Proximal Femoral Metastasis From Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Mimicking Osteosarcoma on Magnetic Resonance Imaging.

The aggressive nature of lung cancer is frequently accompanied by a high incidence of bone metastasis; however, proximal femoral metastasis from lung cancer is comparatively uncommon when compared to other malignancies. In this report, we present the case of a 53-year-old Asian male who presented with pain in the left thigh and back. Magnetic resonance imaging revealed severe bone destruction with involvement of adjacent soft tissue mass at the left thigh, exhibiting imaging findings that mimic osteosarcoma. Subsequent bone biopsy confirmed the diagnosis of epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma with bone metastasis. The patient achieved survival following administration of osimertinib and underwent surgery for femoral metastases without palliative surgery for lung cancer. Therefore, proximal femoral metastasis from EGFR-mutated lung adenocarcinoma should be considered as a differential diagnosis in patients suspected to have osteosarcoma. The imaging findings of proximal femoral metastasis from EGFR-mutated lung adenocarcinoma were presented, and their therapeutic management was discussed.

Mechanism of Lian Hua Qing Wen capsules regulates the inflammatory response caused by M1 macrophage based on cellular experiments and computer simulations.

PURPOSE: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. METHODS: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. RESULTS: Macrophages had 140690 gene targets, inflammatory response had 12192 gene targets, intersection gene targets were 11772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. CONCLUSION: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.

Effect of osmanthus hydrolat on the aroma quality and volatile components of osmanthus black tea.

Osmanthus fragrans is an evergreen shrub with a pleasant fragrance and a wide range of applications in many fields. The condensed hydrolat obtained during the drying process of its fresh flowers was collected in a low-temperature vacuum environment and its sensory evaluation and volatile components were studied. The main aroma compounds in Osmanthus fragrans were dihydro-ß-ionone, nonanal, ß-cyclocitral, ß-ionone, benzaldehyde, α-ionone, and 6-methyl-5-hepten-2-one, whose contents were used as the main evaluation criteria, and the hydrolats obtained under different scenting and drying times were compared. This process can effectively collect the aroma components in Osmanthus fragrans and the optimal drying conditions were 50 °C for 5 h. The hydrolat was used to provide the scent of osmanthus black tea, which had a fresher and mellower taste, while the fragrance of osmanthus was abundant. These results show that osmanthus hydrolat can be used to provide the scent of floral black tea. Chemical compounds studied in this article: (-)-Catechin (PubChem CID: 1203); (-)-epigallocatechin gallate (PubChem CID: 65064); (-)-epicatechin gallate (PubChem CID: 367141); (-)-epigallocatechin (PubChem CID: 72277); (-)-epicatechin (PubChem CID: 72276); (-)-gallocatechin gallate (PubChem CID: 199472); (-)-catechin gallate (PubChem CID: 6419835); (-)-gallocatechin (PubChem CID: 9882981).

Minisci-Type Dehydrogenative Coupling of C(sp3)-H and N-Heteroaromatics Enabled by Photoelectrochemical Hydrogen Atom Transfer.

Minisci-type dehydrogenative coupling of C(sp3)-H and N-heteroaromatics was performed with N-hydroxysuccinimide as a hydrogen atom transfer catalyst in a photoelectrochemical cell composed of a mesoporous BiVO4 photoanode and a Pt electrode. In the absence of metal catalysts and chemical oxidants, a range of N-heteroarenes (e.g., quinolines, isoquinolines, and quinoxaline) can undergo coupling with various C(sp3)-H partners to form the corresponding products in excellent yields.

[Spatio-temporal Differentiation of County Carbon Budget and Territorial Space Optimization Zoning Strategy in Gansu Province from the Perspective of Carbon Neutrality].

