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1.
Int J Nanomedicine ; 19: 3423-3440, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617800

RESUMO

Introduction: Osteoporotic-related fractures remains a significant public health concern, thus imposing substantial burdens on our society. Excessive activation of osteoclastic activity is one of the main contributing factors for osteoporosis-related fractures. While polylactic acid (PLA) is frequently employed as a biodegradable scaffold in tissue engineering, it lacks sufficient biological activity. Microdroplets (MDs) have been explored as an ultrasound-responsive drug delivery method, and mesenchymal stem cell (MSC)-derived exosomes have shown therapeutic effects in diverse preclinical investigations. Thus, this study aimed to develop a novel bioactive hybrid PLA scaffold by integrating MDs-NFATc1-silencing siRNA to target osteoclast formation and MSCs-exosomes (MSC-Exo) to influence osteogenic differentiation (MDs-NFATc1/PLA-Exo). Methods: Human bone marrow-derived mesenchymal stromal cells (hBMSCs) were used for exosome isolation. Transmission electron microscopy (TEM) and confocal laser scanning microscopy were used for exosome and MDs morphological characterization, respectively. The MDs-NFATc1/PLA-Exo scaffold was fabricated through poly(dopamine) and fibrin gel coating. Biocompatibility was assessed using RAW 264.7 macrophages and hBMSCs. Osteoclast formations were examined via TRAP staining. Osteogenic differentiation of hBMSCs and cytokine expression modulation were also investigated. Results: MSC-Exo exhibited a cup-shaped structure and effective internalization into cells, while MDs displayed a spherical morphology with a well-defined core-shell structure. Following ultrasound stimulation, the internalization study demonstrated efficient delivery of bioactive MDs into recipient cells. Biocompatibility studies indicated no cytotoxicity of MDs-NFATc1/PLA-Exo scaffolds in RAW 264.7 macrophages and hBMSCs. Both MDs-NFATc1/PLA and MDs-NFATc1/PLA-Exo treatments significantly reduced osteoclast differentiation and formation. In addition, our results further indicated MDs-NFATc1/PLA-Exo scaffold significantly enhanced osteogenic differentiation of hBMSCs and modulated cytokine expression. Discussion: These findings suggest that the bioactive MDs-NFATc1/PLA-Exo scaffold holds promise as an innovative structure for bone tissue regeneration. By specifically targeting osteoclast formation and promoting osteogenic differentiation, this hybrid scaffold may address key challenges in osteoporosis-related fractures.


Assuntos
Exossomos , Osteoporose , Humanos , RNA Interferente Pequeno/genética , Osteogênese , Porosidade , Poliésteres , Citocinas , Osteoporose/terapia
2.
Adv Med Educ Pract ; 15: 293-300, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38618522

RESUMO

Background: A minor difference in college entrance examination scores can result in vastly different educational resources in China, so it has been debated whether it is the difference in the student population or the difference in educational resources that causes the difference in medical graduates. We aimed to evaluate the effects of entry grades on students' academic performance under homogeneous educational resources. Methods: Students in grade 2016 with 13-point difference in the average admission scores of 2 medicine schools in Sun Yat-sen University were educated in mixed classes and were taught with the same educators during the 5 years of undergraduate period. The grades, graduation, and postgraduate enrollment rates of the students were compared between the two campuses. Results: The average admission scores for Shenzhen Campus (SZC) students are 13 points lower than those of Guangzhou North Campus (GZNC) (613 points vs 626 points). After 5 years of homogeneous education, comparing the GZNC students with the SZC students, there were no significant differences in the average total score (80.2 ± 4.6 vs 80.0 ± 5.6, P = 0.691), the average compulsory course (78.9 ± 3.4 vs 78.4 ± 6.1, P = 0.438), the average core course score (78.8 ± 7.4 vs 78.7 ± 5.0, P=0.860) and the average clerkship score (85.1 ± 7.2 vs 84.6 ± 2.7, P=0.275). However, the completion rate for SZC was higher than for GZNC (93.94% vs 86.27%, P=0.009). There was no statistical difference in postgraduate enrolment between the two institutions (P=0.758). Conclusion: Given the same educational resources, more medical students with lower entrance scores completed their studies and achieved the same percentage of postgraduate acceptance. This finding suggests that a key component of improving the quality of medical higher education in China may be to further rationalize the allocation of high-quality educational resources, rather than to pursuing students with high entrance examination scores.


