In vitro inhalation bioaccessibility and health risk assessment of difenoconazole in the atmosphere.

BACKGROUND: Assessment of the risk of pesticide inhalation in populations around farmland is necessary because inhalation is one of the ways in which pesticides can risk human health. This study aimed to identify the inhalation risk of difenoconazole on humans by using dose-response and exposure assessments. RESULTS: In the field simulation application, respiratory exposure in populations around farmland ranged from 71 to 430 ng/m3 . Using response surface methodology, the maximum bioaccessibility of difenoconazole in three simulated lung fluids was 35.33% in Gamble's solution (GS), 34.12% in artificial lysosomal fluid (ALF), and 42.06% in simulated interstitial lung fluid (SLF). Taking the proliferation activity of the A549 cell model as the endpoint, the benchmark dose limit and benchmark dose of difenoconazole on A549 cells were 16.36 and 5.60 mg/kg, respectively. The margin of exposure to difenoconazole in GS, ALF and SLF were, respectively, 8.66 × 105 to 5.28 × 106 , 8.97 × 105 to 5.47 × 106 and 7.28 × 105 to 4.44 × 106 . CONCLUSION: The risk assessment results indicate that under all circumstances, applying difenoconazole is safe for populations around farmland. However, a fan-shaped nozzle, suspension concentrate and greater inhalation height increase the risk of inhalation. © 2023 Society of Chemical Industry.

Standardization of Panax ginseng: Current Status of Global Trade, Demands, and Development.

Panax ginseng, as a kind of rare and valuable Chinese materia medica with the largest global trade volume, has been widely applied in many fields, such as medicine, food, health care, and production of daily chemical products. It is widely used in Asia, Europe, and America. However, its global trade and standardization present different features and an uneven development in different countries or regions. As the main country for its production and consumption, Panax ginseng in China is characterized by its large cultivation area and high total yield and is mainly sold as a raw material or primary processed product. By contrast, Panax ginseng produced in South Korea is mainly sold in manufactured products. Besides, European countries, as another consumption market of Panax ginseng, pay more attention to the research and development of its products. Although Panax ginseng has been widely recorded in various national pharmacopoeias and regional standards, the current standards of Panax ginseng differ in quantity, composition, and distribution, and the existing standards cannot be enough to meet the demands of its global trade. Based on the above issues, we systemically summarized and analyzed the status and features of Panax ginseng standardization and put forward suggestions on the development needs of international standardization of Panax ginseng to guarantee its quality and safety, regulate the order of its global trade, and resolve trade disputes, thereby promoting the high-quality development of the Panax ginseng industry.

Characterization and Comparison Analysis of WHO Monographs on Selected Medicinal Plants and ISO Standards of Chinese Materia Medica.

Medicinal plants or Chinese materia medica (CMM) are now attracting worldwide attention as they have increasingly prominent advantages over chemical drugs in disease treatment and healthcare. Since the 1990s, World Health Organization (WHO) and International Organization for Standardization established the Technical Committee of Traditional Chinese Medicine (ISO/TC 249) have carried out the development of quality standards on medicinal plants or CMMs respectively, and a considerable number of monographs and international standards have been published. Since the two international organizations adhere to different principles, the standards they develop naturally have different emphasis. Driven by market demand and international trade, ISO mainly takes quality, efficacy and safety into consideration when developing standards, while WHO pays more attention to clinical practice, quality control and medication guidance. Up to now, there is a lack of comparative analysis on the records, background, principles, basic content, and main requirements of quality standards on medicinal plants or CMMs respectively published by WHO and ISO. Therefore, based on international standards of CMM developed by ISO/TC 249 platform and WHO Monographs on Selected Medicinal Plants, this paper systematically compares the purposes, selected principles, standard-developing process, basic content, and main quality requirements to summarize their similarities and differences, and find their merits, aiming to serve as a reference to the development of international standards for CMMs that helps them go global.

Risk factors for the long-term prognosis and recurrence of HIV-negative cytomegalovirus retinitis in North China.

