Ochratoxin A promotes chronic enteritis and early colorectal cancer progression by targeting Rinck signaling.

BACKGROUND: Mycotoxins, such as aflatoxin and ochratoxin A (OTA), are found at measurable levels in many staple foods; the health implications of long-term exposure of such toxins are poorly understood. Increasing evidence has confirmed the important role of OTA in upregulation of oxidative stress- and inflammatory response-induced tissue injury. However, it remains unknown whether ochratoxin A can promote chronic colitis and its associated colon cancer (CRC) development, and potential molecular mechanism. Additionally, RING finger-interacting protein with C kinase (RINCK) is a ubiquitin ligase and mediates immune response. Unfortunately, the potential molecular function of RINCK on regulation of colitis is still largely unknown. PURPOSE: This study aims to provide mechanistic evidence that the role of RINCK in colitis and early colorectal cancer progression in response to OTA treatment via targeting nuclear factor erythroid 2-related factor 2 (NRF2). METHODS: The Cancer Genome Atlas (TCGA) database, GEO database, human subjects with CC phenotype and CC cell lines were used in this work. Pathological links between OTA, RINCK and treatment of CC are revealed through comprehensive means such as biological information analysis, clinical experiments, RNA-seq, and verification experiments. RESULTS: In this study, under oxidative stress in setting of colitis, we first identified RINCK as a key regulatory factor and a novel endogenous suppressor of nuclear factor erythroid 2-related factor 2 (NRF2), and we also confirm that RINCK is a NRF2 partner protein that catalyses its ubiquitination and degradation in intestinal epithelial cells (IECs). Notably, in vivo study, pathological phenotypes triggered by OTA pretreatment, accompanied by post-treatment of dextran sulfate sodium (DSS)-induced colitis was significantly mitigated by IEC-specific deficiency of Rinck, IEC-Rinck(KO) and adenovirus-associated virus (AAV)-triggered suppression of Rinck in rodent model, and lentivirus (LV)-mediated downregulation of Rinck (LV-shRinck) in rabbit model, as determined by decreased endogenous reactive oxygen species (ROS) production, pro-inflammatory cytokines contents, improved body weights, reduced survival rates, restored colon length, assuasive DAI and histological scores. Inversely, transgenic mice by IEC-specific Rinck overexpression, IEC-Rinck(OE) accelerated colitis in acute or chronic colitis rodent models and in vitro experiments. Moreover, we found that OTA pretreatment-promoted azoxymethane (AOM)/DSS-induced colitis-associated early colorectal cancer (CRC) was also dramatically reduced by IEC-Rinck(KO), indicated by the decreased tumor number and corresponding KI-67 levels. Clinical samples analysis revealed that RINCK levels were greatly increased in tumor tissues of patients with CRC phenotypes. In parallel, RINCK deletion remarkably retarded the proliferation of colon cancer and tumor growth in vitro and in vivo, respectively. Mechanistically, in response to onset of colitis, RINCK directly interacts with NRF2 and promotes ubiquitin-proteasome degradation via increasing K48-linkage ubiquitin chain, thus leads in suppression of NRF2 nuclear translocation and its downstream cascade inactivation, which retards antioxidant defense. CONCLUSION: The findings suggested that oral sub-chronic exposure of OTA significantly facilitates DSS-induced colitis and colitis-associated CRC development. These results further elucidated the potential role of RINCK in colitis progression by mediating NRF2 degradation, and could be considered as a therapeutic target for the treatment of such disease.

