Reactions of Ethynyloxy Radical with Hydroperoxyl Radical: Bridging Theoretical Reaction Dynamics and Chemical Modeling of Combustion.

A detailed and accurate combustion reaction mechanism is crucial for understanding the nature of fuel combustion. In this work, a theoretical study of reaction HCCO+HO2 using M06-2X/6-311++G(d,p) for geometry optimization and combined methods based on spin-unrestricted CCSD(T)/CBS level of theory with basis set extrapolation from MP2/aug-cc-pVnZ (n=T and Q) for energy calculations were performed. The temperature- and pressure-dependent rate coefficients at 300-2000 K and 0.01-100 atm, suitable for combustion conditions, were derived using the Rice-Ramsberger-Kassel-Marcus/Master-Equation approach. Furthermore, temperature-dependent thermochemistry data of key species for the HCCO+HO2 system has also been studied. Finally, an updated ketene model is developed by supplementing the most recent theoretical work and the theoretical work in this paper. This updated model was tested to simulate the speciation of ketene oxidation in available experimental research. It is shown that the updated model for predicting ketene oxidation exhibits a high level of agreement with experimental data across a wide range of species profiles. An analysis was conducted to identify the crucial reactions that influence ketene ignition. This paper's research findings are essential for enhancing the combustion mechanism of ketene and other hydrocarbons and oxygenated hydrocarbon fuels.

Exploring the Neural Correlates of Flow Experience with Multifaceted Tasks and a Single-Channel Prefrontal EEG Recording.

Flow experience, characterized by deep immersion and complete engagement in a task, is highly recognized for its positive psychological impacts. However, previous studies have been restricted to using a single type of task, and the exploration of its neural correlates has been limited. This study aimed to explore the neural correlates of flow experience with the employment of multifaceted flow-induction tasks. Six tasks spanning mindfulness, artistic tasks, free recall, and varying levels of Tetris complexity (easy, flow, and hard conditions) were employed to have relatively complete coverage of the known flow-induction tasks for a better induction of individualized flow experience. Twenty-eight participants were recruited to perform these six tasks with a single-channel prefrontal EEG recording. Significant positive correlations were observed between the subjective flow scores of the individual's best-flow-experience task and the EEG activities at the delta, gamma, and theta bands, peaking at latencies around 2 min after task onset. The outcomes of regression analysis yield a maximum R2 of 0.163. Our findings report the EEG correlates of flow experience in naturalistic settings and highlight the potential of portable and unobtrusive EEG technology for an objective measurement of flow experience.

Development and Validation of a Nomogram Model Affecting the ACT Targeting Rate During Radiofrequency Ablation of Atrial Fibrillation in China.

CONTEXT: A nomogram model affecting the activated clotting time (ACT) targeting rate during radiofrequency ablation of atrial fibrillation (RFCA) in China. PURPOSE: The aim of this study is to develop and validate a nomogram model for predicting the activated clotting time targeting rate after the initial bolus heparin dosages during the radiofrequency catheter ablation of atrial fibrillation in China. METHODS AND RESULTS: A retrospective observational study was conducted on the data of 465 patients with atrial fibrillation who underwent radiofrequency catheter ablation (RFCA) from October 2019 to June 2022. All patients were randomized into a training cohort (70%; n = 325) and a validation cohort (30%; n = 140). Independent risk factors were identified using univariate and multifactorial logistic regression analysis. The predictive nomogram model was established using R software. The nomogram was developed and evaluated based on differentiation, calibration, and clinical efficacy using concordance statistic (C-statistic), calibration plots, and decision curve analysis (DCA), respectively. The nomogram was established using three variables, including sex (OR 1.01, 95% CI 0.29-1.76, P = 0.007), heparin dose (OR 0.04; 95%CI 0.02-0.05, P < 0.001), and the baseline ACT (OR 0.03; 95%CI 0.02-0.04, P < 0.001). The C-statistic of the nomogram was 0.736 (95%CI 0.675-0.732) in the training cohort and 0.700 (95%CI 0.622-0.721) in the validation cohort. The calibration plots showed good agreement between the predictions and observations in the training and validation cohorts. The clinical decision curve also proves that the map is useful in clinical settings. CONCLUSION: The nomogram model has good discrimination and accuracy, which can screen attainment groups intuitively and individually, and has a certain predictive value for the probability of ACT reaching the target after the adequate dosage of initial heparin in Chinese patients with atrial fibrillation.

