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1.
Nat Commun ; 15(1): 6215, 2024 Jul 23.
Article de Anglais | MEDLINE | ID: mdl-39043664

RÉSUMÉ

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.


Sujet(s)
Néphrocarcinome , Tumeurs du rein , Récidive tumorale locale , Humains , Néphrocarcinome/génétique , Néphrocarcinome/anatomopathologie , Tumeurs du rein/génétique , Tumeurs du rein/anatomopathologie , Tumeurs du rein/chirurgie , Mâle , Femelle , Récidive tumorale locale/génétique , Adulte d'âge moyen , Sujet âgé , Pronostic , Génomique/méthodes , Adulte , Stadification tumorale , Apprentissage profond , Survie sans rechute
2.
Front Microbiol ; 15: 1395665, 2024.
Article de Anglais | MEDLINE | ID: mdl-38979539

RÉSUMÉ

Early weaning leads to weaning stress in calves, which hinders healthy growth and development. As an excellent sweetener applied in food, steviol glycosides (STE) has also been shown to exhibit positive biological activity in monogastric animals. Therefore, this study aimed to evaluate the impact of incorporating STE as a dietary supplement on rumen development, fermentation, and microbiota of rumen in weaned calves. This study selected 24 healthy Holstein bull calves and randomly allocated them into two groups (CON and STE). The results indicated that supplementation STE group improved rumen development in weaned calves, as demonstrated by a marked increase in the weight of the rumen, as well as the length and surface area of the rumen papilla. Compared with the CON group, the concentrations of total volatile fatty acids (TVFA), propionate, butyrate, and valerate were higher in the STE group. Moreover, STE treatment increased the relative abundance of Firmicutes and Actinobacteria at the phylum level. At the genus level, the STE group showed a significantly increased relative abundance of Succiniclasticum, Lachnospiraceae_NK3A20_group, and Olsenella, and a decreased relative abundance of Acinetobacter compared to the CON group. Pusillimonas, Lachnospiraceae_NK3A20_group, Olsenella, and Succiniclasticum were significantly enriched in rumen chyme after supplementation with STE, as demonstrated by LEfSe analysis. Overall, our findings revealed that rumen bacterial communities altered in response to the dietary supplementation with STE, and some bacterial taxa in these communities may have positive effects on rumen development during this period.

3.
Proc Natl Acad Sci U S A ; 121(29): e2323040121, 2024 Jul 16.
Article de Anglais | MEDLINE | ID: mdl-38985761

RÉSUMÉ

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli.


Sujet(s)
Protéines d'Arabidopsis , Arabidopsis , Stomates de plante , Transduction du signal , Phosphorylation , Stomates de plante/métabolisme , Protéines d'Arabidopsis/métabolisme , Protéines d'Arabidopsis/génétique , Arabidopsis/métabolisme , Arabidopsis/génétique , Protéines membranaires/métabolisme , Protéines membranaires/génétique , Domaines protéiques , Mutation
4.
J Environ Sci (China) ; 146: 251-263, 2024 Dec.
Article de Anglais | MEDLINE | ID: mdl-38969453

RÉSUMÉ

The continuous and rapid increase of chemical pollution in surface waters has become a pressing and widely recognized global concern. As emerging contaminants (ECs) in surface waters, pharmaceutical and personal care products (PPCPs), and endocrine-disrupting compounds (EDCs) have attracted considerable attention due to their wide occurrence and potential threat to human health. Therefore, a comprehensive understanding of the occurrence and risks of ECs in Chinese surface waters is urgently required. This study summarizes and assesses the environmental occurrence concentrations and ecological risks of 42 pharmaceuticals, 15 personal care products (PCPs), and 20 EDCs frequently detected in Chinese surface waters. The ECs were primarily detected in China's densely populated and highly industrialized regions. Most detected PPCPs and EDCs had concentrations between ng/L to µg/L, whereas norfloxacin, caffeine, and erythromycin had relatively high contamination levels, even exceeding 2000 ng/L. Risk evaluation based on the risk quotient method revealed that 34 PPCPs and EDCs in Chinese surface waters did not pose a significant risk, whereas 4-nonylphenol, 4-tert-octylphenol, 17α-ethinyl estradiol, 17ß-estradiol, and triclocarban did. This review provides a comprehensive summary of the occurrence and associated hazards of typical PPCPs and EDCs in Chinese surface waters over the past decade, and will aid in the regulation and control of these ECs in Chinese surface waters.


