The role of anti-citrullinated protein antibody in pathogenesis of RA.

Rheumatoid arthritis (RA) is a common autoimmune rheumatic disease that causes chronic synovitis, bone erosion, and joint destruction. The autoantigens in RA include a wide array of posttranslational modified proteins, such as citrullinated proteins catalyzed by peptidyl arginine deiminase4a. Pathogenic anti-citrullinated protein antibodies (ACPAs) directed against a variety of citrullinated epitopes are abundant both in plasma and synovial fluid of RA patients. ACPAs play an important role in the onset and progression of RA. Intensive and extensive studies are being conducted to unveil the mechanisms of RA pathogenesis and evaluate the efficacy of some investigative drugs. In this review, we focus on the formation and pathogenic function of ACPAs.

Efficient extraction and formation mechanism of fulvic acid from lignite: Experimental and DFT studies.

Enhancing the coal-based fulvic acid (FA) yield through the effect of oxidation methods was of great importance. However, the realization of an efficient and environmentally friendly method for the preparation of FA, along with understanding of its formation mechanism, remains imperative. Herein, coal-based FA was prepared by oxidizing lignite with H2O2 and NaOH/KOH. The experimental data showed that ML lignite was pickled with HCl, metal ions such as iron, aluminum, and calcium can be removed, and this lignite is used as raw material, the reaction time was 150 min, the reaction temperature was 50 °C, and the volume ratio of H2O2 (30%) to KOH (3 mol/L) was 1:1, the effect of H2O2 and KOH on FA extraction was the best. The coal-based FA yield could reach 60.49%. The addition of silicone defoaming agent during the experiment resulted in a significant diminished the presence of bubbles and prevent the production of CO2. A decrease in N2 content was detected by GC. The FTIR, XPS, Py-GC/MS and other characterization results showed that FA has more polar functional groups (-COOH, -OH), and it contains more O-CO structure. Consequently, a greater quantity of FA molecules is generated during the reaction process. Moreover, the partial Gibbs free energies during the formation process of coal-based FA were calculated by density-functional theory (DFT). The highest energy required for free radicals was found to be between 1.3 and 1.7 eV. This study would provide theoretical support for exploring the FA formation process and the promotion of lignite humification by adding H2O2 or alkali to lignite.

Nitro-functionalization on MIL-53(Fe) for PCMX degradation: Elevating Fenton-like catalytic propelled by abundant reaction sites and iron cycle.

To address the issue of excessive residues of 4-chloro-3,5-dimethylphenol (PCMX) in the water environment. In a one-step solvothermal process, iron-based metal-organic frameworks (Fe-MOFs) material MIL-53(Fe) undergoes a synthetic modification strategy. 2-Nitroterephthalic acid as an organic ligand reacted with Fe3+ in a solvothermal process lasting 18 h to yield the nitro-functionalized MIL-53(Fe)-NO2(18h). The objective was to augment the abundance of Fe central unsaturated coordination sites (Fe CUCs) and expedite the Fe(III)/Fe(II) redox cycle, thereby enhancing the heterogeneous Fenton-like treatment capability of pollutants. MIL-53(Fe)-NO2(18h) has excellent hydrogen peroxide (H2O2) catalytic activity and PCMX degradation across a broad pH spectrum (4.0∼8.0). Almost complete removal of PCMX was achieved within 30 min, while pseudo-first-order kinetic rate constants (kobs) increased 4.37 times over MIL-53(Fe). The confirmation of increased Fe CUCs abundance in MIL-53(Fe)-NO2(18h) was achieved through Lewis acidity, oxygen vacancies (OVs) signals, and Fe-O coordination characterization results. Density functional theory (DFT) calculations revealed that Fe CUCs in MIL-53(Fe)-NO2(18h) exhibits heightened affinity for H2O2 adsorption, showcasing stronger charge transfer and enhanced H2O2 dissociation ability. The Fe(III)/Fe(II) redox cycle, a driving force of Fenton-like reactions, was notably improved in the nitro-modified materials. These enhancements significantly expedited the Fenton-like process, resulting in the generation of increased amounts of reactive oxygen species (ROSs), with hydroxyl radicals (OH·) being pivotal components in degradation. The MIL-53(Fe)-NO2(18h)/H2O2 system has demonstrated versatility in treating a variety of emerging contaminants, achieving removal efficiencies exceeding 99.7% for other antibiotics and endocrine disruptors within 60 min. Furthermore, MIL-53(Fe)-NO2(18h) demonstrated outstanding reusability and adaptability in actual water environments. This study introduces a straightforward and environmentally friendly strategy for remediating environmental pollution using Fe-MOF-catalysed heterogeneous Fenton-like technology.