Qingre Qushi formula suppresses atopic dermatitis via a multi-target mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Our previous studies have shown that the Qingre Qushi (QRQS) formula can treat atopic dermatitis (AD), and its possible mechanism is related to the regulation of the IL-33/ST2 signaling pathway. However, the molecular mechanism of AD is complex, and various AD subtypes respond better to therapies aimed at distinct targets. AIM OF THE STUDY: This study aimed to investigate the multi-target mechanism of QRQS using experimental and network pharmacology studies. MATERIALS AND METHODS: Flaky tail (FT) mice were treated with different concentrations of QRQS and cetirizine. The dermatitis score, scratching frequency, and histological evaluation were normatively evaluated. The levels of IgE and IgG1 in serum were tested using ELISAs. Using ELISA and RT-PCR, the expression of associated cytokines was determined. IL-17A-stimulated HaCaT cells were treated with QRQS to assess mRNA and protein expression. To elucidate the mechanism, a network pharmacology analysis based on active components derived from UPLC was conducted. Through molecular docking, we evaluated the binding affinity between the active constituents of QRQS and potential targets. RESULTS: Using UPLC, 177 active ingredients in QRQS were identified. Network pharmacology analysis showed that the anti-AD effect of the active ingredients was related to the IL-17 signaling pathway and its related targets. FT mice are characterized by Th17-dominated immune disorders. QRQS ameliorated AD-like symptoms and decreased dermatitis scores and scratching frequencies. After QRQS treatment, IL-17A expression was inhibited and IL-17 pathway-associated cytokines were downregulated. Along with changes in Th17-differentiation, QRQS suppressed the expression of IL-4, IL-13, and TNF-α. QRQS also decreased the expression of IL-6, IL-8, and COX-2 in HaCaT cells exposed to IL-17A. The anti-AD active doses are 3.86 g/kg/day in vivo and 100 µg/mL in vitro. CONCLUSION: QRQS has a multi-target immunoregulatory effect on AD and can improve the Th17-dominated inflammatory response by regulating the IL-17A signaling pathway. Quercetin, genistein, luteolin, and kaempferol are potential active ingredients.

The apple lipoxygenase MdLOX3 positively regulates zinc tolerance.

Various abiotic stresses, especially heavy metals near factories around the world, limit plant growth and productivity worldwide. Zinc is a light gray transition metal, and excessive zinc will inactivate enzymes in the soil, weaken the biological function of microorganisms, and enter the food chain through enrichment, thus affecting human health. Lipoxygenase (LOX) can catalyze the production of fatty acid derivatives from phenolic triglycerides in plants and is an important pathway of fatty acid oxidation in plants, which usually begins under unfavorable conditions, especially under biotic and abiotic stresses. Lipoxygenase can be divided into 9-LOX and 13-LOX. MdLOX3 is a homolog of AtLOX3 and has been identified in apples (housefly apples). MdLOX3 has a typical conserved lipoxygenase domain, and promoter analysis shows that it contains multiple stress response elements. In addition, different abiotic stresses and hormonal treatments induced the MdLOX3 response. In order to explore the inherent anti-heavy metal mechanism of MdLOX3, this study verified the properties of MdLOX3 based on genetic analysis and overexpression experiments, including plant taproots length, plant fresh weight, chlorophyll, anthocyanins, MDA, relative electrical conductivity, hydrogen peroxide and superoxide anion, NBT\DAB staining, etc. In the experiment, overexpression of MdLOX3 in apple callus and Arabidopsis effectively enhanced the tolerance to zinc stress by improving the ability to clear ROS. Meanwhile, tomato materials with overexpression of ectopia grew better under excessive zinc ion stress. These results indicated that MdLOX3 had a good tolerance to heavy metal zinc. Homologous mutants are more sensitive to zinc, which proves that MdLOX3 plays an important positive role in zinc stressed apples, which broadens the range of action of LOX3 in different plants.

A systematic review of traditional uses, phytochemistry, pharmacology and toxicity of Epimedium koreanum Nakai.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium koreanum Nakai (E. koreanum), a member of the genus Epimedium in the family Berberidaceae, is a well-known and well-liked traditional herb used as a "kidney tonic". For thousands of years, it has been utilized for renal yang deficiency, impotence, spermatorrhea, impotence, weakness of tendons and bones, rheumatic paralysis and discomfort, numbness, and constriction. AIM OF THE STUDY: The paper aims to comprehensively in-depth, and methodically review the most recent research on the traditional uses, phytochemistry, pharmacology, and toxicity of E. koreanum. MATERIALS AND METHODS: Scientific databases including Web of Science, PubMed, Google Scholar, Elsevier, Springer, ScienceDirect, Baidu Scholar, and CNKI and medicine books in China were searched for relevant information on E. koreanum. RESULTS: In traditional uses, E. koreanum is frequently used to treat various diseases like erectile dysfunction, infertility, rheumatoid arthritis, osteoporosis, asthma, kidney-yang deficiency syndrome, etc. To date, more than 379 compounds have been discovered from various parts of E. koreanum, including flavonoids, lignans, organic acids, terpenoids, hydrocarbons, dihydrophenanthrene derivatives, alkaloids, and others. Research has revealed that the compounds and crude extracts have a wide range of pharmacological effects on the reproductive, cardiovascular, and nervous systems, as well as anti-osteoporosis, anti-tumor, antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective, and antiviral properties. Besides, the crude extracts show potential hepatotoxicity. CONCLUSION: Based on recent domestic and international research investigations, E. koreanum contains a wealth of chemical components with pronounced pharmacological activities. Its traditional uses are numerous, and the majority of these traditional uses have been supported by contemporary pharmacological investigations. Crude extracts, on the other hand, can result in hepatotoxicity. Therefore, additional in vivo and in vitro experimental research on the pharmacology and toxicology of E. koreanum are required in the future to assess its safety and efficacy. This will give a firmer scientific foundation for its safe application and the development of new drugs in the future.

