Does the active hydrogen atom in the hydantoin anion affect the physical properties, CO2 capture and conversion of ionic liquids?

Compared to the effect of the active hydrogen atom in the cation in protic ionic liquids (ILs) on their properties and applications, there are very few reports on the role of the active hydrogen atom in the anion. In order to better understand the role of the active hydrogen atom in the anion, the physical properties, CO2 capture and conversion of three hydantoin-based anion-functionalized ILs ([P4442][Hy], [P4442]2[Hy], and [HDBU][Hy]) have been investigated via experiments, spectroscopy, and DFT calculations in this work. The results show that the active hydrogen atom in the anion can form anionic hydrogen bonding networks, which significantly increase the melting point and viscosity and decrease the basicity of the IL, thereby weakening its ability to capture and convert CO2. Interestingly, [P4442][Hy] undergoes a solid/liquid two-phase transition during CO2 absorption/desorption due to the formation of quasi-intramolecular hydrogen bonding between the active hydrogen atom and the O- atom of the absorbed CO2, suggesting that the presence of the active hydrogen atom gives [P4442][Hy] the potential to be an excellent molecular switch. As there is no active hydrogen atom in the anion of [P4442]2[Hy], it shows excellent CO2 capture and conversion performance through the double-site interaction. [HDBU][Hy] shows the weakest catalytic CO2 conversion due to the presence of active hydrogen atoms on both its anion and cation. Therefore, the active hydrogen atom in the anion may play a more important role in the properties and potential applications of ILs than the active hydrogen atom in the cation.

The Inhibition of Fibrosis and Inflammation in Obstructive Kidney Injury via the miR-122-5p/SOX2 Axis Using USC-Exos.

Background: Fibrosis and inflammation due to ureteropelvic junction obstruction substantially contributes to poor renal function. Urine-derived stem-cell-derived exosomes (USC-Exos) have therapeutic effects through paracrine. Methods: In vitro, the effects of USC-Exos on the biological functions of HK-2 and human umbilical vein endothelial cells were tested. Cell inflammation and fibrosis were induced by transforming growth factor-ß1 and interleukin-1ß, and their anti-inflammatory and antifibrotic effects were observed after exogenous addition of USC-Exos. Through high-throughput sequencing of microRNA in USC-Exos, the pathways and key microRNAs were selected. Then, the antifibrotic and anti-inflammatory effects of exosomal miR-122-5p and target genes were verified. The role of the miR-122-5p/SOX2 axis in anti-inflammatory and antifibrotic effects was verified. In vivo, a rabbit model of partial unilateral ureteral obstruction (PUUO) was established. Magnetic resonance imaging recorded the volume of the renal pelvis after modeling, and renal tissue was pathologically analyzed. Results: We examined the role of USC-Exos and their miR-122-5p content in obstructive kidney injury. These Exos exhibit antifibrotic and anti-inflammatory activities. SOX2 is the hub gene in PUUO and negatively related to renal function. We confirmed the binding relationship between miR-122-5p and SOX2. The anti-inflammatory and antifibrotic effects of miR-122-5p were inhibited, indicating that miR-122-5p has anti-inflammatory and antifibrotic effects by inhibiting SOX2 expression. In vivo, the PUUO group showed typical obstructive kidney injury after modeling. After USC-Exo treatment, the shape of the renal pelvis shown a remarkable improvement, and inflammation and fibrosis decreased. Conclusions: We confirmed that miR-122-5p from USC-Exos targeting SOX2 is a new molecular target for postoperative recovery treatment of obstructive kidney injury.

Study on the aging status of insulators based on hyperspectral imaging technology.