Establishment and Validation of the Nomogram Model and the Probability of Silent Cerebral Infarction After Ablation Atrial Fibrillation.

BACKGROUND: The objective of this study is to establish and validate a nomogram model for predicting the probability of silent cerebral infarction following ablation of atrial fibrillation. METHODS AND RESULTS: A retrospective observational study was conducted on the data of 238 patients with atrial fibrillation who underwent radiofrequency ablation in our hospital from October 2019 to December 2022. LASSO regression and multivariate logistics regression analysis were used to assess the independent risk factors for silent cerebral infarction after ablation. The AUC of the predictive model was 0.733 (95% CI, 0.649-0.816) and the internal validation (bootstrap = 1000) of the bootstrap method was 0.733 (95% CI 0.646-0.813). The Hosmer-Lemeshow test yields an insignificant p-value of X-squared = 10.212 and p-value = 0.2504, thus indicating an insignificant difference between predicted and observed values and good calibration results. The clinical impact curve (CIC) and clinical decision curve also prove that this graph is useful in the clinical setting. CONCLUSION: We developed an easy-to-use nomogram model to predict the probability of silent cerebral infarction following radiofrequency ablation of atrial fibrillation. This model can provide a valid assessment of the probability of postoperative silent cerebral infarction in patients undergoing radiofrequency ablation of atrial fibrillation.

Chelerythrine chloride inhibits the progression of colorectal cancer by targeting cancer-associated fibroblasts through intervention with WNT10B/ß-catenin and TGFß2/Smad2/3 axis.

Chelerythrine chloride (CHE) is a benzodiazepine alkaloid derived from natural herbs with significant anti-tumor and anti-inflammatory activities. However, the exact role and underlying mechanisms of CHE in colorectal cancer (CRC) remain unclear. Therefore, this study is aimed to investigate the influence of CHE on the progression of CRC. Cell Counting Kit-8 assay (CCK-8), transwell, apoptosis rate, cell cycle distribution, reactive oxygen species (ROS), and colony formation determined the anti-proliferative activity of CHE in CRC cell lines. Transcriptome sequencing and western blot were used to explore the mechanism. Finally, H&E staining, Ki67, TUNEL, and immunofluorescence were conducted to verify the anti-CRC activity and potential mechanisms of CHE in vivo. CHE had a prominent inhibitory effect on the proliferation of CRC cells. CHE induces G1 and S phase arrest and induces cell apoptosis by ROS accumulation. Cancer-associated fibroblasts (CAFs) play a key role in CRC metastasis. Then, this study found that CHE regulates WNT10B/ß-catenin and TGFß2/Smad2/3 axis, thereby decreasing the expression of α-SMA, which is a maker of CAFs. Taken together, CHE is a candidate drug and a potent compound for metastatic CRC, which can intervene CAFs in a dual pathway to effectively inhibit the invasion and migration of cancer cells, which can provide a new choice for future clinical treatment.

Renoprotective Effects of Tanshinone IIA: A Literature Review.

The kidney is an important organ in the human body, with functions such as urine production, the excretion of metabolic waste, the regulation of water, electrolyte and acid-base balance and endocrine release. The morbidity and mortality of kidney diseases are increasing year by year worldwide, and they have become a serious public health problem. In recent years, natural products derived from fungi, plants and animals have become an important alternative source of treatment for kidney diseases because of their multiple pathways, multiple targets, safety, low toxicity and few side effects. Tanshinone IIA (Tan IIA) is a lipid-soluble diterpene quinone isolated from the Chinese herb Salvia miltiorrhiza, considered as a common drug for the treatment of cardiovascular diseases. As researchers around the world continue to explore its unknown biological activities, it has also been found to have a wide range of biological effects, such as anti-cancer, anti-oxidative stress, anti-inflammatory, anti-fibrotic, and hepatoprotective effects, among others. In recent years, many studies have elaborated on its renoprotective effects in various renal diseases, including diabetic nephropathy (DN), renal fibrosis (RF), uric acid nephropathy (UAN), renal cell carcinoma (RCC) and drug-induced kidney injury caused by cisplatin, vancomycin and acetaminophen (APAP). These effects imply that Tan IIA may be a promising drug to use against renal diseases. This article provides a comprehensive review of the pharmacological mechanisms of Tan IIA in the treatment of various renal diseases, and it provides some references for further research and clinical application of Tan IIA in renal diseases.

