Unraveling the neuroprotective potential of scalp electroacupuncture in ischemic stroke: A key role for electrical stimulation.

This study aims to explore the neuroprotective effects of scalp Electroacupuncture (EA) on ischemic stroke, with a specific focus on the role of electrical stimulation (ES). Employing a rat model of middle cerebral artery occlusion (MCAO), we used methods such as Triphenyl tetrazolium chloride staining, micro-CT scanning, Enzyme linked immunosorbent assay (ELISA), and immunofluorescence to assess the impacts of EA. We further conducted RNA-seq analysis and in vitro experiments with organotypic brain slices and cerebral organoids to explore the underlying mechanisms. Our research revealed that EA notably reduced cerebral infarct volume and improved regional cerebral blood flow in rats following MCAO. Micro-CT imaging showed improved vascular integrity in EA-treated groups. Histological analyses, including HE staining, indicated reduced brain tissue damage. ELISA demonstrated a decrease in pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, suggesting improved blood-brain barrier function. Immunofluorescence and Western blot analyses revealed that EA treatment significantly inhibited microglial and astrocytic overactivation. RNA-seq analysis of brain tissues highlighted a downregulation of immune pathways and inflammatory responses, confirming the neuroprotective role of EA. This was further corroborated by in vitro experiments using organotypic brain slices and cerebral organoids, which showcased the efficacy of electrical stimulation in reducing neuroinflammation and protecting neuronal cells. The study highlights the potential of scalp EA, particularly its ES component, in treating ischemic stroke. It provides new insights into the mechanisms of EA, emphasizing its efficacy in neuroprotection and modulation of neuroinflammation, and suggests avenues for optimized treatment strategies in stroke therapy.

Differentiating Pond-Intensive, Paddy-Ecologically, and Free-Range Cultured Crayfish (Procambarus clarkii) Using Stable Isotope and Multi-Element Analysis Coupled with Chemometrics.

The farming pattern of crayfish significantly impacts their quality, safety, and nutrition. Typically, green and ecologically friendly products command higher economic value and market competitiveness. Consequently, intensive farming methods are frequently employed in an attempt to replace these environmentally friendly products, leading to potential instances of commercial fraud. In this study, stable isotope and multi-element analysis were utilized in conjunction with multivariate modeling to differentiate between pond-intensive, paddy-ecologically, and free-range cultured crayfish. The four stable isotope ratios of carbon, nitrogen, hydrogen, and oxygen (δ13C, δ15N, δ2H, δ18O) and 20 elements from 88 crayfish samples and their feeds were determined for variance analysis and correlation analysis. To identify and differentiate three different farming pattern crayfish, unsupervised methods such as hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used, as well as supervised multivariate modeling, specifically partial least squares discriminant analysis (PLS-DA). The HCA and PCA exhibited limited effectiveness in classifying the farming pattern of crayfish, whereas the PLS-DA demonstrated a more robust performance with a predictive accuracy of 90.8%. Additionally, variables such as δ13C, δ15N, δ2H, Mn, and Co exhibited relatively higher contributions in the PLS-DA model, with a variable influence on projection (VIP) greater than 1. This study is the first attempt to use stable isotope and multi-element analysis to distinguish crayfish under three farming patterns. It holds promising potential as an effective strategy for crayfish authentication.

Research progress of tartaric acid stabilization on wine characteristics.

Tartaric acid is one of the characteristic acids in wine, playing a crucial role in wine characteristics. However, superabundant tartaric acid will form insoluble salts and precipitate in the form of crystals, affecting consumers' purchasing appetite. Therefore, tartaric stability is also one of the important indices for controlling the wine quality. At present, the main processing methods for tartaric stability include cold stabilization, ion exchange treatment, electrodialysis and the addition of exogenous components (gum arabic, metatartaric acid, carboxymethyl cellulose, mannoprotein and potassium polyaspartate). This review summarizes and analyzes the origin of tartaric acid in wine, factors influencing the tartaric stability, detection methods, treatments for tartaric stabilization, and the effects of these methods on the sensory quality of wine. Comparing the effects of these methods on wine quality can provide a basis for the further study of tartaric stabilization methods in order to select an appropriate tartaric stabilization method.