Caseinate-coated zein nanoparticles as potential delivery vehicles for guavinoside B from guava: Molecular interactions and encapsulation properties.

Guavinoside B (GUB) is a characteristic constituent from guava with strong antioxidant activity; however, its low water solubility limits its utilization. Herein, we investigated the interaction between GUB and zein, a prolamin with self-assembling property, using multiple spectroscopic methods and fabricated GUB-zein-NaCas nanoparticles (GUB-Z-N NPs) via the antisolvent coprecipitation approach. GUB caused fluorescence quenching to zein via the static quenching mechanism. Fourier-transform infrared spectroscopy and computational analysis revealed that GUB bound to zein via van der Waals interaction, hydrogen bond, and hydrophobic forces. The GUB-Z-N NPs were in the nanometric size range (< 200 nm) and exhibited promising encapsulation efficiency and redispersibility after freeze-drying. These particles remained stable for up to 31 days at 4 °C and great resistance to salt and pH variation, and displayed superior antioxidant activity to native GUB. The current study highlights the potential of zein-based nanoparticles as delivery vehicles for GUB in the food industry.

Coptisine-mediated downregulation of E2F7 induces G2/M phase arrest in hepatocellular carcinoma cells through inhibition of E2F4/NFYA/NFYB transcription factors.

Coptisine (COP) has been shown to exhibit a wide range of anticancer properties, including in hepatocellular carcinoma (HCC). Nevertheless, the precise mechanism of COP in the treatment of HCC remains elusive. This study aims to investigate the potential mechanism of action of COP against HCC. By evaluating the anti-HCC activity of COP in different HCC cells lines and in xenografted nude mice, it was found that COP inhibited HCC in vitro and in vivo. Through RNA-Seq analysis, E2F7 was identified as a potential target of COP against HCC, as well as the cell cycle as a possible pathway. The overexpression of E2F7 and the inhibition of CHK1 demonstrated that COP inhibits the activity of HCC and induces G2/M phase arrest of HCC cells by down-regulating E2F7 and influencing the CHK1/CDC25A pathway. Finally, the promoter fragmentation experiments and chromatin immunoprecipitation revealed that COP down-regulated E2F7 by inhibiting the E2F4/NFYA/NFYB transcription factors. In conclusion, our study demonstrated that COP downregulates E2F7 by affecting key transcription factors, thereby inducing cell cycle arrest and inhibits HCC cell growth. This provides further evidence of the efficacy of COP in the treatment of tumors.

The study of female college students' consumer psychology mechanism toward male celebrity endorsed products: Tempted or coerced?