N6-methyladenosine demethylase FTO regulates inflammatory cytokine secretion and tight junctions in retinal pigment epithelium cells.

OBJECTIVE: Uveitis is an intraocular inflammatory disease. Epigenetics has been associated with its pathogenesis. However, the role of N6-methyladenosine (m6A) in uveitis has not been reported. We aimed to examine the role of m6A and its regulatory mechanism in experimental autoimmune uveitis (EAU). METHODS: The mRNA expression of m6A-related methylase and demethylase of retinal pigment epithelium (RPE) between mice with EAU and control mice was detected by RT-qPCR. The overall m6A level of ARPE-19 cells was detected by an m6A quantitative detection kit. Cell proliferation was observed by CCK-8 assays, and ELISA was used to test the secretion of inflammatory factors. The expression of tight junction proteins and the target genes of FTO were examined by western blotting and MeRIP-PCR. RESULTS: A decreased expression of FTO in RPE cells was found in mice with EAU. Increased overall m6A%, proliferation of cells and secretion of IL-6, IL-8 and MCP-1 were found after FTO knockdown in ARPE-19 cells. However, ZO-1 and occludin protein expression was decreased. ATF4 protein expression was decreased in the FTO knockdown (shFTO) group as compared with the control (shNC) group. In contrast, the m6A level of ATF4 was elevated, as shown by MeRIP-PCR. Functional analysis showed that p-STAT3 expression was increased in the shFTO group, and the change in occludin expression was reversed in ATF4 rescue experiment. CONCLUSION: FTO may affect the translation of ATF4 by regulating its m6A level, resulting in the increased expression of p-STAT3 and inflammatory factors, and leading to uveitis.

Control of the spatial characteristics of femtosecond laser filamentation in glass via feedback-based wavefront shaping with an annular phase mask.

We propose a feedback-based wavefront shaping with an annular phase mask to control the spatial characteristics of femtosecond laser filamentation in K9 glass. A closed-loop feedback driven by a genetic algorithm was used to search for the optimal phase profile for generating the specified filaments. We demonstrate the flexibility of this method to extend or shorten filaments, improve continuity, and simultaneously control the position of filaments with specified lengths. Our approach offers a flexible regulation of the spatial characteristics of femtosecond laser filamentation for its potential applications.

[Large- scale prospective clinical study on prophylactic intervention of COVID-19 in community population using Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules].

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.

Ultrasensitive electrochemiluminescence immunosensor for the transcriptional co-activator p300 by using a graphene oxide monolayer and tetrahedral DNA-mediated signal amplification.

Protein p300 is a transcriptional co-activator that participates in many physiological processes including cell cycle control, differentiation and apoptosis. It serves (a) as a protein bridge that links specific transcription factors to the fundamental transcription machinery, (b) as a scaffold to complete multiple transcription cofactors, and (c) as an enzyme for acetylating histone and non-histone proteins. An ultrasensitive electrochemiluminescence (ECL) immunosensor is described here that is based on the use of a magnetic glassy carbon electrode modified with tetrahedral DNA with hollow structure, graphene oxide (GO) and gold nanocrystals. The use of a GO monolayer allows for greater carrying capacity and warrants a wider outer Helmholtz plane. Strong and stable ECL signals were achieved due to antigen-antibody interaction by using the ECL probe Ru(phen)32+. This immunosensor has a response that covers the 0.005 to 80 nM p300 concentration range and has a 1 pM detection limit. It was exploited for the determination of p300 in HeLa cell lysate and (spiked) serum. Graphical abstract Schematic presentation of an ultrasensitive Faraday-cage electrochemiluminescence immunosensor toward the transcriptional co-activator p300 analysis is presented based on a graphene oxide monolayer and tetrahedral DNA-mediated signal amplification.