1. Undergraduates from two medical schools with different average admission scores were educated with the same resources during the 5-year undergraduate period. After 5 years of homogeneous education, more students with lower entrance scores completed their studies and achieved the same percentage of postgraduate acceptance. 2. The key to improving educational quality is to optimize educational resources, not just to recruit high-scoring students.

3.
ACS Biomater Sci Eng ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624061

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) causes great health hazards to society because most antibiotics are ineffective. Photodynamic treatment (PDT) has been proposed to combat MRSA due to the advantage of imaging-guided no-drug resistance therapy. However, the traditional photosensitizers for PDT are limited by aggregation-caused quenching for imaging and low photodynamic antibacterial efficiency. In this work, we synthesize a new aggregation-induced emission (AIE) photosensitizer (APNO), which can ultrafast distinguish between Gram-positive and Gram-negative bacteria within 3 s by AIE-active photosensitizer imaging. Meanwhile, APNO can generate antibacterial reactive oxygen species under light irradiation, which holds potential for antibacterial PDT. Then, APNO is loaded by PHEAA hydrogel to obtain a highly efficient photodynamic hydrogel (APNO@gel). In vitro results show complete inhibition of MRSA by APNO@gel under lower-power light irradiation. Transcriptome analysis is performed to investigate antibacterial mechanism of APNO@gel. Most importantly, APNO@gel also exhibits significant inhibition and killing ability of MRSA in the MRSA wound infection model, which will further promote rapid wound healing. Therefore, the photodynamic hydrogel provides a promising strategy toward MRSA ultrafast imaging and killing.

4.
Chemistry ; : e202401008, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624085

RESUMO

Here we report B(C6F5)3/CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity.

5.
Org Lett ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625098

RESUMO

Herein, a cooperative N-heterocyclic carbene- and palladium-catalyzed three-component reaction of alkynes with aldehydes and fluoroalkyl iodides is developed. A series of biologically valuable CF2R-incorporated α-substituted enones was obtained in moderate to good yields. This mild catalytic method exhibits exclusive regio- and stereoselectivity, excellent functional group tolerance, and a broad substrate scope including terminal and internal alkynes. Mechanistic investigations disclose that this alkyne fluoroalkylacylation proceeds via a radical relay process in which vinyl iodides serve as putative reaction intermediates.

6.
Front Genet ; 15: 1378403, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628576

RESUMO

Lagerstroemia indica is an important commercial tree known for the ornamental value. In this study, the complete chloroplast genome sequence of Lagerstroemia indica "Pink Velour" (Lagerstroemia "Pink Velour") was 152,174 bp in length with a GC content of 39.50%. It contained 85 protein coding genes (PCGs), 37 tRNAs, and 8 rRNA genes. 207 simple sequence repeats (SSRs) and 31 codons with relative synonymous codon (RSCU)value > 1 were detected. Phylogenetic analysis divided 10 Lagerstroemia species into evolutionary branches of clade A and clade B. We conducted a comparative analysis of Lagerstroemia "Pink Velours" complete chloroplast genome with the genomes of six closely related Lagerstroemia species from different origins. The structural features of all seven species were similar, except for the deletion of ycf1 nucleobases at the JSA boundary. The large single-copy (LSC) and the small single-copy (SSC) had a higher sequence divergence than the IR region, and 8 genes that were highly divergent (trnK-UUU, petN, psbF, psbJ, ndhE, ndhD, ndhI, ycf1) had been identified and could be used as molecular markers in future studies. High nucleotide diversity was present in genes belonging to the photosynthesis category. Mutation of single nucleic acid was mainly influenced by codon usage. The value percentage of nonsynonymous substitutions (Ka) and synonymous substitutions (Ks) in 6 Lagerstroemia species revealed that more photosynthesis genes have Ka or Ks only in Lagerstroemia fauriei, Lagerstroemia limii, and Lagerstroemia subcostata. These advances will facilitate the breeding of closely related Lagerstroemia species and deepen understanding on climatic adaptation of Lagerstroemia plants.

