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Background: Observational studies indicated that serum uric acid (SUA) was associated with male sexual hormones and erectile dysfunction (ED). However, their relationship was still heterogeneous. Aim: This study conducted 2-sample univariate mendelian randomization (UVMR) and multivariate mendelian randomization (MVMR) to explore the causal relationship between SUA and sexual hormones as well as ED. Methods: Genetic variants associated with SUA were derived from the UK Biobank database (N = 437 354). Outcomes from the IEU Open GWAS and summary data sets were sexual hormones (sex hormone-binding globulin [SHBG], testosterone, estradiol [E2], follicle-stimulating hormone, luteinizing hormone) and ED, with 3301 to 625 650 participants. UVMR analysis primarily utilized the inverse variance weighted method, complemented by MVMR analysis. Thorough sensitivity analyses were carried out to ensure the reliability of results. Moreover, mediation analysis was conducted to estimate the mediated effect between SUA and outcomes. Outcomes: The primary outcomes included results of UVMR and MVMR analysis and mediation analysis, along with sensitivity analyses involving the Cochran Q test, the MR Egger intercept test, leave-1-out analysis, and the MR-PRESSO method (mendelian randomization pleiotropy residual sum and outlier). Results: UVMR analysis revealed that an elevated SUA level could decrease levels of SHBG (ß = -0.10, P = 1.70 × 10-7) and testosterone (ß = -0.10, P = 5.94 × 10-3) and had a positive causal effect on ED (odds ratio, 1.10; P = .018). According to reverse mendelian randomization results, increased levels of SHBG (ß = -0.06, P = 4.82 × 10-4) and E2 (ß = -0.04, P = .037) could also reduce SUA levels. As shown by MVMR analysis, SUA had a negative effect on SHBG and testosterone levels (P < .05), while the significant causal relationship between SUA and ED disappeared. Furthermore, SHBG mediated 98.1% of the effect of SUA on testosterone levels. Results of other mendelian randomization analyses were not statistically significant. No pleiotropy was found by sensitivity analysis in this study. Clinical Implications: Given the causal relationship between SUA and sexual hormones, we must focus on SUA and E2 levels in men, especially patients with hypogonadism and ED. Strengths and Limitations: This study evaluated the causal effect of SUA on male sexual hormones and ED genetically for the first time, clarifying the common biases in observational studies and confirming the negative relationship between SUA and testosterone level. Limitations include a population based on European ancestry, some crossover of the samples, and unobserved confounding factors. Conclusion: Genetic studies provide evidence for the causal relationship between SUA and male sexual hormones (SHBG, testosterone, E2), while the relationship between SUA and ED should be further evaluated.
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Off-flavor is one of the most frequent and serious causes for the aroma deterioration in Jiang-flavor Baijiu. However, the key compounds and their formation mechanism responsible for off-flavor are still unclear. This study identified 271 volatile compounds from 1 normal and 5 types of off-flavor fermented grains (putrid, rancidity, mud, musty, and burnt) by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry. Using VIP and OAV analysis, 47 key flavor compounds including indole, phenol, isoamyl alcohol, diacetyl, acetic acid, isobutyric acid, and isovaleric acid were found to distinguish normal and off-flavor fermented grains. Furthermore, 40 microbial genera (mainly Monascus, Enterococcus, Dyadobacter, Ottowia, Pseudoxanthomonas, Stenotrophomonas, Pseudomonas, and Xanthomonas) were significantly (p < 0.05, Pearson correlation) related to these 47 compounds. Finally, metabolic pathways for off-flavor compounds formation were constructed. This study provides comprehensive information on the off-flavor compounds and their potential formation mechanism during Jiang-flavor Baijiu fermentation.
