RÉSUMÉ
Tert-butylhydroquinone (TBHQ) is easily overused or illegally added to edible oil and attracts a growing concern because of its cytotoxic, liver-damaging, and carcinogenic effects. Thus, a sensitive and intelligent point-of-care testing (iPOCT) method is developed to fulfill the on-site monitoring. This iPOCT method depended on a fluorescent immunochromatographic assay within 15 min. Under optimization, the limit of quantification (LOQ) was calculated as 0.03 µg mL-1. The iPOCT method provided a low limit of detection (LOD) of 0.02 µg mL-1, a wide linear range of 0.03-100 µg mL-1, and great selectivity. Recoveries by the spiking experiments ranged from 97.4% to 103.5% with relative standard deviations (RSDs) of 2.4%-4.9% in soybean, peanut, rapeseed, and corn oil samples. The results showed that the iPOCT method is highly consistent with the high-performance liquid chromatography (HPLC) method.
RÉSUMÉ
BACKGROUND: Accurate prognostic factors for primary ocular adnexal lymphoma (POAL) are scarce. Survival models and prognostic factors derived without considering competing risk factors suffer from major statistical errors. This study aimed to accurately assess prognostic factors in POAL patients using competing risk models, and compare this to the traditional COX proportional hazards model. METHODS: This retrospective study utilised data from the Surveillance, Epidemiology, and End Results (SEER) program 2010-2015 and included patients with B-cell POAL. The cumulative incidence function and Gray's test for cause-specific survival were calculated as univariate analysis. The competing risk models were a Fine-Gray subdistribution hazard model and a cause-specific model, and a traditional COX model was employed as a multivariate analysis. RESULTS: This study enrolled 846 eligible patients with POAL: 60 patients (7.09%) died from POAL and 123 patients (14.54%) died from other causes. Multivariate competing risk models indicated that age, laterality, histology subtype, the 7th edition of American Joint Committee on Cancer stage T, and radiotherapy were independent predictors for cause-specific survival of patients with POAL. There was high consistency between the two competing risk models. The COX model made several misestimations on the statistical significance and hazard ratios of prognostic factors. CONCLUSIONS: This study established competing risk models as a method to assess POAL prognostic factors, which was more accurate than traditional methods that do not consider competing risk elements.
RÉSUMÉ
OBJECTIVES: The objectives of this study are to describe couples' experiences and perceived barriers to participation in the CenteringPregnancy model in southeast of China and to understand whether smartphones could play a potential role in this model. DESIGN: This study employed a descriptive phenomenological qualitative study using semistructured dyadic interviews with women and their partners. The interviews were audiotaped, transcribed verbatim and subjected to thematic analysis. SETTING: This study was conducted in two pilot prenatal clinics in southern China. PARTICIPANTS: A purposive sample of 13 couples who underwent smartphone-assisted CenteringPregnancy were recruited. Data were collected until saturation through semistructured dyadic interviews between December 2022 and March 2023. RESULTS: The study yielded four primary themes: (1) motivation for participation, (2) acceptance of CenteringPregnancy, (3) barriers and suggestions and (4) support for smartphone use of CenteringPregnancy. CONCLUSIONS: CenteringPregnancy was well received by couples. Couples can access additional medical care and engage in intensive social interactions assisted by smartphones. However, certain objective challenges need to be acknowledged, including inadequate activity space, high demand for knowledge by couples and inflexible time for employed partners. Moreover, the risk that smartphones can lead to false expectations among couples needs to be noted.