Rh(III)-catalyzed [4 + 1] annulation of 1-arylindazolones with alkynyl cyclobutanols: access to indazolo[1,2-a]indazolones.

A convenient and efficient synthesis of structurally diverse indazolo[1,2-a]indazolones via a Rh(III)-catalyzed [4 + 1] annulation of 1-arylindazolones with alkynyl cyclobutanols has been achieved by combining C-H and C-C bond cleavage. This cascade reaction features readily available starting materials, good functional group tolerance, broad substrate scope, and excellent atom-economy.

Luobitong Potentiates MTX's Anti-Rheumatoid Arthritis Activity via Targeting Multiple Inflammatory Pathways.

Background: The LuoBiTong (LBT) capsule, a novel traditional Chinese medicine formulation, is currently in Phase III clinical trials. Preliminary preclinical and Phase II clinical studies suggest its efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying mechanisms of its action remain to be elucidated.This research aims to explore the effects and mechanisms of LBT in conjunction with a maintenance dose of methotrexate (M-MTX) on RA. Methods: A Collagen-Induced Arthritis (CIA) mouse model was used to evaluate the anti-RA effects of LBT combined with M-MTX. Assessments included foot swelling, arthritis scoring, serum inflammatory factor analysis, and histopathological examination of the foot. These effects were compared with those of high-dose MTX (H-MTX). Network pharmacology was employed to construct a compound-target network for RA, based on drug composition, to predict its potential mechanism of action. Flow cytometry, Western Blot, and immunohistochemical analyses in animal models identified multiple inflammatory pathways targeted by LBT to augment the anti-RA effects of MTX. Results: The study revealed that LBT combined with M-MTX significantly alleviated CIA-induced arthritis without adverse effects. The combination of LBT and M-MTX showed similar or superior efficacy in regulating macrophage polarization, NF-κB, MAPK signaling pathways, and in the suppression of TH-17 expression in proinflammatory cells. These findings suggest that LBT may exert a multi-pathway therapeutic effect in RA treatment. The predicted pharmacological targets and mechanisms align well with this hypothesis. Conclusion: LBT, when combined with MTX, enhances the anti-RA effect by targeting multiple inflammatory pathways, demonstrating significant therapeutic potential.

Unveiling unconventional CH4-Xe compounds and their thermodynamic properties at extreme conditions.

Inert gases (e.g., He and Xe) can exhibit chemical activity at high pressure, reacting with other substances to form compounds of unexpected chemical stoichiometry. This work combines first-principles calculations and crystal structure predictions to propose four unexpected stable compounds of CH4Xe3, (CH4)2Xe, (CH4)3Xe, and (CH4)3Xe2 at pressure ranges from 2 to 100 GPa. All structures are composed of isolated Xe atoms and CH4 molecules except for (CH4)3Xe2, which comprises a polymerization product, C3H8, and hydrogen molecules. Ab initio molecular dynamics simulations indicate that pressure plays a very important role in the different temperature driving state transitions of CH4-Xe compounds. At lower pressures, the compounds follow the state transition of solid-plastic-fluid phases with increasing temperature, while at higher pressures, the stronger Xe-C interaction induces the emergence of a superionic state for CH4Xe3 and (CH4)3Xe2 as temperature increases. These results not only expand the family of CH4-Xe compounds, they also contribute to models of the structures and evolution of planetary interiors.

A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response.

