A mechanistic review of the pharmacological aspects of Kaempferide as a natural compound.

Background: Kaempferide exhibits a range of pharmacological effects, including anti-tumor activity, kidney protection, oxidative stress relief, gastroprotection, and endocrine regulation. The increasing attention surrounding kaempferide, a promising therapeutic agent, has sparked considerable debate, making it a topic of significant interest in recent research. Purpose: This paper aims to provide a comprehensive review of the clinical applications, pharmacological properties, and underlying molecular mechanisms of kaempferide, while also examining its potential for future therapeutic applications in the field of pharmacology. Methodology: We used the keywords "kaempferide" and "kaempferide derivatives" to search for relevant articles in Science Direct, PubMed, MEDLINE, and Web of Science databases. Results: Kaempferide possesses anti-inflammatory, stomach-protective, antioxidant, anti-tumor, and anti-adipogenic activities, and thus has great potential in different systemic therapies. These interactions involve a multitude of pathways that directly or indirectly affect upstream and downstream key molecules. Conclusions: Although kaempferide has shown promising potential, its practical applications still require further in-depth investigation. Future research should prioritize elucidating its mechanisms of action, identifying specific therapeutic targets, and optimizing the compound to facilitate its translation into drug development.

Comprehensive analysis of biotransformation pathways and products of chloramphenicol by Raoultella Ornithinolytica CT3: Pathway elucidation and toxicity assessment.

Microbial degradation of chloramphenicol (CAP) has become important for reducing the adverse impact of environmental pollution with antibiotics. Although several pathways for CAP degradation have been identified in various bacteria, multiple metabolic pathways and their respective intermediate metabolites within a single strain are rarely reported. Here, Raoultella ornithinolytica CT3 was first isolated from silkworm excrement using CAP as the sole carbon source, and 100 mg/L CAP was almost completely degraded within 48 h. The biodegradation type of CAP followed first-order kinetics. Twenty-two CAP biotransformation products were identified using high-performance liquid chromatography and ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. The CAP biotransformation pathways were predicted mainly in the acetylation and auxiliary pathways of propionylation and butyrylation. The toxicity of CAP biotransformation products was evaluated using the ecological structure-activity relationship (ECOSAR) model and biological indicators. The results showed that the toxicity of the intermediate metabolites changed slightly, but the final metabolite was harmless to the environment. Genomic analysis predicted that genes encoding acetyltransferase, amido-linkage hydrolase, nitroreductase, haloacetate dehalogenase, and protocatechuate 3,4-dioxygenase were associated with CAP biodegradation. This study provides new insights into the microbial degradation pathway of CAP and constitutes an ecological safety assessment for CAP-contaminated environments.

The impact of different dietary flavonoids on the risk of coronary heart disease in cancer patients and that on the prognosis of patients with cancer and coronary heart disease.

The purpose of this study is to explore the risk of coronary heart disease (CHD) in cancer patients who consume different flavonoids, and the impact of flavonoids on the prognosis of cancer patients with CHD. We extracted dietary flavonoids data on 1454 patients diagnosed with cancer from the National Health and Nutrition Examination Survey and Food and Nutrient Database for Dietary Studies. Logistic regression analysis was used to explore the relationship between the intake of flavonoids and the risk of CHD. Cox proportional hazard model was used to explore the impact of flavonoids intake on prognosis in 148 patients with cancer and CHD. Malvidin intake increased the risk of CHD by 1% [odds ratio (OR) = 1.01, 95% confidence interval (CI): 1.00-1.02, P < 0.05] in cancer patients, while epicatechin and isorhamnetin reduced the risk of CHD by 3% (OR = 0.97, 95% CI: 0.94-1.00, P < 0.05) and 15% (OR = 0.85, 95% CI: 0.72-1.00, P < 0.05), respectively. Adjusted by age, sex, and race, malvidin intake increased the risk of CHD in cancer patients by 1% (OR = 1.01, 95% CI: 1.00-1.02, P < 0.05), isorhamnetin decreased the risk by 15% (OR = 0.85, 95% CI: 0.72-1.00, P < 0.05), and epicatechin showed no effect on the risk of CHD (P > 0.05). No flavonoids had impact on the prognosis of patients with cancer and CHD (P > 0.05). For patients with cancer, consuming malvidin increases the risk of CHD, while isorhamnetin reduces the risk. Consuming flavonoids has no impact on the prognosis of patients with cancer and CHD.