The trend of male celebrities endorsing female products is increasing. However, research is lacking on whether this influence is due to the positive emotions generated by the male celebrity's attractiveness or the peer pressure due to mass purchases by the celebrity's fans, and how these effects differ across products with different attributes. This study aims to fill the gap in the existing literature by investigating the influence of male endorsers on female consumers purchase intention, and to deepen the understanding of the mechanisms by which attractiveness and conformity jointly influence purchase decisions. This study used a mixed-design text experiment to investigate the impact of male endorsers' attractiveness and conformity on female college students' positive product attitude and purchase intention for gender-neutral product, female skincare product, and female intimate product, based on the Theory of Planned Behaviour (TPB). The data collected from 456 female college students were analyzed using bootstrap analysis. The study found that both male endorsers' attractiveness and conformity can enhance female college students' positive product attitude and promote their purchase intention for gender-neutral product. However, for female skincare product, male endorsers' attractiveness affects their positive product attitude and purchase intention. Nevertheless, when conformity was present, attractiveness no longer had an effect. Furthermore, for individuals with high levels of loneliness, attractiveness had a detrimental effect on their positive product attitude. On the other hand, conformity had a positive effect by promoting positive product attitude and increasing purchase intention. For female's intimate product, attractiveness did not affect positive product attitude and purchase intention, but the positive effect of conformity remained significant, and both relationships were not moderated by loneliness. It enhances our comprehension of the intricate dynamics underlying the influence of male celebrity endorsements on consumer purchasing decisions, and also offers theoretical justification for the selection of male endorsers for diverse female product.

Bipiperidinyl Derivatives of Cannabidiol Enhance Its Antiproliferative Effects in Melanoma Cells.

Cannabis and its major cannabinoid cannabidiol (CBD) are reported to exhibit anticancer activity against skin tumors. However, the cytotoxic effects of other minor cannabinoids and synthetic CBD derivatives in melanoma are not fully elucidated. Herein, the antiproliferative activity of a panel of phytocannabinoids was screened against murine (B16F10) and human (A375) melanoma cells. CBD was the most cytotoxic natural cannabinoid with respective IC50 of 28.6 and 51.6 µM. Further assessment of the cytotoxicity of synthetic CBD derivatives in B16F10 cells identified two bipiperidinyl group-bearing derivatives (22 and 34) with enhanced cytotoxicity (IC50 = 3.1 and 8.5 µM, respectively). Furthermore, several cell death assays including flow cytometric (for apoptosis and ferroptosis) and lactate dehydrogenase (for pyroptosis) assays were used to characterize the antiproliferative activity of CBD and its bipiperidinyl derivatives. The augmented cytotoxicity of 22 and 34 in B16F10 cells was attributed to their capacity to promote apoptosis (as evidenced by increased apoptotic population). Taken together, this study supports the notion that CBD and its derivatives are promising lead compounds for cannabinoid-based interventions for melanoma management.

Characteristics and risk factors for invasive fungal infection in hospitalized patients with acute-on-chronic hepatitis B liver failure: a retrospective cohort study from 2010 to 2023.

Background and aim: The global burden of invasive fungal infections (IFIs) is emerging in immunologic deficiency status from various disease. Patients with acute-on-chronic hepatitis B liver failure (ACHBLF) are prone to IFI and their conditions are commonly exacerbated by IFI. However, little is known about the characteristics and risk factors for IFI in hospitalized ACHBLF patients. Methods: A total of 243 hospitalized ACHBLF patients were retrospectively enrolled from January 2010 to July 2023. We performed restricted cubic spline analysis to determine the non-linear associations between independent variables and IFI. The risk factors for IFI were identified using logistic regression and the extreme gradient boosting (XGBoost) algorithm. The effect values of the risk factors were determined by the SHapley Additive exPlanations (SHAP) method. Results: There were 24 ACHBLF patients (9.84%) who developed IFI on average 17.5 (13.50, 23.00) days after admission. The serum creatinine level showed a non-linear association with the possibility of IFI. Multiple logistic regression revealed that length of hospitalization (OR = 1.05, 95% CI: 1.02-1.08, P = 0.002) and neutrophilic granulocyte percentage (OR = 1.04, 95% CI: 1.00-1.09, P = 0.042) were independent risk factors for IFI. The XGBoost algorithm showed that the use of antibiotics (SHAP value = 0.446), length of hospitalization (SHAP value = 0.406) and log (qHBV DNA) (SHAP value = 0.206) were the top three independent risk factors for IFI. Furthermore, interaction analysis revealed no multiplicative effects between the use of antibiotics and the use of glucocorticoids (P = 0.990). Conclusion: IFI is a rare complication that leads to high mortality in hospitalized ACHBLF patients, and a high neutrophilic granulocyte percentage and length of hospitalization are independent risk factors for the occurrence of IFI.