Sujet(s)
Prise en charge prénatale , Recherche qualitative , Ordiphone , Humains , Femelle , Chine , Adulte , Grossesse , Mâle , Entretiens comme sujet , Motivation , Conjoints/psychologie , Jeune adulteRÉSUMÉ
KEY MESSAGE: A stable Agrobacterium-mediated transformation system was constructed for B. juncea, and BjuLKP2 was overexpressed, leading to plant yellowing. A stable and efficient transformation system is necessary to verify gene functions in plants. To establish an Agrobacterium-mediated transformation system for B. juncea, various factors, including the explant types, hormone combination and concentration, infection time and concentration, were optimized. Eventually, a reliable system was established, and two BjuLKP2 overexpression (OE) lines, which displayed yellowing of cotyledons, shoot tips, leaves and flower buds, as well as a decrease in total chlorophyll content, were generated. qRT-PCR assays revealed significant upregulation of five chlorophyll synthesis genes and downregulation of one gene in the BjuLKP2 OE line. Furthermore, antioxidant capacity assays revealed reduced activities of APX, CAT and SOD, while POD activity increased in the BjuLKP2 OE26. Additionally, the kinetic determination of chlorophyll fluorescence induction suggested a decrease in the photosynthetic ability of BjuLKP2 OE26. GUS assays revealed the expression of BjuLKP2 in various tissues, including the roots, hypocotyls, cotyledons, leaf vasculature, trichomes, sepals, petals, filaments, styles and stigma bases, but not in seeds. Scanning electron revealed alterations in chloroplast ultrastructure in both the sponge and palisade tissue. Collectively, these findings indicate that BjuLKP2 plays a role in plant yellowing through a reduction in chlorophyll content and changes in chloroplasts structure.
Sujet(s)
Chlorophylle , Régulation de l'expression des gènes végétaux , Moutarde (plante) , Végétaux génétiquement modifiés , Transformation génétique , Chlorophylle/métabolisme , Moutarde (plante)/génétique , Feuilles de plante/génétique , Photosynthèse , Protéines végétales/génétique , Protéines végétales/métabolisme , Agrobacterium/génétiqueRÉSUMÉ
AIM: To elucidate the effects of sleep parameters and renal function on the risk of developing new-onset severe metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: The primary analysis involved a cohort of 305 257 participants. Multivariable Cox models were employed to calculate hazard ratios and 95% confidence intervals. Traditional mediation and two-step Mendelian randomization (MR) analyses were conducted to assess the associations and mediating roles of renal function indicators between sleep and new-onset severe MASLD. RESULTS: Poor sleep score and renal function biomarker score (RFS) were associated with an increased risk of new-onset severe MASLD (all ptrend <0.001). Participants with poor sleep patterns and the highest RFS had a 5.45-fold higher risk of new-onset severe MASLD, compared to those with healthy sleep patterns and the lowest RFS (p < 0.001). The RFS could explain 10.08% of the correlations between poor sleep score and risk of new-onset severe MASLD. Additionally, MR analyses supported a causal link between insomnia and new-onset severe MASLD and revealed a mediating role of chronic kidney disease in the connection between insomnia and new-onset severe MASLD risk. CONCLUSIONS: This study highlights the independent and combined associations of sleep parameters and renal function indicators with new-onset severe MASLD, underscoring the bidirectional communication of the liver-kidney axis and providing modifiable strategies for preventing MASLD.
RÉSUMÉ
Background: Amyotrophic lateral sclerosis (ALS)-related white-matter microstructural abnormalities have received considerable attention; however, gray-matter structural abnormalities have not been fully elucidated. This study aimed to evaluate cortical microstructural abnormalities in ALS and determine their association with disease severity. Methods: This study included 34 patients with ALS and 30 healthy controls. Diffusion-weighted data were used to estimate neurite orientation dispersion and density imaging (NODDI) parameters, including neurite density index (NDI) and orientation dispersion index (ODI). We performed gray matter-based spatial statistics (GBSS) in a voxel-wise manner to determine the cortical microstructure difference. We used the revised ALS Functional Rating Scale (ALSFRS-R) to assess disease severity and conducted a correlation analysis between NODDI parameters and ALSFRS-R. Results: In patients with ALS, the NDI reduction involved several cortical regions [primarily the precentral gyrus, postcentral gyrus, temporal cortex, prefrontal cortex, occipital cortex, and posterior parietal cortex; family-wise error (FWE)-corrected P<0.05]. ODI decreased in relatively few cortical regions (including the precentral gyrus, postcentral gyrus, prefrontal cortex, and inferior parietal lobule; FWE-corrected P<0.05). The NDI value in the left precentral and postcentral gyrus was positively correlated with the ALS disease severity (FWE-corrected P<0.05). Conclusions: The decreases in NDI and ODI involved both motor-related and extra-motor regions and indicated the presence of gray-matter microstructural impairment in ALS. NODDI parameters are potential imaging biomarkers for evaluating disease severity in vivo. Our results showed that GBSS is a feasible method for identifying abnormalities in the cortical microstructure of patients with ALS.
