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Purpose: Strong primary health care (PHC) systems require well-established PHC education systems to enhance the skills of general practitioners (GPs). However, the literature on the experiences of international collaboration in primary care education in low- and middle-income countries remains limited. The purpose of this study was to evaluate the implementation and perceived impact of the McGill-Tongji Blended Education Program for Teacher Leaders in General Practice (referred to as the "Tongji Program"). Methods: In 2020-2021, the McGill Department of Family Medicine (Montreal, Canada) and Tongji University School of Medicine (TUSM, Shanghai, China) jointly implemented the Tongji Program in Shanghai, China to improve the teaching capacity of PHC teachers. We conducted an exploratory longitudinal case study with a mixed methods design for the evaluation. Quantitative (QUAN) data was collected through questionnaire surveys and qualitative (QUAL) data was collected through focus group discussions. Results: The evaluation showed that learners in Tongji Program were primarily female GPs (21/22ï¼95%) with less than 4 years of experience in teaching (16/22ï¼73%). This program was considered a successful learning experience by most participants (19/22, 86%) with higher order learning tasks such as critical thinking and problem-solving. They also agreed that this program helped them feel more prepared to teach (21/22ï¼95%), and developed a positive attitude toward primary care (21/22ï¼95%). The QUAL interview revealed that both the Tongji and McGill organizers noted that TUSM showed strong leadership in organization, education, and coordination. Both students and teachers agreed that by adapting training content into contextualized delivery formats and settings, the Tongji Program successfully overcame language and technology barriers. Conclusions: Committed partnerships and contextualization were key to the success of the Tongji Program. Future research should focus on how international primary care education programs affect learners' behavior in their practice settings, and explore barriers and facilitators to change.
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BACKGROUND: With the rapid advancement of deep learning network technology, the application of facial recognition technology in the medical field has received increasing attention. OBJECTIVE: This study aims to systematically review the literature of the past decade on facial recognition technology based on deep learning networks in the diagnosis of rare dysmorphic diseases and facial paralysis, among other conditions, to determine the effectiveness and applicability of this technology in disease identification. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for literature search and retrieved relevant literature from multiple databases, including PubMed, on 31 December 2023. The search keywords included deep learning convolutional neural networks, facial recognition, and disease recognition. A total of 208 articles on facial recognition technology based on deep learning networks in disease diagnosis over the past 10 years were screened, and 22 articles were selected for analysis. The meta-analysis was conducted using Stata 14.0 software. RESULTS: The study collected 22 articles with a total sample size of 57 539 cases, of which 43 301 were samples with various diseases. The meta-analysis results indicated that the accuracy of deep learning in facial recognition for disease diagnosis was 91.0% [95% CI (87.0%, 95.0%)]. CONCLUSION: The study results suggested that facial recognition technology based on deep learning networks has high accuracy in disease diagnosis, providing a reference for further development and application of this technology.
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[This corrects the article DOI: 10.3389/fimmu.2024.1378359.].
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As a widely used water-based fracturing fluid, the performance of hydroxypropyl guar gum fracturing fluid is closely related to the degree of crosslinking, the quantitative characterization of which can reveal a detailed crosslinking mechanism and guide the preparation of fracturing fluid gels with an excellent performance. However, the commonly used high-temperature rheology method for evaluating the performance of fracturing fluids only qualitatively reflects the degree of crosslinking. In this study, low-field nuclear magnetic resonance (LF-NMR) was used to characterize the degree of crosslinking in guar gum fracturing fluid gels. The spin-spin relaxation time of the H proton in guar gum was molecularly analyzed using LF-NMR. The viscoelastic properties met the requirements when the crosslinking degree of the gel was 88-94 %. The transformation of the linear structure into a membrane structure during the crosslinking process of the guar gum fracturing fluid was confirmed by freeze-drying and scanning electron microscopy (SEM) from a microscopic perspective. The changing trend of the microstructure and viscoelastic properties of the fracturing fluid gel under different crosslinker dosages was consistent with changes in the degree of crosslinking. The LF-NMR test process is non-destructive to the gel structure, and the test results demonstrate good accuracy and repeatability.
