Interaction, Surface Activity, and Application of Mixed Systems of Alcohol Ether Sulfate Anionic Surfactants with Multiple Ethylene Oxide Groups and Gemini Quaternary Ammonium Surfactant.

The surface activities and application properties for the mixtures of cationic surfactants tetramethylene-1,4-bis[N,N-bis(hydroxypropyl)-hexa/decyloxypropylammonium] bromide (GC10-P) and tetramethylene-1,4-bis[N,N-bis(hydroxyethyl)-hexa/decyloxypropylammonium] bromide (GC10-E) and anionic surfactant isomeric sodium fatty alcohol ether sulfates (iso-AE9S) were investigated using both the tensiometry and the conductometry. The interaction parameters and thermodynamic micellization parameters of GC10-P/iso-AE9S and GC10-E/iso-AE9S mixtures were evaluated by Clint-Rubingh and Motomura theoretical models. When the mole fraction of α1 for GC10-P/iso-AE9S mixed system was 0.2, the critical micelle concentration (CMC) reached a minimum of 1.61 × 10-4 mol/L, and the minimum critical micelle concentration of the GC10-E/iso-AE9S mixed system is 2.67 × 10-5 mol/L at α1 = 0.6. The CMC value of the mixed system is 1-2 orders of magnitude lower than that of any single component. The results indicate that the synergistic effects of the investigated mixed systems (evaluated by ßm) are in order of GC10-P/iso-AE9S < GC10-E/iso-AE9S, with maximum ßm values of -17.98 and -9.78, respectively. The change in zeta potential indicates that the poly(ethylene oxide) chain has weakened the charge density of the hydrophilic headgroup of the anionic surfactant. The interfacial tension at the oil-water interface in the mixed system of anionic/cationic surfactants is lower than that of any single component, exhibiting a higher interfacial activity. The mixed system exhibits a decreased contact angle and superior wetting ability over any single component, and it also enhances foam performance, emulsification performance, and degreasing performance.

Enhanced Runge-Kutta-driven feature selection model for early detection of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) profoundly compromises the quality of life, with prolonged untreated cases posing a heightened risk of severe complications such as esophageal injury and esophageal carcinoma. The imperative for early diagnosis is paramount in averting progressive pathological developments. This study introduces a wrapper-based feature selection model based on the enhanced Runge Kutta algorithm (SCCRUN) and fuzzy k-nearest neighbors (FKNN) for GERD prediction, named bSCCRUN-FKNN-FS. Runge Kutta algorithm (RUN) is a metaheuristic algorithm designed based on the Runge-Kutta method. However, RUN's effectiveness in local search capabilities is insufficient, and it exhibits insufficient convergence accuracy. To enhance the convergence accuracy of RUN, spiraling communication and collaboration (SCC) is introduced. By facilitating information exchange among population individuals, SCC expands the solution search space, thereby improving convergence accuracy. The optimization capabilities of SCCRUN are experimentally validated through comparisons with classical and state-of-the-art algorithms on the IEEE CEC 2017 benchmark. Subsequently, based on SCCRUN, the bSCCRUN-FKNN-FS model is proposed. During the period from 2019 to 2023, a dataset comprising 179 cases of GERD, including 110 GERD patients and 69 healthy individuals, was collected from Zhejiang Provincial People's Hospital. This dataset was utilized to compare our proposed model against similar algorithms in order to evaluate its performance. Concurrently, it was determined that features such as the internal diameter of the esophageal hiatus during distention, esophagogastric junction diameter during distention, and external diameter of the esophageal hiatus during non-distention play crucial roles in influencing GERD prediction. Experimental findings demonstrate the outstanding performance of the proposed model, with a predictive accuracy reaching as high as 93.824 %. These results underscore the significant advantage of the proposed model in both identifying and predicting GERD patients.

[Guidelines for post-marketing research on clinical effectiveness of Chinese patent medicines].