7.
Digit Health ; 10: 20552076241247963, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628632

RESUMO

In the past decade, digitization of medical records and multiomics data analysis in lymphoma has led to the accessibility of high-dimensional records. The digitization of medical records, the visualization of extensive volume data extracted from medical images, and the integration of multiomics methods into clinical decision-making have produced many datasets. As a promising auxiliary tool, machine learning (ML) intends to extract homologous features in large-scale data sets and encode them into various patterns to complete complicated tasks. At present, artificial intelligence and digital mining have shown promising prospects in the field of lymphoma pathological image analysis. The paradigm shift from qualitative analysis to quantitative analysis makes the pathological diagnosis more intelligent and the results more accurate and objective. ML can promote accurate lymphoma diagnosis and provide patients with prognostic information and more individualized treatment options. Based on the above, this comprehensive review of the general workflow of ML highlights recent advances in ML techniques in the diagnosis, treatment, and prognosis of lymphoma, and clarifies the boundedness and future orientation of the ML technique in the clinical practice of lymphoma.

8.
Talanta ; 275: 126110, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38631264

RESUMO

Considering that cancer has become the second leading cause of death in humans, it is essential to develop an analytical approach that can sensitively detect tumor markers for early detection. We report an attenuated photoelectrochemical (PEC) immunoassay based on the organic-inorganic heterojunction 10MIL-88B(FeV)/ZnIn2S4 (10M88B(FeV)/ZIS) as a photoactive material for monitoring carcinoembryonic antigen (CEA). The 10M88B(FeV)/ZIS heterojunctions have excellent light-harvesting properties and high electrical conductivity, which are attributed to the advantages of both organic and inorganic semiconductors, namely, remarkable photogenerated carrier separation efficiency and long photogenerated carrier lifetime. Horseradish peroxidase (HRP) in the presence of H2O2 can catalyze 3,3'-diaminofenamide (DAB) producing brown precipitates (oxDAB), which is then loaded onto the 10M88B(FeV)/ZIS heterojunction to reduce the photocurrent and enable the quantitative detection of CEA. Under optimal conditions, the photocurrent values of the PEC biosensor are linearly related to the logarithm of the CEA concentrations, ranging from 0.01 ng mL-1 to 100 ng mL-1 with a detection limit (LOD) of 4.0 pg mL-1. Notably, the accuracy of the PEC biosensor is in agreement with that of the human CEA enzyme-linked immunosorbent assay (ELISA) kit.

9.
Magn Reson Chem ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632498

RESUMO

Three new monacolin analogues, 3,6-dihydroxy-monacolin P (1), 6-methoxy monacolin S (2), and 6-methoxy dehydromonacolin S (3), were isolated from a fraction that strongly inhibited 3-hydroxy-3-methylglutaryl-CoA reductase from the ethyl acetate portion of red yeast rice ethanol extract. Their structures were determined through a combination of 1D and 2D NMR experiments, mass spectrometry analysis, and known literature reports.