RÉSUMÉ
Sensitive, convenient and rapid detection and subtyping of influenza viruses are crucial for timely treatment and management of infected people. Compared with antigen detection, nucleic acid detection has higher specificity and can shorten the detection window. Hence, in this work, we improved the lateral flow assay (LFA, one of the most promising user-friendly and on-site methods) to achieve detection and subtyping of H1N1, H3N2 and H9N2 influenza virus nucleic acids. Firstly, the antigen-antibody recognition mode was transformed into a nucleic acid hybridization reaction. Secondly, Fe3O4-Au heterodimer nanoparticles were prepared to replace frequently used Au nanoparticles to obtain better coloration. Thirdly, four lines were arranged on the LFA strip, which were three test (T) lines and one control (C) line. Three T lines were respectively sprayed by the DNA sequences complementary to one end of H1N1, H3N2 and H9N2 influenza virus nucleic acids, while Fe3O4-Au nanoparticles were respectively coupled with the DNA sequences complementary to the other end of H1N1, H3N2 and H9N2 nucleic acids to construct three kinds of probes. The C line was sprayed by the complementary sequences to the DNAs on all three kinds of probes. In the detection, by hybridization reaction, the probes were combined with their target nucleic acids which were captured by the corresponding T lines to form color bands. Finally, according to the position of the color bands and their grey intensity, simultaneous qualitative and semi-quantitative detection of the three influenza virus nucleic acids was realized. The detection results showed that this multi-channel LFA had good specificity, and there was no significant cross reactivity among the three subtypes of influenza viruses. The simultaneous detection achieved comparable detection limits with individual detections. Therefore, this multi-channel LFA had good application potential for sensitive and rapid detection and subtyping of influenza viruses.
RÉSUMÉ
This study aimed to develop the Dysphagia Handicap Index-Chinese Mandarin (DHI-CM) and to assess its reliability and validity. This prospective study was conducted in China with individuals who speak Mandarin. The DHI-CM was developed according to a five-stage process. 264 patients with oropharyngeal dysphagia (OD) and 187 healthy individuals completed the study. Reliability was assessed using Cronbach's α and test-retest reliability. Differences between healthy participants and patients with OD were analyzed for instrument validity. Convergent and concurrent validity were assessed using the Swallowing Quality of Life Questionnaire (SWAL-QoL) and Functional Oral Intake Scale (FOIS), respectively. The Content Validity Index (CVI) was used to assess content validity. Exploratory and Confirmatory Factor Analyses (EFA and CFA, respectively) were used to assess structural validity. The Cronbach's alpha was > 0.9 for the total score and every individual subscale. The Pearson and intraclass correlation coefficients were both > 0.8. The patients with OD showed significantly higher scores in the DHI-CM and its subscales than the healthy individuals. Significant correlations were found between most subscales of the DHI-CM and both the SWAL-QoL and FOIS. The CVI of the DHI-CM was 0.892 and ranged between 0.878 and 1.000 for the subscales. The EFA identified three components that explained 24.33%, 23.99%, and 22.73% of the variance, respectively. The scale showed good structural validity through CFA. Conclusions. The DHI-CM demonstrated good reliability and validity among Mandarin-speaking Chinese adults.
RÉSUMÉ
Iron-anchored nitrogen/doped carbon single-atom nanozymes (Fe-N/C), which possess homogeneous active sites and adjustable catalytic environment, represent an exemplary model for investigating the structure-function relationship and catalytic activity. However, the development of pyrolysis-free synthesis technique for Fe-N/C with adjustable enzyme-mimicking activity still presents a significant challenge. Herein, Fe-N/C anchored three carrier morphologies were created via a pyrolysis-free approach by covalent organic polymers. The peroxidase-like activity of these Fe-N/C nanozymes was regulated via the pores of the anchored carrier, resulting in varying electron transfer efficiency due to disparities in contact efficacy between substrates and catalytic sites within diverse microenvironments. Additionally, a colorimetric sensor array for identifying antioxidants was developed: (1) the Fe-N/C catalytically oxidized two substrates TMB and ABTS, respectively; (2) the development of a colorimetric sensor array utilizing oxTMB and oxABTS as sensing channels enabled accurate discrimination of antioxidants such as ascorbic acid (AsA), glutathione (GSH), cysteine (Cys), gallic acid (GA), and caffeic acid (CA). Subsequently, the sensor array underwent rigorous testing to validate its performance, including assessment of antioxidant mixtures and individual antioxidants at varying concentrations, as well as target antioxidants and interfering substances. In general, the present study offered valuable insights into the active origin and rational design of nanozyme materials, and highlighting their potential applications in food analysis.
