ABSTRACT
Chloroplasts are key players in photosynthesis and immunity against microbial pathogens. However, the precise and timely regulatory mechanisms governing the control of photosynthesis-associated nuclear genes (PhANGs) expression in plant immunity remain largely unknown. Here we report that TaPIR1, a Pst-induced RING-finger E3 ubiquitin ligase, negatively regulates Pst resistance by specifically interacting with TaHRP1, an atypical transcription factor histidine-rich protein. TaPIR1 ubiquitinates the lysine residues K131 and K136 in TaHRP1 to regulate its stability. TaHRP1 directly binds to the TaHRP1-binding site elements within the PhANGs promoter to activate their transcription via the histidine-rich domain of TaHRP1. PhANGs expression induces the production of chloroplast-derived ROS. Although knocking out TaHRP1 reduces Pst resistance, TaHRP1 overexpression contributes to photosynthesis, and chloroplast-derived ROS production, and improves disease resistance. TaPIR1 expression inhibits the downstream activation of TaHRP1 and TaHRP1-induced ROS accumulation in chloroplasts. Overall, we show that the TaPIR1-mediated ubiquitination and degradation of TaHRP1 alters PhANGs expression to disrupt chloroplast function, thereby increasing plant susceptibility to Pst.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Chloroplasts , Gene Expression Regulation, Plant , Photosynthesis , Reactive Oxygen Species , Ubiquitin-Protein Ligases , Ubiquitination , Chloroplasts/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Arabidopsis/metabolism , Arabidopsis/genetics , Arabidopsis/immunology , Reactive Oxygen Species/metabolism , Plant Diseases/microbiology , Plant Diseases/immunology , Plant Diseases/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Disease Resistance/genetics , Proteolysis , Plants, Genetically Modified , Promoter Regions, Genetic/genetics , Plant Immunity/genetics , Nicotiana/metabolism , Nicotiana/geneticsABSTRACT
Chiral multiferroics offer remarkable capabilities for controlling quantum devices at multiple levels. However, these materials are rare due to the competing requirements of long-range orders and strict symmetry constraints. In this study, we present experimental evidence that the coexistence of ferroelectric, magnetic orders, and crystallographic chirality is achievable in hybrid organic-inorganic perovskites [(R/S)-ß-methylphenethylamine]2CuCl4. By employing Landau symmetry mode analysis, we investigate the interplay between chirality and ferroic orders and propose a novel mechanism for chirality transfer in hybrid systems. This mechanism involves the coupling of non-chiral distortions, characterized by defining a pseudo-scalar quantity, ξ = p â r ( p represents the ferroelectric displacement vector and r denotes the ferro-rotational vector), which distinguishes between (R)- and (S)-chirality based on its sign. Moreover, the reversal of this descriptor's sign can be associated with coordinated transitions in ferroelectric distortions, Jahn-Teller antiferro-distortions, and Dzyaloshinskii-Moriya vectors, indicating the mediating role of crystallographic chirality in magnetoelectric correlations.
ABSTRACT
The synergistic effect and compatibility structure of active anti-inflammatory ingredients(iridoid glycosides: shanzhiside methylester and 8-O-acetylshanzhiside methyl ester, flavonoid glycoside: luteoloside, and phenylethanoid glycoside: forsythoside B) from Lamiophlomis rotata were explored based on network pharmacology and component structure theory. In network pharmacology, CTD, SwisseTargetPrediction, and PharmMapper databases were used to collect and screen the targets of all active ingredients. The inflammation-related targets were obtained from CTD and GeneCards databases. The core targets were obtained by Venny 2.1.0, STRING, and Cytoscape 3.9.1. Core targets were annotated by the GO function and enriched by the KEGG pathway based on the DAVID database. In terms of component structure, based on a uniform design method and xylene-induced ear swelling model in mice, tumor necrosis factor-α and interleukin-6 were taken as the dependent variables, and the compatibility relationship among anti-inflammatory ingredients from L. rotata was explored through the quadratic polynomial stepwise regression. In addition, in vivo pharmacological experiments were conducted to verify the results. A network pharmacology study showed that compared with a single ingredient, the combined action of the three ingredients can synergistically exert anti-inflammatory effects through more biological processes, pathways, and targets. Component structure study showed that the optimal structural ratio of shanzhiside methylester and 8-O-acetylshanzhiside methyl ester in the iridoid glycoside ingredient was 1.21â¶1. The optimal structural ratio among the three types of ingredients(iridoid glycosidesâ¶phenylethanol glycosideâ¶flavonoid glycoside) was 4.8â¶1.6â¶1. In conclusion, each anti-inflammatory ingredient from L. rotata can work synergistically, and there is an optimal compatibility ratio relationship among these ingredients. This work provides a new experimental basis for the intrinsic quality control of L. rotata.