AIM: To demonstrate the clinical features, the risk factors, the visual prognosis and the recurrence of cytomegalovirus (CMV) retinitis (CMVR) in HIV-negative patients. METHODS: HIV-negative patients with CMVR were involved in this study. Best corrected visual acuity (BCVA), intraocular pressure (IOP), CMV-DNA load in aqueous and/or serum samples, treatment, follow-up time, recurrence and complications were recorded. Ocular characteristics were evaluated by fundus photographs. Association between ocular factors and visual prognosis were analyzed by regression analysis. RESULTS: Twenty-five eyes of 16 patients were included. All 25 eyes underwent intravitreal injections of anti-viral agents. The mean logMAR BCVA improved from 0.94±0.98 (0.98-0.78) initially to 0.77±0.73 (0.82-0.68) at last visit, but not significantly. After antiviral treatment, the aqueous CMV DNA load significantly reduced to (3.42±1.47)×102 copies/mL (P=0.001), compared with (2.51±3.11)×105 copies/mL at baseline. Macular involvement (R 2=0.475, P=0.049) and initial visual acuity (R 2=0.475, P=0.017) were significantly associated with the poor visual prognosis (BCVA<20/400). The extent of retinal lesions (R 2=0.064, P=0.04) was significant associated with the risk of recurrence of CMVR. CONCLUSION: Intravitreal injection of anti-viral agents offers a safe and effective treatment for CMVR. Macular involvement and initial visual acuity significantly associate with visual prognosis. The extent of retinal lesions is significantly associated with the recurrence of CMVR. These ocular factors can be used as predictive risk factors for long term visual prognosis in HIV-negative CMVR patients.

Gut microbiota-involved metabolism and intestinal absorption mechanisms in decreasing bioaccessibility of triadimefon in strawberry and grape.

Gut microbiota-involved metabolism and intestinal absorption affecting bioaccessibility of triadimefon in strawberry and grape were investigated for the first time by coupling the in vitro digestion model with the Caco-2 cell model. Results showed that the gut microbiota decreased the bioaccessibility of triadimefon in strawberry by 31.00% but failed in grape, probably due to a negative modulation of the colon bacterial activity by dietary components in grapes. A strain of triadimefon-degrading bacteria, Stenotrophomonas maltophilia, was isolated from the gut microbiota and its degradation products were profiled. This study also clarified a significant reduction in transepithelial transport (up to 32.81%) of triadimefon as a result of the barrier effect of gut microbiota. These findings provide new insights on the function of the gut microbiota in pesticide bioaccessibility and highlight the importance of including gut microbiota in pesticide residue risk assessments.

Robust Electrodes for Flexible Energy Storage Devices Based on Bimetallic Encapsulated Core-Multishell Structures.

Developing flexible electrodes with high active materials loading and excellent mechanical stability is of importance to flexible electronics, yet remains challenging. Herein, robust flexible electrodes with an encapsulated core-multishell structure are developed via a spraying-hydrothermal process. The multilayer electrode possesses an architecture of substrate/reduced graphene oxide (rGO)/bimetallic complex/rGO/bimetallic complex/rGO from the inside to the outside, where the cellulosic fibers serve as the substrate, namely, the core; and the multiple layers of rGO and bimetallic complex, are used as active materials, namely, the shells. The inner two rGO interlayers function as the cement that chemically bind to two adjacent layers, while the two outer rGO layers encapsulate the inside structure effectively protecting the electrode from materials detachment or electrolyte corrosion. The electrodes with a unique core-multishell structure exhibit excellent cycle stability and exceptional temperature tolerance (-25 to 40 °C) for lithium and sodium storage. A combination of experimental and theoretical investigations are carried out to gain insights into the synergetic effects of cobalt-molybdenum-sulfide (CMS) materials (the bimetallic complex), which will provide guidance for future exploration of bimetallic sulfides. This strategy is further demonstrated in other substrates, showing general applicability and great potential in the development of flexible energy storage devices.

Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11ß-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11ß-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11ß-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 µmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2D; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D. Circulating 8 and M2D, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11ß-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.

Features and development trends in international standardization of Chinese materia medica in ISO/TC 249.

Chinese materia medica (CMM) is indispensable component of Traditional Chinese Medicine (TCM) therapy. With the widespread of TCM around the world, the quality control and safe use of CMM become a major concern. This paper introduces the role of ISO standards for industrial development and current development status of CMM standards in ISO/TC 249. Through the comparison of similarities and differences between CMM standards in ISO/TC 249 and pharmacopoeias of main stakeholders, this paper suggests strengthening standard formulation in the following areas to provide more appropriate documents to facilitate the international trade and promote the industrial development of CMM: (1) Develop standards to fill the blanks among the whole industry chain of CMM; (2) Develop standards for new forms of CMM and services; (3) Develop specification and grade standards for CMM with large quantity and high value.

Gut microbiota influence on oral bioaccessibility and intestinal transport of pesticides in Chaenomeles speciosa.

There is limited research focusing on the effects of human gut microbiota on the oral bioaccessibility and intestinal absorption of pesticide residues in food. In the present study, we use a modified setup of the Simulator of the Human Intestinal Microbial Ecosystem for the determination of pesticide residue bioaccessibility in Chaenomeles speciosa, and a Caco-2 cell model of human intestinal absorption. Results showed that gut microbiota played a dual role based their effects on contaminant release and metabolism in the bioaccessibility assay, and Lactobacillus plantarum was one of key bacterial species in the gut microbiota that influenced pesticide stability significantly. The addition of L. plantarum to the system reduced the relative amounts (by 11.40-86.51%) of six pesticides. The interaction between the food matrix and human gut microbiota led to different absorption rates, and the barrier effects increased with an increase in incubation time.

[Pharmacological effects of Huangqin Decoction prepared from roots of multi-originated peony on ulcerative colitis in mice:a comparative study].

Huangqin Decoction(HQD) is a classic prescription for treating dysentery in the Treatise on Cold Damage and now is mainly used for the treatment of ulcerative colitis(UC). Since there are no requirements on specific Paeonia species, both Paeoniae Radix Alba(white peony root, WPR) and Paeoniae Radix Rubra(red peony root, RPR) are clinically used in HQD now. Although the two types of peony roots are close in origin and similar in primary components, the medicinal properties and efficacies are different. Furthermore, the systematic comparative analysis on the efficacy differences in treating UC of HQD with the roots of multi-originated peony has been seldom reported. This study compared and evaluated the pharmacological effects of HQD prepared from the roots of multi-originated peony, including WPR, RPR-l(derived from P. lactiflora), and RPR-v(derived from P. veitchii) based on the mouse model of UC induced by dextran sodium sulfate(DSS) by animal behaviors, pathological section(colon), and cytokine expression(IL-1ß and IL-6), aiming to provide evidence for the identification of the original resource of peony root in HQD. The results indicated that all HQD samples prepared from WPR, RPR-l, and RPR-v could improve the symptoms of UC. Compared with the HQD-WPR, HQD-RPR-l and HQD-RPR-v were significantly different in weight loss, colon length, and disease activity index(DAI) score, but there was no significant difference between HQD-RPR-l and HQD-RPR-v. Moreover, HQD-RPR-v exhibited the most significant improvement in the pathological morphology of colonic tissue and mucosal defects. According to the previous comparative analysis of chemical profiling and content distribution of HQD prepared from the roots of multi-originated peony, RPR-v in HQD was potent in protecting against UC, which was presumedly attributed to a large number of monoterpene glycosides and galloyl glucoses. This study provided a scientific basis for the determination of peony root in HQD and its clinical medication.

In situ chemically encapsulated and controlled SnS2 nanocrystal composites for durable lithium/sodium-ion batteries.