Sujet(s)
Cosmétiques , Perturbateurs endocriniens , Surveillance de l'environnement , Polluants chimiques de l'eau , Chine , Cosmétiques/analyse , Perturbateurs endocriniens/analyse , Préparations pharmaceutiques/analyse , Appréciation des risques , Polluants chimiques de l'eau/analyse
5.
Apoptosis ; 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38980600

RÉSUMÉ

Ferroptosis is a programmed cell death that relies on iron and lipid peroxidation. It differs from other forms of programmed cell death such as necrosis, apoptosis and autophagy. More and more evidence indicates that ferroptosis participates in many types of diseases, such as neurodegenerative diseases, ischemia-reperfusion injury, cardiovascular diseases and so on. Hence, clarifying the role and mechanism of ferroptosis in diseases is of great significance for further understanding the pathogenesis and treatment of some diseases. Hydrogen sulfide (H2S) is a colorless and flammable gas with the smell of rotten eggs. Many years ago, H2S was considered as a toxic gas. however, in recent years, increasing evidence indicates that it is the third important gas signaling molecule after nitric oxide and carbon monoxide. H2S has various physiological and pathological functions such as antioxidant stress, anti-inflammatory, anti-apoptotic and anti-tumor, and can participate in various diseases. It has been reported that H2S regulation of ferroptosis plays an important role in many types of diseases, however, the related mechanisms are not fully clear. In this review, we reviewed the recent literature about the role of H2S regulation of ferroptosis in diseases, and analyzed the relevant mechanisms, hoping to provide references for future in-depth researches.

6.
Front Psychiatry ; 15: 1435394, 2024.
Article de Anglais | MEDLINE | ID: mdl-39045549

RÉSUMÉ

Background: Research from observational studies has demonstrated a link between Alzheimer's disease (AD) and a higher risk of cardiovascular disease (CVD). Uncertainty surrounds the exact genetic cause of AD and coronary heart disease, particularly unstable angina (UA). Mendelian randomization (MR) analysis was used to examine the causal genetic link between AD and UA to evaluate the impact of AD on UA. Methods: The purpose of the bidirectional MR analysis was to investigate the link between exposure and illness causation. Genetic instrumental variables for AD were obtained from European populations using genome-wide association studies (GWAS). The primary causal conclusions were obtained using the inverse variance weighted approach (IVW), and other sensitivity analysis techniques were employed. Sensitivity analyses were carried out to evaluate heterogeneity and horizontal pleiotropy to guarantee accurate MR results. Results: An elevated risk of UA was linked to genetically predicted AD (IVW: OR=3.439, 95% CI: 1.565-7.555, P=0.002). A substantial genetic relationship between UA and the risk of AD was not supported by any evidence in the reverse study (IVW: OR=0.998, 95% CI: 0.995-1.001, P=0.190). Various MR techniques produced consistent results. Sensitivity analysis revealed no discernible heterogeneity or horizontal pleiotropy. Conclusions: One risk factor for UA that we found in our bidirectional Mendelian randomization trial was AD. This highlights the necessity of researching the underlying molecular mechanisms linked to AD and UA as well as the possibility of creating individualized treatment plans based on genetic data.

7.
Injury ; 55(10): 111690, 2024 Jul 06.
Article de Anglais | MEDLINE | ID: mdl-39002323

RÉSUMÉ

BACKGROUND: Femoral neck fractures (FNF) in young and middle-aged adults are primarily caused by high-energy injuries in traffic accidents. Surgical delays often occur due to transportation issues, preoperative evaluations, and economic burdens. METHODS: A retrospective analysis was conducted on young and middle-aged FNF patients undergoing reduction and internal fixation surgeries from 2010 to 2019 with the use of the National Inpatient Sample database. Logistic regression analysis was used to assess the relationship between surgical delays and complications, and the independent risk factors contributing to delays. Categorical variables were investigated via a chi-square test, while continuous variables including Elixhauser Comorbidity Index (ECI) scores, length of hospital stay (LOS), and total medical costs were analyzed via t-test or rank-sum test. RESULTS: 9,204 patients undergoing reduction and internal fixation surgeries were included. In the delayed group, patients had higher ECI scores, longer hospital stays, higher expenses, and increased inpatient mortality (1.61% vs. 0.28 %, P < 0.0001). Longer surgical delays were associated with higher risks of complications, including femoral head osteonecrosis, internal fixation loosening and breakage, and respiratory complications. Fluid and electrolyte disorders, metastatic cancer, pulmonary circulation disorders, and renal failure were identified as independent risk factors for surgical delays. Except for anemia (OR=2.37, P < 0.0001), no significant differences in early postoperative complications were found between open-reduction and closed-reduction internal fixation (ORIF/CRIF) surgeries. CONCLUSION: Early surgical intervention, within a 2-days period after injury, seems to be crucial for young adults with FNF. If CRIF is challenging in some cases, ORIF can be another choice.