Subject(s)
Anti-Inflammatory Agents , Drugs, Chinese Herbal , Network Pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Animals , Mice , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Male , Lamiaceae/chemistry , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/immunology , Drug Synergism , Interleukin-6/immunology , Interleukin-6/metabolism , Interleukin-6/geneticsABSTRACT
BACKGROUND: To investigate alterations in choroidal vascularity index among highly myopic adults with fundus tessellation, utilizing optical coherence tomography. METHODS: Total of 143 highly myopic adults (234 eyes) with fundus tessellation were collected in this cross-sectional study, which was stratified into different lesion groups based on the novel tessellated fundus classification. Subfoveal choroidal thickness (SFCT), choroidal luminal area (LA), stromal area (SA), total choroidal area (TCA), and choroidal vascularity index (CVI) were analyzed utilizing optical coherence tomography (OCT) with enhanced depth imaging (EDI) mode, enabling precise quantification of these parameters. RESULTS: Comparison analysis demonstrated notable distinctions in spherical equivalent (SE), axial length (AL), and SFCT across the four tessellation grades (p < 0.001). Analysis of the choroidal vascularity parameters, including LA, TCA, and CVI, demonstrated notable disparities across the four groups (p < 0.001), while no significant variations were observed in SA when comparing Grade 1 versus Grade 2, as well as Grade 2 versus Grade 3 (p > 0.05). Logistic regression analyses illustrated that the higher grade of tessellated exhibited a positive association with AL (OR = 1.701, p = 0.027), while negatively associated with SFCT (OR = 0.416, p = 0.007), LA (OR = 0.438, p = 0.010) and CVI (OR = 0.529, p = 0.004). Multiple regression analyses demonstrated a significant negative association between CVI and both SE and AL after adjusting for age, while positively associated with SFCT (p < 0.05). CONCLUSION: Subtle choroidal vascularity changes may have a meaningful contribution to the development and progression of fundus tessellation. CVI and LA dramatically decreased during the early stages of tessellation development and maintained a relatively stable status when in the severe tessellated grades.
Subject(s)
Choroid , Fundus Oculi , Myopia, Degenerative , Tomography, Optical Coherence , Humans , Choroid/blood supply , Choroid/diagnostic imaging , Choroid/pathology , Cross-Sectional Studies , Tomography, Optical Coherence/methods , Male , Female , Adult , Myopia, Degenerative/diagnosis , Myopia, Degenerative/physiopathology , Middle Aged , Retrospective Studies , Visual Acuity/physiology , Aged , Young AdultABSTRACT
Network Meta-analysis and multi-criteria decision analysis(MCDA) model were performed to evaluate the benefit-risk of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in the adjuvant treatment of primary liver cancer(PLC). The randomized controlled trial(RCT) of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in treating PLC were retrieved from CNKI, Wanfang, VIP, Web of Science, PubMed, and Cochrane Library. R 4.2 was employed to conduct a network Meta-analysis, on the basis of which the effect values of the three medicines were obtained by indirect comparison. MCDA was performed to establish the value tree based on the benefit-risk indexes. Hiview 3.2 was used to calculate the benefit values, risk values, and benefit-risk values of the three medicines in treating PLC, and a sensitivity analysis was carried out to evaluate the robustness of the results. Oracle Crystal Ball 11.1 was employed to optimize the evaluation results by Monte Carlo simulation. A total of 39 RCTs were included. The results showed that Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules combined with transcatheter arterial chemoembolization(TACE) had the benefit values of 45, 51 and 45, the risk values of 59, 47, and 41, and the benefit-risk values of 52, 49, and 43, respectively. The benefit-risk differences and [95%CI] of Compound Cantharis Capsules vs Huisheng Oral Solution, Compound Cantharis Capsules vs Jinlong Capsules, and Huisheng Oral Solution vs Jinlong Capsules were 3.00[-13.09, 21.82], 9.00[-4.39, 24.62], and 6.00[-8.84, 20.28], respectively. Based on the results of MCDA, Huisheng Oral Solution, Jinlong Capsules, and Compound Cantharis Capsules combined with TACE had the greatest benefit, the greatest risk, and the best overall benefit, respectively. Considering the efficacy and safety, the priority of the three oral Chinese patent medicines combined with TACE for treating PLC followed the trend of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules.