Due to the lack of specialized guidance, the post-marketing research on clinical effectiveness of Chinese patent medicines demonstrates varied quality and lacks high-quality evidence, failing to meet the demands of policy-making, clinical decision-making, and industrial decision-making. To address this issue, this project gathered experts in clinical medicine, clinical pharmacy, evidence-based medicine, drug epidemiology, medical ethics, and policy and regulation in China. They referred to the model of international post-marketing research on medicines and developed Guidelines for post-marketing research on clinical effectiveness of Chinese patent medicines under the framework of relevant laws and regulations and technical guidance documents in China. The guidelines were developed with consideration to the characteristics of Chinese patent medicines, China's national conditions, and all the stakeholders including marketing authorization holders, clinical researchers, drug administration, and users. The development of the guidelines followed the requirements for developing group standards set by the China Association of Chinese Medicine. The guidelines fully implement the concept of full life-cycle research, emphasizing the combination of traditional Chinese medicine(TCM) theory, human use experience, and clinical trials and pay attention to the compliance, scientificity, and ethics of research. The guidelines clarify the topic selection and decision-making path of the post-marketing research on effectiveness of Chinese patent medicines through six steps: determining research purpose, analyzing drug characteristics, evaluating research basis, proposing clinical orientation, clarifying research purpose, and implementing classified research. The general principles of research design and implementation were clarified from eight aspects: research type, research objects, sample size, efficacy indicators, bias, missing data, evidence level, and practicality. It focuses on the research on the TCM syndrome-based efficacy evaluation, clinical value-oriented mechanism of action, and the effectiveness of Chinese patent medicines with different routes of administration. The guidelines provide a universal methodological basis for the post-marketing research on clinical effectiveness of Chinese patent medicines.

[Guidelines for economic evaluation of post-marketing Chinese patent medicine].

With the premise of drug safety and effectiveness, pharmacoeconomic evaluation can provide optimal solutions for diversified decision-making application scenarios from different research perspectives while maximizing the rational utilization of existing healthcare resources. Chinese patent medicine is an essential component of pharmaceutical utilization in China and a significant part of healthcare expenditure in China. However, the economic evaluation of post-marketing Chinese patent medicine is lacking. These evaluations often lack standardization, exhibit varying quality, and are unable to effectively support healthcare decisions, indicating a need for improvement in overall quality. Given this situation, this project has gathered leading experts from China and has strictly adhered to the requirements of the group standards set by the China Association of Traditional Chinese Medicine in developing Guidelines for economic evaluation of post-marketing Chinese patent medicine, aiming to provide methodological guidance for the post-market pharmacoeconomic evaluation of Chinese patent medicine, enhancing the standardization of pharmacoeconomic evaluations of Chinese patent medicine and the scientific validity of research results, and thereby elevating the overall quality of pharmacoeconomic evaluations for post-marketing Chinese patent medicine. The guidelines adhere to the framework provided by relevant laws and regulations in China and technical guidance documents. It is based on guidance from traditional Chinese medicine(TCM) theories, focusing on the unique characteristics of TCM. It covers various aspects of pharmacoeconomic evaluation, including fundamental principles, research topic selection, research question definition, study design type selection, cost identification and measurement, health outcomes, and evaluation methods. The guidelines offer methodological recommendations and decision guidance to address common issues and challenges in the pharmacoeconomic evaluation of post-marketing Chinese patent medicine.

[Economic evaluation of Annao Pills combined with antihypertensive drugs in treatment of primary hypertension: a study based on decision tree model].

The purpose of this study was to evaluate the economics of Annao Pills combined with antihypertensive drugs in the treatment of primary hypertension in the Chinese medical setting. TreeAge pro 2018 was used for cost-effect analysis and sensitivity analysis of the two treatment regimens. The intervention time of the simulation model was 2 weeks. The cost parameters were derived from Yaozhi.com, and the effect parameters were based on Meta-analysis of randomized controlled trial(RCT) involving Annao Pills. The experimental group was treated with Annao Pills combined with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets), and the control group was treated with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets). The basic analysis showed that the incremental cost-effect ratio(ICER) of the two groups was 2 678.67 yuan, which was less than 7.26% of the per capita disposable income in 2022. That is, compared with anti-hypertensive drugs alone, Annao Pills combined with antihypertensive drugs cost 2 678.67 yuan more for each additional patient with primary hypertension. The results of sensitivity analysis verified the robustness of the basic analysis results. The probability sensitivity results showed that when the patient's personal willingness to pay the price was higher than 2 650 yuan, the probability of the regimen in the experimental group was higher, which was consistent with the results of the basic analysis. In conclusion, when the price was higher than 2 650 yuan, Annao Pills combined with anti-hypertensive drugs was more economical than anti-hypertensive drugs alone in terms of improving the response rate of the patients with primary hypertension.