10.
Hepatology ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607725

RESUMO

Heavy alcohol intake induces a wide spectrum of liver diseases ranging from steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Although alcohol consumption is a well-known risk factor for the development, morbidity, and mortality of HCC globally, alcohol-associated HCC (A-HCC) is poorly characterized compared to viral hepatitis-associated HCC. Most A-HCCs develop post alcohol-associated cirrhosis, but the direct carcinogenesis from ethanol and its metabolites to A-HCC remains obscure. The differences between A-HCC and HCCs caused by other etiologies have not been well investigated in terms of clinical prognosis, genetic or epigenetic landscape, molecular mechanisms, and heterogeneity. Moreover, there is a huge gap between basic research and clinical practice due to the lack of pre-clinical models of A-HCC. In the current review, we discuss the pathogenesis, heterogeneity, preclinical approaches, epigenetic and genetic profiles of A-HCC, and discuss the current insights into and the prospects for future research on A-HCC. The potential effect of alcohol on cholangiocarcinoma and liver metastasis are also discussed.

11.
Am J Health Promot ; : 8901171241237016, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38610124

RESUMO

BACKGROUND: Hypertension-related knowledge, attitude and practice (KAP) of hypertensive patients can affect the awareness, treatment and control of hypertension. However, little attention has been paid to the association between the change of hypertension preventive KAP and blood pressure (BP) control in occupational population using longitudinal data. We assess the effectiveness of a workplace-based multicomponent hypertension intervention program on improving the level of KAP of hypertension prevention, and the association between improvement in KAP and BP control during intervention. METHODS: From January 2013 to December 2014, workplaces across 20 urban regions in China were randomized to either the intervention group (n = 40) or control group (n = 20) using a cluster randomized control method. All employees in each workplace were asked to complete a cross-sectional survey to screen for hypertension patients. Hypertension patients in the intervention group were given a 2-year workplace-based multicomponent hypertension intervention for BP control. The level of hypertension prevention KAP and BP were assessed before and after intervention in the two groups. RESULTS: Overall, 3331 participants (2658 in the intervention group and 673 in the control group) were included (mean [standard deviation] age, 46.2 [7.7] years; 2723 men [81.7%]). After 2-year intervention, the KAP qualified rate was 63.2% in the intervention groups and 50.1% in the control groups (odds ratio = 1.65, 95% CI, 1.36∼2.00, P < .001). Compared with the control group decreased in the qualified rate of each item of hypertension preventive KAP questionnaire, all the items in the intervention group increased to different degrees. The increase of KAP score was associated with the decrease of BP level after intervention. For 1 point increase in KAP score, systolic blood pressure (SBP) decreased by .28 mmHg and diastolic blood pressure (DBP) decreased by .14 mmHg [SBP: ß = -.28, 95%CI: -.48∼-.09, P = .004; DBP: ß = -.14, 95%CI: -.26∼-.02, P = .024]. SBP and DBP was significantly in manual labor workers (SBP: ß = -.34, 95%CI: -.59∼-.09, P = .008; DBP: ß = -.23, 95%CI: -.38∼-.08, P = .003), workers from private enterprise, state-owned enterprise (SOE) (SBP: ß = -.40, 95%CI: -.64∼-.16, P = .001; DBP: ß = -.21, 95%CI: -.36∼-.06, P = .005) and a workplace with an affiliated hospital (SBP: ß = -.31, 95%CI: -.52∼-.11, P = .003; DBP: ß = -.16, 95%CI: -.28∼-.03, P = .016). The improvement of knowledge (SBP: ß = -.29, 95%CI: -.56∼-.02, P = .038; DBP: ß = -.12, 95%CI: -.29∼.05, P = .160), as well as attitude (SBP: ß = -.71, 95%CI: -1.25∼-.18, P = .009; DBP: ß = .18, 95%CI: -.23∼.59, P = .385) and behavior (SBP: ß = -.73, 95%CI: -1.22∼-.23, P = .004; DBP: ß = -.65, 95%CI: -.97∼-.33, P < .001) was gradually strengthened in relation to BP control. CONCLUSION: This study found that workplace-based multicomponent hypertension intervention can effectively improve the level of hypertension preventive KAP among employees, and the improvement of KAP levels were significantly associated with BP control. TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR-ECS-14004641.