Under the background of comprehensively practicing the overall system concept of the "living community" in the new era, incorporating the carbon neutral development goal into the territorial spatial planning and construction and establishing the territorial spatial pattern and optimization strategy in line with the actual development of Gansu Province are of great significance for promoting the comprehensive green low-carbon transformation and high-quality development of regional economy and society. Taking counties in Gansu Province as an example, based on the perspective of carbon neutrality research, the land use carbon budget of 87 counties in Gansu Province in 2010, 2015, and 2021 was calculated and analyzed. GIS spatial analysis and social network analysis were used to further explore their spatial differentiation characteristics and the overall characteristics of the carbon emission spatial correlation network. At last, combined with the main function zoning, the low-carbon oriented land space optimization zoning was carried out, and differentiated low-carbon development strategies were proposed. The results were as follows： ① Carbon emissions in Gansu Province showed an upward trend, but the increase rate decreased, showing a spatial distribution of "high in the central and eastern part of the country, low in the southwest." Construction land was the main carbon source. The carbon uptake showed a spatial distribution of "high in the south and low in the north, high in the west and low in the east." Woodlands were the main carbon sinks. The net carbon emissions showed an increasing trend, and approximately 58.62% of the counties in the province were in a carbon imbalance situation. ② In 2021, the spatial network of county carbon emissions was closely related, showing a "core-edge" pattern. The Chenguan District and Qilihe District were in the core position of the network and received more correlation relationships in the network. The network contacts in Longzhong area were frequent, followed by the contacts in Longdongnan area. ③ Based on carbon emissions, carbon sequestration, and ecological carrying capacity coefficients and using the results of spatial correlation of social networks as role positions, the province was divided into four carbon-neutral sub-districts. At the same time, superimposed analysis of the main function zoning, the county area of the province was reconstructed into seven territorial space zones, and the differentiated regional low-carbon optimization development strategy was proposed for each zone.

Zirconaaziridine-Mediated Ni-Catalyzed Diastereoselective C(sp2)-Glycosylation.

In the realm of organic synthesis, the catalytic and stereoselective formation of C-glycosidic bonds is a pivotal process, bridging carbohydrates with aglycones. However, the inherent chirality of the saccharide scaffold often has a substantial impact on the stereoinduction imposed by a chiral ligand. In this study, we have established an unprecedented zirconaaziridine-mediated asymmetric nickel catalysis, enabling the diastereoselective coupling of bench-stable glycosyl phosphates with a range of (hetero)aromatic and glycal iodides as feasible coupling electrophiles. Our developed method showcases a broad scope and a high tolerance for various functional groups. More importantly, precise stereocontrol toward both anomeric configurations of forming C(sp2)-glycosides can be realized by simply utilizing the popular chiral bioxazoline (biOx) ligands in this reductive Ni catalysis. Regarding the operating mechanism, both experimental and computational studies support the occurrence of a redox transmetalation process, leading to the formation of a transient, bimetallic Ni-Zr species that acts as a potent and efficient single-electron reductant in the catalytic process.

Prevalence and Molecular Characterization of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in Cattle in Heilongjiang Province, Northeast China.

Crytosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are important diarrheal pathogens with a global distribution that threatens the health of humans and animals. Despite cattle being potential transmission hosts of these protozoans, the associated risks to public health have been neglected. In the present study, a total of 1155 cattle fecal samples were collected from 13 administrative regions of Heilongjiang Province. The prevalence of Cryptosporidium spp., G. duodenalis, and E. bieneusi were 5.5% (64/1155; 95% CI: 4.2-6.9), 3.8% (44/1155; 95% CI: 2.7-4.9), and 6.5% (75/1155; 95% CI: 5.1-7.9), respectively. Among these positive fecal samples, five Cryptosporidium species (C. andersoni, C. bovis, C. ryanae, C. parvum, and C. occultus), two G. duodenalis assemblages (E and A), and eight E. bieneusi genotypes (BEB4, BEB6, BEB8, J, I, CHS7, CHS8, and COS-I) were identified. Phylogenetic analysis showed that all eight genotypes of E. bieneusi identified in the present study belonged to group 2. It is worth noting that some species/genotypes of these intestinal protozoans are zoonotic, suggesting a risk of zoonotic disease transmission in endemic areas. The findings expanded our understanding of the genetic composition and zoonotic potential of Cryptosporidium spp., G. duodenalis, and E. bieneusi in cattle in Heilongjiang Province.

A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

[Research progress on nitrate isotope coupled multi-tracer tracing groundwater nitrate pollution]. / ç¡é ¸ç›åŒä½ç´ è€¦åˆå¤šç¤ºè¸ªå‰‚æº¯æºåœ°ä¸‹æ°´ç¡é ¸ç›æ±¡æŸ“ç ”ç©¶è¿›å±•.