Subject(s)
Drugs, Chinese Herbal , Liver Neoplasms , Humans , Drugs, Chinese Herbal/administration & dosage , Liver Neoplasms/drug therapy , Risk Assessment , Network Meta-Analysis , Administration, Oral , Decision Support Techniques , Randomized Controlled Trials as Topic , Nonprescription DrugsABSTRACT
Fluxapyroxad (FX), a typical succinate dehydrogenase inhibitor fungicide, is causing increased global concerns due to its fungicide effects. However, the accumulation and grow toxicity of FX to Litopenaeus vannamei (L. vannamei) is poorly understand. Therefore, the accumulation pattern of FX in L. vannamei was investigated for the first time in environmental concentrations. FX accumulated rapidly in shrimp muscle. Meanwhile, growth inhibition was observed and the mechanism derived by primarily accelerated glycolipid metabolism and reduced glycolipid content. Moreover, exposure to environmental concentrations of FX induced significant growth inhibition and oxidative stress and inhibited oxidative phosphorylation and TCA cycle in L. vannamei. The endocytosis signaling pathway genes were activated, thereby driving growth toxicity. Oxidative phosphorylation and cytosolic gene expression were further rescued in elimination experiments, demonstrating the mechanism of growth toxicity by FX exposure. The results revealed that FX persistently altered the gut microbiome of L. vannamei using gut microbiome sequencing, particularly with increased Garcinia Purple Pseudoalteromonas luteoviolacea for organic pollutant degradation. This study provided new insights into the potential toxicity of FX to marine organisms, emphasizing the need for further investigation and potential regulatory considerations.
Subject(s)
Gastrointestinal Microbiome , Hepatopancreas , Penaeidae , Transcriptome , Water Pollutants, Chemical , Animals , Penaeidae/drug effects , Penaeidae/microbiology , Penaeidae/growth & development , Penaeidae/genetics , Gastrointestinal Microbiome/drug effects , Transcriptome/drug effects , Hepatopancreas/drug effects , Hepatopancreas/metabolism , Water Pollutants, Chemical/toxicity , Oxidative Stress/drug effectsABSTRACT
Fluorescent aggregates and ensembles have been widely applied in fabrication of fluorescent sensors due to their capacity of encapsulating fluorophores and modulating their photophysical properties. In the present work, fluorescent ensembles based on anionic surfactant SDS assemblies and perylene derivatives (PBIs) were particularly constructed. Three newly synthesized neutral PBI derivatives with different structures, PO, PC1 and PC2, were used for the purpose to evaluate probe structure influence on constructing fluorescent ensembles. The one with hydrophilic side chains, PO, experienced distinct photophysical modulation effect by SDS assemblies. The ensemble based on PO@SDS assemblies displayed effective fluorescence variation to antibiotic aminoglycosides (AGs). To improve cross-reactivity and discrimination capability of ensembles, a second probe, coumarin, was introduced into PO@SDS assemblies. The resultant ternary sensor, CM-PO@SDS, exhibited good qualitative and quantitative detection capabilities, and achieved differentiation of eight AGs and mixed AG samples both in aqueous solution and actual biological fluid, like human serum. Sensing mechanism studies revealed that hydrogen bonding, electrostatic and hydrophobic interactions are involved in the sensing process. This surfactant-based fluorescent ensemble provides a simple and feasible method for assessing AGs levels. Meanwhile, this work may provide some insights to design reasonable probes for constructing effective single-system based discriminative fluorescent amphiphilic sensors.