Antibiotic-induced dysbiosis is a major risk factor for Clostridioides difficile infection (CDI), and fecal microbiota transplantation (FMT) is recommended for treating CDI. However, the underlying mechanisms remain unclear. Here, we show that Tritrichomonas musculis (T.mu), an integral member of the mouse gut commensal microbiota, reduces CDI-induced intestinal damage by inhibiting neutrophil recruitment and IL-1ß secretion, while promoting Th1 cell differentiation and IFN-γ secretion, which in turn enhances goblet cell production and mucin secretion to protect the intestinal mucosa. T.mu can actively metabolize arginine, not only influencing the host's arginine-ornithine metabolic pathway, but also shaping the metabolic environment for the microbial community in the host's intestinal lumen. This leads to a relatively low ornithine state in the intestinal lumen in C. difficile-infected mice. These changes modulate C. difficile's virulence and the host intestinal immune response, and thus collectively alleviating CDI. These findings strongly suggest interactions between an intestinal commensal eukaryote, a pathogenic bacterium, and the host immune system via inter-related arginine-ornithine metabolism in the regulation of pathogenesis and provide further insights for treating CDI.

Neurotoxicity of Combined Exposure to the Heavy Metals (Pb and As) in Zebrafish (Danio rerio).

Lead (Pb) and arsenic (As) are commonly occurring heavy metals in the environment and produce detrimental impacts on the central nervous system. Although they have both been indicated to exhibit neurotoxic properties, it is not known if they have joint effects, and their mechanisms of action are likewise unknown. In this study, zebrafish were exposed to different concentrations of Pb (40 µg/L, 4 mg/L), As (32 µg/L, 3.2 mg/L) and their combinations (40 µg/L + 32 µg/L, 4 mg/L + 3.2 mg/L) for 30 days. The histopathological analyses showed significant brain damage characterized by glial scar formation and ventricular enlargement in all exposed groups. In addition, either Pb or As staining inhibited the swimming speed of zebrafish, which was enhanced by their high concentrations in a mixture. To elucidate the underlying mechanisms, we examined changes in acetylcholinesterase (AChE) activity, neurotransmitter (dopamine, 5-hydroxytryptamine) levels, HPI axis-related hormone (cortisol and epinephrine) contents and neurodevelopment-related gene expression in zebrafish brain. The observations suggest that combined exposure to Pb and As can cause abnormalities in swimming behavior and ultimately exacerbate neurotoxicity in zebrafish by interfering with the cholinergic system, dopamine and 5-hydroxytryptamine signaling, HPI axis function as well as neuronal development. This study provides an important theoretical basis for the mixed exposure of heavy metals and their toxicity to aquatic organisms.

Influence of GPRC5A-Regulated ABCB1 Expression on Lung Adenocarcinoma Proliferation.

Objective Aberrant expression of ATP binding cassette subfamily B member 1 (ABCB1) plays a key role in several cancers. However, influence of G protein coupled receptor family C group 5 type A (GPRC5A)-regulated ABCB1 expression on lung adenocarcinoma proliferation remains unclear. Therefore, this study investigated the effect of GPRC5A regulated ABCB1 expression on the proliferation of lung adenocarcinoma. Methods ABCB1 expressions in lung adenocarcinoma cell lines, human lung adenocarcinoma tissues, and tracheal epithelial cells and lung tissues of GPRC5A knockout mice and wild-type mice were analyzed with RT-PCR, Western blot, or immunohistochemical analysis. Cell counting kit-8 assay was performed to analyze the sensitivity of tracheal epithelial cells from GPRC5A knockout mice to chemotherapeutic agents. Subcutaneous tumor formation assay was performed to confirm whether down-regulation of ABCB1 could inhibit the proliferation of lung adenocarcinoma in vivo. To verify the potential regulatory relationship between GPRC5A and ABCB1, immunofluorescence and immunoprecipitation assays were performed. Results ABCB1 expression was up-regulated in lung adenocarcinoma cell lines and human lung adenocarcinoma tissues. ABCB1 expression in the tracheal epithelial cells and lung tissues of GPRC5Adeficient mice was higher than that in the wild type mice. Tracheal epithelial cells of GPRC5A knockout mice were much more sensitive to tariquidar and doxorubicin than those of GPRC5A wild type mice. Accordingly, 28 days after injection of the transplanted cells, the volume and weight of lung tumor in ABCB1knockout cell-transplanted GPRC5A-/-C57BL/6 mice were significantly smaller than those in wild type cell-transplanted mice (P= 0.0043, P= 0.0060). Furthermore, immunofluorescence and immunoprecipitation assays showed that GPRC5A regulated ABCB1 expression by direct binding.Conclusion GPRC5A reduces lung adenocarcinoma proliferation via inhibiting ABCB1 expression. The pathway by which GPRC5A regulates ABCB1 expression needs to be investigated.