12.
ACS Synth Biol ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613497

RESUMO

Computer-aided promoter design is a major development trend in synthetic promoter engineering. Various deep learning models have been used to evaluate or screen synthetic promoters, but there have been few works on de novo promoter design. To explore the potential ability of generative models in promoter design, we established a diffusion-based generative model for promoter design in Escherichia coli. The model was completely driven by sequence data and could study the essential characteristics of natural promoters, thus generating synthetic promoters similar to natural promoters in structure and component. We also improved the calculation method of FID indicator, using a convolution layer to extract the feature matrix of the promoter sequence instead. As a result, we got an FID equal to 1.37, which meant synthetic promoters have a distribution similar to that of natural ones. Our work provides a fresh approach to de novo promoter design, indicating that a completely data-driven generative model is feasible for promoter design.

13.
Nutrients ; 16(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38613119

RESUMO

Resveratrol (RES) has been reported to prevent hyperuricemia (HUA); however, its effect on intestinal uric acid metabolism remains unclear. This study evaluated the impact of RES on intestinal uric acid metabolism in mice with HUA induced by a high-fat diet (HFD). Moreover, we revealed the underlying mechanism through metagenomics, fecal microbiota transplantation (FMT), and 16S ribosomal RNA analysis. We demonstrated that RES reduced the serum uric acid, creatinine, urea nitrogen, and urinary protein levels, and improved the glomerular atrophy, unclear renal tubule structure, fibrosis, and renal inflammation. The results also showed that RES increased intestinal uric acid degradation. RES significantly changed the intestinal flora composition of HFD-fed mice by enriching the beneficial bacteria that degrade uric acid, reducing harmful bacteria that promote inflammation, and improving microbial function via the upregulation of purine metabolism. The FMT results further showed that the intestinal microbiota is essential for the effect of RES on HUA, and that Lactobacillus may play a key role in this process. The present study demonstrated that RES alleviates HFD-induced HUA and renal injury by regulating the gut microbiota composition and the metabolism of uric acid.


Assuntos
Microbioma Gastrointestinal , Hiperuricemia , Animais , Camundongos , Hiperuricemia/tratamento farmacológico , Resveratrol/farmacologia , Ácido Úrico , Túbulos Renais , Inflamação
14.
Cancer Med ; 13(7): e7161, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38613173

RESUMO

BACKGROUND: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). RESULTS: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762-0.823), 0.904 (0.835-0.973), 0.759 (0.731-0.787), 0.221 (0.186-0.256), 0.974 (0.967-0.982), 0.353 (0.306-0.399), and 0.834 (0.696-0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753-0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. CONCLUSIONS: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.


Assuntos
Adenocarcinoma de Células Claras , Neoplasias Ovarianas , Feminino , Humanos , Teorema de Bayes , Algoritmos , Carcinoma Epitelial do Ovário , Aprendizado de Máquina
15.
Adv Mater ; : e2403664, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625813

RESUMO

Direct formate fuel cells (DFFCs) receive increasing attention as promising technologies for the future energy mix and environmental sustainability, as formate can be made from carbon dioxide utilization and is carbon neutral. Herein, heterostructured PtPd alloy and oxides nanowires (PtPd-ox NWs) with abundant defect sites are synthesized through a facile self-template method and demonstrated high activity towards formate electrooxidation reaction (FOR). The electronic tuning arising from the heterojunction between alloy and oxides influence the work function of PtPd-ox NWs. The sample with optimal work function reveals the favorable adsorption behavior for intermediates and strong interaction in the d-p orbital hybridization between Pt site and oxygen in formate, favoring the FOR direct pathway with a low energy barrier. Besides the thermodynamic regulation, the heterostructure can also provide sufficient hydroxyl species to facilitate the formation of carbon dioxide due to the ability of combining absorbed hydrogen and carbon monoxide at adjacent active sites, which contributes to the improvement of FOR kinetics on PtPd-ox NW. Thus, heterostructured PtPd-ox NWs achieve dual regulation of FOR thermodynamics and kinetics, exhibiting remarkable performance and demonstrating potential in practical systems. This article is protected by copyright. All rights reserved.