SnS2 as the promising anode for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) still encounters the undesirable rate performance and cycle stability. Herein, a unique stable structure is developed, where the SnS2 nanocrystals (NCs) are sturdily encapsulated by carbon shells anchored on a reduced graphene oxide (rGO) via the one-pot solvothermal process. The well-controlled carbon shells provide the enduring protection for SnS2 NCs through C-S covalent bonds from the corrosion of electrolyte and pulverization of structure. Moreover, both experimental results and density functional theory (DFT) calculations demonstrate that the carbon protective shell effectively enhances the structure stability and conductivity of the resulting materials. Interestingly, the size of SnS2 NCs and the thickness of carbon shells are accurately controlled by regulating the content of glucose. Aided by the advanced electron/ion transfer kinetics and structure stability, the SnS2-based electrode exhibits desired lithium/sodium storage performance and unprecedented long-term cycling stability (capacity retention of 74.7% after 1000 cycles at 2 A g-1 for LIBs and 102% after 200 cycles at 500 mA g-1 for SIBs). This work develops a method for promoting the practical applications and large-scale production of SnS2 composites for energy storage devices.

Analysis on the current quality standards of Chinese materia Medica used in COVID-19 prevention and treatment.

PURPOSE: Traditional Chinese medicine (TCM) has fully engaged and played an essential role in the prevention and treatment of Coronavirus Disease 2019 (COVID-19). This study compares relevant standards on high-frequent Chinese Materia Medicia (CMM) used in this pandemic aiming at reaching a global consensus and ensuring the use of Chinese medicines safely. METHODS: 141 representative Chinese formulas and Chinese Patent Medicines from the National Protocol and the most of Provincial Protocols for controlling COVID-19 in China have been collected to statistical analyze the composition and characteristics of CMM. Among them, the domestic and international standards of 47 varieties with the frequency usage over 10 times were selected to compare their quality requirements in the mainstream pharmacopoeias and international standards. RESULTS: The quality requirements of used CMM for fighting COVID-19 on the terms of overall quality control, marker compounds, and safety indicators showed different patterns in these mainstream pharmacopoeias and international standards. The uniformed and scientific quality standards of CMM were urgently needed to promote global acceptation and trade. CONCLUSIONS: These findings will provide evidence for building unified quality and safety standards that can adapt to the characteristics of CMM and promote international trade, and also will be stated that it is of the highest priority for ISO/TC 249 to formulate high-quality standards that consolidate international consensus to ensure quality and safety of the urgently needed CMM.

[Simultaneous determination of four anthraquinones in Polygonum multiflorum by QAMS].

A simple, specific and selective quantitative analysis of multi-components by single marker(QAMS) method for simultaneous determination of anthraquinones and anthraquinone glycosides in Polygonum multiflorum was developed. Four main anthraquinones and its glycosides, emodin, emodin-8-O-ß-D-glucoside, physcion and physcion-8-O-ß-D-glucoside were selected as analytes to evaluate the quality of P. multiflorum. Emodin was used as the internal standard, and the relative correction factors(RCFs) between emodin and the other three anthraquinones were calculated. Comparison of the contents of the four components in 30 batches of P. multiflorum from different regions and 12 batches decoction pieces from different manufacturers by QAMS and external standard method(ESM) showed that there was no significant difference between QAMS and ESM for quantification of the four main components by using relative error results, and the QAMS method was accurate and reliable, and had a good repeatability. In addition, compared with the results calculated by the difference method between total anthraquinone and free anthraquinone in the content determination of P. multiflorum in Chinese Pharmacopoeia, the results of direct determination combined anthraquinone by QAMS were very close to that by measured the external standard method. Therefore, simultaneous quantification of four main anthraquinones by using QAMS is suitable to evaluate the quality of P. multiflorum. Then the optimized assay method of the combined anthraquinone contents showed simple and feasible, which could be replaced and improved the quantification method of the combined anthraquinone in the current Chinese Pharmacopeia.