The acidic environment is one of the main factors leading to the aging of silicone rubber (SiR) insulators. Aging can reduce the surface hydrophobicity and pollution flashover resistance of insulators, threatening the safe and stable operation of the power grid. Therefore, evaluating the aging state of insulators is essential to prevent flashover accidents on the transmission line. This paper is based on an optical hyperspectral imaging (HSI) technology for pixel-level assessment of insulator aging status. Firstly, the SiR samples were artificially aged in three typical acidic solutions with different concentrations of HNO3, H2SO4, and HCl, and six aging grades of SiR samples were prepared. The HSI of SiR at each aging grade was extracted using a hyperspectral imager. To reduce the calculation complexity and eliminate the interference of useless information in the band, this paper proposes a joint random forest- principal component analysis (RF-PCA) dimensionality reduction method to reduce the original 256-dimensional hyperspectral data to 7 dimensions. Finally, to capture local features in hyperspectral images more effectively and retain the most significant information of the spectral lines, a convolutional neural network (CNN) was used to build a classification model for pixel-level assessment of the SiR's aging state of and visual prediction of insulators' defects. The research method in this paper provides an important guarantee for the timely detection of safety hazards in the power grid.

New Local Composition Model for Correlating of the Molar Conductivity of Ionic Liquid-Solvent Systems over the Whole Concentration Range.

Considering that traditional electrolyte models are limited to use in the solvent-rich region, the development of new models to describe the molar conductivity (Λm) over the whole concentration range of ionic liquid (IL)-solvent systems is a meaningful study. Based on the idea of local composition and the law of independent ion migration, a new model is proposed in this study and used to successfully correlate the relationship between Λm and composition over the whole concentration range for 18 IL-solvent systems with satisfactory fitting accuracy. Meanwhile, the electrical conductivity (κ) of the systems is estimated using the calculated Λm. Moreover, the strength of anion-cation, anion-solvent, and cation-solvent interactions in the systems is explored by the obtained energy parameters, and the effect of the solvent on the interactions is investigated. The proposed model provides a new method to accurately describe the conductivity property of IL-solvent systems over the whole concentration range.

Small extracellular vesicles derived from tendon stem cells promote the healing of injured Achilles tendons by regulating miR-145-3p.

The therapeutic role of tendon stem cells (TSCs) in tendon-related injuries has been well documented. Small extracellular vesicles (sEVs) are being increasingly used as new biotherapeutic agents for various diseases. Therefore, the potential function of TSC-sEVs in tendon injury repair warrants further investigation. In this study, we explored the effects of TSC-sEVs on TSC proliferation, migration, and differentiation in vitro in an autocrine manner. We further used a novel exosomal topical treatment with TSC-sEVs loaded with gelatin methacryloyl (GelMA) hydrogel in vivo; we mixed sufficient amounts of TSC-sEVs with GelMA hydrogel to cover the damaged molded Achilles tendon tissue and then exposed them to UV irradiation for coagulation. GelMA loading ensured that TSC-sEVs were slowly released at the injury site over a long period, thereby achieving their full local therapeutic effects. Treatment with TSC-sEVs loaded with GelMA significantly improved the histological score of the regenerated tendon by increasing the tendon expression while inhibiting the formation of excessive ossification and improving the mechanical properties of the tissue. Moreover, miRNA sequencing in TSC-sEVs, TSCs, and TSCs receiving sEVs revealed that TSC-sEVs altered the miRNA expression profile of TSCs, with increased expression of miR-145-3p. In conclusion, our study demonstrates that TSC-sEVs can play a key role in treating tendon injuries and that loading them with GelMA can enhance their effect in vivo. Moreover, miR-145-3p has a major functional role in the effect of TSC-sEVs. This study offers new therapeutic ideas for the local treatment of Achilles tendon injuries using sEVs. STATEMENT OF SIGNIFICANCE: In this study, we demonstrated that TSC-sEVs play a key role in treating tendon injuries and that loading them with GelMA hydrogel can act as a fixation and slow release in vivo. Moreover, it identifies the major functional role of miR-145-3p in the effect of TSCs that were identified and validated by miRNA sequencing. Our study provides a basis for further research on GelMA slow-release assays that have potential clinical applications. It offers new therapeutic ideas for the local treatment of Achilles tendon injuries using TSC-sEVs.