16.
Bioorg Chem ; 147: 107367, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626492

RESUMO

Lung cancer is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers. Euphorbia kansui yielded 13-oxyingenol-dodecanoate (13OD), an ingenane-type diterpenoid, which had a strong cytotoxic effect on NSCLC cells. The underlying mechanism and potential target, however, remained unknown. The study found that 13OD effectively inhibited the cell proliferation and colony formation of NSCLC cells (A549 and H460 cells), with less toxicity in normal human lung epithelial BEAS-2B cells. Moreover, 13OD can cause mitochondrial dysfunction, and apoptosis in NSCLC cells. Mechanistically, the transcriptomics results showed that differential genes were mainly enriched in the mTOR and AMPK signaling pathways, which are closely related to cellular autophagy, the related indicators were subsequently validated. Additionally, bafilomycin A1 (Baf A1), an autophagy inhibitor, reversed the mitochondrial damage caused by 13OD. Furthermore, the Omics and Text-based Target Enrichment and Ranking (OTTER) method predicted ULK1 as a potential target of 13OD against NSCLC cells. This hypothesis was further confirmed using molecular docking, the cellular thermal shift assay (CETSA), and Western blot analysis. Remarkably, ULK1 siRNA inhibited 13OD's toxic activity in NSCLC cells. In line with these findings, 13OD was potent and non-toxic in the tumor xenograft model. Our findings suggested a possible mechanism for 13OD's role as a tumor suppressor and laid the groundwork for identifying targets for ingenane-type diterpenoids.

17.
Arch Toxicol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627326

RESUMO

All areas of the modern society are affected by fluorine chemistry. In particular, fluorine plays an important role in medical, pharmaceutical and agrochemical sciences. Amongst various fluoro-organic compounds, trifluoromethyl (CF3) group is valuable in applications such as pharmaceuticals, agrochemicals and industrial chemicals. In the present study, following the strict OECD modelling principles, a quantitative structure-toxicity relationship (QSTR) modelling for the rat acute oral toxicity of trifluoromethyl compounds (TFMs) was established by genetic algorithm-multiple linear regression (GA-MLR) approach. All developed models were evaluated by various state-of-the-art validation metrics and the OECD principles. The best QSTR model included nine easily interpretable 2D molecular descriptors with clear physical and chemical significance. The mechanistic interpretation showed that the atom-type electro-topological state indices, molecular connectivity, ionization potential, lipophilicity and some autocorrelation coefficients are the main factors contributing to the acute oral toxicity of TFMs against rats. To validate that the selected 2D descriptors can effectively characterize the toxicity, we performed the chemical read-across analysis. We also compared the best QSTR model with public OPERA tool to demonstrate the reliability of the predictions. To further improve the prediction range of the QSTR model, we performed the consensus modelling. Finally, the optimum QSTR model was utilized to predict a true external set containing many untested/unknown TFMs for the first time. Overall, the developed model contributes to a more comprehensive safety assessment approach for novel CF3-containing pharmaceuticals or chemicals, reducing unnecessary chemical synthesis whilst saving the development cost of new drugs.

