Investigation into the impact of proton pump inhibitors on sertraline transport across the blood-brain barrier.

As a widely used antidepressant that works by inhibiting the reuptake of serotonin, sertraline exerts an antidepressant effect depending on its concentration in the brain, which might be limited by the blood-brain barrier (BBB). It is highly possible to combine proton pump inhibitors (PPIs) with sertraline in clinical trials. Nevertheless, the role played by PPIs in regulating the transport of sertraline across the BBB remains unclear. Here, the impact of PPIs on the distribution of sertraline in the brain and the mechanisms involved were investigated. A mouse brain distribution study showed that Omeprazole (OME), Pantoprazole (PAN), Ilaprazole (ILA), and Esomeprazole (ESO) increased the area under the brain concentration-time curves (AUC) for sertraline by 2.02-, 3.18-, 3.04-, and 4.21-fold, respectively, after the 14-day administration of PPIs. Besides, PPIs significantly increased the permeability of sertraline in brain perfusion experiments, with PAN having the highest rank order, followed by ILA, OME, and ESO. In the tail suspension test (TST), co-administration PPI groups showed significantly shorter immobility time than the control group. In vitro, four PPIs inhibited sertraline efflux in breast cancer resistance protein (BCRP)-overexpressing MDCKII cells, and showed a mixed inhibition type. In this study, PPIs were further found to inhibit the mRNA and protein expression of brain BCRP. To sum up, the findings of this study revealed that PPIs could enhance the brain distribution and antidepressant effect of sertraline, which may be attributed to the inhibition of BCRP expression at the BBB by PPIs.

Enhancing Paclitaxel Efficacy with Piperine-Paclitaxel Albumin Nanoparticles in Multidrug-Resistant Triple-Negative Breast Cancer by Inhibiting P-Glycoprotein.

Triple-negative breast cancer (TNBC) is a highly aggressive disease with rapid progression and poor prognosis due to multidrug resistance (MDR). Piperine (PIP) shows promise as a P-gp inhibitor, capable of sensitizing chemotherapeutic drugs and exhibiting antitumor properties. This study explores the inhibitory mechanism of PIP on P-glycoprotein (P-gp) and its capacity to enhance the sensitivity of paclitaxel (PTX). We subsequently evaluated the efficacy and safety of albumin nanoparticles that co-encapsulate PTX and PIP (PP@AN). The results demonstrated that PIP enhanced the accumulation of PTX intracellularly, as determined with HPLC/MS/MS analysis. PIP was also found to increase cell sensitivity to PTX. Furthermore, we explored the inhibitory mechanism of PIP on P-gp, utilizing molecular docking simulations, RT-qPCR, and Western blot analysis. PIP appears to compete with the active paclitaxel binding site on P-gp, affecting ATPase activity and downregulating the MDR1 gene and P-gp expression. In summary, PIP could inhibit P-gp and act as a sensitizer in the treatment of TNBC with PTX. Moreover, stable and uniform PP@AN was successfully formulated, resulting in a significant increase in drug accumulation within cells as well as the downregulation of P-gp in tumors at the optimal ratio (PTX:PIP = 1:2). This led to an improvement in the antitumor effect in vivo while also reducing hepatotoxicity and hemototoxicity following chemotherapy. This study comprehensively investigated PIP's inhibitory effect and mechanism on P-gp. We present a new approach for co-delivering PIP and PTX using albumin nanoparticles, which reduced toxicity and improved therapeutic efficacy both in vivo and in vitro.

Multilingual Language Diversity Protects Native Language Production under Different Control Demands.

The use of multiple languages has been found to influence individuals' cognitive abilities. Although some studies have also investigated the effect of multilingualism on non-native language proficiency, fewer studies have focused on how multilingual experience affects native language production. This study investigated the effect of multilingualism on native language production, specifically examining control demands through a semantic Go/No-Go picture naming task. The multilingual experience was quantified using language entropy, which measures the uncertainty and diversity of language use. Control demands were achieved by manipulating the proportion of Go (i.e., naming) trials in different conditions. Results showed that as control demands increased, multilingual individuals exhibited poorer behavioral performance and greater brain activation throughout the brain. Moreover, more diverse language use was associated with higher accuracy in naming and more interconnected brain networks with greater involvement of domain-general neural resources and less domain-specific neural resources. Notably, the varied and balanced use of multiple languages enabled multilingual individuals to respond more efficiently to increased task demands during native language production.