Micro/Nanoengineered α-Fe2 O3 Nanoaggregate Conformably Enclosed by Ultrathin N-Doped Carbon Shell for Ultrastable Lithium Storage and Insight into Phase Evolution Mechanism.

The Fe-based transition metal oxides are promising anode candidates for lithium storage considering their high specific capacity, low cost, and environmental compatibility. However, the poor electron/ion conductivity and significant volume stress limit their cycle and rate performances. Furthermore, the phenomena of capacity rise and sudden decay for α-Fe2 O3 have appeared in most reports. Here, a uniform micro/nano α-Fe2 O3 nanoaggregate conformably enclosed in an ultrathin N-doped carbon network (denoted as M/N-α-Fe2 O3 @NC) is designed. The M/N porous balls combine the merits of secondary nanoparticles to shorten the Li+ transportation pathways as well as alleviating volume expansion, and primary microballs to stabilize the electrode/electrolyte interface. Furthermore, the ultrathin carbon shell favors fast electron transfer and protects the electrode from electrolyte corrosion. Therefore, the M/N-α-Fe2 O3 @NC electrode delivers an excellent reversible capacity of 901 mA h g-1 with capacity retention up to 94.0 % after 200 cycles at 0.2 A g-1 . Notably, the capacity rise does not happen during cycling. Moreover, the lithium storage mechanism is elucidated by ex situ XRD and HRTEM experiments. It is verified that the reversible phase transformation of α↔γ occurs during the first cycle, whereas only the α-Fe2 O3 phase is reversibly transformed during subsequent cycles. This study offers a simple and scalable strategy for the practical application of high-performance Fe2 O3 electrodes.

Analysis of the pesticide behavior in Chaenomelis speciosa and the role of digestive enzyme in vitro oral bioaccessibility.

Problems with pesticide residues in medicinal and edible plant have received great attention. The dietary exposure risk induced by presence of pesticide residues depends on its release from the food matrix, i.e., its bioaccessibility. The bioaccessibility of pesticide residues in human food is poorly understood and thus, we used in vitro digestive method to measure the bioaccessibility of six pesticides in Chaenomelis speciosa. Results showed that the lower and upper boundary bioaccessibility values of the six pesticides in C. speciosa was 4.26 and 86.52%, and the bioaccessibility varied for the pesticide types and digestion phase. The α-amylase and pancreatin play an important role in vitro bioaccessibility. Our findings suggest that risk assessment studies should be taken into account the pesticide metabolism, and that previous studies may have underestimated pesticide bioaccessibility.

Validation in China of a non-invasive salivary pepsin biomarker containing two unique human pepsin monoclonal antibodies to diagnose gastroesophageal reflux disease.

OBJECTIVES: Peptest is a new non-invasive reflux diagnostic test based on lateral flow technology that containing two highly specific human pepsin monoclonal antibodies for detecting pepsin, a biomarker for reflux disease. The primary aim of this multicenter clinical study was to validate the efficacy of Peptest in patients diagnosed with gastroesophageal reflux and healthy controls in China. METHODS: Patients with suspected gastroesophageal reflux underwent an endoscopy and were classified into non-erosive reflux disease and erosive esophagitis subgroups. A healthy control group was also recruited. All participants were given a reflux disease questionnaire-patients scoring greater than 12 and controls scoring zero. All participants provided a postprandial saliva sample and most patients gave an additional post-symptom sample for pepsin analysis. RESULTS: Altogether 1032 participants aged between 19 and 78 years were recruited. They consisted of 488 patients with non-erosive reflux disease, 221 with erosive esophagitis and 323 healthy controls. The number of postprandial and post-symptom samples analyzed totaled 1031 and 692, respectively. The results across all centers showed an overall pepsin-positive sensitivity of 85%, a specificity of 60%, a positive predictive value of 82%, a negative predictive value of 65% and a positive likelihood ratio of 2.12. CONCLUSION: The sensitivity of Peptest was high, but the specificity achieved in some centers was low, resulting overall in only a moderate specificity. Further diagnostic investigative studies are warranted.