Dialdehyde starch-enclosed silver nanoparticles substrate with controlled-release "hotspots" for ultrasensitive SERS detection of thiabendazole.

Pesticide residues have long been a major concern for food safety. In this study, a dialdehyde starch-encapsulated silver nanoparticles composite with controlled-release "hotspots" was developed as a surface-enhanced Raman scattering (SERS) substrate. At room temperature, most of the Ag NPs were encapsulated in dialdehyde starch, which is beneficial for improving stability, and when heated to the gelatinization point, Ag NPs are completely released and abundant hot spots are formed. We demonstrated sensitive detection of thiabendazole (TBZ) in or on the surface of an apple by means of two ways, i.e., detecting the analyte in solution after pretreatment and in-situ detecting the analyte by using a flexible paper-based substrate. The results showed that the detection limits of TBZ by the two ways were 0.052 ppm and 0.051 ppm respectively, and the recoveries of TBZ range from 96.80 % to 105.46 %. Overall, this SERS substrate shows great potential for pesticide residue detection in food.

The 2022 report of synergetic roadmap on carbon neutrality and clean air for China: Accelerating transition in key sectors.

China is now confronting the intertwined challenges of air pollution and climate change. Given the high synergies between air pollution abatement and climate change mitigation, the Chinese government is actively promoting synergetic control of these two issues. The Synergetic Roadmap project was launched in 2021 to track and analyze the progress of synergetic control in China by developing and monitoring key indicators. The Synergetic Roadmap 2022 report is the first annual update, featuring 20 indicators across five aspects: synergetic governance system and practices, progress in structural transition, air pollution and associated weather-climate interactions, sources, sinks, and mitigation pathway of atmospheric composition, and health impacts and benefits of coordinated control. Compared to the comprehensive review presented in the 2021 report, the Synergetic Roadmap 2022 report places particular emphasis on progress in 2021 with highlights on actions in key sectors and the relevant milestones. These milestones include the proportion of non-fossil power generation capacity surpassing coal-fired capacity for the first time, a decline in the production of crude steel and cement after years of growth, and the surging penetration of electric vehicles. Additionally, in 2022, China issued the first national policy that synergizes abatements of pollution and carbon emissions, marking a new era for China's pollution-carbon co-control. These changes highlight China's efforts to reshape its energy, economic, and transportation structures to meet the demand for synergetic control and sustainable development. Consequently, the country has witnessed a slowdown in carbon emission growth, improved air quality, and increased health benefits in recent years.

CARD9 deficiency aggravated nonalcoholic steatohepatitis in mice through increasing inflammatory response.

Nonalcoholic steatohepatitis (NASH), a subtype of nonalcoholic fatty liver disease (NAFLD), is the leading cause of liver-related morbidity worldwide. Caspase recruitment domain family member 9 (CARD9), a myeloid cell-specific signaling protein, belongs to the CARD protein family. However, its role in NASH is unknown. Therefore, this study aimed to investigate the role of CARD9 in the development of NASH. NASH models were established using CARD9-knockout and wild-type mice. They were either fed a methionine/choline deficient (MCD) diet for 6 weeks or a high-fat high-cholesterol (HFHC) diet for 16 weeks. Liver fibrosis model was also developed using CCl4. CARD9 deficiency accelerated steatohepatitis development in MCD or HFHC diet-fed mice, accompanied by an upregulation of fibrosis, adipogenesis, and proinflammatory genes. CARD9 deficiency was found to exacerbate CCl4-induced liver fibrosis. In vitro studies demonstrated that CARD9 deficiency induced the expression of S100a8/a9 through Toll-like receptor in Kupffer cells treated with palmitate. This led to an increased expression of proinflammatory, fibrosis, and lipid metabolism-related genes in NASH progression. These results highlight the role of CARD9 in the development of NASH and provide new insights into the therapeutic strategies for NASH.