Polymer Microspheres Copolymerized with Deep Red Fluorescent Molecules as a Label for Lateral Flow Immunochromatography.

The development of fluorescently labeled microspheres is a critical aspect of advancing the technology of lateral flow immunochromatography (LFIA) for biological detection. Nevertheless, potential interference posed by the background fluorescence originating from the nitrocellulose (NC) membrane would significantly impact the sensitivity and accuracy of microsphere-based detection in LFIA. In this work, an attempt was made to extend the π-conjugated system and asymmetric structure of rhodamine fluorophore, resulting in the synthesis of dye molecules (RB2) incorporating double bonds, which can reach an absolute photoluminescence quantum yield (PLQY) of 30.01% in EtOH. Subsequently, carboxyl group functionalized fluorescent microspheres were prepared in a two-step copolymerization via soap-free emulsion polymerization. The obtained microspheres were characterized by scanning electron microscopy, transmission electron microscopy, DLS, Fourier transform infrared spectroscopy, ultraviolet spectrophotometry, and fluorescence spectrophotometry. The results showed that RB2 was successfully copolymerized into the microspheres, and the resulting microspheres had good dispersion and stability with high red fluorescence intensity (λabs ∼ 610 nm, λem ∼ 660 nm). Utilizing these microspheres, the resulting lateral flow immunoassay was successfully found to detect SARS-CoV-2 N protein with a detection limit of 2.5 pg/mL and the linear concentration spanning from 2.5 pg/mL to 10 ng/mL. The results confirm the effectiveness of the synthetic fluorescent microspheres as the label for LFIA.

Molecular and structural basis of the dual regulation of the polycystin-2 ion channel by small-molecule ligands.

Mutations in the PKD2 gene, which encodes the polycystin-2 (PC2, also called TRPP2) protein, lead to autosomal dominant polycystic kidney disease (ADPKD). As a member of the transient receptor potential (TRP) channel superfamily, PC2 functions as a non-selective cation channel. The activation and regulation of the PC2 channel are largely unknown, and direct binding of small-molecule ligands to this channel has not been reported. In this work, we found that most known small-molecule agonists of the mucolipin TRP (TRPML) channels inhibit the activity of the PC2_F604P, a gain-of-function mutant of the PC2 channel. However, two of them, ML-SA1 and SF-51, have dual regulatory effects, with low concentration further activating PC2_F604P, and high concentration leading to inactivation of the channel. With two cryo-electron microscopy (cryo-EM) structures, a molecular docking model, and mutagenesis results, we identified two distinct binding sites of ML-SA1 in PC2_F604P that are responsible for activation and inactivation, respectively. These results provide structural and functional insights into how ligands regulate PC2 channel function through unusual mechanisms and may help design compounds that are more efficient and specific in regulating the PC2 channel and potentially also for ADPKD treatment.

Preparation of dyed polymer microspheres by a physical-chemical dual-binding method and their application in lateral flow immunoassay.