Subject(s)
Aminoglycosides , Anti-Bacterial Agents , Fluorescent Dyes , Perylene , Spectrometry, Fluorescence , Surface-Active Agents , Surface-Active Agents/chemistry , Aminoglycosides/chemistry , Aminoglycosides/analysis , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Fluorescent Dyes/chemistry , Humans , Perylene/chemistry , Perylene/analogs & derivatives , Sodium Dodecyl Sulfate/chemistryABSTRACT
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disorder predominantly affecting preterm infants. Oxygen therapy, a common treatment for BPD, often leads to hyperoxia-induced pulmonary damage, particularly targeting alveolar epithelial cells (AECs). Crucially, disrupted lung epithelium-fibroblast interactions significantly contribute to BPD's pathogenesis. Previous studies on interleukin-11 (IL-11) in lung diseases have yielded conflicting results. Recent research, however, highlights IL-11 as a key regulator of fibrosis, stromal inflammation, and epithelial dysfunction. Despite this, the specific role of IL-11 in BPD remains underexplored. Our transcriptome analysis of normal and hyperoxia-exposed murine lung tissues revealed an increased expression of IL-11 RNA. This study aimed to investigate IL-11's role in modulating the disrupted interactions between AECs and fibroblasts in BPD. METHODS: BPD was modeled in vivo by exposing C57BL/6J neonatal mice to hyperoxia. Histopathological changes in lung tissue were evaluated with hematoxylin-eosin staining, while lung fibrosis was assessed using Masson staining and immunohistochemistry (IHC). To investigate IL-11's role in pulmonary injury contributing to BPD, IL-11 levels were reduced through intraperitoneal administration of IL-11RαFc in hyperoxia-exposed mice. Additionally, MLE-12 cells subjected to 95% oxygen were collected and co-cultured with mouse pulmonary fibroblasts (MPFs) to measure α-SMA and Collagen I expression levels. IL-11 levels in the supernatants were quantified using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Both IHC and Masson staining revealed that inhibiting IL-11 expression alleviated pulmonary fibrosis in neonatal mice induced by hyperoxia, along with reducing the expression of fibrosis markers α-SMA and collagen I in lung tissue. In vitro analysis showed a significant increase in IL-11 levels in the supernatant of MLE-12 cells treated with hyperoxia. Silencing IL-11 expression in MLE-12 cells reduced α-SMA and collagen I concentrations in MPFs co-cultured with the supernatant of hyperoxia-treated MLE-12 cells. Additionally, ERK inhibitors decreased α-SMA and collagen I levels in MPFs co-cultured with the supernatant of hyperoxia-treated MLE-12 cells. Clinical studies found increased IL-11 levels in tracheal aspirates (TA) of infants with BPD. CONCLUSION: This research reveals that hyperoxia induces IL-11 secretion in lung epithelium. Additionally, IL-11 derived from lung epithelium emerged as a crucial mediator in myofibroblast differentiation via the ERK signaling pathway, highlighting its potential therapeutic value in BPD treatment.
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Urea is intensively utilized as a nitrogen fertilizer in agriculture, originating either from root uptake or from catabolism of arginine by arginase. Despite its extensive use, the underlying physiological mechanisms of urea, particularly its adverse effects on seed germination and seedling growth under salt stress remains unclear. In this study, we demonstrate that salt stress induces excessive hydrolysis of arginine-derived urea, leading to an increase in cytoplasmic pH within seed radical cells, which, in turn, triggers salt-induced inhibition of seed germination (SISG) and hampers seedling growth. Our findings challenge the long-held belief that ammonium accumulation and toxicity are the primary causes of SISG, offering a novel perspective on the mechanism underlying these processes. This study provides significant insights into the physiological impact of urea hydrolysis under salt stress, contributing to a better understanding of SISG.