Seawater alkalization via an energy-efficient electrochemical process for CO2 capture.

Electrochemical pH-swing strategies offer a promising avenue for cost-effective and energy-efficient carbon dioxide (CO2) capture, surpassing the traditional thermally activated processes and humidity-sensitive techniques. The concept of elevating seawater's alkalinity for scalable CO2 capture without introducing additional chemical as reactant is particularly intriguing due to its minimal environmental impact. However, current commercial plants like chlor-alkali process or water electrolysis demand high thermodynamic voltages of 2.2 V and 1.23 V, respectively, for the production of sodium hydroxide (NaOH) from seawater. These high voltages are attributed to the asymmetric electrochemical reactions, where two completely different reactions take place at the anode and cathode. Here, we developed a symmetric electrochemical system for seawater alkalization based on a highly reversible and identical reaction taking place at the anode and cathode. We utilize hydrogen evolution reaction at the cathode, where the generated hydrogen is looped to the anode for hydrogen oxidation reaction. Theoretical calculations indicate an impressively low energy requirement ranging from 0.07 to 0.53 kWh/kg NaOH for established pH differences of 1.7 to 13.4. Experimentally, we achieved the alkalization with an energy consumption of 0.63 kWh/kg NaOH, which is only 38% of the theoretical energy requirements of the chlor-alkali process (1.64 kWh/kg NaOH). Further tests demonstrated the system's potential of enduring high current densities (~20 mA/cm2) and operating stability over an extended period (>110 h), showing its potential for future applications. Notably, the CO2 adsorption tests performed with alkalized seawater exhibited remarkably improved CO2 capture dictated by the production of hydroxide compared to the pristine seawater.

Impact of baseline body mass index on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy.

BACKGROUND: Primary liver cancer is the sixth most common cancer worldwide, with hepatocellular carcinoma (HCC) being the most prevalent form. Despite the current availability of multiple immune or immune combination treatment options, the prognosis is still poor, so how to identify a more suitable population is extremely important. AIM: To evaluate the clinical effectiveness of combining lenvatinib with camrelizumab for patients with hepatitis B virus (HBV)-related HCC in Barcelona Clinic Liver Cancer (BCLC) stages B/C, considering various body mass index (BMI) in different categories. METHODS: Retrospective data were collected from 126 HCC patients treated with lenvatinib plus camrelizumab. Patients were divided into two groups based on BMI: The non-overweight group (BMI < 25 kg/m2, n = 51) and the overweight/obese group (BMI ≥ 25 kg/m2, n = 75). Short-term prognosis was evaluated using mRECIST criteria, with subgroup analyses for non-overweight (BMI: 18.5-24.9 kg/m2), overweight (BMI: 25-30 kg/m2), and obese (BMI ≥ 30 kg/m2) patients. A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival (OS), leading to the development of a column-line graph model. RESULTS: Median progression-free survival was significantly longer in the obese/overweight group compared to the non-overweight group. Similarly, the median OS was significantly prolonged in the obese/overweight group than in the non-overweight group. The objective remission rate and disease control rate for the two groups of patients were, respectively, objective remission rate (5.88% vs 28.00%) and disease control rate (39.22% vs 62.67%). Fatigue was more prevalent in the obese/overweight group, while other adverse effects showed no statistically significant differences (P > 0.05). Subgroup analysis based on BMI showed that obese and overweight patients had better progression-free survival and OS than non-overweight patients, with obese patients showing the best outcomes. Multifactorial regression analysis identified BCLC grade, alpha-fetoprotein level, portal vein tumor thrombosis, and BMI as independent prognostic factors for OS. The column-line graph model highlighted the importance of BMI as a major predictor of patient prognosis, followed by alpha-fetoprotein level, BCLC classification, and portal vein tumor thrombosis. CONCLUSION: BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab, and obese/overweight patients have a better prognosis.