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In light of the crucial role of marine ecosystems and the escalating environmental conservation challenges, it is essential to conduct marine monitoring to help implement targeted environmental protection measures efficiently. Energy harvesting technologies, particularly triboelectric nanogenerators (TENGs), have great potential for prolonging the lifespan and enhancing the reliability of sensors in remote areas. However, the high internal resistance, low current, and friction-induced abrasion issues of TENGs limit their performance in practical applications. This work presents a rolling mode triboelectric nanogenerator that utilizes multi-tunnel grating electrodes and the opposite-charge-enhancement mechanism to harvest wave energy efficiently. The device achieves significant instantaneous and root mean square power density of 185.4 W/(m3·Hz) and 10.92 W/(m3·Hz), respectively. By utilizing stacked devices and an exclusively designed power management module, a self-powered ocean sensing system including computing and long-range wireless communication (0.8 km) capabilities was developed. Laboratory and in-situ ocean tests were conducted to assess and validate the system. This work offers a potential solution for the challenging deployment of marine self-powered sensing nodes.
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To instruct the production of millet porridge, the effect of cooking methods on flavor and texture of millet porridge was investigated. A total of 91 volatiles were detected and most volatile compounds decreased with cooking time, e.g. alcohols. The esters as major volatiles had a high content in electric rice cooker (IC). Multiple chemometric results indicated that volatiles from different cooking methods were distinguished respectively. Texture analysis indicated that the hardness of millet porridge prepared in IC had a more dominant decrease trend than electromagnetic oven and the electric pressure cooker before 40 min. In conclusion, different cooking methods had a more significant influence on the volatiles than cooking time, while the texture is opposite. The comprehensive sensory score reached its peak in IC-30 min. The comprehensive sensory scores of IC and EC decreased with the prolongation of cooking time. This study helps to improve the sensory attributes of millet porridge.
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Background and purpose: Nutrition is associated with tuberculosis drug-induced liver injury (TBLI). How dietary patterns relate to tuberculosis drug-induced liver injury is still unknown. The objective of this study is to explore the relation between dietary patterns and the risk of tuberculosis drug-induced liver injury. Methods: This cohort study was conducted at two hospitals in Shandong Province, China, between 2011 and 2013. A total of 605 tuberculosis patients were included in the final analysis. The blood aspartate aminotransferase or alanine aminotransferase level was monitored through the 6-month tuberculosis treatment. The semi-quantitative food frequency questionnaires were used to survey dietary intake in the second month of the tuberculosis treatment. The China Healthy Diet Index (CHDI), which was previously validated in the Chinese population, was used as an a priori dietary pattern. A posteriori dietary patterns were extracted by principal component analysis (PCA). Results: The CHDI was negatively associated with the risk of liver injury [adjusted odds ratio (aOR) per standard deviation (SD) (95% CI): 0.61 (0.40-0.94)] and liver dysfunction [aOR per SD (95% CI): 0.47 (0.35-0.64)] in the multivariate logistic model. A positive association between "Organ meat, poultry, and vegetable oil" dietary pattern scores (extracted by PCA) and the risk of liver injury [aOR (95% CI): 3.02 (1.42-6.41)] and liver dysfunction [aOR (95% CI): 1.83 (1.09-3.05)] was observed. Conclusion: In conclusion, a high CHDI score was a protective factor for tuberculosis drug-induced liver injury, while the "Organ meat, poultry, and vegetable oil" dietary pattern, which was rich in organ meat, poultry, and vegetable oil and low in vegetables, was an independent risk factor for tuberculosis drug-induced liver injury.
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Irreversible curing distortion represents a significant limiting factor in the application of high-performance composite structures. Curing distortion is the deviation of a component's profile from the theoretical profile after demolding. Introducing the optimal compensation profile into the traditional compensation algorithm represents an effective method to enhance CFRPs' forming accuracy. For this method, it is necessary to obtain the optimal compensating profile by establishing the coordinate model of the curing process parameter and mold profile compensation. The coordinated control model consists of four parameters: the mean value (Dav), root mean square value (Dmsr), minimum (Dmin), and maximum (Dmax) of curing distortion. Two sizes of composite structural parts are manufactured using the global compensation method. We investigate the influence mechanisms of heating, holding, and cooling times on curing distortion and residual stresses and develop a multi-field coupled finite element model. Strong agreement between the numerical and experimental findings serves as evidence for the effectiveness of the numerical model. The middle layer of the fabricated parts exhibit a reduction in residual stresses as the heating and holding times increase, while an opposite trend is noted with an increase in cooling time. Refining the design of curing process parameters can yield the minimum value of curing deformation within the specified resin system interval. Comparisons indicate that the distortion of the composite wall panel structure is reduced by 86.2% through the use of the global compensation method, demonstrating the validity of this approach for composite structures.