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Galactanes , Spectroscopie par résonance magnétique , Mannanes , Gommes végétales , Galactanes/composition chimique , Gommes végétales/composition chimique , Mannanes/composition chimique , Spectroscopie par résonance magnétique/méthodes , Viscosité , Réactifs réticulants/composition chimique , Rhéologie , Gels/composition chimique , Élasticité , PolyosidesRÉSUMÉ
The P-glycoprotein (ABCB1)-mediated multidrug resistance (MDR) has emerged as a significant impediment to the efficacy of cancer chemotherapy in clinical therapy, which could promote the development of effective agents for MDR reversal. In this work, we reported the exploration of novel pyrazolo [1,5-a]pyrimidine derivatives as potent reversal agents capable of enhancing the sensitivity of ABCB1-mediated MDR MCF-7/ADR cells to paclitaxel (PTX). Among them, compound 16q remarkably increased the sensitivity of MCF-7/ADR cells to PTX at 5 µM (IC50 = 27.00 nM, RF = 247.40) and 10 µM (IC50 = 10.07 nM, RF = 663.44). Compound 16q could effectively bind and stabilize ABCB1, and does not affect the expression and subcellular localization of ABCB1 in MCF-7/ADR cells. Compound 16q inhibited the function of ABCB1, thereby increasing PTX accumulation, and interrupting the accumulation and efflux of the ABCB1-mediated Rh123, thus resulting in exhibiting good reversal effects. In addition, due to the potent reversal effects of compound 16q, the abilities of PTX to inhibit tubulin depolymerization, and induce cell cycle arrest and apoptosis in MCF-7/ADR cells under low-dose conditions were restored. These results indicate that compound 16q might be a promising potent reversal agent capable of revising ABCB1-mediated MDR, and pyrazolo [1,5-a]pyrimidine might represent a novel scaffold for the discovery of new ABCB1-mediated MDR reversal agents.
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Sous-famille B de transporteurs à cassette liant l'ATP , Antinéoplasiques , Multirésistance aux médicaments , Résistance aux médicaments antinéoplasiques , Tests de criblage d'agents antitumoraux , Pyrazoles , Pyrimidines , Humains , Pyrimidines/pharmacologie , Pyrimidines/composition chimique , Pyrimidines/synthèse chimique , Multirésistance aux médicaments/effets des médicaments et des substances chimiques , Sous-famille B de transporteurs à cassette liant l'ATP/métabolisme , Sous-famille B de transporteurs à cassette liant l'ATP/antagonistes et inhibiteurs , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Pyrazoles/pharmacologie , Pyrazoles/composition chimique , Pyrazoles/synthèse chimique , Relation structure-activité , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Antinéoplasiques/synthèse chimique , Structure moléculaire , Paclitaxel/pharmacologie , Paclitaxel/composition chimique , Cellules MCF-7 , Découverte de médicament , Relation dose-effet des médicaments , Prolifération cellulaire/effets des médicaments et des substances chimiques , Apoptose/effets des médicaments et des substances chimiquesRÉSUMÉ
As a food contaminant that can be quickly absorbed through the gastrointestinal system, furan has been shown to disrupt the intestinal flora and barrier. Investigation of the intestinal toxicity mechanism of furan is of great significance to health. We previously identified the regulatory impact of salidroside (SAL) against furan-provoked intestinal damage, and the present work further explored whether the alleviating effect of SAL against furan-caused intestinal injury was based on the intestinal flora; three models, normal, pseudo-germ-free, and fecal microbiota transplantation (FMT), were established, and the changes in intestinal morphology, barrier, and inflammation were observed. Moreover, 16S rDNA sequencing observed the variation of the fecal flora associated with inflammation and short-chain fatty acids (SCFAs). Results obtained from the LC-MS/MS suggested that SAL increased furan-inhibited SCFA levels, activated the mRNA expressions of SCFA receptors (GPR41, GPR43, and GPR109A), and inhibited the furan-activated TLR4/MyD88/NF-κB signaling. Analysis of protein-protein interaction further confirmed the aforementioned effects of SAL, which inhibited furan-induced barrier damage and intestinal inflammation.