Separation techniques for manufacturing fruit spirits: From traditional distillation to advanced pervaporation process.

Separation process is one of the key processes in the production of fruit spirits, including the traditional distillation method and the new pervaporation membrane method. The separation process significantly determines the constituents and proportions of compounds in the fruit spirit, which has a significant impact on the spirit quality and consumer acceptance. Therefore, it is important and complex to reveal the changing rules of chemical substances and the principles behind them during the separation process of fruit spirits. This review summarized the traditional separation methods commonly used in fruit spirits, covering the types, principles, and corresponding equipment of distillation methods, focused on the enrichment or removal of aroma compounds and harmful factors in fruit spirits by distillation methods, and tried to explain the mechanism behind it. It also proposed a new separation technology for the production of fruit spirits, pervaporation membrane technology, summarized its working principle, operation, working parameters, and application in the production of fruit spirits, and outlined the impact of the separation method on the production of fruit spirits based on existing research, focusing on the separation of flavor compounds, sensory qualities, and hazard factors in fruit spirits, along with a preliminary comparison with distillation. Finally, according to the current researches of the separation methods and the development requirement of the separation process of fruit spirits, the prospect of corresponding research is put forward, in order to propose new ideas and development directions for the research in this field.

Antidepressant-like effects of Jieyu Chufan capsules in the olfactory bulbectomy rat model.

The olfactory bulbectomy (OBX) animal model of depression reproduces the behavioral and neurochemical changes observed in depressed patients. We assessed the therapeutic effects of the Jieyu Chufan (JYCF) capsule on OBX rats. JYCF ameliorated the hedonic and anxiety-like behavior of OBX rats and attenuated the cortical and hippocampal damage. JYCF enhanced the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and adiponectin (ADPN) in the cortex and hippocampus of OBX rats. JYCF also reduced cortisol levels and restored the levels of excitatory neurotransmitters, such as 5-hydroxytryptamine (5-HT), acetylcholine (ACH), and glutamic acid (Glu), in the brain tissue of OBX rats. Our results suggest that JYCF preserves the synaptic structure by increasing the levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) and alleviates the histological alterations of brain tissue by activating AKT/PKA-CREB-BDNF pathways, and by upregulating ADPN and FGF2 expression in OBX rats. JYCF exerts multiple therapeutic effects on depression, including modulating neurotransmitters, repairing neuronal damage, and maintaining synaptic integrity. These findings support the potential of JYCF as a novel antidepressant agent with therapeutic effects on depression and related neurological disorders.

Ultra-low time jitter transform-limited dissipative Kerr soliton microcomb.

Microresonator soliton frequency combs offer unique flexibility in synthesizing microwaves over a wide range of frequencies. Therefore, it is very important to study the time jitter of soliton microcombs. Here, we fabricate optical microresonators with perfect transmission spectrum that characterizes highly uniform extinction ratio and absence of mode interactions by laser machining high-purity silica fiber preforms. Based on such perfect whispering-gallery-mode cavity, We demonstrate that K-band microwave with ultra-low phase noise (-83 dBc/Hz@100 Hz; -112 dBc/Hz@1kHz; -133 dBc/Hz@10kHz) can be generated by photo-detecting the repetition rate of a soliton microcomb. Also, with the Raman scattering and dispersive wave emission largely restricted, we show that ultra-low time jitter soliton has a wide existence range. Our work illuminates a pathway toward low-noise photonic microwave generation as well as the quantum regime of soliton microcombs.