RÉSUMÉ
The aim of this study was to modify phytase YiAPPA via protein surficial residue mutation to obtain phytase mutants with improved thermostability and activity, enhancing its application potential in the food industry. First, homology modeling of YiAPPA was performed. By adopting the strategy of protein surficial residue mutation, the lysine (Lys) and glycine (Gly) residues on the protein surface were selected for site-directed mutagenesis to construct single-site mutants. Thermostability screening was performed to obtain mutants (K189R and K216R) with significantly elevated thermostability. The combined mutant K189R/K216R was constructed via beneficial mutation site stacking and characterized. Compared with those of YiAPPA, the half-life of K189R/K216R at 80°C was extended from 14.81 min to 23.35 min, half-inactivation temperature (T50 30) was increased from 55.12°C to 62.44°C, and Tm value was increased from 48.36°C to 53.18°C. Meanwhile, the specific activity of K189R/K216R at 37°C and pH 4.5 increased from 3960.81 to 4469.13 U/mg. Molecular structure modeling analysis and molecular dynamics simulation showed that new hydrogen bonds were introduced into K189R/K216R, improving the stability of certain structural units of the phytase and its thermostability. The enhanced activity was primarily attributed to reduced enzymesubstrate binding energy and shorter nucleophilic attack distance between the catalytic residue His28 and the phytate substrate. Additionally, the K189R/K216R mutant increased the hydrolysis efficiency of phytate in food ingredients by 1.73-2.36 times. This study established an effective method for the molecular modification of phytase thermostability and activity, providing the food industry with an efficient phytase for hydrolyzing phytate in food ingredients.
RÉSUMÉ
Purpose: This study aimed to investigate the clinical and pathological characteristics, treatment strategies, and prognosis of cervical clear cell carcinoma (CCCC) in patients not exposed to diethylstilbestrol in utero. Methods: The patients diagnosed with CCCC at West China Second University Hospital of Sichuan University between January 2011 and Jun 2023 were enrolled for this retrospective study. The clinical characteristics and information on treatment and follow-up were collected. The Kaplan-Meier method and Cox regression analysis were performed to identify the relative variables for predicting progression-free survival (PFS) and overall survival (OS). Results: Of the 49 patients included, the Federation International of Gynecology and Obstetrics (FIGO) (2018) stage distribution was 37 (75.5%) stage I, 6 (12.2%) stage II, and 6 (12.2%) stage III. The median follow-up interval was 24.1 months. Six (12.2%) patients had a recurrence, and five (10.2%) patients died. The 5-year PFS rate was 86.8%, and the 5-year OS rate was 88.2%. No recurrence or death was detected in two patients who successfully completed fertility-preserving treatment and seven patients who underwent surgery to preserve ovaries. Two patients became pregnant, giving birth to two babies. The univariate analysis showed that FIGO stage, Pelvic lymph node (PLN) metastasis, lymph vascular space invasion, and depth of stromal invasion (P < 0.05) were significantly associated with PFS and OS. However, no significant prognostic factors were identified in the multivariate analysis. Conclusion: Ovary-preserving treatment and fertility-preserving surgery are safe and feasible in early-stage CCCC. Surveillance other than adjuvant treatment may be a better choice for early-stage CCCC without any pathological risk factors. More targeted therapies and immunotherapy should be pursued in future studies.