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Bactéries , Acides gras volatils , Furanes , Microbiome gastro-intestinal , Glucosides , Phénols , Transduction du signal , Récepteur de type Toll-4 , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Glucosides/pharmacologie , Phénols/pharmacologie , Récepteur de type Toll-4/métabolisme , Récepteur de type Toll-4/génétique , Animaux , Transduction du signal/effets des médicaments et des substances chimiques , Furanes/pharmacologie , Mâle , Acides gras volatils/métabolisme , Humains , Souris , Bactéries/génétique , Bactéries/classification , Bactéries/isolement et purification , Bactéries/métabolisme , Bactéries/effets des médicaments et des substances chimiques , Muqueuse intestinale/métabolisme , Muqueuse intestinale/effets des médicaments et des substances chimiques , Facteur de transcription NF-kappa B/métabolisme , Facteur de transcription NF-kappa B/génétique , Rhodiola/composition chimique , Inflammation/métabolisme , Inflammation/traitement médicamenteux , Souris de lignée C57BLRÉSUMÉ
BACKGROUND: Chronic exposure to microorganisms inside homes can impact respiratory health. Few studies have used advanced sequencing methods to examine adult respiratory outcomes, especially continuous measures. We aimed to identify metagenomic profiles in house dust related to the quantitative traits of pulmonary function and airway inflammation in adults. Microbial communities, 1264 species (389 genera), in vacuumed bedroom dust from 779 homes in a US cohort were characterized by whole metagenome shotgun sequencing. We examined two overall microbial diversity measures: richness (the number of individual microbial species) and Shannon index (reflecting both richness and relative abundance). To identify specific differentially abundant genera, we applied the Lasso estimator with high-dimensional inference methods, a novel framework for analyzing microbiome data in relation to continuous traits after accounting for all taxa examined together. RESULTS: Pulmonary function measures (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio) were not associated with overall dust microbial diversity. However, many individual microbial genera were differentially abundant (p-value < 0.05 controlling for all other microbial taxa examined) in relation to FEV1, FVC, or FEV1/FVC. Similarly, fractional exhaled nitric oxide (FeNO), a marker of airway inflammation, was unrelated to overall microbial diversity but associated with differential abundance for many individual genera. Several genera, including Limosilactobacillus, were associated with a pulmonary function measure and FeNO, while others, including Moraxella to FEV1/FVC and Stenotrophomonas to FeNO, were associated with a single trait. CONCLUSIONS: Using state-of-the-art metagenomic sequencing, we identified specific microorganisms in indoor dust related to pulmonary function and airway inflammation. Some were previously associated with respiratory conditions; others were novel, suggesting specific environmental microbial components contribute to various respiratory outcomes. The methods used are applicable to studying microbiome in relation to other continuous outcomes. Video Abstract.
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Poussière , Métagénome , Microbiote , Poussière/analyse , Humains , Femelle , Mâle , États-Unis , Microbiote/génétique , Adulte d'âge moyen , Poumon/microbiologie , Adulte , Bactéries/classification , Bactéries/génétique , Bactéries/isolement et purification , Volume expiratoire maximal par seconde , Agriculture , Tests de la fonction respiratoire , Capacité vitale , Métagénomique/méthodesRÉSUMÉ
As worldwide plastic pollution continues to rise, innovative ideas for effective reuse and recycling of waste plastic are needed. Single-atom catalysts (SACs), which are known for their high activity and selectivity, present unique advantages in facilitating plastic degradation and conversion. Waste plastic can be used as a support or raw material to create SACs, which reduces waste generation while simultaneously utilizing waste as a resource. This work successfully utilized waste plastic polyurethane (PU) as a support, through a unique Rapid Thermal Processing Reactor (RTPR) to synthesize an efficient Pd1/PU SACs. At 25 °C and 0.5 MPa H2, Pd1/PU displayed outstanding activity and selectivity in the hydrogenation of styrene, as well as remarkable stability. Pd1/PU performed well in hydrogenating a variety of common substrates. These findings highlight the great potential of SACs in plastic waste reuse and recycling, offering intriguing solutions to the global plastic pollution problem.
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Background: The use of point-of-care (POC) tests prior to the COVID-19 pandemic was relatively infrequent outside of the health care context. Little is known about how public opinions regarding POC tests have changed during the pandemic. Methods: We redeployed a validated survey to uncompensated volunteers to assess preferences for point-of-care testing (POCT) benefits and concerns between June and September 2022. We received a total of 292 completed surveys. Linear regression analysis was used to compare differences in survey average response scores (ARSs) from 2020 to 2022. Results: Respondent ARSs indicated agreement for all 16 POCT benefits in 2022. Of 14 POCT concerns, there were only 2 statements that respondents agreed with most frequently, which were that "Insurance might not cover the costs of the POC test" (ARS 0.9, ± 1.0) and "POC tests might not provide a definitive result" (ARS 0.1, ± 1.0). Additionally, when comparing survey responses from 2020 to 2022, we observed 8 significant trends for POCT harms and benefits. Conclusion: The public's opinion on POC tests has become more favorable over time. However, concerns regarding the affordability and reliability of POCT results persist. We suggest that stakeholders address these concerns by developing accurate POC tests that continue to improve care and facilitate access to health care for all.