Nitrate pollution in groundwater has become a global concern. One of the most important issues in controlling the nitrate pollution of groundwater is to identify the pollution source quickly and accurately. In this review, we firstly summarized the isotopic background values of potential sources of nitrate pollution in groundwater in 17 provinces (cities, autonomous regions) and 29 study areas in China, which could provide the fundamental database for subsequent research. Secondly, we reviewed the research progress of nitrate isotopes combined with multiple tracers for tracing nitrate in groundwater, and discussed their applicable conditions, advantages, and disadvantages. We found that halides and microorganisms combined with nitrate isotopes could accurately trace the pollution sources of domestic sewage, excrement and agricultural activities. The combination of Δ17O and nitrate isotopes could effectively distinguish the source of atmospheric deposition of nitrate in groundwater. The combination of groundwater age and nitrate isotopes could further determine the time scale of nitrate pollution. In addition, we summarized the application cases and compared the characteristics of mass balance mixing model, IsoSource model, Bayesian isotope mixing model, and EMMTE model for quantitative identification of nitrate pollution in groundwater. For the complexity and concealment of groundwater pollution sources, the coupling of nitrate isotopes with other chemical and biological tracing methods, as well as the application of nitrate isotope quantitative models, are effective tools for reliably identifying groundwater nitrate sources and transformation processes.

Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.

[Clinical Characteristics and Prognosis of Patients with Acute Leukemia Complicated with Mucormycosis after Chemotherapy].

OBJECTIVE: To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease. METHODS: 7 cases of acute leukemia (AL) patients diagnosed with mucormycosis by metagenomic next generation sequencing (mNGS) after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected, and their clinical data, including clinical characteristics, diagnosis, treatment, and prognosis, were retrospectively analyzed. RESULTS: Among the 7 patients with AL complicated with mucormycosis, there were 3 males and 4 females, with a median age of 52(20-59) years. There were 6 cases of acute myeloid leukemia (AML) and 1 case of acute lymphocytic leukemia (ALL). Extrapulmonary involvement in 4 cases, including 1 case suspected of central nervous system involvement. The median time for the occurrence of mucor infection was 16(6-69) days after chemotherapy and 19(14-154) days after agranulocytosis. The main clinical manifestations of mucormycosis were fever (7/7), cough (3/7), chest pain (3/7) and dyspnea (1/7). The most common chest CT imaging findings were nodules, patchy or mass consolidation (6/7). All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase. 5 patients died within 8 months, and the median time from diagnosis to death was 1 month. CONCLUSION: Although prophylactic antifungal therapy is adopted, patients with acute leukemia still have a risk of mucor infection during the neutropenia phase. Fever is the main manifestation in the early stage of mucor infection. The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.

Standard-definition White-light, High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population. METHODS: This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression. RESULTS: Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80). CONCLUSION: HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.

Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes.

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

HHO optimized support vector machine classifier for traditional Chinese medicine syndrome differentiation of diabetic retinopathy.

AIM: To develop a classifier for traditional Chinese medicine (TCM) syndrome differentiation of diabetic retinopathy (DR), using optimized machine learning algorithms, which can provide the basis for TCM objective and intelligent syndrome differentiation. METHODS: Collated data on real-world DR cases were collected. A variety of machine learning methods were used to construct TCM syndrome classification model, and the best performance was selected as the basic model. Genetic Algorithm (GA) was used for feature selection to obtain the optimal feature combination. Harris Hawk Optimization (HHO) was used for parameter optimization, and a classification model based on feature selection and parameter optimization was constructed. The performance of the model was compared with other optimization algorithms. The models were evaluated with accuracy, precision, recall, and F1 score as indicators. RESULTS: Data on 970 cases that met screening requirements were collected. Support Vector Machine (SVM) was the best basic classification model. The accuracy rate of the model was 82.05%, the precision rate was 82.34%, the recall rate was 81.81%, and the F1 value was 81.76%. After GA screening, the optimal feature combination contained 37 feature values, which was consistent with TCM clinical practice. The model based on optimal combination and SVM (GA_SVM) had an accuracy improvement of 1.92% compared to the basic classifier. SVM model based on HHO and GA optimization (HHO_GA_SVM) had the best performance and convergence speed compared with other optimization algorithms. Compared with the basic classification model, the accuracy was improved by 3.51%. CONCLUSION: HHO and GA optimization can improve the model performance of SVM in TCM syndrome differentiation of DR. It provides a new method and research idea for TCM intelligent assisted syndrome differentiation.

Enhancement of silicon vacancy fluorescence intensity in silicon carbide using a dielectric cavity.