RÉSUMÉ
Objective.Vital rules learned from fluorodeoxyglucose positron emission tomography (FDG-PET) radiomics of tumor subregional response can provide clinical decision support for precise treatment adaptation. We combined a rule-based machine learning (ML) model (RuleFit) with a heuristic algorithm (gray wolf optimizer, GWO) for mid-chemoradiation FDG-PET response prediction in patients with locally advanced non-small cell lung cancer.Approach.Tumors subregions were identified using K-means clustering. GWO+RuleFit consists of three main parts: (i) a random forest is constructed based on conventional features or radiomic features extracted from tumor regions or subregions in FDG-PET images, from which the initial rules are generated; (ii) GWO is used for iterative rule selection; (iii) the selected rules are fit to a linear model to make predictions about the target variable. Two target variables were considered: a binary response measure (ΔSUVmean ⩾ 20% decline) for classification and a continuous response measure (ΔSUVmean) for regression. GWO+RuleFit was benchmarked against common ML algorithms and RuleFit, with leave-one-out cross-validated performance evaluated by the area under the receiver operating characteristic curve (AUC) in classification and root-mean-square error (RMSE) in regression.Main results.GWO+RuleFit selected 15 rules from the radiomic feature dataset of 23 patients. For treatment response classification, GWO+RuleFit attained numerically better cross-validated performance than RuleFit across tumor regions and sets of features (AUC: 0.58-0.86 vs. 0.52-0.78,p= 0.170-0.925). GWO+Rulefit also had the best or second-best performance numerically compared to all other algorithms for all conditions. For treatment response regression prediction, GWO+RuleFit (RMSE: 0.162-0.192) performed better numerically for low-dimensional models (p= 0.097-0.614) and significantly better for high-dimensional models across all tumor regions except one (RMSE: 0.189-0.219,p< 0.004).Significance. The GWO+RuleFit selected rules were interpretable, highlighting distinct radiomic phenotypes that modulated treatment response. GWO+Rulefit achieved parsimonious models while maintaining utility for treatment response prediction, which can aid clinical decisions for patient risk stratification, treatment selection, and biologically driven adaptation. Clinical trial: NCT02773238.
Sujet(s)
Carcinome pulmonaire non à petites cellules , Chimioradiothérapie , Fluorodésoxyglucose F18 , Tumeurs du poumon , Apprentissage machine , Tomographie par émission de positons , Carcinome pulmonaire non à petites cellules/imagerie diagnostique , Carcinome pulmonaire non à petites cellules/radiothérapie , Carcinome pulmonaire non à petites cellules/thérapie , Humains , Tumeurs du poumon/imagerie diagnostique , Tumeurs du poumon/radiothérapie , Tumeurs du poumon/thérapie , Heuristique , Mâle , Adulte d'âge moyen , Femelle , Résultat thérapeutique , Sujet âgé , Traitement d'image par ordinateur/méthodesRÉSUMÉ
Microcystin-leucine arginine (MC-LR) has been reported to exhibit placental toxicity, leading to potential adverse pregnancy outcomes. Placental abnormalities often coincide with congenital heart defects (CHD). However, the extent to which MC-LR-induced placental abnormalities contribute to CHD and the cellular mechanisms underlying this association remain unknown. In this study, we observed abnormal polarization of placental macrophages in pregnant mice exposed to MC-LR during pregnancy, and the embryos developed cardiac developmental defects that persisted into adulthood. Trophoblast-derived extracellular vesicles (T-EVs) increase in number during pregnancy and act as a critical signal in macrophage polarization. However, MC-LR significantly affected the miRNA expression profile of T-EVs. Upon internalization into macrophages, T-EV-derived miR-377-3p specifically targets the 3'UTR region of NR6A1 to inhibit gene expression. Silencing of transcription suppressor NR6A1 leads to abnormal activation of the downstream mTOR/S6K1/SREBP pathway, inducing metabolic reprogramming and ultimately leading to M1 polarization of macrophages. This study elucidated the placental mechanism underlying MC-LR-induced CHD for the first time, providing insights into the environmental risks associated with CHD.