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A sensitive and robust multiclass analytical method was established to simultaneously determine 55 antibiotics in aquatic products through liquid chromatography-tandem mass spectrometry. A simple one-step purification process was successfully developed, which combined post-acidic acetonitrile extraction directly by an enhanced matrix removal cartridge. This approach eliminated the need for solvent transition. The established method for 55 antibiotics achieved an excellent linear relationship with R2 values ≥ 0.9921 in the range of 0.05-200 µg/L. The quantitation limits ranged within 0.04-5.0 µg/kg. Satisfactory recoveries (76.2%-99.7 %) were achieved with the relative standard deviations below 13.9 %. Furthermore, the antibiotic residues in aquatic products were analyzed, and the health and antibiotic resistance risk assessments were conducted. Although the health risks of target antibiotics were acceptable, a resistance risk was observed. Therefore, monitoring antibiotic residue levels in aquatic products requires considerable attention and further research to ensure the quality of marine products and consumer safety.
Subject(s)
Anti-Bacterial Agents , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Anti-Bacterial Agents/analysis , Chromatography, High Pressure Liquid/methods , Risk Assessment , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/isolation & purification , Animals , FishesABSTRACT
Aspergillus cristatus is a crucial edible fungus used in tea fermentation. In the industrial fermentation process, the fungus experiences a low to high osmotic pressure environment. To explore the law of material metabolism changes during osmotic pressure changes, NaCl was used here to construct different osmotic pressure environments. Liquid chromatography-mass spectrometry (LC-MS) combined with multivariate analysis was performed to analyze the distribution and composition of A. cristatus under different salt concentrations. At the same time, the in vitro antioxidant activity was evaluated. The LC-MS metabolomics analysis revealed significant differences between three A. cristatus mycelium samples grown on media with and without NaCl concentrations of 8% and 18%. The contents of gibberellin A3, A124, and prostaglandin A2 related to mycelial growth and those of arabitol and fructose-1,6-diphosphate related to osmotic pressure regulation were significantly reduced at high NaCl concentrations. The biosynthesis of energy-related pantothenol and pantothenic acid and antagonism-related fluvastatin, aflatoxin, and alternariol significantly increased at high NaCl concentrations. Several antioxidant capacities of A. cristatus mycelia were directly related to osmotic pressure and exhibited a significant downward trend with an increase in environmental osmotic pressure. The aforementioned results indicate that A. cristatus adapts to changes in salt concentration by adjusting their metabolite synthesis. At the same time, a unique set of strategies was developed to cope with high salt stress, including growth restriction, osmotic pressure balance, oxidative stress response, antioxidant defense, and survival competition.
Subject(s)
Antioxidants , Aspergillus , Metabolomics , Salt Stress , Aspergillus/metabolism , Aspergillus/growth & development , Metabolomics/methods , Chromatography, Liquid , Antioxidants/metabolism , Metabolome , Osmotic Pressure , Mycelium/metabolism , Mycelium/growth & development , Mycelium/chemistry , Mass Spectrometry , Sodium Chloride/pharmacology , Liquid Chromatography-Mass Spectrometry , Sugar AlcoholsABSTRACT
Skin cutaneous melanoma (SKCM) is malignant cancer known for its high aggressiveness and unfavorable prognosis, particularly in advanced tumors. Anoikis is a specific pattern of programmed cell death associated with tumor regeneration, migration, and metastasis. Nevertheless, limited research has been conducted to investigate the function of anoikis in SKCM. Anoikis-related genes (ARGs) were extracted from Genecards to identify SKCM subtypes and to explore the immune microenvironment between the different subtypes. Prognostic models of SKCM were developed by LASSO COX regression analysis. Subsequently, the predictive value of risk scores in SKCM and the association with immunotherapy were further explored. Finally, the expression of 6 ARGs involved in the model construction was detected by immunohistochemistry and PCR. This study identified 20 ARGs significantly associated with SKCM prognosis and performed disease subtype analysis of samples based on these genes, different subtypes exhibited significantly different clinical features and tumor immune microenvironment (TIME) landscapes. The risk score prognostic model was generated by further screening and identification of the six ARGs. The model exhibited a high degree of sensitivity and specificity to predict the prognosis of individuals with SKCM. These high- and low-risk populations showed different immune statuses and drug sensitivity. Further immunohistochemical and PCR experiments identified significant differential expression of the six ARGs in tumor and normal samples. Anoikis-based features may serve as novel prognostic biomarkers for SKCM and may provide important new insights for survival prediction and individualized treatment development.