Transient absorption study on fluorescence quenching of InP/ZnS quantum dots by MXene.

Fluorescence quenching due to energy transfer from InP/ZnS quantum dots (QDs) to Ti3C2Tx MXene materials was investigated by the transient absorption spectroscopy. During the fluorescence quenching, the photo-induced absorption feature in the transient spectrum was blue-shifted due to the higher photon energy required for the upward transition. The lifetime of stimulated emission was gradually extended from 0.86 µs to 2.28 µs with increasing Ti3C2Tx MXene. The fluorescence quenching of QDs can be quantitatively characterized by analyzing the lifetime of the stimulated emission feature in the transient absorption spectrum, which was used as a Ti3C2Tx MXene detection with the sensitivity of 6.63 mL/mg. The results of this study provide the basis for the design of optical sensors.

Preclinical Evidence for the Effectiveness of Mesenchymal Stromal Cells for Diabetic Cardiomyopathy: A Systematic Review and Meta-analysis.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus that endangers human health. DCM results in cardiac dysfunction, which eventually progresses to heart failure. Mesenchymal stromal cells (MSCs), a type of multipotent stem cell, have shown promising therapeutic effects in various cardiovascular diseases and diabetic complications in preclinical studies due to their immunomodulatory and regenerative abilities. However, there is still a lack of evidence to summarize the effectiveness of MSCs in the treatment of DCM. Therefore, a meta-analysis and systematic review are warranted to evaluate the therapeutic potential of MSCs for DCM in preclinical studies. METHODS: A comprehensive literature search in English or Chinese was conducted in PubMed, EMBASE, web of Science, Cochrane Library, and China National Knowledge Internet from inception to June 30, 2022. The summarized outcomes included echocardiography, morphology, and pathology. Data were independently extracted and analyzed by two authors. The software we adopted was Review Manager5.4.1. This systematic review was written in compliance with PRISMA 2020 and the review protocol was registered on PROSPERO, registration no. CRD42022350032. RESULTS: We included 20 studies in our meta-analysis to examine the efficacy of MSCs in the treatment of DCM. The MSC-treated group showed a statistically significant effect on left ventricular ejection fraction (WMD=12.61, 95% CI 4.32 to 20.90, P=0.003) and short axis fractional shortening (WMD=6.84, 95% CI 4.09 to 9.59, P < 0.00001). The overall effects on the ratio of early to late diastolic mitral annular velocity, left ventricular end-diastolic pressure, maximum positive pressure development, maximum negative pressure development, left ventricular relaxation time constant, heart weight to body weight ratio, fibrosis area, and arteriole density were analyzed, suggesting that MSCs represent an effective therapy for the treatment of DCM. CONCLUSION: Our results suggest a therapeutic role for MSCs in the treatment of DCM, and these results provide support for the use of MSCs in clinical trials of patients with DCM.

In situ synthesis of self-supporting conductive CuCo-based bimetal organic framework for sensitive nonenzymatic glucose sensing in serum and beverage.

Most MOFs are associated with the inherent defect of low conductivity, limiting their further application in electrochemical sensing. Herein, a self-supporting conductive CuCo-based bimetal organic framework with HHTP as the organic ligand was in situ synthesized on carbon cloth via a one-step hydrothermal method, namely CuCo-MOF/CC. Benefiting from the advantages of electrical conductivity and bimetallic synergies, CuCo-MOF/CC exhibited remarkable electrocatalytic performance toward glucose. Consequently, the prepared sensor demonstrated an outstanding sensitivity of 9317 µA mM-1 cm-2, a wide range of 0.25-2374.5 µM, a low determination limit (0.27 µM), and a rapid response time (1.6 s). The reproducibility, stability, and selectivity were also proved to be satisfactory. Furthermore, the remarkable feasibility of proposed sensor was confirmed in serum and beverages. With the convenience of the one-step hydrothermal method and portability of self-supporting electrode, CuCo-MOF/CC has emerged as a promising candidate for commercial glucose sensors.

Residential greenspace and blood lipids in an essential hypertension population: Mediation through PM2.5 and chemical constituents.