Sujet(s)
Vésicules extracellulaires , Macrophages , Microcystines , Trophoblastes , Animaux , Femelle , Grossesse , Souris , Trophoblastes/effets des médicaments et des substances chimiques , Vésicules extracellulaires/métabolisme , Macrophages/effets des médicaments et des substances chimiques , Microcystines/toxicité , Maladie coronarienne/induit chimiquement , Toxines de la flore et de la faune marines , Effets différés de l'exposition prénatale à des facteurs de risque , Exposition maternelle/effets indésirables , microARN/métabolisme , PlacentaRÉSUMÉ
BACKGROUND: Immunotherapy has revolutionized the treatment of various types of tumors, but there has been no breakthrough in the treatment of gliomas. The aim of this study is to discover valuable immunotherapy target in glioma, analyze its expression in glioma and the related microenvironment, explore potential immunotherapy strategies, and propose new possibilities for the treatment of gliomas. METHODS: Immunohistochemistry (IHC) and multiplex fluorescence immunohistochemistry (mIHC) were used to analyze the expression of common immune markers and checkpoints in 187 glioma patients from Sun Yat-sen University Caner Center (SYSUCC). Bioinformatics analysis was used to examine the expression of TIM-3 in different macrophages using the Chinese Glioma Genome Atlas (CGGA) single-cell sequencing database. The Kaplan-Meier curve was used to predict the prognostic value of samples with high TIM-3 and CD68 expression. The R package was used to analyze the somatic mutation status and the sensitivity of small molecule inhibitors in TIM-3/CD68 double-high expression samples. RESULTS: TIM-3 is a relatively highly expressed immune checkpoint in glioma. Unlike other tumors, TIM-3 is mainly expressed on macrophages in the glioma microenvironment. TIM-3/CD68 double-high expression suggests poor survival in glioma and may be a new upgrade marker in both IDH-mutant glioma and IDH-wildtype low-grade glioma (LGG) glioma (P < 0.01). Exploring the combination of TIM-3 inhibitors and p38 MAPK inhibitor may be a potential treatment direction for TIM-3/CD68 double high expression gliomas in the future. CONCLUSIONS: The combination of TIM-3 and CD68 holds significant importance as a potential target for both prognosis and therapeutic intervention in glioma.
Sujet(s)
Antigènes CD , Antigènes de différenciation des myélomonocytes , Marqueurs biologiques tumoraux , Tumeurs du cerveau , Gliome , Récepteur cellulaire-2 du virus de l'hépatite A , Microenvironnement tumoral , Humains , Récepteur cellulaire-2 du virus de l'hépatite A/métabolisme , Récepteur cellulaire-2 du virus de l'hépatite A/génétique , Gliome/métabolisme , Gliome/thérapie , Gliome/génétique , Gliome/mortalité , Gliome/diagnostic , Tumeurs du cerveau/métabolisme , Tumeurs du cerveau/génétique , Tumeurs du cerveau/thérapie , Tumeurs du cerveau/mortalité , Pronostic , Antigènes de différenciation des myélomonocytes/métabolisme , Antigènes de différenciation des myélomonocytes/génétique , Antigènes CD/métabolisme , Antigènes CD/génétique , Microenvironnement tumoral/immunologie , Femelle , Mâle , Marqueurs biologiques tumoraux/métabolisme , Marqueurs biologiques tumoraux/génétique , Adulte d'âge moyen , Immunothérapie/méthodes , Adulte , Macrophages/immunologie , Macrophages/métabolisme , Régulation de l'expression des gènes tumoraux ,RÉSUMÉ
Sulfoxides have emerged as pivotal constituents in modern carbohydrate chemistry. As anomeric leaving groups, sulfinyl moieties may occupy positions directly at the anomeric position or at a more remote site. This feature article is focused on the evolution and notable advancements of glycosyl sulfoxide donors in glycosylation reactions. Its objective is to elucidate the obstacles and prospects within this evolving research domain, with the aim of enhancing comprehension and progress in the field of carbohydrate chemistry.
RÉSUMÉ
Acute kidney injury (AKI) frequently emerges as a consequential non-neurological sequel to traumatic brain injury (TBI), significantly contributing to heightened mortality risks. The intricate interplay of oxidative stress in the pathophysiology of TBI underscores the centrality of the Keap1-Nrf2/HO-1 signaling pathway as a pivotal regulator in this context. This study endeavors to elucidate the involvement of the Keap1-Nrf2/HO-1 pathway in modulating oxidative stress in AKI subsequent to TBI and concurrently explore the therapeutic efficacy of dimethyl fumarate (DMF). A rat model of TBI was established via the Feeney free-fall method, incorporating interventions with varying concentrations of DMF. Assessment of renal function ensued through measurements of serum creatinine and neutrophil gelatinase-associated lipocalin. Morphological evaluation of renal pathology was conducted employing quantitative hematoxylin and eosin staining. The inflammatory response was scrutinized by quantifying interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α levels. Oxidative stress levels were discerned through quantification of malondialdehyde and superoxide dismutase. The apoptotic cascade was examined via the terminal deoxynucleotidyl transferase dUTP deletion labeling assay. Western blotting provided insights into the expression dynamics of proteins affiliated with the Keap1-Nrf2/HO-1 pathway and apoptosis. The findings revealed severe kidney injury, heightened oxidative stress, inflammation, and apoptosis in the traumatic brain injury model. Treatment with DMF effectively reversed these changes, alleviating oxidative stress by activating the Keap1-Nrf2/HO-1 signaling pathway, ultimately conferring protection against AKI. Activating Keap1-Nrf2/HO-1 signaling pathway may be a potential therapeutic strategy for attenuating oxidative stress-induced AKI after TBI.