18.
Huan Jing Ke Xue ; 45(5): 2651-2664, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629529

RESUMO

In order to enhance the support for groundwater development and utilization, as well as pollution control and prevention in Fengtai District, Beijing, a comprehensive study was conducted based on long-term monitoring data of shallow groundwater in the eastern area of Yongding River during the dry season. The mathematical statistics, Piper diagram, Gibbs diagram, and ion ratio analysis and other methods were employed to explore the pattern of groundwater hydrochemical evolution, the formation mechanism, and sources of pollution in Fengtai District. The findings were as follows:① Overall, the current groundwater quality in the study area was poor. The average concentration of each index in groundwater increased and then decreased from 1976 to the present. The pollution range of Cl-, SO42-, and TH generally expanded, whereas the pollution range of TDS and NO3- expanded before 2005 and then decreased with 2005 as the turning point. ② The hydrochemical types of groundwater samples displayed a complex regional variation each year, as well as along the groundwater direction. The dominant anion in groundwater was HCO3-, and the dominant cation was Ca2+ each year. The number of groundwater hydrochemical types in 1976 was 8, in which the predominant type was HCO3·SO4-Ca·Mg·Na, accounting for 40%. However, the number of groundwater hydrochemical types in 2021 was 17, in which the predominant type was HCO3·Cl·SO4-Ca·Na·Mg, accounting for 23.88%. The groundwater hydrochemical type showed a complex trend within the region and upstream along the flow direction each year, whereas the migration characteristics of groundwater samples, as depicted on the Piper diagram, indicated that the hydrochemical components of groundwater were significantly affected by human activities during its evolution. ③ The groundwater chemistry in the study area was influenced by both rock weathering and evaporative crystallization processes, with evaporation playing a major role. The alternation of groundwater cations was relatively weak, and the dissolution of carbonate minerals served as the primary source of Ca2+ and Mg2+. ④ The ion ratio analysis suggested that exogenous sources, mainly agricultural activities and urban sewage, contributed to the input of NO3- and Cl-. The pollution impact from agricultural activities was significant before 2005, which aligned with the historical presence of numerous seepage pits, seepage wells, and direct discharge of industrial and domestic sewage for irrigation purposes in the study area. These activities were closely associated with the high levels of pollution. However, pollution input from agricultural activities notably decreased in 2021, likely due to the effective implementation of water environmental protection programs and action plans in recent years.

19.
Wei Sheng Yan Jiu ; 53(2): 257-266, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38604962

RESUMO

OBJECTIVE: To analyse potential differences towards liver impairment status on vinyl chloride monomer(VCM) exposed population from technique under acetylene hydrochlorination to the one of ethylene oxychlorination respectively and to explore the possible reasons, which will pave the way for occupational health promotion in terms of hazard reduction. METHODS: a cross-sectional study was initiated between June and September in 2022 towards 2 groups of VCM exposed population from the facility of acetylene hydrochlorination(n=78) and the one of ethylene oxychlorination(n=69) in a PVC petrochemical complex enterprise(abbreviation of H) in Tianjin City. The demographic information concerning age, gender, messages on occupational history, field investigation were inquired through questionnaire interview. Then, venous blood(4 mL/person) and urine(10-50 mL/person) were collected during the physical exam phase and indices of 8-hydroxy-2 deoxyguanosine(8-OHdG) in blood and thiodiglycolic acid(TDGA) in urine were detected through ELISA and solid phase extraction-ion chromatography respectively. RESULTS: The 2 groups of population were matched well in terms of average age distribution and gender composition ratio, with significant differences on population composition ratio were found on variables of working years, alcohol consumption and daily sleeping duration(P<0.01 or P<0.05). It was found that the average content of TDGA in acetylene hydrochlorination group was(0.81±0.05)mg/L while the content in ethylene oxychlorination group reached to(0.83±0.06)mg/L, noteworthy differences were only found among 6 posts in the acetylene hydrochlorination group and 5 others in the ethylene oxychlorination group after classification for specific posts, however, the average concentration of 8-OHdG in acetylene hydrochlorination group(122(78.3, 168.8) µg/m~3) was different from the one in ethylene oxychlorination group(101.7(79.6, 149.7) µg/m~3)(Z=6.82, P<0.05). Moreover, a series of positive correlations in moderate intensity between 8-OHdG concentration and TDGA content were observed among posts of polymerization cleaners(r=0.53), aggregation operators(r=0.47), maintenance repairers(r=0.45), sampling operators(r=0.41) in acetylene hydrochlorination group(P<0.05) and posts of cracking reactants(r=0.64), DCS operators(r=0.51), oxychlorination operators(r=0.50) and chemical loaders(r=0.44) in ethylene oxychlorination group(P<0.05). Liver function indices such as content on ALT(χ~2=15.41, P<0.01), AST(χ~2=9.95, P<0.01) and ALP(χ~2=3.79, P<0.01) were different in the 2 groups population with statistical significance, then proportions on population composition ratio that exceeded normal ranges of indices on ALT, AST, AST/ALT ratio, ALP and Alb/Glb ratio were higher in acetylene hydrochlorination group than ones in ethylene oxychlorination group with great significance(P<0.05), so as to the abnormalities in liver B altrosonography test between groups(χ~2=17.33, P<0.01). Binary logistic regression model indicated that 8-OHdG concentration in blood that exceed 90 µg/m~3, TDGA content in urine that exceed 0.60 mg/L, working years that were over 10a, alcohol consumption, sleeping duration less than 6 h per day and male workers were potential risky factors for liver impairment(P<0.05). CONCLUSION: The degree on liver impairment status was higher in acetylene hydrochlorination group than ones in in ethylene oxychlorination group under the same PVC factory, which might be associated with the oxidative stress injury induced from the combination of higher VCM concentration at workplaces, longer cumulative exposure time, longer working years, alcohol consumption habits and sleep shortage caused by shift work patterns.