Three new sesquiterpenes from the stems of Nicotiana tabacum and their bioactivities.

Three new sesquiterpenes, methyl 4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (1), methyl 2-hydroxy-4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (2), and methyl 2-hydroxy-6-(hydroxymethyl)-4-isopropyl-7-methoxynaphthalene-1-carboxylate (3), together with three known sesquiterpenes (4-6), were isolated from the stems of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. The results showed that compounds 2, 3, and 5 exhibited high anti-TMV activity with inhibition rates of 33.6, 35.8, and 36.7%. Compounds 1-6 showed weak inhibitory activities against some tested human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) with IC50 values in the range of 6.7-9.6 µM.

Three new benzolactones from Lavandula angustifolia and their bioactivities.

Three new benzolactones (1-3), together with four known ones (4-7), were isolated from the whole herb of Lavandula angustifolia. Their structures were established on the basis of detailed spectroscopic analysis (1D- and 2D-NMR, HRESIMS, UV, and IR) and comparison with data reported in the literature. New compounds were evaluated for their anti-tobacco mosaic virus (TMV) activities and cytotoxic activities. The results revealed that compounds 1-3 showed obvious anti-TMV activities with inhibition rates of 26.9, 30.2, and 28.4%, which were at the same grade as positive control. Compounds 1-3 also showed weak inhibitory activities against some tested human tumor cell lines with IC50 values in the range of 32.1-7.6 µM.

Cyclic-AMP-dependent protein kinase (PKA) activity assay based on FRET between cationic conjugated polymer and chromophore-labeled peptide.

A sensitive fluorescence turn-on biosensing platform for protein kinase activity assay has been developed based on fluorescence resonance energy transfer (FRET) between a fluorophore labeled peptide and a water soluble cationic conjugated polymer (CCP). The CCP-based assay is based on the electrostatic interaction between the peptide and the CCP. The FRET efficiency will change with the changing charges around the peptide after phosphorylation. The feasibility of this method has been demonstrated by sensitive measurement of the activity of cAMP-dependent protein kinase (PKA) with a low detection limit (0.3 mU µL(-1)). Based on its simple mechanism, this assay is also sensitive and robust enough to be applied to the evaluation of PKA inhibitor H-89. The IC50 value, the half maximal inhibitory concentration, was 40 nM. Furthermore, our method has excellent selectivity. CCP-based assay is sensitive, versatile, cost-effective and easy to operate, so, this method is a promising candidate for kinase activity assay and inhibitor screening.

Jin-Gui-Shen-Qi Wan alleviates fibrosis in mouse diabetic nephropathy via MHC class II.

ETHNOPHARMACOLOGICAL RELEVANCE: Jin-Gui-Shen-Qi Wan (JGSQW) is a traditional Chinese medicine formula that has been traditionally used to alleviate urinary system ailments such as frequent urination and polyuria. Clinical studies have indicated that when combined with hypoglycaemic drugs, JGSQW exhibits a synergistic effect and can improve diabetic nephropathy (DN), yet its underlying mechanism and targets remain unclear. AIM OF THE STUDY: This study aims to investigate the therapeutic efficacy of JGSQW and its underlying mechanisms using a DN db/db mouse model. MATERIALS AND METHODS: Ultrahigh-performance liquid chromatography coupled with mass spectrometry was utilized to analyse the primary active compounds, blood levels, and pharmacokinetics of JGSQW. Additionally, the therapeutic effects of JGSQW and metformin on blood glucose levels, lipid levels, renal function, and renal pathology in diabetic nephropathy mice were investigated using a db/db mouse model. Proteomic analysis was carried out to identify the primary target of JGSQW in treating DN. The mechanism of action was verified by western blotting, immunohistochemistry, and immunofluorescence. Then, molecular docking and molecular dynamics, transfection, drug affinity responsive target stability (DARTS) assay and cell thermal migration assay (CETSA) further validated the targeted binding effect. RESULTS: JGSQW combined with metformin significantly improved the blood glucose levels, blood lipids, renal function, and renal pathology of DN mice. JGSQW mainly exerted its therapeutic effect on DN by targeting major histocompatibility complex class II (MHC class II) molecules. Immunohistochemistry results showed that JGSQW inhibited the expression of collagen I, fibronectin, and alpha smooth muscle actin (α-SMA) expression. Immunofluorescence and Western blot results showed that JGSQW inhibited the expression of H2-Ab1 and H2-Aa, which are MHC class II molecules, thereby suppressing CD4+ T-cell infiltration and improving diabetic kidney fibrosis. The binding ability of paeoniflorin to H2-Aa was predicted and verified by molecular, DARTS, and CETSA assays. Treatment with 80 µM paeoniflorin effectively alleviated high glucose-induced injury in the MPC-5 injury model. H2-Aa was overexpressed at this model concentration, and Western blotting further confirmed that paeoniflorin reduced glomerular podocyte fibrosis by regulating H2-Aa. CONCLUSIONS: JGSQW combined with metformin may have a synergistic effect to alleviates renal fibrosis in diabetic nephropathy by downregulating immune complex MHC class II molecules and attenuating the antigen presentation effect of MHC class II on CD4.