Interactions of food matrix and dietary components on neonicotinoid bioaccessibility in raw fruit and vegetables.

Humans are frequently exposed to the residues of various neonicotinoids, highlighting the need to understand human exposure through oral ingestion of contaminated foods. In this study, the effects of different food matrices (tomato, cucumber, and carrot) and their interaction with dietary component additives, including proteins and dietary fiber, was investigated. The results showed that the presence of a food matrix had a significant effect on the bioaccessibility of neonicotinoids (imidacloprid, thiamethoxam, acetamiprid, and thiacloprid) in both the gastric and intestinal environments. Neonicotinoids in tomato presented relatively low bioaccessibility, indicating that the daily intake of the tomato can be regarded as being relatively safer. Moreover, the addition of protein or dietary fiber to fruit and vegetables had a marked influence on neonicotinoid bioaccessibility and the effects varied between the different matrices. In particular, the addition of 2.0% dietary fiber significantly reduced the bioaccessibility (18.38-67.91%). Therefore, we recommend that consuming an increased intake of dietary fiber could improve the safety of fruit and vegetables in daily life. The present results can support the identification of suitable food intake conditions for the significant reduction of pesticide residue levels.

Three-dimensional hierarchical Ni3Se2 nanorod array as binder/carbon-free electrode for high-areal-capacity Na storage.

A three-dimensional hierarchical Ni3Se2 nanorod array (NA) grown in situ on foam Ni is the first to act as a carbon/binder-free electrode of SIBs via a one-step reversible conversion reaction. By a special decomposition-fusion process, the morphology and composition of the NA are regulated to obtain ultrahigh areal capacity, which is three times greater than that reported for other metal selenides.

Abietane Diterpenoids from the Roots of Clerodendrum trichotomum and Their Nitric Oxide Inhibitory Activities.

Twelve new abietane diterpenoids (1-12) and 31 known analogues (13-43) were isolated from a medicinal Chinese herb, Clerodendrum trichotomum Thunberg. The absolute configurations of 1-3 were established on the basis of ECD and X-ray crystallography data, whereas that of 4 was elucidated by comparison of experimental and calculated ECD data. Eight diterpenoids, 15,16-dehydroteuvincenone G (1), trichotomin A (4), 2α-hydrocaryopincaolide F (7), villosin C (20), 15-dehydro-17-hydroxycyrtophyllone A (22), demethylcryptojaponol (38), 6ß-hydroxydemethylcryptojaponol (39), and trichotomone (43), exerted inhibitory effects against NO production with IC50 values of 5.6-16.1 µM. The structure-activity relationships of the isolated diterpenoids are also estimated.

Study of Factors Influencing the Bioaccessibility of Triazolone in Cherry Tomatoes Using a Static SHIME Model.

Estimating the influence of bioaccessibility of pesticide residues in fruits and vegetables on dietary exposure is a challenge for human health risk assessment. This study investigated the bioaccessibility of pesticide residues in cherry tomatoes and contributing factors (digestion time, pH, solid/liquid ratio, and dietary nutrition) using an in vitro test simulating the human gastrointestinal tract. pH had the largest effect on triazolone precipitation in the simulated gastric intestinal juice, which had a significant impact on the bioaccessibility. The bioaccessibility of triazolone in the intestinal stage was slightly higher than that in the stomach stage, owing to bile salts and pancreatic enzymes present in the intestinal juice. The bioaccessibility of triazolone did not change significantly with digestion time. In the gastric stage, there was a logarithmic relationship between the bioaccessibility and solid/liquid ratio (R² = 0.9941). The addition of oil significantly changed the bioaccessibility in the gastrointestinal stage. Protein and dietary fiber only affected bioaccessibility in the stomach stage. Dietary nutrition can reduce the release of pesticides from fruits and vegetables into the stomach, sharply reducing the bioaccessibility, and the dietary exposure of pesticide residues in fruits and vegetables can be properly evaluated.