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Autonomous outdoor moving objects like cars, motorcycles, bicycles, and pedestrians present different risks to the safety of Visually Impaired People (VIPs). Consequently, many camera-based VIP mobility assistive solutions have resulted. However, they fail to guarantee VIP safety in practice, i.e., they cannot effectively prevent collisions with more dangerous threats moving at higher speeds, namely, Critical Moving Objects (CMOs). This paper presents the first practical camera-based VIP mobility assistant scheme, ARAware, that effectively identifies CMOs in real-time to give the VIP more time to avoid danger through simultaneously addressing CMO identification, CMO risk level evaluation and classification, and prioritised CMO warning notification. Experimental results based on our real-world prototype demonstrate that ARAware accurately identifies CMOs (with 97.26% mAR and 88.20% mAP) in real-time (with a 32 fps processing speed for 30 fps incoming video). It precisely classifies CMOs according to their risk levels (with 100% mAR and 91.69% mAP), and warns in a timely manner about high-risk CMOs while effectively reducing false alarms by postponing the warning of low-risk CMOs. Compared to the closest state-of-the-art approach, DEEP-SEE, ARAware achieves significantly higher CMO identification accuracy (by 42.62% in mAR and 10.88% in mAP), with a 93% faster end-to-end processing speed.
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Pessoas com Deficiência Visual , Humanos , AlgoritmosRESUMO
Carbon dioxide (CO2) coupled with epoxide to generate cyclic carbonate stands out in carbon neutrality due to its 100% atom utilization. In this work, the mechanism of CO2 cycloaddition with propylene oxide (PO) cocatalyzed by windmill-shaped polyoxovanadate, [(C2N2H8)4(CH3O)4VIV4VV4O16]·4CH3OH (V8-1), and n-Bu4NX (X = Br, I) was thoroughly investigated using density functional theory (DFT) calculations. The ring-opening, CO2-insertion, and ring-closing steps of the process were extensively studied. Our work emphasizes the synergistic effect between V8-1 and n-Bu4NX (X = Br, I). Through the analysis of an independent gradient model based on Hirshfeld partition (IGMH), it was found that the attack of n-Bu4NX (X = Br, I) on Cß of PO triggers a distinct attractive interaction between the active fragment and the surrounding framework, serving as the primary driving force for the ring opening of PO. Furthermore, the effect of different cocatalysts was explored, with n-Bu4NI being more favorable than n-Bu4NBr. Moreover, the role of V8-1 in the CO2 cycloaddition reaction was clarified as not only acting as Lewis acid active sites but also serving as "electron sponges". This work is expected to advance the development of novel catalysts for organic carbonate formation.
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Rust diseases, including leaf rust, stripe/yellow rust, and stem rust, significantly impact wheat (Triticum aestivum L.) yields, causing substantial economic losses every year. Breeding and deployment of cultivars with genetic resistance is the most effective and sustainable approach to control these diseases. The genetic toolkit for wheat breeders to select for rust resistance has rapidly expanded with a multitude of genetic loci identified using the latest advances in genomics, mapping and cloning strategies. The goal of this review was to establish a wheat genome atlas that provides a comprehensive summary of reported loci associated with rust resistance. Our atlas provides a summary of mapped quantitative trait loci (QTL) and characterised genes for the three rusts from 170 publications over the past two decades. A total of 920 QTL or resistance genes were positioned across the 21 chromosomes of wheat based on the latest wheat reference genome (IWGSC RefSeq v2.1). Interestingly, 26 genomic regions contained multiple rust loci suggesting they could have pleiotropic effects on two or more rust diseases. We discuss a range of strategies to exploit this wealth of genetic information to efficiently utilise sources of resistance, including genomic information to stack desirable and multiple QTL to develop wheat cultivars with enhanced resistance to rust disease.