Efficient catalytic conversion of CO2 to quinazoline-2,4(1H,3H)-diones by a dual-site anion-functionalized ionic liquid: reconsidering the mechanism.

In order to elucidate the reaction mechanism of ionic liquid-catalyzed CO2 with 2-aminobenzonitrile, [P4442]2[Hy] with two N- sites is designed for the efficient preparation of quinazoline-2,4(1H,3H)-diones. The results show that [Hy]2- can activate 2-aminobenzonitrile by hydrogen bonding with -NH2 in addition to activating CO2, and the key intermediate is revealed.

Efficacy of metoprolol combined with torasemide in elderly patients with degenerative valvular heart disease and heart failure and its influence on NT-proBNP levels.

Objective: To investigate the efficacy of metoprolol combined with torasemide in elderly patients with degenerative valvular heart disease (DVHD) and heart failure and its influence on N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations. Methods: The records of 129 DVHD patients ≥60 years old with heart failure diagnosed and treated in our hospital from January 2020 to February 2022 were retrospectively selected. According to the treatment records, 62 patients received metoprolol treatment (Control-group), and 67 patients received metoprolol combined with torasemide treatment (Observation-group). The changes in cardiac function, NT-proBNP and inflammatory factor concentrations and clinical efficacy were analyzed and compared between the two groups before and after treatment. Results: After treatment, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and the mitral ratio of peak early to late diastolic filling velocity (E/A) were lower, with a greater decrease in the Observation-group compared to the Control-group (P<0.05). After treatment, NT-proBNP and interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) concentrations were lower in both groups, with a greater decrease in the Observation-group compared to the Control-group (P<0.05). The total clinical efficacy of the Observation-group was significantly higher than the Control-group (P<0.05). There was no significant difference in the total incidence of adverse drug reactions between the two groups (P>0.05). Conclusion: Metoprolol combined with torasemide has a significant therapeutic effect on DVHD patients with heart failure. This drug combination improved cardiac function, reduced NT-proBNP concentrations and has good safety.

A Novel Anti-Flashover Superhydrophobic Coating with Self-Assembly Characteristic of Surface Energy Differences.

Because of the versatility of superhydrophobic materials, they have attracted a lot of attention even in power electronics, transportation, engineering, and other fields. The volume fraction of fluorinated silicon oxide nanoparticles in superhydrophobic materials is one of the most important factors. Increasing the volume fraction will decrease the stability between the coating and the hydrophobic surface. Especially, the flashover voltage of the coating gradually decreases from 10 to 35 vol.%. Meanwhile, the flashover voltage dispersion of the coating increases drastically after 30 vol.%. In order to improve the electrical properties of the superhydrophobic coating, self-assembly of surface energy differences strategy is proposed in this work. A binary filling phase of the coating is introduced by 2D boron nitride nanosheets and silicon oxide nanoparticles. Although Hexagonal boron nitride with high surface energy and low roughness, it will be spontaneously assembled and wrapped by silicon oxide nanoparticle based on surface energy differences, which forming a low surface energy filled phase. Experiment results prove that the flashover voltage of the superhydrophobic coating is optimized by the binary filling phase coating. This method offers new ideas for the selection of filling phase and application of superhydrophobic materials.

Near-Infrared Light Driven ZnIn2S4-Based Photocatalysts for Environmental and Energy Applications: Progress and Perspectives.