Fine particulate matter (PM2.5) adversely affects blood lipids, while residential greenspace exposure may improve blood lipids levels. However, the association between exposure to residential greenspace and blood lipids has not been adequately studied, especially in vulnerable populations (e.g. people with essential hypertension). This study aimed to assess the association between residential greenspace exposure and blood lipids, and to clarify whether PM2.5 and chemical constituents was mediator of it. We used a period (May 2010 to December 2011) from the Chinese national hypertension project. The residential greenspace was estimated using satellite-derived normalized difference vegetation index (NDVI). The generalized additive mixed model (GAMM) was used to assess the association between exposure to residential greenspace and blood lipids, and the mediation model was used to examine whether there was a mediating effect of PM2.5 and chemical constituents on that association. The exposure to residential greenspace was negatively associated with the decreased risk of dyslipidemia, especially short-term exposure. For example, the odd ratioshort-term for dyslipidemia was 0.915 (95% CI：0.880 to 0.950). This association was strengthened by physical activity and participants living in the North. PM2.5 and chemical constituents were important mediators in this association, with the proportion of mediators ranging from -5.02% to 26.33%. The association between exposure to residential greenspace and dyslipidemia in this essential hypertensive population, especially participants living in the North and doing daily physical activity, was mediated by PM2.5 and chemical constituents.

Green synthesis and anti-tumor efficacy via inducing pyroptosis of novel 1H-benzo[e]indole-2(3H)-one spirocyclic derivatives.

Pyroptosis induction is anticipated to be a new approach to developing anti-tumor medications. A novel class of spirocyclic compounds was designed by hybridization of 1H-Benzo[e]indole-2(3H)-one with 1,4-dihydroquinoline and synthesized through a new green "one-pot" synthesis method using 10 wt% SDS/H2O as a solvent to screen novel tumor cell pyroptosis inducers. The anti-tumor activity of all compounds in vitro was determined by the MTT method, and a fraction of the compounds showed good cell growth inhibitory activity. The quantitative structure-activity relationship models of the compounds were established by artificial intelligence random forest algorithm (R2 = 0.9656 and 0.9747). The ideal compound A9 could, in a concentration-dependent manner, prevent ovarian cancer cells from forming colonies, migrating, and invading. Furthermore, A9 could significantly induce pyroptosis and upregulate the expression of pyroptosis-related proteins GSDME-N, in addition to inducing apoptosis and mediating the expression of apoptosis-related proteins in ovarian cancer cells. A9 (5 mg/kg) significantly reduced tumor volume and weight of ovarian cancer in vivo, decreased caspase-3 expression in tumor tissue, and induced the production of GSDME-N. This study provides a green and efficient atom-economic synthesis method for 1H-Benzo[e]indole-2(3H)-one spirocyclic derivatives and a promising pyroptosis inducer with anti-tumor activity.

Modulation of pea protein isolate nanoparticles by interaction with OSA-corn starch: Enhancing the stability of the constructed Pickering emulsions.

The impact of particle concentration (0.5-2.5%) on the stability of Pickering emulsions was investigated in this work. Pickering emulsion was prepared using pea protein isolate (PPI)/octenyl succinic anhydrate corn starch (OSA-CS) composite nanoparticles (PPI/OSA-CS) as stabilizers. PPI/OSA-CS was prepared with pH adjustment and ultrasonic treatment, and the particle size was 100.05 ± 0.46 nm. The formation of PPI/OSA-CS through hydrophobic interaction and hydrogen bond was confirmed by Fourier transform infrared spectroscopy, intrinsic fluorescence spectroscopy and dissociation analysis. The results indicated that the emulsion stabilized with composite nanoparticles at 1.5% particle concentration had smaller particle size and better stability than at other concentrations. This could be attributed to the presence of sufficient composite nanoparticles wrapped around the surface of oil droplets. At high temperature (100 °C) and high ionic strength (500 mM), the emulsion remained stable. These results provide a potential method for preparing a novel and stable Pickering emulsion, which could have important applications in various fields.

Hydrangea-like MoS2/carbon dots anode for high-performance sodium storage.