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BACKGROUND: The challenges posed by an aging society are increasingly recognized, particularly regarding the potential impacts of high-fat diets and the trend toward younger ages of disease onset. The purpose of this study was to clarify the relationships between the prevalence of stroke in the general US population and PhenoAge (PA) and PhenoAgeAccel (PAA). METHODS: Key methods included a correlation heatmap to explore linear relationships between some of the variables and weighted multivariable logistic regression to assess associations between PA, PAA, and stroke. Restricted cubic spline (RCS) analysis was used to investigate nonlinear relationships and dose-response effects. The ability of the PAA to predict stroke risk was assessed by a nomogram model and a receiver operating characteristic curve. RESULTS: After adjusting for confounding variables, both continuous and categorical PA and PAA were significantly associated with stroke prevalence. RCS analysis revealed a significant nonlinear relationship between PA and stroke prevalence. Further subgroup RCS analysis indicated that maintaining PA below 31.6 could provide greater benefits across all races and genders, specifically for individuals aged 40-80 years and those who are overweight or obese. CONCLUSION: This study highlights the importance of stroke prevention in overweight and obese populations. Monitoring intermediary factors such as high-density lipoprotein cholesterol and waist circumference may reduce stroke risk. Additionally, PA and PAA may serve as novel markers for stroke, offering new directions for health management in an aging society.
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Introduction: Oral epithelial cells were recently shown to be able to differentiate into corneal epithelium, and the efficacy of cultured autologous oral mucosal epithelial cells (CAOMEC) has been suggested by the presence of epithelium replacement. Therefore, the aim of this study was to evaluate the treatment outcome in limbal stem cell deficiency (LSCD) by adding CAOMEC to regular amniotic membrane (AM) treatment. Material and methods: Eyes with LSCD were randomized to two groups to undergo either autologous oral mucosal epithelial cell sheet (CAOMECS) combined with AM transplantation (A group) or AM transplantation alone (B group). Clinical outcome measures were corneal epithelium healing, best corrected visual acuity, symblepharon, corneal transparency, corneal neovascularization and ocular surface inflammation. Results: The normal corneal epithelialization rate in group A (73.33%) was higher than that in group B (35.48%), and the average healing time was shorter (3.45 ±2.12 weeks vs. 4.64 ±1.63 weeks). The symblepharon in the above two groups was improved in the first 3 months after surgery, but after 6 months, part of the B group had recurrence. In improving corneal transparency, group A has obvious advantages. Corneal neovascularization (CNV) was improved to some extent in the first 3 months after surgery, but group A (1.47 ±0.64) was better than group B (1.94 ±0.85) after 6 months. Both groups can improve the inflammatory state to some extent. Conclusions: The transplantation of CAOMECS offers a viable and safe alternative in the reconstruction of a stable ocular surface. The effect is better than that of traditional AM transplantation, mainly in promoting corneal epithelialization, improving ocular surface structure, and reducing fiber and vascular infiltration.
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Previous studies have demonstrated that thinking dispositions and working memory are closely related to students' critical thinking ability. However, little is known about whether bidirectionality between thinking dispositions, working memory, and critical thinking ability exists in adolescence. This study, therefore, explored this aspect across two time points. Participants were 509 Chinese adolescents (mean age at Time 1 = 14.09 years; 59.7% girls). At Time 1, adolescents were administered the measures of thinking dispositions, working memory, and critical thinking ability. They were reassessed using these measures at Time 2 one year later. The results revealed a bidirectional longitudinal relationship between adolescents' thinking dispositions and critical thinking ability, suggesting that thinking dispositions at Time 1 predicted critical thinking ability at Time 2; critical thinking ability at Time 1 also predicted subsequent thinking dispositions in adolescents. Furthermore, working memory at Time 1 showed a larger predictive effect on critical thinking ability at Time 2 compared with thinking dispositions at Time 1. These findings underscore the role of early thinking dispositions and working memory in promoting adolescents' critical thinking ability.
