Multidrug resistance (MDR) is a pressing obstacle in clinical chemotherapy for breast cancer. Based on the fact that the drug efflux is an important factor in MDR, we designed a codelivery system to ...guide the drug efflux inhibitor verapamil (VRP) and the chemotherapeutic agent novantrone (NVT) synergistically into breast cancer cells to reverse MDR.
This co-delivery system consists of following components: the active targeting peptide RGD, an inorganic calcium phosphate (CaP) shell and an organic inner core. VRP and NVT were loaded into CaP shell and phosphatidylserine polyethylene glycol (PS-PEG) core of nanoparticles (NPs) separately to obtain NVT- and VRP-loaded NPs (NV@CaP-RGD). These codelivered NPs allowed VRP to prevent the efflux of NVT from breast cancer cells by competitively combining with drug efflux pumps. Additionally, NV@CaP-RGD was effectively internalized into breast cancer cells by precise delivery through the effects of the active targeting peptides RGD and EPR. The pH-triggered profile of CaP was also able to assist the NPs to successfully escape from lysosomes, leading to a greatly increased effective intracellular drug concentration.
The concurrent administration of VRP and NVT by organic/inorganic NPs is a promising therapeutic approach to reverse MDR in breast cancer.
Battery energy storage systems (BESSs) have been widely deployed in microgrids to deal with uncertain output power of renewable distributed generation (DG) and improve renewable energy utilization ...efficiency. However, due to the short-term dispatch mode and BESS capacity limitation, current BESS dispatch decisions may not be efficient from a whole-day perspective, leading to an inadequate/excessive state of charge (SoC) for subsequent dispatch. To address this issue, an adaptive BESS dispatch method with SoC interval management is proposed for unbalanced three-phase microgrids, aiming to minimize the operating cost. In a day-ahead stage, an SoC interval is optimized considering the uncertainties of renewable DG, loads and market prices. During the day, the BESS is dispatched inside the SoC interval with a rolling horizon procedure to track uncertainty realization. Accordingly, a hybrid interval-robust optimization method is developed to solve the proposed scheduling problem under the uncertainties and procure the optimal SoC interval. Particularly, a decomposing and alternating solution algorithm is developed to identify the pessimistic case based on robust optimization while the SoC interval is determined on the basis of interval optimization. Simulation results verify high efficiency and solution robustness of the proposed hybrid interval-robust adaptive BESS scheduling method.
Electrochemical reduction of CO2 has been studied in 1-butyl-3-methylimidazolium trifluoromethanesulfonate (BmimCF3SO3)/propylene carbonate (PC) solution on Au electrode. The linear sweep voltammetry ...measurements show that BmimCF3SO3 has significant catalytic effect toward CO2 reduction. In order to study the mechanism of CO2 reduction in BmimCF3SO3/PC on Au electrode, the electrochemical impedance spectroscopy is employed. The experiment results show that the electrochemical impedance spectroscopy detected in BmimCF3SO3/PC is different from that detected in tetrabutylammonium trifluoromethanesulfonate (Bu4NCF3SO3)/PC solution. The reasonable explanation is that Bmim+ is absorbed on the Au electrode, leading to the formation of ionic liquid film. During the CO2 reduction process, absorbed CO2 is reduced to CO2− radical via single electron transfer. The generated CO2− radical interacts with Bmim+ and inducing the formation of Bmim-CO2(ad). Thus, the activation energy and overpotential of CO2 reduction are reduced. The electrochemical impedance spectroscopy can be used as a methods to investigate the mechanism of CO2 reduction in non-aqueous solution.
This letter proposes a machine learning-based linear programming model that quickly establishes the nonparametric prediction intervals of wind power by integrating extreme learning machine and ...quantile regression. The proportions of quantiles can be adaptively determined via sensitivity analysis. The proposed method has been proven to be significantly efficient and reliable, with a high application potential in power systems.
In recent years, accelerated transcranial magnetic stimulation (aTMS) has been developed, which has a shortened treatment period. The aim of this study was to evaluate the efficacy and long-term ...maintenance effects of aTMS in patients with major depressive disorder (MDD).
We systematically searched online databases for aTMS studies in patients with MDD published before February 2023 and performed a meta-analysis on the extracted data.
Four randomized controlled trials (RCTs) and 10 before-and-after controlled studies were included. The findings showed that depression scores significantly decreased following the intervention (SMD = 1.80, 95% CI (1.31, 2.30), p < 0.00001). There was no significant difference in antidepressant effectiveness between aTMS and standard TMS (SMD = -0.67, 95% CI (-1.62, 0.27), p = 0.16). Depression scores at follow-up were lower than those directly after the intervention based on the depression rating scale (SMD = 0.22, 95% CI (0.06, 0.37), p = 0.006), suggesting a potential long-term maintenance effect of aTMS. Subgroup meta-analysis results indicated that different modes of aTMS may have diverse long-term effects. At the end of treatment with the accelerated repetitive transcranial magnetic stimulation (arTMS) mode, depressive symptoms may continue to improve (SMD = 0.29, 95% CI (0.10, 0.49), I
= 22%, p = 0.003), while the accelerated intermittent theta burst stimulation (aiTBS) mode only maintains posttreatment effects (SMD = 0.01, 95% CI (-0.45, 0.47), I
= 66%, p = 0.98).
Compared with standard TMS, aTMS can rapidly improve depressive symptoms, but there is no significant difference in efficacy. aTMS may also have long-term maintenance effects, but longer follow-up periods are needed to assess this possibility.
This article is original and not under simultaneous consideration for publication. The study was registered on PROSPERO ( https://www.crd.york.ac.uk/prospero/ ) (number: CRD42023406590).
Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, yet the precise mechanisms underlying PTSD remains ...largely to be determined. Using an animal model of PTSD induced by a single prolonged stress (SPS), we assessed the role of hippocampal nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and parvalbumin (PV) interneurons in the development of PTSD symptoms. In the present study, behavioral tests were performed by the open field (day 13 after SPS) and fear conditioning tests (days 13 and 14 after SPS). For the interventional study, rats were chronically treated with a NADPH oxidase inhibitor apocynin either by early or delayed administration. The levels of tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, IL-10, malondialdehyde, superoxide dismutase, NOX2, 4-hydroxynonenal, and PV in the hippocampus were measured at the indicated time points. In the present study, we showed that SPS rats displayed anxiety-like and enhanced fear learning behavior, which was accompanied by the increased expressions of malondialdehyde, IL-6, NOX2, 4-hydroxynonenal, and decreased PV expression. Notably, early but not delayed treatment with apocynin reversed all these abnormalities after SPS. In conclusion, our results provided evidence that NOX2 activation in the hippocampus, at least in part, contributes to oxidative stress and neuroinflammation, which further results in PV interneuron loss and consequent PTSD symptoms in a rat model of PTSD induced by SPS.
Severe acute respiratory syndrome coronavirus (SARS-CoV-1) and SARS-CoV-2 are highly pathogenic to humans and have caused pandemics in 2003 and 2019, respectively. Genetically diverse SARS-related ...coronaviruses (SARSr-CoVs) have been detected or isolated from bats, and some of these viruses have been demonstrated to utilize human angiotensin-converting enzyme 2 (ACE2) as a receptor and to have the potential to spill over to humans. A pan-sarbecovirus vaccine that provides protection against SARSr-CoV infection is urgently needed. In this study, we evaluated the protective efficacy of an inactivated SARS-CoV-2 vaccine against recombinant SARSr-CoVs carrying two different spike proteins (named rWIV1 and rRsSHC014S, respectively). Although serum neutralizing assays showed limited cross-reactivity between the three viruses, the inactivated SARS-CoV-2 vaccine provided full protection against SARS-CoV-2 and rWIV1 and partial protection against rRsSHC014S infection in human ACE2 transgenic mice. Passive transfer of SARS-CoV-2-vaccinated mouse sera provided low protection for rWIV1 but not for rRsSHC014S infection in human ACE2 mice. A specific cellular immune response induced by WIV1 membrane protein peptides was detected in the vaccinated animals, which may explain the cross-protection of the inactivated vaccine. This study shows the possibility of developing a pan-sarbecovirus vaccine against SARSr-CoVs for future preparedness.
The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlight the necessity of developing wide-spectrum vaccines against infection of various SARSr-CoVs. In this study, we tested the protective efficacy of the SARS-CoV-2 inactivated vaccine (IAV) against two SARSr-CoVs with different spike proteins in human ACE2 transgenic mice. We demonstrate that the SARS-CoV-2 IAV provides full protection against rWIV1 and partial protection against rRsSHC014S. The T-cell response stimulated by the M protein may account for the cross protection against heterogeneous SARSr-CoVs. Our findings suggest the feasibility of the development of pan-sarbecovirus vaccines, which can be a strategy of preparedness for future outbreaks caused by novel SARSr-CoVs from wildlife.
Hyperthermostable proteins are highly resistant to various extreme conditions. Many factors have been proposed to contribute to their ultrahigh structural stability. Some thermostable proteins have ...larger oligomeric size when compared to their mesophilic homologues. The formation of compact oligomers can minimize the solvent accessible surface area and increase the changes of Gibbs free energy for unfolding. Similar to mesophilic proteins, hyperthermostable proteins also face the problem of unproductive aggregation. In this research, we investigated the role of high-order oligomerization in the fight against aggregation by a hyperthermostable superoxide dismutase identified from Tengchong, China (tcSOD). Besides the predominant tetramers, tcSOD could also form active high-order oligomers containing at least eight subunits. The dynamic equilibrium between tetramers and high-order oligomers was not significantly affected by pH, salt concentration or moderate temperature. The secondary and tertiary structures of tcSOD remained unchanged during heating, while cross-linking experiments showed that there were conformational changes or structural fluctuations at high temperatures. Mutational analysis indicated that the last helix at the C-terminus was involved in the formation of high-order oligomers, probably via domain swapping. Based on these results, we proposed that the reversible conversion between the active tetramers and high-order oligomers might provide a buffering system for tcSOD to fight against the irreversible protein aggregation pathway. The formation of active high-order oligomers not only increases the energy barrier between the native state and unfolded/aggregated state, but also provides the enzyme the ability to reproduce the predominant oligomers from the active high-order oligomers.
Aluminum (Al) is present in approximately 50% of the arable land worldwide and is regarded as the main limiting factor of crop yield on acidic soil. Al-induced root malate efflux plays an important ...role in the Al tolerance of plants. Here, the aluminum induced malate transporter
(KF322104) was cloned from cabbage (
).
showed higher expression in roots than in shoots. The expression of
was specifically induced by Al treatment, but not the trivalent cations lanthanum (La), cadmium (Cd), zinc (Zn), or copper (Cu). Subcellular localization studies were performed in onion epidermal cells and revealed that BoALMT1 was localized at the plasma membrane. Scanning Ion-selective Electrode Technique was used to analyze H
flux.
oocytes and
expressing
excreted more H
under Al treatment. Overexpressing
in transgenic
resulted in enhanced Al tolerance and increased malate secretion. The results suggested that
functions as an Al-resistant gene and encodes a malate transporter. Expressing
in
oocytes or
indicated that BoALMT1 could increase malate secretion and H+ efflux to resist Al tolerance.
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