VEGFB ameliorates insulin resistance in NAFLD via the PI3K/AKT signal pathway.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most universal liver diseases with complicated pathogenesis throughout the world. Insulin resistance is a leading risk factor that contributes to the development of NAFLD. Vascular endothelial growth factor B (VEGFB) was described by researchers as contributing to regulating lipid metabolic disorders. Here, we investigated VEGFB as a main target to regulate insulin resistance and metabolic syndrome. METHODS: In this study, bioinformatics, transcriptomics, morphological experiments, and molecular biology were used to explore the role of VEGFB in regulating insulin resistance in NAFLD and its molecular mechanism based on human samples, animal models, and cell models. RNA-seq was performed to analyze the signal pathways associated with VEGFB and NAFLD; Palmitic acid and High-fat diet were used to induce insulin-resistant HepG2 cells model and NAFLD animal model. Intracellular glucolipid contents, glucose uptake, hepatic and serum glucose and lipid levels were examined by Microassay and Elisa. Hematoxylin-eosin staining, Oil Red O staining, and Periodic acid-schiff staining were used to analyze the hepatic steatosis, lipid droplet, and glycogen content in the liver. Western blot and quantitative real-time fluorescent PCR were used to verify the expression levels of the VEGFB and insulin resistance-related signals PI3K/AKT pathway. RESULTS: We observed that VEGFB is genetically associated with NAFLD and the PI3K/AKT signal pathway. After VEGFB knockout, glucolipids levels were increased, and glucose uptake ability was decreased in insulin-resistant HepG2 cells. Meanwhile, body weight, blood glucose, blood lipids, and hepatic glucose of NAFLD mice were increased, and hepatic glycogen, glucose tolerance, and insulin sensitivity were decreased. Moreover, VEGFB overexpression reduced glucolipids and insulin resistance levels in HepG2 cells. Specifically, VEGFB/VEGFR1 activates the PI3K/AKT signals by activating p-IRS1Ser307 expression, inhibiting p-FOXO1pS256 and p-GSK3Ser9 expressions to reduce gluconeogenesis and glycogen synthesis in the liver. Moreover, VEGFB could also enhance the expression level of GLUT2 to accelerate glucose transport and reduce blood glucose levels, maintaining glucose homeostasis. CONCLUSIONS: Our studies suggest that VEGFB could present a novel strategy for treating NAFLD as a positive factor.

Knowledge, attitude, and practice of chronic insomnia management among general practitioners in China: a cross-sectional survey.

BACKGROUND: Chronic insomnia is a common yet often overlooked issue in primary health care. This study investigated the knowledge, attitude, and practices of chronic insomnia management among general practitioners (GPs). METHODS: A cross-sectional online survey was conducted among GPs providing routine care to adults with insomnia in health facilities at all levels in Sichuan Province, China. Additionally, we designed an online questionnaire that included basic information and knowledge, attitudes, and practices regarding chronic insomnia management. RESULTS: We included 420 GPs, 66.2% of whom were female and 58.1% were from community health service centers. Total 198 (47.1%) GPs had received specific training and only 2 GPs (0.5%) correctly answered the knowledge-related questions. Furthermore, only 44 GPs (10.5%) demonstrated excellent practice behaviors, while most GPs (70.2%) expressed high demand for training in insomnia management. Insomnia training experience was associated with higher practice scores (ß = 3.318, p < 0.001). CONCLUSION: This study established an association and correlation between knowledge, attitude, and practice scores in treating insomnia and the sociodemographic characteristics of GPs in China. Although knowledge and practice performance in this field need to be improved, they mostly displayed a positive attitude towards insomnia management. Thus, offering continuing education opportunities to GPs would be highly beneficial.

A hovering bubble with a spontaneous horizontal oscillation.

Active matters, characterized by multi-mode motions, have been emerging for both engineering and biological applications. Generally, active objects rely on the symmetry-broken structures, compositions, or interfacial activities through a physical or chemical approach. Here, we report an active bubble spontaneously hovering with a horizontal oscillation at the solid/liquid interface by impacting a stationary laser beam into a liquid through a transparent solid cover. This spontaneous oscillation mode of the bubble synchronizes with that of the interfacial temperature and hydrodynamical flow. A physical mechanism is proposed, and the scaling analysis of the oscillation frequency agrees well with experiments in various liquids under different laser powers. Additionally, the bubble trajectory rotates azimuthally, arising from the symmetry breaking of the vortex pair accompanying the oscillation. Moreover, the double pendulum of oscillation bubbles has been demonstrated, achieving a preferable oscillation direction in a controllable way. These findings would not only advance our understanding of active matters but also shed light on the bubble-mediated technological applications, such as microrobots and drug deliveries.

Adsorption-desorption mechanisms and migration behavior of fluchlordiniliprole in four different soils under varied conditions.