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The recent emergence of hepatitis-hydropericardium syndrome caused by highly pathogenic fowl adenovirus serotype 4 (FAdV-4) has resulted in significant economic losses to the poultry industry. However, the early innate immune response of immune organs within 24 hpi and the induction of autophagy in vivo after FAdV-4 infection have not been fully elucidated. In this study, 35-day-old specific pathogen-free (SPF) chickens were artificially infected with hypervirulent FAdV-4, which resulted in a mortality rate of up to 90%. The results showed that FAdV-4 infection rapidly triggered the innate immune response in vivo of chickens, with the spleen eliciting a stronger innate immune response than the thymus and bursa. During the early stage of viral infection within 24 hpi, the main receptors TLR3/7/21, MDA5, and cGAS were activated via the NF-κB and TBK1/IRF7-dependent signaling pathways, which up-regulated production of inflammatory cytokines and type I interferons. Additionally, the expression levels of the autophagy-related molecules LC3B, Beclin1, and ATG5 were significantly up-regulated at 24 hpi, while degradation of SQSTM1/p62 was observed, suggesting that FAdV-4 infection elicits a complete autophagy response in the spleen. Besides, the colocalization of Fiber2 and LC3B suggested that FAdV-4 infection induced autophagy which benefits FAdV-4 replication in vivo. This study provides new insights into the immunoregulation signal pathways of the early innate immunity in response to hypervirulent FAdV-4 infection in vivo within 24 hpi and the close relationship between viral replication and autophagy.
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Infections à Adenoviridae , Autophagie , Aviadenovirus , Poulets , Immunité innée , Maladies de la volaille , Rate , Animaux , Infections à Adenoviridae/médecine vétérinaire , Infections à Adenoviridae/immunologie , Infections à Adenoviridae/virologie , Maladies de la volaille/virologie , Maladies de la volaille/immunologie , Poulets/immunologie , Rate/virologie , Rate/immunologie , Aviadenovirus/physiologie , Aviadenovirus/immunologie , Aviadenovirus/pathogénicité , Organismes exempts d'organismes pathogènes spécifiques , Sérogroupe , VirulenceRÉSUMÉ
Hydrogen peroxide (H2O2) is one of the most valuable clean energy sources with a rapidly growing requirement in industry and daily life. The direct synthesis of H2O2 from hydrogen and oxygen is considered to be an economical and environmentally friendly manufacturing route to replace the traditional anthraquinone method, although it remains a formidable challenge owing to low H2O2 selectivity and production. Here, we report a catalyst consisting of Pd(111) nanocrystals on TiO2 modified with single Pt atoms (Pt1Pd(111)/TiO2), which displays outstanding reactivity, producing 1921.3 µmol of H2O2, a H2 conversion of 62.2% and H2O2 selectivity of 80.3% over 30 min. Kinetic and isotope experiments confirm that the extraordinary catalytic properties are due to stronger H2 activation (the rate-determining step). DFT calculations confirm that Pt1Pd(111) exhibits lower energy barriers for H2 dissociation and two-step O2 hydrogenation, but higher energy barriers for side reactions than Pt1Pd(100), demonstrating clear facet dependence and resulting in greater selectivity and amount of H2O2 produced.
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Fluoride, a ubiquitous environmental compound, carries significant health risks at excessive levels. This study investigated the reproductive toxicity of fluoride exposure during puberty in mice, focusing on its impact on testicular development, spermatogenesis, and underlying mechanisms. The results showed that fluoride exposure during puberty impaired testicular structure, induced germ cell apoptosis, and reduced sperm counts in mice. Additionally, the SOD activity and GSH content were significantly decreased, while MDA content was significantly elevated in the NaF group. Immunohistochemistry showed an increase in the number of cells positive for GRP78, a key ER stress marker. Moreover, qRT-PCR and Western blot analyses confirmed the upregulation of both Grp78 mRNA and protein expression, as well as increased mRNA expression of other ER stress-associated genes (Grp94, chop, Atf6, Atf4, and Xbp1) and enhanced protein expression of phosphorylated PERK, IRE1α, eIF2α, JNK, XBP-1, ATF-6α, ATF-4, and CHOP. In conclusion, our findings demonstrate that fluoride exposure during puberty impairs testicular structure, induces germ cell apoptosis, and reduces sperm counts in mice. ER stress may participate in testicular cell apoptosis, and contribute to the testicular damage and decreased sperm counts induced by fluoride.