Subject(s)
Anoikis , Biomarkers, Tumor , Immunotherapy , Melanoma , Skin Neoplasms , Tumor Microenvironment , Humans , Melanoma/immunology , Melanoma/diagnosis , Melanoma/mortality , Melanoma/therapy , Melanoma/genetics , Skin Neoplasms/immunology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Skin Neoplasms/mortality , Skin Neoplasms/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Tumor Microenvironment/immunology , Prognosis , Immunotherapy/methods , Female , Male , Melanoma, Cutaneous Malignant , Middle Aged , Gene Expression Regulation, NeoplasticABSTRACT
BACKGROUND: Coronary inflammation induces changes in pericoronary adipose tissue (PCAT) can be detected by coronary computed tomography angiography (CCTA). Our aim was to investigate whether different PCAT radiomics model based on CCTA could improve the prediction of major adverse cardiovascular events (MACE) within 3 years. METHODS: This retrospective study included 141 consecutive patients with MACE and matched to patients with non-MACE (n = 141). Patients were randomly assigned into training and test datasets at a ratio of 8:2. After the robust radiomics features were selected by using the Spearman correlation analysis and the least absolute shrinkage and selection operator, radiomics models were built based on different machine learning algorithms. The clinical model was then calculated according to independent clinical risk factors. Finally, an overall model was established using the radiomics features and the clinical factors. Performance of the models was evaluated for discrimination degree, calibration degree, and clinical usefulness. RESULTS: The diagnostic performance of the PCAT model was superior to that of the RCA-model, LAD-model, and LCX-model alone, with AUCs of 0.723, 0.675, 0.664, and 0.623, respectively. The overall model showed superior diagnostic performance than that of the PCAT-model and Cli-model, with AUCs of 0.797, 0.723, and 0.706, respectively. Calibration curve showed good fitness of the overall model, and decision curve analyze demonstrated that the model provides greater clinical benefit. CONCLUSION: The CCTA-based PCAT radiomics features of three major coronary arteries have the potential to be used as a predictor for MACE. The overall model incorporating the radiomics features and clinical factors offered significantly higher discrimination ability for MACE than using radiomics or clinical factors alone.
Subject(s)
Computed Tomography Angiography , Coronary Angiography , Epicardial Adipose Tissue , Aged , Female , Humans , Male , Middle Aged , Case-Control Studies , Computed Tomography Angiography/methods , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Epicardial Adipose Tissue/diagnostic imaging , Machine Learning , Radiomics , Retrospective StudiesABSTRACT
Background: The efficacy and safety of potassium-competitive acid blockers (P-CABs) in the eradication of Helicobacter pylori (Hp) remains controversial when compared with proton pump inhibitors (PPIs). Objectives: The current study set out to compare the differences in the eradication rate and adverse reactions between eradication regimens based on P-CAB or PPI drugs and the differences between the vonoprazan-based and the tegoprazan-based regimens to explore the efficacy and safety of different Hp eradication regimens. Data sources and methods: Databases including PubMed, EMBASE, Cochrane Library, and WOS were searched from the inception of these databases up to July 2023, and eligible randomized controlled trials (RCTs) were included. The outcome measures were the eradication rate and the incidence of adverse reactions of different regimens in treating Hp. The results were estimated as relative risk (RR) and its 95% confidence interval (CI), and R 4.2.1 software was used to perform the network meta-analysis (NMA). Results: A total of 20 studies were included in the analysis, involving 5815 patients with Hp. In terms of eradication rate, the 2-week vonoprazan-based triple regimen (V-Tri-2w) was the best, which was superior to the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 0.9, 95% CI: (0.85-0.95)] and the 1-week tegoprazan-based triple regimen [T-Tri-1w, RR = 0.79, 95% CI: (0.64-0.97)]; the 2-week tegoprazan-based quadruple regimen (T-Qua-2w) was superior to the 1-week PPI-based triple regimen [P-Tri-1w, RR = 0.82, 95% CI: (0.67-0.99)], and there was no difference between the remaining tegoprazan-based regimens and the PPI-based or vonoprazan-based regimens. In terms of the incidence of adverse reactions, the 2-week vonoprazan-based binary regimen (V-Bi-2w) was lower than that of the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 1.98, 95% CI: (1.57-2.52)]; there was no significant difference between 1 and 2 weeks for each regimen, such as the vonoprazan-based triple regimen [RR = 1.11, 95% CI: (0.82-1.52)]. Conclusion: In the eradication treatment of Hp, the efficacy and safety of vonoprazan-based regimens are generally better than those of PPI-based regimens. Among them, the V-Tri-2w regimen has the highest eradication rate and may be the preferred choice for Hp eradication.