Zinc indium sulfide (ZnIn2S4), as a significant visible-light-responsive photocatalyst, has become a research hotspot to tackle energy demand and environmental issues owing to its excellent properties of high stability, easy fabrication, and remarkable catalytic activity. However, its drawbacks, including low utilization of solar light and fast photoinduced charge carriers, limit its applications. Promoting the response for near-infrared (NIR) light (~52% solar light) of ZnIn2S4-based photocatalysts is the primary challenge to overcome. In this review, various modulation strategies of ZnIn2S4 have been described, which include hybrid with narrow optical gap materials, bandgap engineering, up-conversion materials, and surface plasmon materials for enhanced NIR photocatalytic performance in the applications of hydrogen evolution, pollutants purification, and CO2 reduction. In addition, the synthesis methods and mechanisms of NIR light-driven ZnIn2S4-based photocatalysts are summarized. Finally, this review presents perspectives for future development of efficient NIR photon conversion of ZnIn2S4-based photocatalysts.

Attitude Disparity and Worrying Scenarios in Genetic Discrimination-Based on Questionnaires from China.

Objectives: As genetic testing is increasingly used in non-medical fields, the judgment of people's potential conditions based on predictive genetic information inevitably causes genetic discrimination (henceforth GD). This article aimed to systematically investigate the disparity in attitudes and worrying scenarios concerning GD in China. Methods: A questionnaire survey of 555 respondents was conducted. Statistical tests were used to examine disparity in attitudes between gender, age, and education. A descriptive analysis was also conducted to explore other worrying scenarios. Results: It shows that (1) men are more tolerant of GD compared to women, and (2) participants aged between 18 and 30 years old possess the highest objection to GD. However, (3) no indication can attest to the relationship between educational level and perspective on GD. In addition, (4) the acceptance of gene testing in the three most common scenarios is ranked in descending order as follows: partner choice, insurance services, and recruitment. Moreover, (5) worrying scenarios relating to GD include: education, social occasions, medical services, fertility, shopping, and so on. Conclusions: Based on the results, suggestions proposed include developing a blacklist mechanism in the field of genetic data application and strengthening the security regulations for the commercial use of genetic data.

Association between abnormal plasma metabolism and brain atrophy in alcohol-dependent patients.

Objective: In this study, we aimed to characterize the plasma metabolic profiles of brain atrophy and alcohol dependence (s) and to identify the underlying pathogenesis of brain atrophy related to alcohol dependence. Methods: We acquired the plasma samples of alcohol-dependent patients and performed non-targeted metabolomic profiling analysis to identify alterations of key metabolites in the plasma of BA-ADPs. Machine learning algorithms and bioinformatic analysis were also used to identify predictive biomarkers and investigate their possible roles in brain atrophy related to alcohol dependence. Results: A total of 26 plasma metabolites were significantly altered in the BA-ADPs group when compared with a group featuring alcohol-dependent patients without brain atrophy (NBA-ADPs). Nine of these differential metabolites were further identified as potential biomarkers for BA-ADPs. Receiver operating characteristic curves demonstrated that these potential biomarkers exhibited good sensitivity and specificity for distinguishing BA-ADPs from NBA-ADPs. Moreover, metabolic pathway analysis suggested that glycerophospholipid metabolism may be highly involved in the pathogenesis of alcohol-induced brain atrophy. Conclusion: This plasma metabolomic study provides a valuable resource for enhancing our understanding of alcohol-induced brain atrophy and offers potential targets for therapeutic intervention.

Chicken CDS2 isoforms presented distinct spatio-temporal expression pattern and regulated by insulin in a breed-specific manner.

