college or higher education, and 11.7% drank alcohol >3 times per week in the past six months. The average total score of stigmatizing and discriminatory attitude was 37.4 ± 4.4. More frequent episodes of alcohol use were independently associated with higher levels of HIV/AIDS-related stigma and discrimination, unprotected anal sex, bisexual identity, multiple male sex partners, drug use, and lower levels of education. Expressing higher levels of HIV/AIDS-related stigmatizing and discriminatory attitudes was independently associated with alcohol use, unprotected male anal sex, bisexuals, more male sex partners, commercial sex with men, and non-receipt of peer education in the past year. Conclusion. HIV/AIDS-related stigmatizing and discriminatory attitudes are common and associated with alcohol use and unprotected sex among MSM. The finding highlights the needs to develop programs that would reduce HIV/AIDS-related stigmatizing and discriminatory attitudes and strengthen alcohol use prevention and risk reduction initiatives among MSM

Enthalpies of Dilution of Penicillamines in <i>N</i>,<i>N</i>‑Dimethylformamide + Water Mixtures at 298.15 K

Dilution enthalpies of two penicillamine enantiomers, namely, d-penicillamine, l-penicillamine, and their racemate d,l-penicillamine, in <i>N</i>,<i>N</i>-dimethylformamide (DMF) + water mixtures of various compositions have been determined at 298.15 K respectively, using an isothermal titration calorimeter (MicroCal ITC200). According to the McMillan–Mayer theory, homochiral enthalpic pairwise interaction coefficients (<i>h</i>_XX) of the three penicillamines in DMF + water mixtures of different mass fractions (<i>w</i>_DMF = 0 to 0.3) have been calculated regressively. It is found that <i>h</i>_XX coefficients of each enantiomer and their racemate change increasingly with <i>w</i>_DMF to the maxima at <i>w</i>_DMF = 0.20 and then decrease relatively rapidly, which follows the order <i>h</i>_LL > <i>h</i>_DD ≈ <i>h</i>_RR > 0 (R represents the racemate mixture of penicillamine). The results are discussed from the point of view of competitive equilibrium between hydrophobic and hydrophilic interactions in solutions