Lateral flow immunoassay (LFIA) has shown great competitiveness in point-of-care testing due to its flexibility and simplicity. Dyed polymer microspheres are one of the most widely used marker particles for signal presentation as they are very convenient for visual interpretation, which is one of the most attractive features of LFIA. The color intensity, as the most critical factor, is directly related to the visual effect. In this work, a physical-chemical dual-binding strategy was proposed for the preparation of functionalized dyed microspheres. Bifunctional seed microspheres were synthesized by introducing 4-vinylbenzyl chloride (VBC) into the soap-free emulsion polymerization process, and the effective immobilization of dyes inside and on the surface of the polymer microspheres was achieved by covalent bonding and swelling methods. The microspheres were characterized by SEM, FT-IR spectroscopy and UV-vis spectroscopy. The results showed that the microspheres containing VBC were spherical with an average particle size of 300 nm. When the microspheres were prepared by adding 10 wt% VBC relative to the total monomer, the immobilization amount of 1-[[4-[(dimethylphenyl)azo]dimethyl phenyl]azo]-2-naphthol (Red-27) was increased to 180 mg g-1, which was 1.8 times that of the microspheres without VBC. The resulting nanomaterials were successfully used to establish a lateral flow immunoassay for the detection of COVID-19 virus N protein. The linear response concentration range was 2.64-87.84 COI, and the detection limit was 14.95 COI.

Effect of icariin on depressive behaviour in rat pups. Evidences for its mechanism of action by integrating network pharmacology, metabolomics and gut microbiota composition.

BACKGROUND: Prenatal stress (PS) can cause cognitive disorder and a range of psychological illnesses, including anxiety and depression. Icariin (ICA) has shown promising effects in improving PS-induced depressive behaviour. However, its mechanism of action remains unclear. PURPOSE: This study was performed to reveal the key targets, metabolites and gut microbiota for ICA in improving depressive behaviour in PS rat pups. METHODS: A prenatal restraint stress animal model was established for Sprague-Dawley (SD) rats in late pregnancy. Male pups were randomly divided into six groups: no stress group (NS), PS group, PS + saline group (PS_S), PS + high-dose ICA group (ICAH, 80 mg/kg*day), PS + low-dose ICA group (ICAL, 40 mg/kg*day) and PS + fluoxetine group (FLU, 10 mg/kg*day). The depressive behaviour of each group of rat pups was evaluated using open field test, forced swimming test and sucrose preference test. Different metabolites were identified using untargeted metabolomics of serum and faeces, and metabolic pathways were analyzed through MetaboAnalyst. Targets for ICA acting on depression were determined after network pharmacology was applied. An integrated network of network pharmacology and metabolomics were constructed using Cytoscape software, and molecular docking were performed to verify the interactions between ICA and key targets. Finally, gut microbiota of rat pups in each group were analyzed after 16S rDNA sequencing. RESULTS: PS could cause rat pups to exhibit depressive behaviour, and ICA could significantly improve this depressive behaviour. A total of 49 differential metabolites were found in serum and 23 differential metabolites were found in faeces, and 24 metabolites in serum and 6 metabolites in faeces could be reversed following ICA administration. Integrated analysis focused on five key targets (i.e. adenosyl homocysteinase; medium-chain specific acyl-CoA dehydrogenase, mitochondrial; thymidine phosphorylase; cGMP-specific 3',5'-cyclic phosphodiesterase and xanthine dehydrogenase/oxidase) and three metabolites (i.e. palmitoylcarnitine, methionine and hypoxanthine). Molecular docking indicated that ICA combined well with key targets. Gut microbiota analysis showed that g_Bacteroides, f_Bacteroidaceae and s_Lactobacillus reuteri were required for ICA to improve depressive behaviour. CONCLUSION: In this study, the antidepressant mechanism of ICA was clarified with a strategy of integrating metabolomics, network pharmacology and gut microbiota. ICA has a good effect on improving metabolism and increasing the abundance of probiotics in the intestine. The present research provided new insights into the anti-depressant mechanism of ICA.

Electroacupuncture ameliorates neuroinflammation by inhibiting TRPV4 channel in ischemic stroke.