8.
J Nanobiotechnology ; 22(1): 457, 2024 Jul 31.
Article de Anglais | MEDLINE | ID: mdl-39085827

RÉSUMÉ

Intervertebral disc degeneration (IVDD) is characterized by the senescence and declining vitality of nucleus pulposus cells (NPCs), often driven by mitochondrial dysfunction. This study elucidates that mesenchymal stem cells (MSCs) play a crucial role in attenuating NPC senescence by secreting mitochondria-containing microvesicles (mitoMVs). Moreover, it demonstrates that static magnetic fields (SMF) enhance the secretion of mitoMVs by MSCs. By distinguishing mitoMV generation from exosomes, this study shifts focus to understanding the molecular mechanisms of SMF intervention, emphasizing cargo transport and plasma membrane budding processes, with RNA sequencing indicating the potential involvement of the microtubule-based transport protein Kif5b. The study further confirms the interaction between Rab22a and Kif5b, revealing Rab22a's role in sorting mitoMVs into microvesicles (MVs) and potentially mediating subsequent plasma membrane budding. Subsequent construction of a gelatin methacrylate (GelMA) hydrogel delivery system further addresses the challenges of in vivo application and verifies the substantial potential of mitoMVs in delaying IVDD. This research not only sheds light on the molecular intricacies of SMF-enhanced mitoMV secretion but also provides innovative perspectives for future IVDD therapeutic strategies.


Sujet(s)
Microparticules membranaires , Dégénérescence de disque intervertébral , Champs magnétiques , Cellules souches mésenchymateuses , Mitochondries , Nucleus pulposus , Cellules souches mésenchymateuses/métabolisme , Dégénérescence de disque intervertébral/thérapie , Dégénérescence de disque intervertébral/métabolisme , Mitochondries/métabolisme , Animaux , Microparticules membranaires/métabolisme , Nucleus pulposus/métabolisme , Humains , Rats , Kinésine/métabolisme , Cellules cultivées , Rat Sprague-Dawley , Protéines G rab/métabolisme , Mâle
9.
Int J Nanomedicine ; 19: 5245-5267, 2024.
Article de Anglais | MEDLINE | ID: mdl-38855732

RÉSUMÉ

The development of metallic joint prostheses has been ongoing for more than a century alongside advancements in hip and knee arthroplasty. Among the materials utilized, the Cobalt-Chromium-Molybdenum (Co-Cr-Mo) and Titanium-Aluminum-Vanadium (Ti-Al-V) alloys are predominant in joint prosthesis construction, predominantly due to their commendable biocompatibility, mechanical strength, and corrosion resistance. Nonetheless, over time, the physical wear, electrochemical corrosion, and inflammation induced by these alloys that occur post-implantation can cause the release of various metallic components. The released metals can then flow and metabolize in vivo, subsequently causing potential local or systemic harm. This review first details joint prosthesis development and acknowledges the release of prosthetic metals. Second, we outline the metallic concentration, biodistribution, and elimination pathways of the released prosthetic metals. Lastly, we discuss the possible organ, cellular, critical biomolecules, and significant signaling pathway toxicities and adverse effects that arise from exposure to these metals.


Sujet(s)
Métaux , Humains , Animaux , Métaux/composition chimique , Métaux/pharmacocinétique , Prothèses articulaires métal-métal/effets indésirables , Distribution tissulaire , Titane/composition chimique , Titane/pharmacocinétique , Titane/toxicité , Titane/effets indésirables , Prothèse articulaire/effets indésirables , Conception de prothèse , Alliages/pharmacocinétique , Alliages/composition chimique , Alliages/toxicité
10.
Crit Care Med ; 2024 Jun 04.
Article de Anglais | MEDLINE | ID: mdl-38832833