IL-33 Accelerates Chronic Atrophic Gastritis through AMPK-ULK1 Axis Mediated Autolysosomal Degradation of GKN1.

Chronic atrophic gastritis (CAG) is a complex disease characterized by atrophy and inflammation in gastric mucosal tissue, especially with high expression of interleukins. However, the interaction and mechanisms between interleukins and gastric mucosal epithelial cells in CAG remain largely elusive. Here, we elucidate that IL-33 stands out as the predominant inflammatory factor in CAG, and its expression is induced by H. pylori and MNNG through the ROS-STAT3 signaling pathway. Furthermore, our findings reveal that the IL-33/ST2 axis is intricately involved in the progression of CAG. Utilizing phosphoproteomics mass spectrometry, we demonstrate that IL-33 enhances autophagy in gastric epithelial cells through the phosphorylation of AMPK-ULK1 axis. Notably, inhibiting autophagy alleviates CAG severity, while augmentation of autophagy exacerbates the disease. Additionally, ROS scavenging emerges as a promising strategy to ameliorate CAG by reducing IL-33 expression and inhibiting autophagy. Intriguingly, IL-33 stimulation promotes GKN1 degradation through the autolysosomal pathway. Clinically, the combined measurement of IL-33 and GKN1 in serum shows potential as diagnostic markers. Our findings unveil an IL-33-AMPK-ULK1 regulatory mechanism governing GKN1 protein stability in CAG, presenting potential therapeutic targets for its treatment.

Childhood environmental unpredictability and hoarding: Mediating roles of attachment and security.

Life history theory provides a unified perspective for understanding human behaviors as adaptive strategies to specific environmental conditions. Within this theoretical framework, hoarding emerges as a behavior reflecting an evolved strategy in response to unpredictable environmental challenges, serving as a buffer against resource scarcity and enhancing survival prospects. This study aimed to explore the key roles of childhood environmental unpredictability, attachment, and sense of security in the development of hoarding. 662 participants completed scales on childhood environmental unpredictability, Revised Experiences in Close Relationships (ECR-R), sense of insecurity, and Savings Inventory-Revised (SI-R). The results showed that childhood environmental unpredictability was significantly positively correlated with hoarding. Attachment anxiety and sense of security individually mediate the effect of childhood environmental unpredictability on hoarding. Additionally, 'attachment anxiety--sense of security' and 'attachment avoidance--sense of security' serve as chain mediators in this relationship separately. This study offers insights into the cognitive-behavioral model of hoarding, highlighting the importance of life history theory in examining childhood environmental unpredictability's relationship with hoarding. It also integrates insights from the psychosocial acceleration theory into our comprehension of hoarding's development. Future research directions are also discussed.