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In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beanii was developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A-J (1-10), and nine known PPAPs (11-19) were obtained from H. beanii. Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1 and 2 are two new rare 2,3-seco-spirocyclic PPAPs, 3 and 4 are two novel 12,13-seco-spirocyclic PPAPs, 5 and 6 are two novel spirocyclic PPAPs, 7 and 8 are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9 and 10 are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC50 values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 µM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.
Subject(s)
Glycoside Hydrolase Inhibitors , Hypericum , Molecular Docking Simulation , Plant Extracts , alpha-Glucosidases , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , alpha-Glucosidases/chemistry , alpha-Glucosidases/metabolism , Hypericum/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Molecular Structure , Ligands , Structure-Activity Relationship , KineticsABSTRACT
The solubility of eplerenone (EP) in 13 pure solvents (acetonitrile, N,N-dimethylformamide (DMF), acetone, 2-butanone, 4-methyl-2-pentanone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propionate, ethyl propionate, ethanol, and 1-propanol) was determined by the gravimetric method at atmospheric pressure and various temperatures (from 283.15 to 323.15 K). The results showed that the solubility of EP in the selected solvents was positively correlated with the thermodynamic temperature, and the order of solubility of EP at 298.15 K was acetonitrile > DMF > 2-butanone > methyl acetate > 4-methyl-2-pentanone > methyl propionate > ethyl acetate > propyl acetate > ethyl formate > acetone > butyl acetate > ethanol >1-propanol. The modified Apelblat model, van't Hoff model, λh model, and polynomial empirical model were used for fitting the solubility data, and then the λh model was found to have the highest fitting accuracy with a minimum ARD of 7.0 × 10-3 and a minimum RMSD of 6.1 × 10-6. The solvent effect between the solute and the solvent was analyzed using linear solvation energy relationship (LSER), and the enthalpy of solvation (ΔsolH°), entropy of solvation (ΔsolS°), and Gibbs free energy of solvation (ΔsolG°) of the dissolution process of EP were calculated by the van't Hoff model, which indicated that the dissolution process of EP in the selected solvents was endothermic, nonspontaneous, and entropy-increasing. In this work, the solubility, dissolution characteristics, and thermodynamic parameters of EP were studied, which will provide data support for the production, crystallization, and purification of EP and will provide important guidance for the crystallization optimization of EP in industry.
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Optimizing the local electronic structure of electrocatalysts can effectively lower the energy barrier of electrochemical reactions, thus enhancing the electrocatalytic activity. However, the intrinsic contribution of the electronic effect is still experimentally unclear. In this work, the electron injection-incomplete discharge approach to achieve the electron accumulation (EA) degree on the nickel-iron layered double hydroxide (NiFe LDH) is proposed, to reveal the intrinsic contribution of EA toward oxygen evolution reaction (OER). Such NiFe LDH with EA effect results in only 262 mV overpotential to reach 50 mA cm-2, which is 51 mV-lower compared with pristine NiFe LDH (313 mV), and reduced Tafel slope of 54.8 mV dec-1 than NiFe LDH (107.5 mV dec-1). Spectroscopy characterizations combined with theoretical calculations confirm that the EA near concomitant Vo can induce a narrower energy gap and lower thermodynamic barrier to enhance OER performance. This study clarifies the mechanism of the EA effect on OER activity, providing a direct electronic structure modulation guideline for effective electrocatalyst design.