Structural insights into the allosteric inhibition of P2X4 receptors.

P2X receptors are ATP-activated cation channels, and the P2X4 subtype plays important roles in the immune system and the central nervous system, particularly in neuropathic pain. Therefore, P2X4 receptors are of increasing interest as potential drug targets. Here, we report the cryo-EM structures of the zebrafish P2X4 receptor in complex with two P2X4 subtype-specific antagonists, BX430 and BAY-1797. Both antagonists bind to the same allosteric site located at the subunit interface at the top of the extracellular domain. Structure-based mutational analysis by electrophysiology identified the important residues for the allosteric inhibition of both zebrafish and human P2X4 receptors. Structural comparison revealed the ligand-dependent structural rearrangement of the binding pocket to stabilize the binding of allosteric modulators, which in turn would prevent the structural changes of the extracellular domain associated with channel activation. Furthermore, comparison with the previously reported P2X structures of other subtypes provided mechanistic insights into subtype-specific allosteric inhibition.

Prediction of a reservoir of N-rich high-energy density material at the Earth's mantle.

Water and nitrogen are abundant in the Earth's interior and atmosphere, and their mixture under high pressure is a fundamental and valuable scientific issue for physics and chemical science. Based on structural prediction and first-principles simulations, we propose that the two nitrogen-rich stoichiometries, H2ON6 and H2ON10, become energetically stable above ∼70 GPa. Further ab initio molecular dynamics calculations indicate that H2ON6 and H2ON10 undergo phase transitions from solid to superionic and finally to fluid phase with increasing temperature. The superionic regions in their phase diagram correspond to the extreme conditions of Earth's mantle, implying that the Earth's interior might be a possible reservoir of the N-rich hydrates. In addition, H2ON6 remains dynamically stable under ambient conditions with an estimated energy density of 6.53 kJ g-1, indicating that it might be a high-energy density material. These results not only provide essential information for the understanding of the Earth's interior, but also provide guidance for the design of high-energy density materials.

The interplay between innate lymphoid cells and microbiota.

Innate lymphoid cells (ILCs) are mainly resident in mucosal tissues such as gastrointestinal tract and respiratory tract, so they are closely linked to the microbiota. ILCs can protect commensals to maintain homeostasis and increase resistance to pathogens. Moreover, ILCs also play an early role in defense against a variety of pathogenic microorganisms including pathogenic bacteria, viruses, fungi and parasites, before the intervention of adaptive immune system. Due to the lack of adaptive antigen receptors expressed on T cells and B cells, ILCs need to use other means to sense the signals of microbiota and play a role in corresponding regulation. In this review, we focus on and summarize three major mechanisms used in the interaction between ILCs and microbiota: the mediation of accessory cells represented by dendritic cells; the metabolic pathways of microbiota or diet; the participation of adaptive immune cells.

Visible light/copper catalysis enabled alkylation of silyl enol ethers with arylsulfonium salts.

An efficient protocol has been developed herein for the site-selective alkylation of silyl enol ethers with arylsulfonium salts giving access to valuable aryl alkyl thioethers under visible light conditions. Enabled by copper (I) photocatalysis, the C-S bond of arylsulfonium salts can be selectively cleaved to deliver C-centered radicals under mild conditions. This developed method provides a straightforward approach to utilize arylsulfonium salts as sulfur sources for the synthesis of aryl alkyl thioethers.

Visible-Light Copper Catalysis for the Synthesis of α-Alkyl-Acetophenones by the Radical-Type Ring Opening of Sulfonium Salts and Oxidative Alkylation of Alkenes.