Polygonati Rhizoma: A review on the extraction, purification, structural characterization, biosynthesis of the main secondary metabolites and anti-aging effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonati Rhizome (PR) is a plant that is extensively widespread in the temperate zones of the Northern Hemisphere. It is a member of the Polygonatum family of Asparagaceae. PR exhibits diverse pharmacological effects and finds applications in ethnopharmacology, serving as a potent tonic for more than two millennia. PR's compounds endow it with various pharmacological properties, including anti-aging, antioxidant, anti-fatigue, anti-inflammatory, and sleep-enhancing effects, as well as therapeutic potential for osteoporosis and age-related diseases. AIM OF THE STUDY: This review seeks to offer a thorough overview of the processing, purification, extraction, structural characterization, and biosynthesis pathways of PR. Furthermore, it delves into the anti-aging mechanism of PR, using organ protection as an entry point. MATERIALS AND METHODS: Information on PR was obtained from scientific databases (Google Scholar, Web of Science, ScienceDirect, SciFinder, PubMed, CNKI) and books, doctoral theses, and master's dissertations. RESULTS: In this investigation, 49 polysaccharides were extracted from PR, and the impact of various processing, extraction, and purification techniques on the structure and activity of these polysaccharides was evaluated. Additionally, 163 saponins and 46 flavonoids were identified, and three key biosynthesis pathways of secondary metabolites were outlined. Notably, PR and Polygonat Rhizomai polysaccharides (PRP) exhibit remarkable protective effects against age-induced injuries to the brain, liver, kidney, intestine, heart, and vessels, thereby promoting longevity and ameliorating the aging process. CONCLUSIONS: PR, a culinary and therapeutic herb, is rich in active components and pharmacological activities. Based on this review, PR plays a meaningful role in lifespan extension and anti-aging, which can be attributed to PRP. Future research should delve deeper into the structural aspects of PRP that underlie its anti-aging effects and explore potential synergistic interactions with other compounds. Moreover, exploring the potential applications of PR in functional foods and pharmaceutical formulations is recommended to advance the development of industries and resources focused on healthy aging.

Fe2+-NTA synergized UV254 photolytic defluorination of perfluorooctane sulfonate (PFOS): Enhancing through intramolecular electron density perturbation via electron acquisition.

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant posing a risk in environmental persistence, bioaccumulation and biotoxicity. This study was to reach a comprehensive and deeper understanding of PFOS elimination in a UV254 photolytic treatment with the co-presence of Fe2+ and nitrilotriacetic acid trisodium salt (NTA). PFOS defluorination was noticeably enhanced in the UV/Fe2+-NTA treatment compared with UV/NTA, UV/Fe2+ and our previously studied UV/Fe3+ treatments. UV-vis, FTIR, and UPLC/MS-MS results indicated the formation of PFOS-Fe2+-NTA complex in PFOS, Fe2+ and NTA mixture. The transition energy gap of PFOS-Fe2+-NTA decreased below the excitation energy supplied by UV254 irradiation, corresponding with red shift appearing in UV-vis scanning spectrum. This favored intramolecular electron transfer from Fe2+-NTA to PFOS under UV254 irradiation to form electron-accepting PFOS. Molecular electrostatic potential and atom charge distribution analyses suggested electron density rearrangement and perturbation in the perfluorinated carbon chain of electron-accepting PFOS, leading to the decrease in bond dissociation energies. Intermediate products detection suggested the parallel defluorination pathways of PFOS desulfonation, middle carbon chain scission and direct C-F cleavage. NTA exhibited crucial functions in the UV/Fe2+-NTA treatment by holding Fe2+/Fe3+ in soluble form as a chelant and favoring water activation to generate hydrated electrons (eaq-) under UV irradiation as a photosensitizer. Fe2+ acting as the conduit for electron transfer and the bridge of PFOS anion and NTA was thought functioning best at 200 µM in this study. The degree of UV/Fe2+-NTA -synergized PFOS defluorination also depended on eaq- yield and UV254 photon flux. The structure dependence on the electron transfer process of PFOS and PFOA was explored incorporating molecular structure descriptors. Because of possessing greater potential to acquire electrons or less likeliness to donate its electrons than PFOA, PFOS exhibited faster defluorination kinetics in the published "reduction treatments" than "oxidation" ones. Whereas, PFOA defluorination kinetics were at similar level in both "reduction" and "oxidation" treatments.

Borneol serves as an adjuvant agent to promote the cellular uptake of curcumin for enhancing its photodynamic fungicidal efficacy against Candida albicans.