Flexible molecularly imprinted fiber library for the metabolic analysis of bisphenol F and ecological risk evaluation.

Bisphenol F (BPF) has evoked global attentions due to its ubiquity and detrimental effects. Herein, a flexible molecularly imprinted fiber library was firstly proposed for the metabolic analysis of BPF in aquatic ecosystems. The library includes flexible single fibers and fiber arrays to precisely identify BPF and its metabolites with a wide range of polarities. Compared to commercial polyacrylate, the performance increased 11.56-570.98-fold. The adsorption capacity and the LogKow value were positively related. These arrays were used for the acquisition of environmental metabolomics data from aquatic ecosystems. In-depth data analysis showed that risk quotient was lower than 0.76, and bioaccumulation factor was lower than 2000 L/kg. Distribution concentration of BPF and its metabolites changed seasonally, and accumulation in sediment was much larger than that in surface water and hydrobionts. The risk is gradually increasing in sediment, but it does not reach high risk. The likelihood of bioaccumulation of parent compounds was greater than its metabolites. The library can be used in the metabolic diagnosis of pollutants with a broad range of polarities, providing a new method to acquire data for further ecological risk assessment, and offering a revolutionary strategy for environmental metabolomics investigation in aquatic ecosystems.

Network pharmacology combined with Mendelian randomization analysis to identify the key targets of renin-angiotensin-aldosterone system inhibitors in the treatment of diabetic nephropathy.

Background: Diabetic Nephropathy (DN) is one of the microvascular complications of diabetes. The potential targets of renin-angiotensin-aldosterone system (RAAS) inhibitors for the treatment of DN need to be explored. Methods: The GSE96804 and GSE1009 datasets, 729 RAAS inhibitors-related targets and 6,039 DN-related genes were derived from the public database and overlapped with the differentially expressed genes (DN vs. normal) in GSE96804 to obtain the candidate targets. Next, key targets were screened via the Mendelian randomization analysis and expression analysis. The diagnostic nomogram was constructed and assessed in GSE96804. Additionally, enrichment analysis was conducted and a 'core active ingredient-key target-disease pathway' network was established. Finally, molecular docking was performed. Results: In total, 60 candidate targets were derived, in which CTSC and PDE5A were screened as the key targets and had a causal association with DN as the protective factors (P < 0.05, OR < 1). Further, a nomogram exhibited pretty prediction efficiency. It is indicated that Benadryl hydrochloride might play a role in the DN by affecting the pathways of 'cytokine cytokine receptor interaction', etc. targeting the CTSC. Moreover, PDE5A might be involved in 'ECM receptor interaction', etc. for the effect of NSAID, captopril, chlordiazepoxide on DN. Molecular docking analysis showed a good binding ability of benadryl hydrochloride and CTSC, NSAID and PDE5A. PTGS2, ITGA4, and ANPEP are causally associated with acute kidney injury. Conclusion: CTSC and PDE5A were identified as key targets for RAAS inhibitors in the treatment of DN, which might provide some clinical significance in helping to diagnose and treat DN. Among the targets of RAAS inhibitors, PTGS2, ITGA4 and ANPEP have a causal relationship with acute kidney injury, which is worthy of further clinical research.