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Basidiomycota , Mapeamento Cromossômico , Resistência à Doença , Doenças das Plantas , Locos de Características Quantitativas , Triticum , Triticum/genética , Triticum/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Resistência à Doença/genética , Basidiomycota/patogenicidade , Melhoramento Vegetal , Genoma de Planta , Genes de Plantas , Cromossomos de Plantas/genéticaRESUMO
The progressive decline of the coal industry necessitates the development of effective treatment solutions for acid mine drainage (AMD), which is characterized by high acidity and elevated concentrations of heavy metals. This study proposes an innovative approach leveraging sulfate-reducing bacteria (SRB) acclimated to contaminated anaerobic environments. The research focused on elucidating the physiological characteristics and optimal growth conditions of SRB, particularly in relation to the pH level and temperature. The experimental findings reveal that the SRB exhibited a sulfate removal rate of 88.86% at an optimal temperature of 30 °C. Additionally, SRB gel particles were formulated using sodium alginate (SA) and carboxymethyl cellulose (CMC), and their performance was assessed under specific conditions (pH = 6, C/S = 1.5, T = 30 °C, CMC = 4.5%, BSNa = 0.4 mol/L, and cross-linking time = 9 h). Under these conditions, the SRB gel particles demonstrated an enhanced sulfate removal efficiency of 91.6%. Thermal analysis via differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) provided further insights into the stability and properties of the SRB gel spheres. The findings underscore the potential of SRB-based bioremediation as a sustainable and efficient method for AMD treatment, offering a novel and environmentally friendly solution to mitigating the adverse effects of environmental contamination.
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Biodegradação Ambiental , Mineração , Concentração de Íons de Hidrogênio , Alginatos/química , Sulfatos/química , Bactérias/metabolismo , Temperatura , Géis/química , Carboximetilcelulose Sódica/química , Metais Pesados/química , Metais Pesados/isolamento & purificação , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificaçãoRESUMO
The protein kinase B (Akt) pathway can regulate the growth, proliferation, and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes, thus affecting the development and treatment of a range of diseases. Thioesterase superfamily member 4 (THEM4), a member of the thioesterase superfamily, is one of the Akt kinase-binding proteins. Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation. Initially, THEM4 was considered an endogenous inhibitor of Akt, which can inhibit the phosphorylation of Akt in diseases such as lung cancer, pancreatic cancer, and liver cancer, but subsequently, THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma, which contradicts previous findings. Considering these two distinct views, this review summarizes the important roles of THEM4 in the Akt pathway, focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases, especially cancer. This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.
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Neoplasias , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosforilação , Neoplasias/metabolismo , Proliferação de Células , Animais , Neoplasias da Mama/metabolismo , Feminino , Proteínas Adaptadoras de Transdução de SinalRESUMO
Background: Due to its obscure etiology and diverse clinical manifestations, the treatment of subdural effusion, presents challenges, and the condition's progression to chronic subdural hematoma(cSDH) often necessitates surgical intervention.This study reports on two pediatric patients who developed progressive subdural effusion following minor head injuries. Both cases were notable for the detection of low levels of human herpesvirus in the cerebrospinal fluid, despite other tests returning negative. Immunotherapy led to a dramatic absorption of their subdural effusions, resulting in very positive clinical outcome. Case description: Case 1: This involved a 4-year and 1-month-old boy who was diagnosed with acute cerebellitis due to an unstable gait following a fall. After being discharged, he sustained another minor head injury. A follow-up Magnetic Resonance Imaging (MRI) revealed an increasing and shifting subdural effusion, which was rapidly absorbed following treatment with high doses of methylprednisolone.Case 2: A 6-year and 3-month-old boy presented with headaches following a minor fall. He improved after treatment with intravenous immunoglobulin and low-dose methylprednisolone. The subdural effusion was completely absorbed, and his health remained stable four months after discharge. Conclusion: Our findings suggest that immune inflammation may play a critical role in the development of subdural effusion. The successful treatment outcomes emphasize the potential of immunotherapy as a non-invasive option for managing subdural effusion, particularly in children with unexplained conditions following minor trauma.