Candida albicans (C. albicans), a major opportunistic pathogenic fungus, is known to cause superficial skin infections. Unfortunately, the misuse of antibiotics has led to the emergence of drug resistance in fungi. Antimicrobial photodynamic therapy (aPDT), a non-antibiotic alternative, has shown potential in treating drug-resistant fungal infections. Curcumin is a photodynamically active phytochemical whose photodynamic fungicidal efficacy is largely dependent on its intracellular accumulation. However, curcumin faces challenges in penetrating the cytoplasm due to its poor water solubility and the fungal cell wall. Borneol, another monoterpenoid phytochemical, is known for its ability to enhance drug absorption. In this study, we showed that borneol improved the cellular uptake of curcumin, thereby enhancing its photodynamic fungicidal efficacy against C. albicans. This effect was attributed to borneol's ability to increase cell permeability. Transcriptomic analysis further confirmed that borneol disrupted the normal structure and function of the C. albicans cell wall and membrane, resulting in dysregulated mRNA expression of related genes and ultimately increased cell permeability. As a result, the excessive accumulation of curcumin in C. albicans triggered the overproduction of intracellular ROS upon exposure to blue light. These excessive intracellular ROS disrupted various cellular structures, interfered with essential cellular processes, inhibited biofilm formation and reduced virulence. Remarkably, borneol was also found to enhance curcumin uptake by C. albicans within biofilms, further enhancing the anti-biofilm efficacy of curcumin-mediated aPDT (Cur-aPDT). In conclusion, the results of this study strongly support the potential of borneol as an adjuvant agent to Cur-aPDT in treating superficial cutaneous fungal infections.

Anti-Ferroptotic Effect of Cannabidiol in Human Skin Keratinocytes Characterized by Data-Independent Acquisition-Based Proteomics.

Skin cells are susceptible to oxidative stress and various types of cell death, including an iron-dependent form known as ferroptosis. Cannabidiol (CBD) can protect skin cells against oxidative stress, but whether this is attributed to the inhibition of ferroptosis is unknown. Herein, we evaluated the anti-ferroptotic effect of CBD in human keratinocytes using biochemical assays (radical scavenging and iron chelating) and cell-based models (for lipid peroxidation and intracellular iron). CBD's anti-ferroptotic effect was further characterized by proteomic analysis. This study identifies anti-ferroptosis as a mechanism of CBD's skin protective effects.

Application of power battery under thermal conductive silica gel plate in new energy vehicles.

This study aims to improve the performance of automotive battery thermal management systems (BTMS) to achieve more efficient heat dissipation and thus reduce hazards during driving. Firstly, the research parameters and properties of composite thermally conductive silicone materials are introduced. Secondly, the heating principle of the power battery, the structure and working principle of the new energy vehicle battery, and the related thermal management scheme are discussed. Finally, the research results are presented from the experimental test and controller design. In addition, to achieve the research goal, the composite thermally conductive silica gel plate (CSGP) material is studied in detail and parametrically analyzed, and the heating mechanism of the power battery is discussed in depth. The temperature characteristics after adding CSGP are experimentally tested, and the controller of the BTMS of the new energy vehicle is designed, including hardware circuits and software modules. The findings show that the temperature characteristics of the battery module have obvious limitations without CSGP. When the battery module operates at a 4C magnification, the temperature exceeds the safety threshold by 38.4%, with particular potential safety risks. Then, the maximum temperature of the battery module with CSGP can be controlled within 50 °C, and the temperature characteristics are prominently improved. Lastly, the controller of the BTMS is tested, and the results reveal that it has remarkable voltage recovery ability. According to the research results, the performance of automotive BTMS can be significantly improved, and better heat dissipation can be effectively achieved by adding CSGP. This helps reduce the hazards of driving. Moreover, the designed controller performs well in voltage recovery, providing solid theoretical support for further developing the CSGP battery management system.

Physical "lying flat": The negative effect of personal relative deprivation on health-promoting lifestyles.