Owing to their quantum size, edge effects, and abundant surface functional groups, carbon dots (CDs) have attracted significant attention. In this study, chitin-derived carbon dots (CT-CDs) were prepared and used to synthesize MoS2/CT-CDs. The abundant functional groups on the surface of the CT-CDs facilitated the orderly arrangement of MoS2 nanosheets, resulting in a hydrangea-like structure. When employed as the anode in a sodium-ion battery, MoS2/CT-CDs exhibited an excellent initial charging capacity of 492.6 mAh·g-1 at 0.1 A·g-1 with an initial Coulomb efficiency of 74.4%. Even after 100 cycles, the reversible capacity remained at 338.9 mAh·g-1. Furthermore, the reversible capacity of MoS2/CT-CDs remained at 219.9 mAh·g-1 after 260 cycles when subjected to 1 A·g-1. The hydrangea-like structure of MoS2/CT-CDs, with expanded layer spacing, enhances ion/electron transport while providing additional active sites for sodium-ion storage, resulting in exceptional cycling and rate performances.

EEG microstate analysis reveals large-scale brain network alterations in depressed adolescents with suicidal ideation.

BACKGROUND: Accumulating evidence showed abnormalities in brain network connectivity in depressive individuals with suicidal ideation (SI). We aimed to investigate the large-scale brain network dynamics in adolescents with SI and major depressive disorder (MDD). METHODS: We recruited 47 first-episode drug-naïve adolescents with MDD and SI, 26 depressed adolescents without SI (noSI), and 26 age-matched healthy controls (HC). The Columbia Suicidal Ideation Severity Scale (C-SSRS) was utilized to assess suicide ideation. We acquired 64-channel resting-state EEG recordings from all subjects and used microstate analysis to investigate the large-scale brain network dynamics. RESULTS: We observed a significant reduction in the occurrence and coverage of microstate B within the SI group when contrasted with the noSI group. Conversely, there was a significant increase in the occurrence and coverage of microstate A in the SI group as compared to the HC group. Additionally, we observed heightened transition probabilities from microstates D and C to microstate A in the SI group; meanwhile, transitions from microstate D to B were more prevalent in the noSI group. Furthermore, the noSI group exhibited a significant decline in the transition probabilities from microstate D to microstate C. LIMITATIONS: The cross-sectional nature limits the capacity to determine whether microstate dynamics have prognostic significance for SI. CONCLUSION: We provided evidence that depressed adolescents with SI have a distinct pattern in microstate dynamics compared to those without SI. These findings suggest that microstate dynamics might serve as a potential neurobiomarker for identifying SI in depressed adolescents.

Escitalopram population pharmacokinetics and remedial strategies based on CYP2C19 phenotype.

BACKGROUND AND PURPOSE: CYP2C19 is a key factor influencing escitalopram (SCIT) exposure. However, different studies reported various results. This study aims to develop a population pharmacokinetic (popPK) model characterizes the disposition of SCIT in the Chinese population. Based on the popPK model, the study simulates non-adherence scenarios and proposes remedial strategies to facilitate SCIT personalized therapy. METHODS: Nonlinear mixed-effects modeling using data from two Chinese bioequivalence studies was employed. Monte-Carlo simulation was used to explore non-adherence scenarios and propose remedial strategies based on the proportion of time within the therapeutic window. RESULTS: Results showed that a one-compartment model with transit absorption and linear elimination described the data well, CYP2C19 phenotypes and weight were identified as significant covariates impacting SCIT exposure. Patients were recommended to take the entire delayed dose immediately if the delay time was no >12 h, followed by the regular regimen at the next scheduled time. When there is one or two doses missed, taking a double dose immediately was recommended to the CYP2C19 intermediate and extensive population, and a 1.5-fold dose was recommended to the CYP2C19 poor metabolizers with the consideration of adverse effects. LIMITATION: All samples were derived from the homogenized Chinese healthy population for model building, which may pose certain constraints on the ability to identify significant covariates, such as age. CONCLUSION: The study highlights the importance of considering patient characteristics for personalized medication and offers a unique perspective on utilizing the popPK repository in precision dosing.

A ratiometric electrochemical sensing strategy based on the self-assembly of Co NC/CNT and methylene blue for effective detection of the food additive tert-butylhydroquinone.