The cytidine diphosphate diacylglycerol synthases (CDSs) gene encodes the cytidine diphosphate-diacylglycerol (CDP-DAG) synthase enzyme that catalyzes the formation of CDP-diacylglycerol from phosphatidic acid. At present, there are no reports of CDS2 in birds. Here, we identified chicken CDS2 transcripts by combining conventional RT-PCR amplification, 5' rapid amplification of cDNA ends (RACE), and 3' RACE, explored the spatio-temporal expression profiles of total CDS2 and the longest transcript variant CDS2-4, and investigated the effect of exogenous insulin on the mRNA level of total CDS2 via quantitative RT-PCR. Four transcripts of chicken CDS2 (CDS2-1, -2, -3, and -4) were identified, which were alternatively spliced at the 3'-untranslated region (UTR). Both total CDS2 and CDS2-4 were prominently expressed in adipose tissue, and exhibited low expression in liver and pectoralis of 49-day-old chickens. Regarding the spatio-temporal expression patterns of CDS2 in chicken, total CDS2 exhibited a similar temporal expression tendency with a high level in the later period of incubation (embryonic day 19 [E19] or 1-day-old) in the brain, liver, and pectoralis. While CDS2-4 presented a distinct temporal expression pattern in these tissues, CDS2-4 levels peaked at 21 d in the brain and pectoralis, while liver CDS2-4 mRNA levels were highest at the early stage of hatching (E10). Total CDS2 (P < 0.001) and CDS2-4 (P = 0.0090) mRNA levels in the liver were differentially regulated throughout the development of the chicken. Total CDS2 levels in the liver of Silky chickens were higher than that of the broiler in the basal state and after insulin stimulation. Exogenous insulin significantly down-regulated the level of total CDS2 at 240 min in the pectoralis of Silky chickens (P < 0.01). In conclusion, chicken CDS2 isoforms with variation at the 3'-UTR were identified, which was prominently expressed in adipose tissue. Total CDS2 and CDS2-4 presented distinct spatio-temporal expression patterns, that is they were differentially regulated with age in brain, liver, and pectoralis. Insulin could regulate chicken CDS2 levels in a breed- and tissue-specific manner.

A ceRNA Network Composed of Survival-Related lncRNAs, miRNAs, and mRNAs in Clear Cell Renal Carcinoma.

Clear cell renal carcinoma (ccRCC) is one of the most common renal carcinomas worldwide, which has worse prognosis compared with other subtypes of tumors. We propose a potential RNA regulatory mechanism associated with ccRCC progression. Accordingly, we screened out clinical factors and the expression of RNAs and miRNAs of ccRCC from the TCGA database. 9 lncRNAs (FGF12-AS2, WT1-AS, TRIM36-IT1, AC009093.1, LINC00443, TCL6, COL18A1-AS1, AC110619.1, HOTTIP), 2 miRNAs (mir-155 and mir-21), and 3 mRNAs (COL4A4, ERMP1, PRELID2) were selected from differential expression RNAs and built predictive survival models. The survival models performed very well in predicting prognosis and were found to be highly correlated with tumor stage. In addition, the survival-related lncRNA-miRNA-mRNA (ceRNA) network was constructed by 18 RNAs including 12 mRNAs, 2 miRNAs, and 4 lncRNAs. It is found that the "ECM-receptor interaction," "Pathways in cancer," and "Chemokine signaling pathway" as the main pathways in KEGG pathway analysis. Overall, we established predictive survival model and ceRNA network based on multivariate Cox regression analysis. It may open a new approach and potential biomarkers for clinical prognosis and treatment of ccRCC patients.

Self-cleaning of superhydrophobic nanostructured surfaces at low humidity enhanced by vertical electric field.

Self-cleaning is the key factor that makes superhydrophobic nanostructured materials have wide applications. The self-cleaning effect, however, strongly depends on formations and movement of water droplets on superhydrophobic nanostructured surfaces, which is greatly restricted at low humidity (< 7.6 g·kg-1). Therefore, we propose a self-cleaning method at low humidity in which the pollution is electro-aggregated and driven in the electric field to achieve the aggregation and cleaning large areas. The cleaning efficiency of this method is much higher than that of water droplet roll-off, and will not produce "pollution bands". A simplified numerical model describing pollution movements is presented. Simulation results are consistent with experimental results. The proposed method realizes the self-cleaning of superhydrophobic nanostructured surfaces above dew point curve for the first time, which extends applications of superhydrophobic nanostructured materials in low humidity, and is expected to solve self-cleaning problems of outdoor objects in low humidity areas (< 5.0 g·kg-1). Electronic Supplementary Material: Supplementary material (experimental procedures, computational details, modeling process, supplementary figures, tables, and videos) is available in the online version of this article at 10.1007/s12274-022-4093-0.