RÉSUMÉ
BACKGROUND: Developmental dyslexia, a complex neurodevelopmental disorder, not only affects children's academic performance but is also associated with increased healthcare costs, lower employment rates, and reduced productivity. The pathogenesis of dyslexia remains unclear and it is generally considered to be caused by the overlap of genetic and environmental factors. Systematically exploring the close relationship between exposure to environmental compounds and susceptibility genes in the development of dyslexia is currently lacking but high necessary. METHODS: In this study, we systematically compiled 131 publicly reported susceptibility genes for dyslexia sourced from DisGeNET, OMIM, and GeneCards databases. Comparative Toxicogenomics Database database was used to explore the overlap between susceptibility genes and 95 environmental compounds, including metals, persistent organic pollutants, polycyclic aromatic hydrocarbons, and pesticides. Chemical bias towards the dyslexia risk genes was taken into account in the observation/expectation ratios > 1 and the corresponding P value obtained by hypergeometric probability test. RESULTS: Our study found that the number of dyslexia risk genes targeted by each chemical varied from 1 to 109. A total of 35 chemicals were involved in chemical reactions with dyslexia-associated genes, with significant enrichment values (observed/expected dyslexia risk genes) ranging from 1.147 (Atrazine) to 66.901 (Dibenzo(a, h)pyrene). CONCLUSION: The results indicated that dyslexia-associated genes were implicated in certain chemical reactions. However, these findings are exploratory, and further research involving animal or cellular experiments is needed.
Sujet(s)
Dyslexie , Polluants environnementaux , Prédisposition génétique à une maladie , Humains , Dyslexie/génétique , Prédisposition génétique à une maladie/génétique , Polluants environnementaux/effets indésirables , Hydrocarbures aromatiques polycycliques/effets indésirables , ToxicogénétiqueRÉSUMÉ
We have developed a highly effective glycosylation method that involves the activation of 2-(2-propylsulfinyl)benzyl 1,2-orthoester glycosides using triflic anhydride (Tf2O). Our research indicates that half of the glycosyl donor is activated through Tf2O via an interrupted Pummerer reaction mechanism, while the remaining portion is activated by triflic acid (TfOH) generated in situ. As a result, as little as 0.5 equiv of Tf2O is adequate for activating the orthoester glycoside donors. This glycosylation procedure offers several benefits, such as high efficiency, wide applicability, and the utilization of a recyclable leaving group.
RÉSUMÉ
Bogie hunting instability is one of the common faults in railway vehicles. It not only affects ride comfort but also threatens operational safety. Due to the lower operating speed of metro vehicles, their bogie hunting stability is often overlooked. However, as wheel tread wear increases, metro vehicles with high conicity wheel-rail contact can also experience bogie hunting instability. In order to enhance the operational safety of metro vehicles, this paper conducts field tests and simulation calculations to study the bogie hunting instability behavior of metro vehicles and proposes corresponding solutions from the perspective of wheel-rail contact relationships. Acceleration and displacement sensors are installed on metro vehicles to collect data, which are processed in real time in 2 s intervals. The lateral acceleration of the frame is analyzed to determine if bogie hunting instability has occurred. Based on calculated safety indicators, it is determined whether deceleration is necessary to ensure the safety of vehicle operation. For metro vehicles in the later stages of wheel wear (after 300,000 km), the stability of their bogies should be monitored in real time. To improve the stability of metro vehicle bogies while ensuring the longevity of wheelsets, metro vehicle wheel treads should be reprofiled regularly, with a recommended reprofiling interval of 350,000 km.