AIMS: We investigated the potential mechanisms underlying the therapeutic efficacy of electroacupuncture (EA) at the Shuigou (GV26) and Baihui (GV20) acupoints in the treatment of ischemic stroke. METHODS: We assessed the therapeutic effects of EA on MCAO mice through behavioral studies and TTC staining. Various techniques, such as RT-PCR, immunofluorescence, and Western blots, were employed to evaluate the activation and polarization of microglia/macrophages, and changes in the TRPV4 ion channel. We used the TRPV4 antagonist GSK2193874 (GSK219) to verify the involvement of TRPV4 in the therapeutic effects of EA. RESULTS: EA effectively improved neurological impairments and reduced cerebral infarction volume in MCAO mice. It suppressed activated microglia/macrophages and inhibited their polarization toward the M1 phenotype post-MCAO. EA also downregulated the expression of pro-inflammatory cytokines, including Tnf-α, Il-6, Il-1ß, and Ccl-2 mRNA. Furthermore, EA reduced the elevated expression of TRPV4 following MCAO. Treatment with the TRPV4 antagonist GSK219 mirrored the effects of EA in MCAO mice. Notably, the combination of EA and GSK219 did not demonstrate an additive or synergistic effect. CONCLUSION: EA may inhibit neuroinflammation and exhibit a protective effect against ischemic brain injury by suppressing TRPV4 and the subsequent M1 polarization of microglia/macrophages.

Metabolic Nanoregulator Remodels Gut Microenvironment for Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is strongly related to the occurrence of accumulation of toxic reactive oxygen species (ROS), inflammation of the mucosa, and an imbalance of intestinal microbes. However, current treatments largely focus on a single factor, yielding unsatisfactory clinical outcomes. Herein, we report a biocompatible and IBD-targeted metabolic nanoregulator (TMNR) that synergistically regulates cellular and bacterial metabolism. The TMNR comprises a melanin-gallium complex (MNR) encapsulated within a thermosensitive and colitis-targeting hydrogel, all composed of natural and FDA-approved components. The TMNR confers superior broad-spectrum antioxidant properties, effectively scavenging reactive oxygen species (ROS) and blocking inflammatory signaling pathways. The presence of Ga3+ in TMNR selectively disrupts iron metabolism in pathogenic microorganisms due to its structural resemblance to the iron atom. Additionally, incorporating a thermosensitive injectable hydrogel enables targeted delivery of TMNR to inflammatory regions, prolonging their retention time and providing a physical barrier function for optimizing IBD treatment efficacy. Collectively, TMNR effectively modulates the redox balance of inflamed colonic epithelial tissue and disrupts iron metabolism in pathogenic microorganisms, thereby eliminating inflammation and restoring intestinal homeostasis against IBD. Hence, this work presents a comprehensive approach for precise spatiotemporal regulation of the intestinal microenvironmental metabolism for IBD treatment.

Anisotropic Magnetic Polymeric Particles with a Controllable Structure via Seeded Emulsion Polymerization.

Magnetic polymer composites have been widely utilized in potential applications in material science, such as reduction of dyes, immunodiagnostics, biomedicals, and magnetically controllable photonic crystals owing to large surface areas, fast separation, and recyclable performance. In this work, anisotropic magnetic particles were prepared by seeded emulsion polymerization, with morphologies of "Fe3O4-shell", "hemisphere-like", "raspberry-like", "multiple lobes-like", and "sandwich-like". Poly(styrene/divinylbenzene/mono-2-(methacryloxy)ethyl succinate)@ Fe3O4 (P(St/DVB/MMES)@Fe3O4) were the seed microspheres, and P(St/DVB/MMES)@Fe3O4@polymer particles are achieved by seeded emulsion polymerizations. The morphology of the particles depends on polymerization conditions (monomer ratios and surfactant), particle properties, and so on. Then, the minimum surface free energy change principles were used to predict the equilibrium morphologies of the magnetic polymer composites. Through theory, the model gives the correct tendency and good agreement with the equilibrium morphology which was in tandem with TEM results. Lastly, after in situ surface deposition of Ag nanoparticles, magnetic composite particles with sandwich-like morphology were applied for the catalytic degradation of 4-nitrophenol (4-NP) reacting with NaBH4. The apparent rate coefficient is 0.0069 s-1, and it can keep mainly about 80% efficiency in catalysis after five cycles.