Acidification of drinking water improved tibia mass of broilers through the alterations of intestinal barrier and microbiota.

OBJECTIVE: Diet acidification supplementation is known to influence intestinal morphology, gut microbiota, and on phosphorus (P) utilization of broilers. Alterations in intestinal barrier and microbiota have been associated with systemic inflammation and thus regulating bone turnover. Hence the effect of acidifier addition to drinking water on tibia mass and the linkages between intestinal integrity and bone were studied. METHODS: One-d-old male broilers were randomly assigned to normal water (control) or continuous supply of acidified water (2% the blend of 2-hydroxy-4-methylthiobutyric acid, lactic, and phosphoric acid) group with 5 replicates of 10 chicks per replicate for 42 d. RESULTS: Acidification of drinking water improved the ash percentage and calcium content of tibia at 42 d. Broilers receiving acidified water had increased serum P concentration compared to control birds. The acidified group showed improved intestinal barrier, evidenced by increased wall thickness, villus height, the villus height to crypt depth ratio, and upregulated mucin-2 expression in ileum. Broilers receiving drinking water containing mixed organic acids had a higher proportion of Firmicutes and the ratio of Firmicutes and Bacteroidetes, as well as a lower population of Proteobacteria. Meanwhile, the addition of acidifier to drinking water resulted in declined ileal and serum proinflammatory factors level and increased immunoglobulin concentrations in serum. Concerning bone remodeling, acidifier addition was linked to a decrease in serum C-terminal cross-linked telopeptide of type I collagen and tartrate-resistant acid phosphatase reflecting bone resorption, whereas it did not apparently change serum alkaline phosphatase activity that is a bone formation marker. CONCLUSION: Acidified drinking water increased tibia mineral deposition of broilers, which was probably linked with higher P utilization and decreased bone resorption through improved intestinal integrity and gut microbiota and through decreased systemic inflammation.

Incidence rate of angel wing and its effect on wing bone development and serum biochemical parameters in geese.

The first purpose of this study was to reveal the distribution of the angel wing (AW) of geese. Our data showed that the total incidence of AW was 6.67% in 150-day-old White Zhedong (ZD) geese, the occurrence of AW in left wing is higher than that in right wing and bilateral wing than unilateral wing (both P < 0.01). In 70-day-old Hybrid-Wanxi (HW) geese, the total incidence of AW was 8.86%, with similar incidence rate between unilateral and bilateral. The sex has not apparently affected the incidence of AW in both ZD and HW geese. To explore the potential relationship between wing type with body weight, organ index, bone characteristic, or blood biochemical parameters in 70-day-old HW geese. We found that the body weight and organ index were similar between normal wing (NW) and AW geese. The length for the humerus, metacarpal and phalanx, and the phalanx weights, as well as the angle between the humerus and the radial ulna (HRU) in NW geese were pronounced greater than that in AW geese (P < 0.05). Furthermore, the angel wing was strongly associated with lower platelet size indicators. Collectively, AW affected the wing bone length, phalanx weight, and HRU, and the occurrence of AW may be related with dysfunctional platelet activation in geese.

Ginsenoside Rg3 attenuates angiotensin II-induced myocardial hypertrophy through repressing NLRP3 inflammasome and oxidative stress via modulating SIRT1/NF-κB pathway.