Utilizing infrared spectroscopy coupled with batch equilibrium methods, the adsorption and desorption characteristics of the novel Insecticide fluchlordiniliprole were assessed in four different soil types. It was found that fluchlordiniliprole's adsorption and desorption in these soils were consistent with the Freundlich isotherm, exhibiting adsorption capacities (KF-ads) ranging from 8.436 to 36.269. Temperature fluctuations, encompassing both high and low extremes, impaired the ability of soil to adsorb fluchlordiniliprole. In addition, adsorption dynamics were modulated by several other factors, including soil pH, ionic strength, amendments (e.g., biochar and humic substances), and the presence of various surfactants and microplastics. Although capable of leaching, fluchlordiniliprole exhibited weak mobility in most soils. Therefore, it appears that fluchlordiniliprole seems to pose a threat to surface soil and aquatic biota, but a minimal threat to groundwater. SYNOPSIS STATEMENT: This research examines the dynamics of fluchlordiniliprole in soil, an will aid in maintaining ecological safety and managing agricultural pesticides. The study's comprehensive analysis of adsorption, desorption, and soil migration patterns significantly contributes to our understanding of pesticide interactions with diverse soil types. The results of this study will enable the development of environmentally responsible agricultural practices.

Enhanced nitrogen removal and microbial community of the mainstream deammonification treating fluctuating influent C/N wastewater by the novel functional carriers.

The plug-flow fixed bed reactors with zeolite/tourmaline-modified polyurethane carriers (PFBRZTP) and polyurethane carriers (PFBRPU) were operated to assess the fluctuating influent C/N impact on the system performance and the carrier effect on the enhancing the system operation. Result suggested that fluctuations in influent C/N and variations in operational temperature reduced the removal performance and system stability within PFBRPU. The negative impact of C/N fluctuation could be effectively mitigated by effluent reflux. In contrast, PFBRZTP performance and operational stability of maintained at high level with a greater nitrogen removal rate (0.18 kg N·(m³·d)-1). Redundancy analyses showed that the fluctuations in influent C/N dramatically affected the microbiome structure in PFBRPU, and the leading influencing factor was shifted to the fluctuating amount of influent C/N, which in turn reduced the system performance and stability. ZTP carriers could maintain the balance of main functional bacterial activity and abundance and promote the partial denitrification process with a higher Thauera abundance of 0.48%.

Urinary bladder matrix scaffold improves the impact of adipose-mesenchymal stem cells on the function and structure of transplanted rat ovaries.

Ovarian transplantation presents significant advantages for the preservation of female fertility. Nonetheless, a substantial number of follicles are apoptosis during the process of ovarian tissue transplantation as a result of ischemic conditions. This study aimed to assess whether adipose-derived mesenchymal stem cells combined with urinary bladder matrix (ADSC/UBM) confer a greater therapeutic benefit compared to ADSCs alone. To achieve this, ADSC/UBM was applied during the autotransplantation of rat ovaries. Thirty rats were divided into five sets of six: the untreated control group (Normal), the oophorectomy group, the autograft group, the autograft + ADSCs group (ADSC), and the autograft + ADSC/UBM group (ADSC/UBM). After transplantation, the number of follicles in the ADSC/UBM group was significantly higher than that in the autograft group. Angiogenesis was enhanced following ADSC/UBM transplantation. Follicle-stimulating hormone (FSH) levels were significantly lower, and Anti-Müllerian hormone (AMH) levels were significantly higher in rats in the ADSC/UBM group than in the Autograft group. The apoptosis rate in the ADSC/UBM group decreased. The estrous cycle in the ADSC/UBM group recovered more quickly than the ADSC group. The data indicate that UBM improves ADSC retention in graft ovaries and aids in permanently restoring ovarian function, making ADSC/UBM a promising option for ovarian transplantation.

Comprehensive review of Hesperetin: Advancements in pharmacokinetics, pharmacological effects, and novel formulations.