It is crucial to achieve accurate and rapid detection of tert-butylhydroquinone (TBHQ) in the field of food safety, for the excessive addition of TBHQ in food is harmful to human health and evil to the environment and aquatic life. Therefore, researchers have done a lot of work on signal amplification through nanomaterials to achieve TBHQ detection, but the conventional single-signal detection strategy results in limited accuracy. In this work, an innovative and facile ratiometric electrochemical sensor for TBHQ detection was built based on advanced nanomaterial complexes carbon nanotube-encapsulated Co/nitrogen-doped carbon (Co NC/CNT) and selected internal reference signal methylene blue (MB) enhancing the accuracy by offering effective self-calibration. A linear relationship between the net peak current ratio between TBHQ and MB (ΔI (TBHQ)/ΔI (MB)) and the TBHQ concentration was obtained under the optimal experimental conditions, with two linear ranges of 0.1-20 µM and 20-100 µM and a limit of detection (LOD) of 0.054 µM (S/N = 3). Benefiting from the synergistic effects between Co NC and CNT and the ratiometric sensing strategy, the as-designed sensor for TBHQ detection showcased excellent selectivity, repeatability, reproducibility, stability, and satisfactory applicability in real edible oil samples.

Natural terpene-based derivatives to control postharvest sclerotinia rot and the involved potential mechanism.

In an effort to develop novel postharvest preservatives of satisfactory environmental compatibility from natural monoterpene, a series of terpene-based derivatives containing oxime ester were designed and prepared. In this research, the inhibitory effect of target compounds against S. sclerotiorum were evaluated though in vitro and in vivo tests. It was investigated that most compounds exhibited promising antifungal activity, especially compound 4k with EC50 value of 3.02 µg/mL, which was significantly superior to commercial fungicide trifloxystrobin. Notably, compound 4k improved the physicochemical quality of carrot including weight loss, contents of titratable acidity, ascorbic acid, carotenoid, malondialdehyde, and enzymes activities, ensuring post-harvest preservation. Simultaneously, the mycelial morphology, ultrastructure, cell wall permeability, and defense/respiration-related enzymes of S. sclerotiorum were destructed. The preliminary toxicity evaluation of target compounds indicated that the prepared target compounds possessed safety and low toxicity. Additionally, the essential chemical features for activity and interaction mode between molecule and cytochrome bc1 complex were inquired by computer-aid technology. The study provided meaningful insight into formulation of natural terpene-based fresh-keeping agent to resist postharvest decay infected by S. sclerotiorum.

Field migration of veterinary antibiotics via surface runoff from chicken-raising orchard in responding to natural rainfalls.

Knowledge on runoff transport of manure-sourced antibiotics from farmland soil to aquatic environment is limited due to complexity of hydrological regime and pathways. This study monitored natural rainfalls in sloping orchard plots with free-range chickens, with an attempt to investigate the migration characteristics of typical antibiotics via surface runoff as well as the impact of manure presence. Results showed that rainstorms continuously carried away antibiotics in surface runoff and all target antibiotics including those with high affinities to soil were detected at the beginning of runoff production. Concentration of antibiotics was found to respond strongly to the instantaneous rainfall intensity, showing consistent fluctuations during rainfalls. Concentrations of sulfonamides and florfenicol were two orders of magnitude higher than that of tetracyclines and fluoroquinolones. Compared to the control without raising chickens, antibiotics migration was considerably increased with the increased runoff production due to soil surface changes caused by chicken activities. Additionally, dynamics of antibiotic concentration significantly correlated with variations of fluorescent DOM components. Chicken manure-derived DOM mainly contained tryptophan moiety, and laboratory fluorescence quenching test with 2D-COS analysis indicated that all antibiotics interacted more strongly and preferentially with tryptophan than humic-like species. Antibiotics bonded to manure DOM with an affinity corresponding to the significance level of their correlations. In this light, potential use of fluorescence indices based on the established correlations may provide a convenient tool for tracing runoff migration of antibiotics during rainfalls.

Saliva Analysis Based on Microfluidics: Focusing the Wide Spectrum of Target Analyte.

Saliva is one of the most critical human body fluids that can reflect the state of the human body. The detection of saliva is of great significance for disease diagnosis and health monitoring. Microfluidics, characterized by microscale size and high integration, is an ideal platform for the development of rapid and low-cost disease diagnostic techniques and devices. Microfluidic-based saliva testing methods have aroused considerable interest due to the increasing need for noninvasive testing and frequent or long-term testing. This review briefly described the significance of saliva analysis and generally classified the targets in saliva detection into pathogenic microorganisms, inorganic substances, and organic substances. By using this classification as a benchmark, the state-of-the-art research results on microfluidic detection of various substances in saliva were summarized. This work also put forward the challenges and future development directions of microfluidic detection methods for saliva.