BACKGROUND: Ginsenoside Rg3 (Rg3), one of the most potent components extracted from the roots of the traditional Chinese herb Panax ginseng, has prominent roles in anti-tumor and anti-inflammation. However, the applications of Rg3 against myocardial hypertrophy are not fully revealed. METHODS: Transverse aortic constriction (TAC) was adopted to build the myocardial hypertrophy model in rats. The in vitro model of myocardial hypertrophy was induced by angiotensin II (Ang II) in the human cardiomyocyte cell line AC16 and HCM, which were then treated with different doses of Rg3. The levels of myocardial hypertrophy markers (ANP, BNP, and ß-MHC) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot (WB) was conducted to verify the expressions of myocardial fibrosis-associated proteins (MyHc, Collagen Ⅰ, and TGF-ß1) and oxidative stress (OS) proteins (HO-1 and Nrf2). The markers of fibrosis, hypertrophy, NLRP3 inflammasome and OS in cardiomyocytes were evaluated by qRT-PCR, western blot (WB), enzyme-linked immunosorbent assay (ELISA), and cellular immunofluorescence, respectively. Furthermore, pharmacological intervention on sirtuin-1 (SIRT1) was performed to clarify the function of SIRT1 in Rg3-mediated effects. RESULTS: Rg3 dose-dependently attenuated the Ang II-induced myocardial hypertrophy and fibrosis. What's more, Rg3 markedly inhibited NLRP3-ASC-Caspase1 inflammasome and OS (reflected by SOD, MDA, HO-1, and Nrf2) in cardiomyocytes treated with Ang II. Mechanistically, Rg3 attenuated NF-κB activation and promoted SIRT1 expression. Inhibiting SIRT1 (by AGK2) mostly reversed Rg3-mediated effects against Ang II-induced myocardial hypertrophy and fibrosis. In the TAC rat model, administration of Rg3 mitigated myocardial hypertrophy and fibrosis through pressing overproduced inflammation and OS. CONCLUSION: Rg3 prevents Ang II-induced myocardial hypertrophy via inactivating NLRP3 inflammasome and oxidative stress by modulating the SIRT1/NF-κB pathway.

Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice.

Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins.

Understanding the Efficiency and Selectivity of Two-Electron Production of Metalloporphyrin-Embedded Zirconium-Pyrogallol Scaffolds in Electrochemical CO2 Reduction.

Because of the high efficiency and mild reaction conditions, electrocatalytic CO2 reduction (ECR) has attracted significant attention in recent years. However, the specific mechanism of the formation of the two-electron production (CO or HCOOH) in this reaction is still unclear. Herein, with density functional theory calculation and experimental manipulation, the specific mechanism of the selective two-electron reduction of CO2 has been systematically investigated, employing the polyphenolate-substituted metalloporphyrinic frameworks, ZrPP-1-M (M = Fe, Co, Ni, Cu, and Zn), as model catalysts. Experimental observations and theoretical calculations discovered that ZrPP-1-Co is a more favorable catalyst for ECR among them. Compared with the formation of HCOOH, electroreduction of CO2 into CO has more beneficial thermodynamic and kinetic routes with ZrPP-1-Co as a catalyst. After introducing the r-GO for improving the conductivity, the Faradaic efficiency for CO formation is 82.4% at -0.6 v (vs RHE).

Cholesterol regulates cannabinoid analgesia through glycine receptors.

Cholesterol plays vital roles in many central physiological and pathological processes. As a key component in the cell membrane, cholesterol can regulate a variety of ion channels, including ligand-gated ion channels (LGICs). However, relatively little is known about the molecular detail and in vivo consequence of cholesterol-LGIC interaction. Here, we reveal that membrane cholesterol depletion significantly inhibits the potentiating effects of dehydroxylcannabidiol (DH-CBD) on glycine-activated currents (IGly) in HEK 293T cells expressing α1/α3 glycine receptors (GlyRs). Simvastatin considerably decreases cholesterol levels and DH-CBD-induced potentiation of IGly in the spinal cord of mice. Simvastatin also significantly decreases DH-CBD analgesia in acute and chronic pain of mice. The cholesterol levels in the dorsal horn of spinal cord, measured by mass spectrometry imaging, are specifically correlated with cannabinoid potentiation of spinal GlyRs and cannabinoid-induced analgesia. These findings suggest that spinal cholesterol is critical for the efficacy of glycinergic cannabinoid-induced analgesia.