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OBJECTIVE: This study aimed to define the calf proportion index (CPI) and investigate its association with malnutrition and survival in overweight and obese patients with cancer. METHODS: This multicenter observational cohort study included 3499 patients diagnosed with cancer, including 3145 overweight and 354 obese individuals. The CPI was defined as the ratio of the cross-sectional area of the calf circumference (CC) to the body surface area (BSA). A CPI calculator that automatically calculated the CPI and survival probability based on the patient's sex, height, weight, and CC was developed. RESULTS: During a median follow-up of 44.1 months, 935 deaths were recorded. Receiver operating characteristic curves revealed that the CPI was better than CC and BSA as a predictor of survival, with AUCs for the 3-year mortality rate were 0.574, 0.553 and 0.529, respectively. In overweight and obese patients with cancer, the optimal CPI cut-off value was 0.65 % for men and 0.57 % for women. The Kaplan-Meier curve revealed that patients with a low CPI had lower survival. After adjusting confounding factors, a low CPI was an independent risk factor for overweight (hazard ratio [HR]: 1.29, 95 % confidence interval [CI]: 1.11-1.51, P < 0.001) and obesity (HR: 1.92, 95 % CI: 1.20-3.09, P = 0.007) in patients with cancer. The CPI exhibited significant prognostic value in patients with lung and digestive system cancers. The risk of malnutrition was significantly higher in patients with a low CPI (HR: 1.25, 95 % CI: 1.04-1.50, P = 0.019). CONCLUSIONS: The CPI is a useful prognostic indicator in overweight and obese patients with cancer, especially in obese patients.
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The most important optical component in an optical fiber endoscope is its objective lens. To achieve a high imaging performance level, the development of an ultra-compact objective lens is thus the key to an ultra-thin optical fiber endoscope. In this work, we use femtosecond laser 3D printing to develop a series of micro objective lenses with different optical designs. The imaging resolution and field-of-view performances of these printed micro objective lenses are investigated via both simulations and experiments. For the first time, multiple micro objective lenses with different fields of view are printed on the end face of a single imaging optical fiber, thus realizing the perfect integration of an optical fiber and objective lenses. This work demonstrates the considerable potential of femtosecond laser 3D printing in the fabrication of micro-optical systems and provides a reliable solution for the development of an ultrathin fiber endoscope.
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The construction of lunar bases represents a fundamental challenge for deep space exploration, lunar research, and the exploitation of lunar resources. In-situ resource utilization (ISRU) technology constitutes a pivotal tool for constructing lunar bases. Using lunar regolith to create geopolymers as construction materials offers multiple advantages as an ISRU technique. This paper discusses the principle of geopolymer for lunar regolith, focusing on the reaction principle of geopolymer. It also analyzes the applicability of geopolymer under the effects of the lunar surface environment and the differences between the highland and mare lunar regolith. This paper summarizes the characteristics of existing lunar regolith simulants and the research on the mechanical properties of lunar regolith geopolymers using lunar regolith simulants. Highland lunar regolith samples contain approximately 36% amorphous substances, the content of silicon is approximately 28%, and the ratios of Si/Al and Si/Ca are approximately 1.5 and 2.6, respectively. They are more suitable as precursor materials for geopolymers than mare samples. The compressive strength of lunar regolith geopolymer is mainly in the range of 18~30 MPa. Sodium silicate is the most commonly utilized activator for lunar regolith geopolymers; alkalinity in the range of 7% to 10% and modulus in the range of 0.8 to 2.0 are suitable. A vacuum environment and multiple temperature cycles reduce the mechanical properties of geopolymers by 8% to 70%. Future research should be concentrated on the precision control of the lunar regolith's chemical properties and the alkali activation efficacy of geopolymers in the lunar environment.
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Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.