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Apoptose , Chaperonne BiP du réticulum endoplasmique , Stress du réticulum endoplasmique , Fluorures , Testicule , Animaux , Mâle , Stress du réticulum endoplasmique/effets des médicaments et des substances chimiques , Apoptose/effets des médicaments et des substances chimiques , Testicule/effets des médicaments et des substances chimiques , Testicule/métabolisme , Fluorures/toxicité , Souris , Maturation sexuelle/effets des médicaments et des substances chimiques , Protéines du choc thermique/métabolisme , Protéines du choc thermique/génétique , Numération des spermatozoïdes , Spermatogenèse/effets des médicaments et des substances chimiquesRÉSUMÉ
Skin tissue-resident memory T (Trm) cells are produced by antigenic stimulation and remain in the skin for a long time without entering the peripheral circulation. In the healthy state Trm cells can play a patrolling and surveillance role, but in the disease state Trm cells differentiate into various phenotypes associated with different diseases, exhibit different localizations, and consequently have local protective or pathogenic roles, such as disease recurrence in vitiligo and maintenance of immune homeostasis in melanoma. The most common surface marker of Trm cells is CD69/CD103. However, the plasticity of tissue-resident memory T cells after colonization remains somewhat uncertain. This ambiguity is largely due to the variation in the functionality and ultimate destination of Trm cells produced from memory cells differentiated from diverse precursors. Notably, the presence of Trm cells is not stationary across numerous non-lymphoid tissues, most notably in the skin. These cells may reenter the blood and distant tissue sites during the recall response, revealing the recycling and migration potential of the Trm cell progeny. This review focuses on the origin and function of skin Trm cells, and provides new insights into the role of skin Trm cells in the treatment of autoimmune skin diseases, infectious skin diseases, and tumors.
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Plasticité cellulaire , Homéostasie , Mémoire immunologique , Cellules T mémoire , Maladies de la peau , Peau , Humains , Homéostasie/immunologie , Cellules T mémoire/immunologie , Cellules T mémoire/métabolisme , Peau/immunologie , Peau/anatomopathologie , Plasticité cellulaire/immunologie , Animaux , Maladies de la peau/immunologie , Antigènes CD/métabolisme , Antigènes CD/immunologieRÉSUMÉ
Myrosinase (Myr) catalyzes the hydrolysis of glucosinolates, yielding biologically active metabolites. In this study, glucoraphanin (GRA) extracted from broccoli seeds was effectively hydrolyzed using a Myr-obtained cabbage aphid (Brevicoryne brassicae) (BbMyr) to produce (R)-sulforaphane (SFN). The gene encoding BbMyr was successfully heterologously expressed in Escherichia coli, resulting in the production of 1.6 g/L (R)-SFN, with a remarkable yield of 20.8 mg/gbroccoli seeds, achieved using recombination E. coli whole-cell catalysis under optimal conditions (pH 4.5, 45 °C). Subsequently, BbMyr underwent combinatorial simulation-driven mutagenesis, yielding a mutant, DE9 (N321D/Y426S), showing a remarkable 2.91-fold increase in the catalytic efficiency (kcat/KM) compared with the original enzyme. Molecular dynamics simulations demonstrated that the N321D mutation in loopA of mutant DE9 enhanced loopA stability by inducing favorable alterations in hydrogen bonds, while the Y426S mutation in loopB decreased spatial resistance. This research lays a foundation for the environmentally sustainable enzymatic (R)-SFN synthesis.
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Aphides , Brassica , Glycosidases , Isothiocyanates , Sulfoxydes , Sulfoxydes/composition chimique , Sulfoxydes/métabolisme , Animaux , Isothiocyanates/métabolisme , Isothiocyanates/composition chimique , Aphides/enzymologie , Aphides/génétique , Glycosidases/génétique , Glycosidases/métabolisme , Glycosidases/composition chimique , Brassica/génétique , Brassica/enzymologie , Brassica/composition chimique , Protéines d'insecte/génétique , Protéines d'insecte/métabolisme , Protéines d'insecte/composition chimique , Glucosinolates/métabolisme , Glucosinolates/composition chimique , Cinétique , Simulation de dynamique moléculaire , Oximes/composition chimique , Oximes/métabolisme , Escherichia coli/génétique , Escherichia coli/métabolisme , Évolution moléculaire dirigée , Imidoesters/métabolisme , Imidoesters/composition chimiqueRÉSUMÉ
Thermal processing of food is likely to form acrylamide (AA) and elaidic acid (EA), which are both mainly metabolized by the liver. The two substances are associated with the pathogenesis of liver disease. In the current study, we investigated the toxic effects of the combined action of AA and EA on HSC-T6 cells, and the mechanism of apoptosis exacerbated by the co-exposure. The results showed a synergistic effect of AA and EA, which exacerbated the damage and oxidative stress (OS) in HSC-T6. Meanwhile, the expression of endoplasmic reticulum stress (ERS) proteins, such as GRP78 and CHOP, was increased, the ERS pathway was activated, and Ca2+ in cells was increased, which exacerbated mitochondrial damage, and opened IP3R-Grp75-VDAC1 channel. Both ERS and mitochondrial damage caused the process of cell apoptosis. Inhibition of ERS by 4-phenylbutyric acid (4-PBA) significantly reversed the synergistic effects on mitochondrial damage via ERS, suggesting that AA and EA exacerbated mitochondrial damage through ERS-mediated Ca2+ overload. AA and EA synergistically damaged the function of mitochondria through exacerbating ERS and led to cell apoptosis.