BACKGROUND: Social comparison is an inevitable aspect of human life, often leading to personal relative deprivation, wherein individuals experience a sense of unfair treatment when they perceive themselves as being at a disadvantage in comparison to others. Earlier research has observed a phenomenon called "lying flat" associated with personal relative deprivation, characterized by a lack of motivation for self-improvement. The purpose of this study is to investigate whether this pattern is suitable for the domains of health-promoting lifestyles given that health-promoting is driven by self-improvement motivation. METHODS: In three studies conducted in China, an understudied non-Western society, we investigated the association between personal relative deprivation and health-promoting lifestyles by utilizing diverse measures and samples. RESULTS: Findings from Study 1 (N = 12,465) indicated a negative relationship between personal relative deprivation and health-promoting behavior. This effect was particularly prominent among older individuals (Study 2, N = 11,378). Study 3 (N = 234) indirectly explored the possibility that a decreased priority given to health goals explains the reduced adoption of health-promoting behaviors when experiencing personal relative deprivation. LIMITATIONS: First, all health-promoting lifestyles are self-reported. Second, the mechanism between PRD and health-promoting lifestyles was not directly examined. CONCLUSION: Overall, this research confirms the physical "lying flat" phenomenon, highlighting that personal relative deprivation contributes to unhealthy diets and physical inactivity. Moreover, our findings also suggest that the lower significance placed on health goals relative to other life goals may serve as an underlying reason for this phenomenon.

Effectiveness of Acupoint Application in Patients with Pharyngeal Pain: Evidence from CHUNBO, A Prospective Real-World Study.

OBJECTIVE: To assess the outcomes after acupoint application in patients with pharyngeal pain in a real-world settings, and analyze the characteristics of effective population and prescription characteristics of acupoint application. METHODS: Based on CHUNBO platform, patients with pharyngeal pain who were candidates for acupoint application on the basis of physician-evaluation, were enrolled in a nationwide, prospective, 69-week multicenter observational study from August 2020 to February 2022. Propensity score matching (PSM) was used to match the confounding factors and the association rules were used to analyze the characteristics of effective population and prescription characteristics of acupoint application. Outcome assessments included the disappearance rate of pharyngeal pain (within 3, 7, and 14 days), disappearance time of pharyngeal pain, as well as adverse events. RESULTS: Of 7,699 enrolled participants, 6,693 (86.9%) received acupoint application and 1,450 (21.7%) with non-acupoint application. After PSM, there were 1,004 patients each in the application group (AG) and non-application group (NAG). The disappearance rate of pharyngeal pain in the AG at 3, 7, and 14 days were all higher than those in the NAG (P<0.05). The disappearance time of pharyngeal pain in the AG were shorter than that in the NAG (logrank P<0.001, hazard ratio=1.51, 95% confidence interval: 1.41-1.63). The median age of effective cases was 4 years, mainly 3-6 years old (40.21%). The disappearance rate of pharyngeal pain in the application group with tonsil diseases was 2.19 times higher than that in the NAG (P<0.05). The commonly used acupoints for the effective cases were Tiantu (RN 22), Shenque (RN 8) and Dazhui (DU 14). The commonly used herbs for the effective cases were Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae. Among them, Natrii sulfas was applied to RN 8 most frequently (support 84.39%). A total of 1,324 (17.2%) patients experienced AEs, and mainly occurred in the AG, with significant difference in the incidence of AEs between goups (P<0.05). All AEs reported were the first grade, and the average regression days of AEs was 2.8 days. CONCLUSIONS: Acupoint application in patients with pharyngeal pain resulted in improved effective rate and shortened duration, especially children aged 3-6 years old, and those with tonsil diseases. Acupoint of RN 22, RN 8 and DU 14, Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae were the most commonly used herbs in the treatment of pharyngeal pain.

Epiberberine induced p53/p21-dependent G2/M cell cycle arrest and cell apoptosis in gastric cancer cells by activating γ-aminobutyric acid receptor- ß3.