Effects of fertilizer application on the growth of Stranvaesia davidiana D. seedlings.

Wild plants represent a potential source of urban landscape trees. Stranvaesia davidiana Dcne. is a member of the Stranvaesia Lindl. Genus, which belongs to family Rosaceae Juss. It has great ornamental value. It can contribute to urban color foliage and fruit species. However, the most effective fertilizer application strategy required for its cultivation is unknown. Therefore, we conducted an orthogonal experiment to investigate the fertilizer type and level (pure nitrogen) using ten experimental groups, including an untreated control group. Pot experiments were used to determine the growth indices of seedlings, including plant height, basal diameter, and chlorophyll content post-fertilizer treatment. This study explored the most appropriate fertiler application model for the growth of S. davidiana seedlings. The results revealed that enhanced seedling growth depended on the type and amount of fertilizer used, and their interaction. Fertilizer application increased the plant height by 2.67 cm to 12.26 cm, basal diameter by 0.39 cm to 0.75 cm, and chlorophyll content by 5.66 to 19.86. Among the different types of fertilizer, organic fertilizer increased the plant height by 0.42 cm to 9.59 cm and basal diameter by 0.01 cm to 0.05 cm, compared with the control group. Organic fertilizer had the maximum effect on seedling growth, especially at medium levels. The total growth of basal diameter and chlorophyll content was 1.58 ± 0.04 cm and 39.53 ± 2.37, respectively. Basal diameter is the most critical index in seedling reproduction . The study results suggest that the application of 4.06 g of organic fertilizer per plant was the most effective, and served as a basis for further field trials.

Quality of systematic reviews with meta-analyses of resveratrol: A methodological systematic review.

Recently, several meta-analyses (MAs) have focused on the health effects of resveratrol. However, the methodological and reporting quality of these MAs has not yet been fully evaluated so far. Therefore, the present study evaluated the quality of these MAs through a methodological systematic review. Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception until May 20, 2022, and PubMed was used to update the search until September 6, 2023. The methodological and reporting quality of the selected MAs was evaluated using AMSTAR-2 and PRISMA 2009. Fifty-one MAs published during 2013-2023 were included. In each review, the number of primary studies ranged from 3 to 37, and the number of participants ranged from 50 to 2114. Among the first-listed primary outcomes, only 23 (45.10%) were "positive." As for the methodological quality, most MAs (44, 86.27%) on resveratrol were rated critically low. Inadequate reporting of the included MAs mainly involved items 2 ("Structured summary"), 5 ("Protocol and registration"), 8 ("Search"), 9 ("Study selection"), 10 ("Data collection process"), 12 ("Risk of bias in individual studies"), and 24 ("Summary of evidence") based on the PRISMA 2009. Additionally, journal's impact factor, number of authors, and funding support were positively associated with the overall methodological quality but were not statistically significant (p > 0.05). Future MAs on resveratrol require better design, implementation, and reporting by following the Cochrane Handbook, AMSTAR-2, and PRISMA.

A flavonoid salt probe for distinguishing between tumor and normal cells.

YH-2 represents an innovative, non-invasive fluorescent probe featuring a structure based on flavonoid onium salts. It is characterized by a well-suited Stokes shift and emits in the near-infrared (NIR) wavelength range. Its capacity to distinguish between HeLa cells, HepG2 cells, and LO2 cells is attributed to differential intracellular viscosity. Experimental results validate the heightened viscosity of organelles, such as the endoplasmic reticulum (ER), mitochondria and lysosomes in tumor cells compared to LO2 cells. Of paramount importance, YH-2 demonstrates the capability to swiftly image tumors within a mere 20 min following tail vein injection and this imaging ability can be sustained for an extended period of up to 5 h. This method offers a potential tumor diagnostic strategy in vivo.

Reporting quality and risk of bias of systematic reviews of ultra-processed foods: a methodological study.