Current trends in the detection and removal of heavy metal ions using functional materials.

The shortage of freshwater resources caused by heavy metal pollution is an acute global issue, which has a great impact on environmental protection and human health. Therefore, the exploitation of new strategies for designing and synthesizing green, efficient, and economical materials for the detection and removal of heavy metal ions is crucial. Among the various methods for the detection and removal of heavy ions, advanced functional systems including nanomaterials, polymers, porous materials, and biomaterials have attracted considerable attention over the past several years due to their capabilities of real-time detection, excellent removal efficiency, anti-interference, quick response, high selectivity, and low limit of detection. In this tutorial review, we review the general design principles underlying the aforementioned functional materials, and in particular highlight the fundamental mechanisms and specific examples of detecting and removing heavy metal ions. Additionally, the methods which enhance water purification quality using these functional materials have been reviewed, also current challenges and opportunities in this exciting field have been highlighted, including the fabrication, subsequent treatment, and potential future applications of such functional materials. We envision that this tutorial review will provide invaluable guidance for the design of functional materials tailored towards the detection and removal of heavy metals, thereby expediting the development of high-performance materials and fostering the development of more efficient approaches to water pollution remediation.

Constructing A Solar Evaporator by Stacking Exhausted Wood Sponges for Freshwater Generation and Fertilizer Recovery.

Solar water evaporation is an efficient and sustainable technology. To reduce energy consumption and improve cost efficiency, the surface modification of wood sponge by polypyrrole-glutathione (PGWS) was achieved using an in-situ synthetic method. The PGWS exhibits excellent adsorption efficiency for Hg(II) ions with adsorption capacity of 330.8 mg g-1 at 25 °C. Following Hg(II) absorption, the PGWS could be upcycled for solar steam generation. A stackable device was constructed by placing two wood sponges under a Hg(II) saturated PGWS [PGWS-Hg(II)], this system exhibited the highest water evaporation rate of 2.14 kg m-2 h-1 under 1 kW m-2 . Moreover, collecting paper was inserted between the stacked PGWS-Hg(II) and wood sponge for the collection of salts. As such salt can be successfully collected from simulated fertilizer plant effluent and then used as a nutrient for growing plants using a hydroponic system. The facile design of stackable evaporation provides an opportunity for wastewater utilization by harvesting solar energy.

A fast RT-qPCR system significantly shortens the time for SARS-CoV-2 nucleic acid test.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious threat to global development. Rapid and accurate diagnosis is critical for containing the pandemic and treating patients in time. As the gold standard for SARS-CoV-2 diagnosis, the qualitative reverse transcription-PCR (RT-qPCR) test has long been criticized for its long detection time. In this study, we optimized the primers and probes targeting SARS-CoV-2 ORF1ab and N gene designed by the Chinese Center for Disease Control and Preventions (CDC) to increase their Tm values to meet the optimal elongation temperature of Taq DNA polymerase, thus greatly shortened the elongation time. The higher elongation temperature in turn narrowed the temperature range of the reaction and saved more time. In addition, by shortening the distance between the fluorophore at the 5' end and the quencher in the middle we got a probe with higher signal-to-noise ratio. Finally, by using all these measures and optimized RT-qPCR program we successfully reduced the time (nucleic acid extraction step is not included) for nucleic acid test from 74 min to 26 min.

Changes in target ability of nanoparticles due to protein corona composition and disease state.

Many studies have shown the influence of protein corona (PC) on the active targeting capability of ligand-modified nanoparticles; however, the influence of clinical status on PC composition and targeting capacity is rarely discussed. In this study, when transferrin-modified PEGylated polystyrene nanoparticles (Tf-PNs) is intravenously injected into mice with non-small cell lung cancer (NSCLC) comorbid with type 2 diabetes mellitus (T2DM), more Tf-PNs accumulated in the tumor tissue than in those of NSCLC model mice. This indicated that PC derived from different states of disease changed the active targeting ability of Tf-PNs. To explain the occurrence of this phenomenon, our analysis of PC from different disease states revealed that Tf (transferrin) modification had no significant effect on the formation of PC, and that the PC from the NSCLC comorbid with T2DM model contained more proteins like fibrin and clusterin. This work demonstrates the impacts of comorbidity, such as with T2DM, on the active targeting capability of ligand-modified nanoparticles, and the results promote the application of nanoparticles for precision medicine.