BACKGROUND AND PURPOSE: Epiberberine (EPI) is one of the most important bioalkaloid found in the rhizome of Coptis chinensis, which has been observed to exhibit pharmaceutical effects against gastric cancer (GC). Nevertheless, the potential mechanism of EPI against GC cells still remains unclear. This study aimed to identify the core receptor on GC cells through which EPI inhibited the growth of GC cells and to explore the underlying inhibitory mechanisms. METHODS: To identify hub receptor targets that respond to EPI treatment, RNA sequencing (RNA-Seq) data from a tumor-bearing mouse model were analyzed using bioinformatics method and molecular docking. The binding interaction between EPI and GABRB3 was validated through western blotting based-cellular thermal shift assay (WB-CETSA). To further verify the binding region between EPI and GABRB3 through circular dichroism (CD) chromatography, fragments of the extracellular and transmembrane domains of the GABRB3 protein were expressed and purified in vitro. Stable cell lines with the overexpression or knockdown of GABRB3 were established using the recombinant lentivirus system. MTT ((3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide)) assay, colony formation assay, invasion and migration experiments, and flow cytometry were conducted to validate the inhibitory effect of EPI on the GC cells via GABRB3. Additionally, western blotting was utilized to explore the potential inhibitory mechanisms. RESULTS: Through the combination of multiple bioinformatics methods and molecular docking, we found that the γ-aminobutyric acid type A receptor subunit -ß3 (GABRB3) might be the critical receptor target in response to EPI treatment. The results of WB-CETSA analysis indicated that EPI significantly promoted the thermostability of the GABRB3 protein. Importantly, EPI could directly bind to GABRB3 and alter the secondary structure of GABRB3 fragments similar to the natural agonist, γ-aminobutyric acid (GABA). The EPI-induced suppression of the malignant phenotype of GC cells was dependent on the presence of GABRB3. GABRB3 expression was positively correlated with TP53 in patients with GC. The binding of EPI to GABRB3 stimulated p53 accumulation in GC cells. This activated the p21/CDK1/cyclinB1 pathway, resulting in G2/M cell cycle arrest, and induced the Bcl-2/BAX/Caspase axis-dependent cell apoptosis. CONCLUSION: This study revealed the target receptor for EPI in GC cells and provided new insights into its anticancer mechanisms.

Exploring immunoregulatory properties of a phenolic-enriched maple syrup extract through integrated proteomics and in vitro assays.

Our laboratory has established a comprehensive program to investigate the phytochemical composition and nutritional/medicinal properties of phenolic-enriched maple syrup extract (MSX). Previous studies support MSX's therapeutic potential in diverse disease models, primarily through its anti-inflammatory effects. We recently demonstrated MSX's ability to regulate inflammatory signaling pathways and modulate inflammatory markers and proteins in a lipopolysaccharide (LPS)-induced peritonitis mouse model. However, MSX's immunoregulatory properties remain unknown. Herein, we investigated MSX's immunoregulatory properties for the first time using an integrated approach, combining data-dependent acquisition (DDA) and data-independent acquisition (DIA) strategies in a proteomic analysis of spleen tissue collected from the aforementioned peritonitis mouse model. Additionally, we conducted immune cell activation assays using macrophages and T lymphocytes. The DIA analysis unveiled a distinctive expression pattern involving three proteins-Krt83, Thoc2, and Vps16-which were present in both the control and MSX-treated groups but absent in the LPS-induced model group. Furthermore, proteins Ppih and Dpp9 exhibited significant reductions in the MSX-treated group. Ingenuity pathway analysis indicated that MSX may modulate several critical signaling pathways, exerting a suppressive effect on immune responses in various cell types involved in both innate and adaptive immunity. Our in vitro cell assays supported findings from the proteomics, revealing that MSX significantly reduced the levels of interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) in LPS-stimulated human macrophage cells, as well as the levels of IL-2 in anti-CD3/anti-CD28-induced Jurkat T cells. Taken together, our investigations provide evidence that MSX exerts immune regulatory effects that impact both innate and adaptive immunity, which adds to the data supporting MSX's development as a functional food.