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Previous studies have primarily focused on the influence of temperature and precipitation on phenology. It is unclear if the easily ignored climate factors with drivers of vegetation growth can effect on vegetation phenology. In this research, we conducted an analysis of the start (SOS) and end (EOS) of the growing seasons in the northern region of China above 30°N from 1982 to 2014, focusing on two-season vegetation phenology. We examined the response of vegetation phenology of different vegetation types to preseason climatic factors, including relative humidity (RH), shortwave radiation (SR), maximum temperature (Tmax), and minimum temperature (Tmin). Our findings reveal that the optimal preseason influencing vegetation phenology length fell within the range of 0-60 days in most areas. Specifically, SOS exhibited a significant negative correlation with Tmax and Tmin in 44.15% and 42.25% of the areas, respectively, while EOS displayed a significant negative correlation with SR in 49.03% of the areas. Additionally, we identified that RH emerged as the dominant climatic factor influencing the phenology of savanna (SA), whereas temperature strongly controlled the SOS of deciduous needleleaf forest (DNF) and deciduous broadleaf forest (DBF). Meanwhile, the EOS of DNF was primarily influenced by Tmax. In conclusion, this study provides valuable insights into how various vegetation types adapt to climate change, offering a scientific basis for implementing effective vegetation adaptation measures.
Subject(s)
Forests , Plant Development , China , Climate Change , Seasons , Temperature , EcosystemABSTRACT
Dry eye disease (DED) is a multifactorial condition affecting the ocular surface. It is characterized by loss of tear film homeostasis and accompanied by ocular symptoms that may potentially result in damage to the ocular surface and even vision loss. Unmodifiable risk factors for DED mainly include aging, hormonal changes, and lifestyle issues such as reduced sleep duration, increased screen exposure, smoking, and ethanol consumption. As its prevalence continues to rise, DED has garnered considerable attention, prompting the exploration of potential new therapeutic targets. Recent studies have found that when the production of ROS exceeds the capacity of the antioxidant defense system on the ocular surface, oxidative stress ensues, leading to cellular apoptosis and further oxidative damage. These events can exacerbate inflammation and cellular stress responses, further increasing ROS levels and promoting a vicious cycle of oxidative stress in DED. Therefore, given the central role of reactive oxygen species in the vicious cycle of inflammation in DED, strategies involving antioxidants have emerged as a novel approach for its treatment. This review aims to enhance our understanding of the intricate relationship between oxidative stress and DED, thereby providing directions to explore innovative therapeutic approaches for this complex ocular disorder.
ABSTRACT
Defect-engineered bimetallic oxides exhibit high potential for the electrolysis of small organic molecules. However, the ambiguity in the relationship between the defect density and electrocatalytic performance makes it challenging to control the final products of multi-step multi-electron reactions in such electrocatalytic systems. In this study, controllable kinetics reduction is used to maximize the oxygen vacancy density of a CuâCo oxide nanosheet (CuCo2O4 NS), which is used to catalyze the glycerol electrooxidation reaction (GOR). The CuCo2O4-x NS with the highest oxygen-vacancy density (CuCo2O4-x-2) oxidizes C3 molecules to C1 molecules with selectivity of almost 100% and a Faradaic efficiency of ≈99%, showing the best oxidation performance among all the modified catalysts. Systems with multiple oxygen vacancies in close proximity to each other synergistically facilitate the cleavage of CâC bonds. Density functional theory calculations confirm the ability of closely spaced oxygen vacancies to facilitate charge transfer between the catalyst and several key glycolic-acid (GCA) intermediates of the GOR process, thereby facilitating the decomposition of C2 intermediates to C1 molecules. This study reveals qualitatively in tuning the density of oxygen vacancies for altering the reaction pathway of GOR by the synergistic effects of spatial proximity of high-density oxygen vacancies.