Hesperetin is a flavonoid compound naturally occurring in the peel of Citrus fruits from the Rutaceae family. Previous studies have demonstrated that hesperetin exhibits various pharmacological effects, such as anti-inflammatory, anti-tumor, antioxidative, anti-aging, and neuroprotective properties. In recent years, with the increasing prevalence of diseases and the rising awareness of traditional Chinese medicine, hesperetin has garnered growing attention for its wide-ranging pharmacological effects. To substantiate its health benefits and elucidate potential mechanisms, knowledge of pharmacokinetics is crucial. However, the limited solubility of hesperetin restricts its bioavailability, thereby diminishing its efficacy as a beneficial health agent. To enhance the bioavailability of hesperetin, various novel formulations have been developed, including nanoparticles, liposomes, and cyclodextrin inclusion complexes. This article reviews recent advances in the pharmacokinetics of hesperetin and methods to improve its bioavailability, as well as its pharmacological effects and mechanisms, aiming to provide a theoretical basis for clinical applications.

Early Warning Models Using Machine Learning to Predict Sepsis-Associated Chronic Critical Illness: A Study Based on the Medical Information Mart for Intensive Care Database.

Background Patients with chronic critical illness (CCI) experience poor prognoses and incur high medical costs. However, there is currently limited clinical awareness of sepsis-associated CCI, resulting in insufficient vigilance. Therefore, it is necessary to build a machine learning model that can predict whether sepsis patients will develop CCI. Methods Clinical data on 19,077 sepsis patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were analyzed. Predictive factors were identified using the Student's t-test, Mann-Whitney U test, or χ 2 test. Six machine learning classification models, namely, the logistic regression, support vector machine, decision tree, random forest, extreme gradient enhancement, and artificial neural network, were established. The optimal model was selected on the basis of its performance. Calibration curves were used to evaluate the accuracy of model classification, while the external validation dataset was used to evaluate the performance of the model. Results Thirty-seven characteristics, such as elevated alanine aminotransferase, rapid heart rate, and high Logistic Organ Dysfunction System scores, were identified as risk factors for developing CCI. The area under the receiver operating characteristic curve (AUROC) values for all models were above 0.73 on the internal test set. Among them, the extreme gradient enhancement model exhibited superior performance (F1 score = 0.91, AUROC = 0.91, Brier score = 0.052). It also exhibited stable prediction performance on the external validation set (AUROC = 0.72). Conclusion A machine learning model was established to predict whether sepsis patients will develop CCI. It can provide useful predictive information for clinical decision-making.

Degradation of the novel herbicide tiafenacil in aqueous solution: Kinetics, various influencing factors, hydrolysis products identification, and toxicity assessment.

As new pesticides are continually introduced into agricultural systems, understanding their environmental behavior and potential toxicity effects is crucial for effective risk assessment. This study utilized QuEChERS and UPLC-QTOF-MS/MS techniques to analyze Tiafenacil (TFA) and its six hydrolysis products (HP1 to HP6) in water, marking the first comprehensive report on these degradation products. Calibration curves demonstrated strong linearity (R2 ≥ 0.9903) across concentrations ranging from 0.02 to 3.50 mg L-1. TFA's hydrolysis followed single first-order kinetic (SFOK) model, with rapid degradation observed under alkaline and high-temperature conditions, resulting in half-lives ranging from 0.22 to 84.82 days. The ECOSAR model predicts that TFA's hydrolysis products exhibit acute and chronic toxicity to fish, Daphnia, and green algae. Additionally, hydrolysis products HP1, HP5, and HP6 were detected in irrigation water from citrus orchards, posing higher predicted toxicity risks to fish and green algae. This highlights the necessity for further risk assessments considering transformation products. Overall, this study enhances our understanding of TFA's environmental fate and supports its safe agricultural application and monitoring practices.

Modular Synthesis of α-Aryl Acrylamido Carboxylic Acids by Triple C-F Bond Cleavage of (Trifluoromethyl)alkenes with Unprotected Amino Acids.

A straightforward and efficient strategy for the construction of tertiary and secondary α-aryl acrylamido carboxylic acids is reported. This N-acrylation protocol of unprotected amino acids is achieved by triple C-F bond cleavage of (trifluoromethyl)alkenes. This method features mild conditions, is operationally simple, is free of transition metals and racemization, can be used on a gram scale, and is compatible with various functional moieties. Mechanistic studies indicate that oxygen atom exchange happens among H2O, NaOH, and amino acids, and the oxygen atom of the amide moiety of the product is incorporated by the ipso-defluorooxylation of (trifluoromethyl)alkene.

Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy.

BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

Chemoselective Thioacylation of Amines Enabled by Synergistic Defluorinative Coupling.