Direct difunctionalization of simple alkenes has been treated as a powerful synthetic strategy for the construction of highly functionalized skeletons. In this study, direct oxidative coupling of sulfonium salts with alkenes was achieved under mild conditions by a blue-light-driven photoredox process using a copper complex as a photosensitizer. This protocol allows regioselective synthesis of aryl/alkyl ketones from simple sulfonium salts and aromatic alkenes via selective C-S bond cleavage of sulfonium salts and oxidative alkylation of aromatic alkenes using dimethyl sulfoxide (DMSO) as a mild oxidant.

Heavy metal stabilization remediation in polluted soils with stabilizing materials: a review.

The remediation of soil contaminated by heavy metals has long been a concern of academics. This is due to the fact that heavy metals discharged into the environment as a result of natural and anthropogenic activities may have detrimental consequences for human health, the ecological environment, the economy, and society. Metal stabilization has received considerable attention and has shown to be a promising soil remediation option among the several techniques for the remediation of heavy metal-contaminated soils. This review discusses various stabilizing materials, including inorganic materials like clay minerals, phosphorus-containing materials, calcium silicon materials, metals, and metal oxides, as well as organic materials like manure, municipal solid waste, and biochar, for the remediation of heavy metal-contaminated soils. Through diverse remediation processes such as adsorption, complexation, precipitation, and redox reactions, these additives efficiently limit the biological effectiveness of heavy metals in soils. It should also be emphasized that the effectiveness of metal stabilization is influenced by soil pH, organic matter content, amendment type and dosage, heavy metal species and contamination level, and plant variety. Furthermore, a comprehensive overview of the methods for evaluating the effectiveness of heavy metal stabilization based on soil physicochemical properties, heavy metal morphology, and bioactivity has also been provided. At the same time, it is critical to assess the stability and timeliness of the heavy metals' long-term remedial effect. Finally, the priority should be on developing novel, efficient, environmentally friendly, and economically feasible stabilizing agents, as well as establishing a systematic assessment method and criteria for analyzing their long-term effects.

Superconducting H7 chain in gallium hydrides at high pressure.

Pressure-stabilized hydrides have potential as an outstanding reservoir for high-temperature (Tc) superconductors. We undertook a systematic study of crystal structures and superconducting properties of gallium hydrides using an advanced structure-search method together with first-principles calculations. We identified an unconventional stoichiometric GaH7 gallium hydride that is thermodynamically stable at pressures above 247 GPa. Interestingly, the H atoms are clustered to form a unique H7 chain intercalating the Ga framework. Further calculations show a high estimated Tc above 100 K at 200-300 GPa for GaH7, closely related to the strong coupling between electrons of Ga and H atoms, and phonon vibrations of H7 chains. Our work provides an example of exploration for diverse superconducting hydrogen motifs under high pressure, and may stimulate further experimental syntheses.

Primary Malignant Peripheral Nerve Sheath Tumor of the Stomach: A Rare Case Report and Review of Literature.

Malignant peripheral nerve sheath tumor (MPNST) is a spindle cell sarcoma originating from peripheral nerves or showing differentiation of nerve sheath components. Primary MPNST of the stomach is an extremely rare neoplasm with only a few published reports in the literature. We present the case of a 58-year-old male patient with MPNST in the stomach. The patient was admitted due to upper abdomen discomfort. Gastroscopy revealed a huge ulcer lesion in the stomach, and biopsy revealed a spindle cell malignant neoplasm. No other specific findings were found in the whole-body imaging examination. Subtotal gastrectomy was performed. Histologically, an ulcer-type, push-infiltrating mass composed of dense, woven-like spindle cells with frequent mitosis could be seen. In immunohistochemistry, the tumor cells were negative for expression of H3K27 trimethylation (H3K27me3), keratin (AE1/AE3), epithelial membrane antigen (EMA), CD34, KIT, DOG1 (ANO1), S-100, SOX10, smooth muscle actin, desmin, myogenin, MDM2, CDK4, P16 (CDKN2A) and SS18-SSX (SS18::SSX). Primary MPNST of the stomach was diagnosed based on histological and immunohistochemical results. During the 2.5 years follow-up period after surgery, no recurrence was observed.