Assuntos
Hepatopatias , Exposição Ocupacional , Cloreto de Vinil , Humanos , Masculino , Cloreto de Vinil/toxicidade , Estudos Transversais , Etilenos , Alcinos , Exposição Ocupacional/efeitos adversos
20.
Food Res Int ; 184: 114262, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609241

RESUMO

There are complex and diverse substances in traditional vinegars, some of which have been identified as biologically active factors, but the variety of functional compounds is currently restricted. In this study, it was aimed to determine the bioactive compounds in 10 typical functional vinegars. The findings shown that total flavonoids (0.21-7.19 mg rutin equivalent/mL), total phenolics (0.36-3.20 mg gallic acid equivalent/mL), and antioxidant activities (DPPH: 3.17-47.63 mmol trolox equivalent/L, ABTS: 6.85-178.29 mmol trolox equivalent/L) varied among different functional vinegars. In addition, the concentrations of the polysaccharides (1.17-44.87 mg glucose equivalent/mL) and total saponins (0.67-12.46 mg oleanic acid equivalent/mL) were determined, which might play key role for the function of tested vinegars. A total of 8 organic acids, 7 polyphenol compounds and 124 volatile compounds were measured and tentatively identified. The protocatechuic acid (4.81-485.72 mg/L), chlorogenic acid (2.69-7.52 mg/L), and epicatechin (1.18-97.42 mg/L) were important polyphenol compounds in the functional vinegars. Redundancy analysis indicated that tartaric acid, oxalic acid and chlorogenic acid were significantly positively correlated with antioxidant capacity. Various physiologically active ingredients including cyclo (Pro-Leu), cyclo (Phe-Pro), cyclo (Phe-Val), cyclo (Pro-Val), 1-monopalmitin and 1-eicosanol were firstly detected in functional vinegars. Principle component analysis revealed that volatiles profile of bergamot Monascus aromatic vinegar and Hengshun honey vinegar exhibited distinctive differences from other eight vinegar samples. Moreover, the partial least squares regression analysis demonstrated that 11 volatile compounds were positively correlated with the antioxidant activity of vinegars, which suggested these compounds might be important functional substances in tested vinegars. This study explored several new functionally active compounds in different functional vinegars, which could widen the knowledge of bioactive factor in vinegars and provide new ideas for further development of functional vinegar beverages.


Assuntos
Ácido Acético , Antioxidantes , Ácido Clorogênico , Ácido Gálico , Polifenóis
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