Rethinking Sweetener Discovering: Multiparameter Modeling of Molecular Docking Results between the T1R2-T1R3 Receptor and Compounds with Different Tastes.

Molecular docking has been widely applied in the discovery of new sweeteners, yet the interpretation of computational results sometimes remains difficult. Here, the interaction between the T1R2-T1R3 sweet taste receptor and 66 tasting compounds, including 26 sweet, 19 bitter, and 21 sour substances was investigated by batch molecular docking processes. Statistical analysis of the docking results generated two novel methods of interpreting taste properties. Quantitative correlation between relative sweetness (RS) and docking results created a multiparameter model to predict sweetness intensity, whose correlation coefficient r = 0.74 is much higher than r = 0.17 for the linear correlation model between sweetness and binding energy. The improved correlation indicated that docking results besides binding energy contain undiscovered information about the ligand-protein interaction. Qualitative discriminant analysis of different tasting molecules generated an uncorrelated linear discriminant analysis (UDLA) model, which achieved an overall 93.1% accuracy in discriminating the taste of molecules, with specific accuracy for verifying sweet, bitter, and sour compounds reaching 88.0%, 92.1%, and 100%. These unprecedented models provide a unique perspective for interpreting computational results and may inspire future research on sweetener discovery.

Systemic immune-inflammatory biomarkers (SII, NLR, PLR and LMR) linked to non-alcoholic fatty liver disease risk.

Background: Systemic immune-inflammatory biomarkers including systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be associated with the risk and severity of various liver diseases. However, studies on their role and clinical significance in metabolic diseases, especially in nonalcoholic fatty liver disease (NAFLD), are limited and results are inconsistent. Methods: 10821 adults aged 20 years or older were enrolled in this cross-sectional study, sourced from six cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression was employed to investigate the correlation between systemic immune-inflammatory biomarkers (SII, NLR, PLR, and LMR) and NAFLD risk. Restricted cubic spline regression models and segmented regression models were used to describe nonlinear relationships and threshold effects. Subgroup and sensitivity analyses were also conducted. Results: After adjusting for all confounding variables, there was a significant positive association observed between ln-transformed SII (OR= 1.46, 95% CI: 1.27-1.69, P <0.001), NLR (OR= 1.25, 95% CI: 1.05-1.49, P =0.015), LMR (OR= 1.39, 95% CI: 1.14-1.69, P = 0.002) with NAFLD. A nonlinear dose-response relationship with an inverted "U"-shaped threshold of 4.64 was observed between ln(PLR) and NAFLD risk. When ln(PLR) was below 4.64, each unit increase in ln(PLR) was associated with a 0.55-fold increase in the risk of NAFLD (OR= 1.55, 95% CI: 1.05-2.31, P <0.05). Conversely, when ln(PLR) exceeded 4.64, each unit increase in ln(PLR) was associated with a 0.40-fold decrease in the risk of NAFLD (OR= 0.60, 95% CI. 0.44-0.81, P <0.05). Conclusion: ln-transformed SII, NLR, and LMR were linearly associated with NAFLD risk. ln(PLR) showed an inverted "U"-shaped nonlinear dose-response relationship with the risk of NAFLD.

Natural products in traditional Chinese medicine: molecular mechanisms and therapeutic targets of renal fibrosis and state-of-the-art drug delivery systems.

Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of renal tubular cells, fibroblast activation, immune cell infiltration, and renal cell apoptosis. RF can eventually lead to renal dysfunction or even renal failure. A large body of evidence suggests that natural products in traditional Chinese medicine (TCM) have great potential for treating RF. In this article, we first describe the recent advances in RF treatment by several natural products and clarify their mechanisms of action. They can ameliorate the RF disease phenotype, which includes apoptosis, endoplasmic reticulum stress, and EMT, by affecting relevant signaling pathways and molecular targets, thereby delaying or reversing fibrosis. We also present the roles of nanodrug delivery systems, which have been explored to address the drawback of low oral bioavailability of natural products. This may provide new ideas for using natural products for RF treatment. Finally, we provide new insights into the clinical prospects of herbal natural products.

Corrigendum: The science behind TCM and Gut microbiota interaction-their combinatorial approach holds promising therapeutic applications.

[This corrects the article DOI: 10.3389/fcimb.2022.875513.].