A dramatic shift in the global food system is occurring with the rapid growth of ultra-processed foods (UPFs) consumption, which poses potentially serious health risks. Systematic review (SR) method has been used to summarise the association between UPF consumption and multiple health outcomes; however, a suboptimal-quality SR may mislead the decision-making in clinical practices and health policies. Therefore, a methodological review was conducted to identify the areas that can be improved regarding the risk of bias and reporting quality of relevant SRs. Systematic searches to collect SRs with meta-analyses of UPFs were performed using four databases from their inception to April 14, 2023. The risk of bias and reporting quality were evaluated using ROBIS and PRISMA 2020, respectively. The key characteristics of the included SRs were summarised descriptively. Excel 2019 and R 4.2.3 were used to analyse the data and draw graphs. Finally, 16 relevant SRs written in English and published between 2020 and 2023 in 12 academic journals were included. Only one SR was rated as low risk of bias, and the others were rated as higher risk of bias mainly because the risk of bias in the original studies was not explicitly addressed when synthesising the evidence. The reporting was required to be advanced significantly, involving amendments of registration and protocol, data and analytic code statement, and lists of excluded studies with justifications. The reviews' results could improve the quality, strengthen future relevant SRs' robustness, and further underpin the evidence base for supporting clinical decisions and health policies.

Puerarin attenuates valproate-induced features of ASD in male mice via regulating Slc7a11-dependent ferroptosis.

Autism spectrum disorder (ASD) is a complicated, neurodevelopmental disorder characterized by social deficits and stereotyped behaviors. Accumulating evidence suggests that ferroptosis is involved in the development of ASD, but the underlying mechanism remains elusive. Puerarin has an anti-ferroptosis function. Here, we found that the administration of puerarin from P12 to P15 ameliorated the autism-associated behaviors in the VPA-exposed male mouse model of autism by inhibiting ferroptosis in neural stem cells of the hippocampus. We highlight the role of ferroptosis in the hippocampus neurogenesis and confirm that puerarin treatment inhibited iron overload, lipid peroxidation accumulation, and mitochondrial dysfunction, as well as enhanced the expression of ferroptosis inhibitory proteins, including Nrf2, GPX4, Slc7a11, and FTH1 in the hippocampus of VPA mouse model of autism. In addition, we confirmed that inhibition of xCT/Slc7a11-mediated ferroptosis occurring in the hippocampus is closely related to puerarin-exerted therapeutic effects. In conclusion, our study suggests that puerarin targets core symptoms and hippocampal neurogenesis reduction through ferroptosis inhibition, which might be a potential drug for autism intervention.

Single-Cell RNA Sequencing Transcriptomics Revealed HCMV IE2-Related Microglia Responses in Alzheimer's-Like Disease in Transgenic Mice.

    Although multiple factors are known to concur with Alzheimer's disease (AD), the relationship between human cytomegalovirus (HCMV) and AD-like disease is unclear. Here, we propose a hypothesis that HCMV immediate-early 2 (IE2) protein promotes microglia activation and thus leads to AD-like disease. We successfully constructed IE2 transgenic mice expressing IE2 in the hippocampus. Single-cell sequencing analysis revealed that IE2 promoted the activation of microglia and upregulated the expression of disease-associated microglia genes. Differentially expressed gene analysis and pathway enrichment revealed that IE2 upregulated immune and nervous system disease-related genes. Immunohistochemical analysis showed that the expressions of both amyloid precursor protein (APP) and p-Tau were significantly upregulated in the brains of IE2 mice and were markers of AD. Taken together, these findings provide useful insights into AD-like disease activated by HCMV IE2.

Structural basis for human Cav1.2 inhibition by multiple drugs and the neurotoxin calciseptine.

Cav1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Cav1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSDII. Calciseptine sits on the shoulder of the pore domain, away from the permeation path. In contrast, when pinaverium bromide, an antispasmodic drug, is inserted into a cavity reminiscent of the IFM-binding site in Nav channels, a series of structural changes occur, including upward movement of VSDII coupled with dilation of the selectivity filter and its surrounding segments in repeat III. Meanwhile, S4-5III merges with S5III to become a single helix, resulting in a widened but still non-conductive intracellular gate.