Assessing the difference of tolerance and phytoremediation potential in mercury contaminated soil of a non-food energy crop, Helianthus tuberosus L. (Jerusalem artichoke).

This study was conducted to evaluate the effects of mercury stress on growth, photosynthesis and mercury accumulation in different cultivars of a non-food energy crop, Jerusalem artichoke, and to screen appropriate cultivars for their efficacy in the phytoremediation of mercury (Hg2+) contaminated soil. Cultivars LZJ033 (high above-ground biomass and nutrient content, and strongly sexual reproduction) and LZJ119 (a long period of vegetative growth) exhibited more tolerance to mercury stress than LZJ047 (the highest tuber yield and total sugar content). The lines LZJ119 and LZJ047 showed delays in emergence time of about four weeks, and LZJ047 exhibited the highest mortality rate, 85.19%, under treatment with 10 mg kg-1 mercury. The MDA (malondialdehyde) content increased whereas and the Pn (net photosynthetic rate), Fv ∕Fm (the maximum quantum yield of PSII photochemistry) and chlorophyll content decreased in response to mercury stress. The stem diameter, stem biomass and photosynthetic rate of Jerusalem artichoke showed some modest increases in response to mercury stress and exhibited hormesis at least 1 mg kg-1 mercury treatment. Overall, LZJ119 produced more biomass under mercury stress, whereas LZJ033 exhibited a greater capacity for mercury bioaccumulation. Accordingly, LZJ119 may be a good candidate cultivar for use in cases of moderate-low mercury contamination, whereas LZJ033 may be a better candidate under conditions of high mercury contamination. When Jerusalem artichoke was cultivated in mercury contaminated soil, it not only removed the mercury from soil but also produced large amounts of tubers and shoots which could be used as feedstock for the production of bioethanol.

[Comparison of the children's oral health habits and oral-health-related quality of life following treatment under dental general anesthesia and passive restraint].

OBJECTIVE: To compare the children's oral health habits and oral-health-related quality of life following treatment under dental general anesthesia (DGA) and passive restraint (PR). METHODS: In the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, twenty eight 2 to 4-year-old patients treated under DGA and thirty five treated under PR were collected in this non-randomized controlled trial. The general information including age and decayed, missed and filled teeth(dmft), dental plaque index was recorded preoperatively. Two questionnaires, questionnaire of oral health habits and early childhood oral health impact scale (ECOHIS) were completed by parents before and 6 months after treatment (including restoration, root canal treatment, stainless steel crown, tooth extraction, etc.). Six months after treatment, dental plaque index and restoration were reexamined. RESULTS: The patients were significantly elder in DGA group [(3.1 ± 0.6) years old, P < 0.05], and the mean dmft was significantly higher (13.1 ± 4.1, P < 0.001) in DGA group. The postoperative dietary habits and brushing habits significantly improved in PR group, but not in the DGA group. However, according to the results of ECOHIS, the occurrence of pain, the impacts of patients on daily life, psychology and family due to the oral diseases significantly decreased in DGA group (P < 0.05), while in PR group, only the occurrence of pain reduced (P < 0.05). No statistical difference was found between the two groups in new caries or recurrent caries (PR group: 37.1%, DGA group: 39.3%), secondary caries (PR group: 4.1%, DGA group: 2.3%), and failure of the restoration (PR group:1.5%, DGA group: 2.7%). CONCLUSIONS: Each behavior management technique has advantages and drawbacks, and no statistical differences were found in the treatment results between the two techniques.

Non-Bragg resonance of surface water waves in a trough with periodic walls.

The non-Bragg resonance of surface water waves is investigated, both theoretically and experimentally, in a trough with square-wave corrugated sidewalls. Unlike the familiar Bragg resonances, the non-Bragg resonances occur far from the edges of the Brillouin zone and open additional forbidden bands. The experimental observations confirm the existence of these resonances, and the measurements for the transmission properties showing both Bragg and non-Bragg band gaps agree fairly well with the theoretical predictions obtained by the plane-wave expansion method. It is shown that both Bragg and non-Bragg resonances highly depend on the symmetry of the corrugations on the opposite sidewall. As the relative shift between the two corrugations increases from zero to the half period of the corrugations, the Bragg gap shrinks and vanishes, but the non-Bragg gap varies in the opposite way, reaching its maximum, which is impressively wide and much more efficient in reflecting water waves.