Over the past decades, spin qubits in silicon carbide (SiC) have emerged as promising platforms for a wide range of quantum technologies. The fluorescence intensity holds significant importance in the performance of quantum photonics, quantum information process, and sensitivity of quantum sensing. In this work, a dual-layer Au/SiO2 dielectric cavity is employed to enhance the fluorescence intensity of a shallow silicon vacancy ensemble in 4H-SiC. Experimental results demonstrate an effective fourfold augmentation in fluorescence counts at saturating laser power, corroborating our theoretical predictions. Based on this, we further investigate the influence of dielectric cavities on the contrast and linewidth of optically detected magnetic resonance (ODMR). There is a 1.6-fold improvement in magnetic field sensitivity. In spin echo experiments, coherence times remain constant regardless of the thickness of dielectric cavities. These experiments pave the way for broader applications of dielectric cavities in SiC-based quantum technologies.

Advances and optimization strategies in bacteriophage therapy for treating inflammatory bowel disease.

In the advancement of Inflammatory Bowel Disease (IBD) treatment, existing therapeutic methods exhibit limitations; they do not offer a complete cure for IBD and can trigger adverse side effects. Consequently, the exploration of novel therapies and multifaceted treatment strategies provides patients with a broader range of options. Within the framework of IBD, gut microbiota plays a pivotal role in disease onset through diverse mechanisms. Bacteriophages, as natural microbial regulators, demonstrate remarkable specificity by accurately identifying and eliminating specific pathogens, thus holding therapeutic promise. Although clinical trials have affirmed the safety of phage therapy, its efficacy is prone to external influences during storage and transport, which may affect its infectivity and regulatory roles within the microbiota. Improving the stability and precise dosage control of bacteriophages-ensuring robustness in storage and transport, consistent dosing, and targeted delivery to infection sites-is crucial. This review thoroughly explores the latest developments in IBD treatment and its inherent challenges, focusing on the interaction between the microbiota and bacteriophages. It highlights bacteriophages' potential as microbiome modulators in IBD treatment, offering detailed insights into research on bacteriophage encapsulation and targeted delivery mechanisms. Particular attention is paid to the functionality of various carrier systems, especially regarding their protective properties and ability for colon-specific delivery. This review aims to provide a theoretical foundation for using bacteriophages as microbiome modulators in IBD treatment, paving the way for enhanced regulation of the intestinal microbiota.

Synthesis of Nitrones and Nitroalkanes via Chiral Cyclic Imines.

A series of structurally chiral cyclic imines efficiently yields chiral nitrones and nitroalkanes. This is the first report of the synthesis of nitro groups by C═N bond cleavage of imines through a nitrone intermediate.

Myricetin Acts as an Inhibitor of Type II NADH Dehydrogenase from Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus. RESULTS: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50) of 2 µM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 µg/mL. Time-kill assays showed that myricetin was a bactericidal agent against S. aureus. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner. CONCLUSIONS: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.

Bioaccessibility and human health risks of arsenic from geological origin in lateritic red soil on construction land.

Current human health risk assessments of soil arsenic (As) contamination rarely consider bioaccessibility (IVBA), which may overestimate the health risks of soil As. The IVBA of As (As-IVBA) may differ among various soil types. This investigation of As-IVBA focused As from geological origin in a typical subtropical soil, lateritic red soil, and its risk control values. The study used the SBRC gastric phase in vitro digestion method and As speciation sequential extraction based upon phosphorus speciation extraction method. Two construction land sites (CH and HD sites) in the Pearl River Delta region were surveyed. The results revealed a high content of residual As (including scorodite, mansfieldite, orpiment, realgar, and aluminum arsenite) in the lateritic red soils at both sites (CH: 84.9%, HD: 91.7%). The content of adsorbed aluminum arsenate (CH: 3.24%, HD: 0.228%), adsorbed ferrum arsenate (CH: 8.55%, HD: 5.01%), and calcium arsenate (CH: 7.33%, HD: 3.01%) were found to be low. The bioaccessible As content was significantly positively correlated with the As content in adsorbed aluminum arsenate, adsorbed ferrum arsenate, and calcium arsenate. A small portion of these sequential extractable As speciation could be absorbed by the human body (CH: 14.9%, HD: 3.16%), posing a certain health risk. Adsorbed aluminum arsenate had the highest IVBA, followed by calcium arsenate, and adsorbed ferrum arsenate had the lowest IVBA. The aforementioned speciation characteristics of As from geological origin in lateritic red soil contributed to its lower IVBA compared to other soils. The oxidation state of As did not significantly affect As-IVBA. Based on As-IVBA, the carcinogenic and non-carcinogenic risks of soil As in the CH and HD sites decreased greatly in human health risk assessment. The results suggest that As-IVBA in lateritic red soil should be considered when assessing human health risks on construction land.