A mild and chemoselective method for the thioacylation of amines, including amino acids and peptides, using gem-difluoroalkenes and sulfide, is reported. The distinguishing of the different nucleophilic sites (S-site and diverse N-sites) by the chemoselective C-F bond functionalization of gem-difluoroalkenes enables the unique synergistic defluorinative coupling reaction. This reaction features mild conditions, is operationally simple, efficient, and gram-scalable, tolerates various functional groups, and is activator-free and without racemization. Thioamide moieties were incorporated site-specifically into bioactive compounds. The proposed mechanism is illustrated by a DFT calculation.

Low complexity equalization in coherent optical communication based on Fermat number transform.

In order to reduce the power consumption of digital signal processing (DSP) in a coherent optical communication system, a low complexity equalization scheme in DSP flow of a 400 Gb/s DP-16QAM system has been proposed. This scheme is based on Fermat number transform (FNT), which sequentially performs static equalization (SE) and dynamic equalization (DE) in the transform domain. For different distances, the proposed scheme finds the optimal solution under the condition that transform length and data bit width are mutually restricted under different transmission distances while achieving low complexity and optimal performance. The experimental results show that the adopted transform-domain equalization (TrDE) scheme has much lower computational complexity than the traditional frequency-domain equalization (FDE) and time-domain equalization (TDE) nearly without any performance loss. In the 80, 160, and 240 km scenarios, the number of multiplier is reduced by more than 72%, and the advantage becomes more obvious as the transmission capacity increases.

Chelerythrine ameliorates Aspergillus fumigatus keratitis through suppressing the LOX-1/p38 MAPK signaling pathway.

PURPOSE: Aspergillus fumigatus (A. fumigatus) keratitis is a type of infectious corneal disease that significantly impairs vision. The objective of this study is to evaluate the therapeutic potential of chelerythrine (CHE) on A. fumigatus keratitis. METHODS: The antifungal activity of CHE was assessed through various tests including the minimum inhibitory concentration test, scanning electron microscopy, transmission electron microscopy, propidium iodide uptake test and plate count. Neutrophil infiltration and activity were assessed using immunofluorescence staining and the myeloperoxidase test. RT-PCR, western blotting assay, and ELISA were performed to measure the expression levels of proinflammatory cytokines (IL-1ß and IL-6), NF-E2-related factor (Nrf2), heme oxygenase-1 (HO-1), and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), as well as to determine the ratio of phosphorylated-p38 (p-p38) mitogen-activated protein kinase (MAPK) to p38 MAPK. RESULTS: In vitro, CHE inhibited the growth of A. fumigatus conidia, reduced fungal hyphae survival, and prevented fungal biofilm formation. In vivo, CHE reduced the severity of A. fumigatus keratitis and exhibited an excellent anti-inflammatory effect by blocking neutrophil infiltration. Furthermore, CHE decreased the expression levels of proinflammatory cytokines and LOX-1 at both mRNA and protein levels, while also decreasing the p-p38 MAPK/p38 MAPK ratio. Additionally, CHE increased the expression levels of Nrf2 and HO-1. CONCLUSION: CHE provides protection against A. fumigatus keratitis through multiple mechanisms, including reducing fungal survival, inducing anti-inflammatory effects, enhancing Nrf2 and HO-1 expression, and suppressing the signaling pathway of LOX-1/p38 MAPK.

Energy transition: Cap-and-trade and carbon capture and storage for achieving net-zero emissions with sustainable insurance.

This paper introduces an energy transition model featuring a carbon-intensive manufacturer that adopts sustainable insurance, participates in a cap-and-trade scheme, and implements carbon capture and storage (CCS) transit, all aimed at achieving the net-zero carbon emission target. The model utilizes a down-and-out call (DOC) approach to evaluate the manufacturer's equity, considering the bankruptcy risk prior to maturity due to carbon intensity. The equity of the life insurer providing funds is assessed using a capped DOC method to address the capped credit risk from the manufacturer. The findings reveal that increased adoption of CCS transit diminishes manufacturer equity, heightens default risk, and reduces insurer equity, with these effects exacerbated by advanced CCS technology and stringent cap-and-trade caps. Both stringent cap-and-trade schemes and rapid advancements in CCS transit practices, particularly with the use of advanced CCS technology, deviate from the net-zero target. A critical policy implication is the necessity for the precise calibration of cap-and-trade schemes and the pace of CCS transit adoption to ensure alignment with net-zero targets.