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Linfócitos T CD8-Positivos , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Camundongos , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Humanos , Feminino , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Receptores CXCR5/metabolismo , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Adulto , Pessoa de Meia-Idade , Linfócitos B/imunologia , Linfócitos B/metabolismo , Imunoglobulinas/metabolismo , Imunoglobulinas/imunologia , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/patologiaRESUMO
BACKGROUND AND AIM: Diabetes and Urinary Tract Infections (UTIs) are both common and serious health problems. Shuangdong capsule, a Chinese patent medicine, has been used to treat these conditions. This study assesses its efficacy and mechanism in treating diabetes combined with UTIs. METHODS: We induced diabetes in rats using streptozotocin and UTIs with Escherichia coli, dividing the rats into five groups: control, model, levofloxacin, Shuangdong capsule, and levofloxacin + Shuangdong capsule. After two weeks, we measured blood glucose, insulin, infection indicators, and bladder histology. We also detected the expression of insulin receptor substrate 1 (IRS1)-phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt)-C-X-C motif chemokine ligand 2 (CXCL2) signaling pathway by Western Blot and the myeloperoxidase (MPO) levels by Enzyme-Linked Immunosorbent Assay (ELISA). Additionally, we conducted a Mendelian randomization study using genetic variants of the insulin receptor to assess its causal effect on UTI risk. RESULTS: Shuangdong capsule improved bladder pathology and infection indicators, similar to levofloxacin. It did not affect blood glucose or insulin levels. Moreover, it reversed the suppression of the IRS1-PI3K-Akt-CXCL2 pathway and MPO levels caused by UTI in diabetic rats. The Mendelian randomization study showed that increased insulin receptor expression reduced UTI risk, which was consistent with the results of the animal experiments. CONCLUSION: The Shuangdong capsule was effective in treating diabetes with UTIs. It may function by activating the IRS1-PI3K-Akt signaling pathway, thereby increasing CXCL2 and MPO levels, enhancing innate immunity, and promoting bacterial clearance. The Mendelian randomization study provided further evidence supporting the causal role of the insulin receptor in UTI prevention.
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Background: Cytochrome P450 2E1 (CYP2E1) converts isoniazid (INH) to toxic metabolites and is critical in INH-induced liver injury. The aim is to investigate the effect of folic acid (FA) on CYP2E1 and INH-induced liver injury. Methods: Male Balb/c mice were used. The mice in the control group only received an AIN-93M diet. The AIN-93M diet was supplemented with 0.66 g INH/kg diet for the mice in the INH and FA groups. The mice in the FA group were treated with additional 0.01 g FA/kg diet. The one-carbon cycle metabolites, the expressions of CYP2E1 and the DNA and RNA methylation levels were detected to reveal the potential mechanism. Results: FA treatment significantly reduced the alanine aminotransferase level and alleviated the liver necrosis. The mRNA and protein expressions of CYP2E1 were significantly lower in the FA group than those in the INH group. The N6-methyladenosine RNA methylation level of Cyp2e1 significantly increased in the FA group compared with the INH group, while the DNA methylation levels of Cyp2e1 were similar between groups. Additionally, the liver S-adenosyl methionine (SAM)/S-adenosyl homocysteine (SAH) was elevated in the FA group and tended to be positively correlated with the RNA methylation level of Cyp2e1. Conclusion: FA alleviated INH-induced liver injury which was potentially attributed to its inhibitory effect on CYP2E1 expressions through enhancing liver SAM/SAH and RNA methylation.
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Here, we describe a novel strategy for chemoselective synthesis of α-halo-α,α-difluoromethyl ketones (-COCF3 and -COClCF2 motifs) from trimethyl(phenylethynyl)silane under catalyst-free and mild conditions. Commercially available Selectfluor or additional NaCl as halogen reagent was employed to complete this transformation, thereby demonstrating the potential synthetic value of this new reaction in organic synthesis.
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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system primarily mediated by CD4+ T helper cells. This study investigated the dynamic changes of natural killer (NK) cells and follicular T helper (Tfh) cells and their associations in relapsing-remitting MS patients. The findings revealed inverse relationships between NK cells and CD4+ T cells or Tfh cells. Specifically, CD56dim NK cells, not CD56bright NK cells, were negatively correlated with CD4+ T cells and Tfh cells. However, no significant correlations were found between NK cells and sNfL levels or EDSS scores. The ratio of CD56dim NK cells to circulating Tfh (cTfh) cells demonstrated superior discriminatory ability in distinguishing relapsing MS patients from healthy controls (HCs) and remitting patients, as determined by receiver operating characteristic (ROC) analysis. Following treatment with immunosuppressants or disease-modifying therapies (DMTs), a significant increase in the CD56dim NK/cTfh ratio was observed. These findings suggest that the CD56dim NK/cTfh ratio holds promise as a prognostic indicator for clinical relapse and treatment response in MS.