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Acrylamide , Apoptose , Stress du réticulum endoplasmique , Acides oléiques , Apoptose/effets des médicaments et des substances chimiques , Stress du réticulum endoplasmique/effets des médicaments et des substances chimiques , Acrylamide/toxicité , Animaux , Lignée cellulaire , Acides oléiques/pharmacologie , Stress oxydatif/effets des médicaments et des substances chimiques , Calcium/métabolisme , Rats , Mitochondries/effets des médicaments et des substances chimiques , Mitochondries/métabolisme , Facteur de transcription CHOP/métabolisme , Facteur de transcription CHOP/génétique , Synergie des médicaments , Chaperonne BiP du réticulum endoplasmique , PhénylbutyratesRÉSUMÉ
Infectious diseases pose a significant threat to global health, yet traditional microbiological identification methods suffer from drawbacks, such as high costs and long processing times. Raman spectroscopy, a label-free and noninvasive technique, provides rich chemical information and has tremendous potential in fast microbial diagnoses. Here, we propose a novel Combined Mutual Learning Net that precisely identifies microbial subspecies. It demonstrated an average identification accuracy of 87.96% in an open-access data set with thirty microbial strains, representing a 5.76% improvement. 50% of the microbial subspecies accuracies were elevated by 1% to 46%, especially for E. coli 2 improved from 31% to 77%. Furthermore, it achieved a remarkable subspecies accuracy of 92.4% in the custom-built fiber-optical tweezers Raman spectroscopy system, which collects Raman spectra at a single-cell level. This advancement demonstrates the effectiveness of this method in microbial subspecies identification, offering a promising solution for microbiology diagnosis.
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Escherichia coli , Pinces optiques , Analyse spectrale Raman/méthodesRÉSUMÉ
OBJECTIVES: In observational studies, the 25-hydroxyvitamin D (25(OH)D) level in body has been found to be closely related to particulate matter (PM) air pollution. In this study, we used the two-sample mendelian randomisation (MR) method to investigate and discuss the potential causal relationship and mode of influence. STUDY DESIGN: MR study. METHODS: PM data (PM10, PM2.5-10, PM2.5, PM2.5 absorbance) came from the UK Biobank database, and 25(OH)D data came from European Bioinformatics Institute (EBI) database. The analysis was conducted utilising three prominent methods (inverse-variance-weighted [IVW], MR-Egger, weighted median, weighted mode, and simple mode). The primary emphasis was placed on IVW, accompanied by heterogeneity and horizontal pleiotropy tests. Furthermore, sensitivity analysis was undertaken. RESULTS: The MR analysis revealed a significant association between exposure to PM10 and a decrease in levels of 25(OH)D (odds ratio [OR]: 0.878, 95% confidence interval [CI]: 0.789-0.977). However, no significant relationship was observed between PM2.5 exposure and 25(OH)D (OR: 0.943, 95%CI: 0.858-1.037). Further analysis indicated that the main contributor to the decline in 25(OH)D levels is linked to PM2.5-10 exposure (OR: 0.840, 95%CI: 0.751-0.940) and PM2.5 absorbance (OR: 0.875, 95%CI: 0.824-0.929). No heterogeneity and horizontal pleiotropy existed. CONCLUSIONS: The MR results suggest that PM (PM10, PM2.5-10 and PM2.5 absorbance) exposure lowers vitamin D (VD) levels, but PM2.5 was not found to have a significant effect on VD in humans.