RÉSUMÉ

OBJECTIVES: This study aimed to systematically assess the methodological quality and key recommendations of the guidelines for the diagnosis and treatment of liver failure (LF), furnishing constructive insights for guideline developers and equipping clinicians with evidence-based information to facilitate informed decision-making. DATA SOURCES: Electronic databases and manual searches from January 2011 to August 2023. STUDY SELECTION: Two reviewers independently screened titles and abstracts, then full texts for eligibility. Fourteen guidelines were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and checked by two others. Methodological quality of the guidelines was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Of the 14 guidelines, only the guidelines established by the Society of Critical Care Medicine and the American College of Gastroenterology (2023) achieved an aggregate quality score exceeding 60%, thereby meriting clinical recommendations. It emerged that there remains ample room for enhancement in the quality of the guidelines, particularly within the domains of stakeholder engagement, rigor, and applicability. Furthermore, an in-depth scrutiny of common recommendations and supporting evidence drawn from the 10 adult LF guidelines unveiled several key issues: controversy exists in the recommendation, the absence of supporting evidence and confusing use of evidence for recommendations, and a preference in evidence selection. CONCLUSIONS: There are high differences in methodological quality and recommendations among LF guidelines. Improving these existing problems and controversies will benefit existing clinical practice and will be an effective way for developers to upgrade the guidelines.

11.
Front Biosci (Landmark Ed) ; 29(5): 199, 2024 May 21.
Article de Anglais | MEDLINE | ID: mdl-38812322

RÉSUMÉ

BACKGROUND: Due to its non-invasive and widely applicable features, photodynamic therapy (PDT) has been a prominent treatment approach against cancer in recent years. However, its widespread application in clinical practice is limited by the dark toxicity of photosensitizers and insufficient penetration of light sources. This study assessed the anticancer effects of a novel photosensitizer 5-(4-amino-phenyl)-10,15,20-triphenylporphyrin with diethylene-triaminopentaacetic acid (ATPP-DTPA)-mediated PDT (hereinafter referred to as ATPP-PDT) under the irradiation of a 450-nm blue laser on colorectal cancer (CRC) in vivo and in vitro. METHODS: After 450-nm blue laser-mediated ATPP-PDT and the traditional photosensitizer 5-aminolevulinic acid (5-ALA)-PDT treatment, cell viability was detected through Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Reactive oxygen species (ROS) generation was quantified by flow cytometry and fluorescence microscopy. Western blotting and transcriptome RNA sequencing and functional experiments were used to evaluate cell apoptosis and its potential mechanism. Anti-tumor experiment in vivo was performed in nude mice with subcutaneous tumors. RESULTS: ATPP-DTPA had a marvelous absorption in the blue spectrum. Compared with 5-ALA, ATPP-DTPA could achieve significant killing effects at a lower dose. Owing to generating an excessive amount of ROS, 450-nm blue laser-mediated PDT based on ATPP-DTPA resulted in evident growth inhibition and apoptosis in CRC cells in vitro. After transcriptome RNA sequencing and functional experiments, p38 MAPK signaling pathway was confirmed to be involved in the regulation of apoptosis induced by 450-nm blue laser-mediated ATPP-PDT. Additionally, animal studies using xenograft model confirmed that ATPP-PDT had excellent anti-tumor effect and reasonable biosafety in vivo. CONCLUSIONS: PDT mediated by 450-nm blue laser combined with ATPP-DTPA may be a novel and effective method for the treatment of CRC.


Sujet(s)
Apoptose , Tumeurs colorectales , Souris nude , Photothérapie dynamique , Photosensibilisants , Espèces réactives de l'oxygène , Photothérapie dynamique/méthodes , Tumeurs colorectales/traitement médicamenteux , Tumeurs colorectales/anatomopathologie , Tumeurs colorectales/radiothérapie , Apoptose/effets des médicaments et des substances chimiques , Animaux , Photosensibilisants/pharmacologie , Photosensibilisants/usage thérapeutique , Humains , Espèces réactives de l'oxygène/métabolisme , Souris , Lignée cellulaire tumorale , Tests d'activité antitumorale sur modèle de xénogreffe , Souris de lignée BALB C , Lasers , Survie cellulaire/effets des médicaments et des substances chimiques , Acide amino-lévulinique/pharmacologie , Acide amino-lévulinique/usage thérapeutique
12.
J Org Chem ; 89(11): 7970-7981, 2024 Jun 07.
Article de Anglais | MEDLINE | ID: mdl-38788145

RÉSUMÉ

Benzothiadiazine-1-oxide scaffolds with S-stereogenic centers are prevalent in bioactive and pharmaceutical molecules. Reported works mainly focused on the metal-catalyzed asymmetric C-H amination/cyclization reaction for the synthesis of benzothiadiazine-1-oxides. Here, we reported a chiral phosphoric acid-catalyzed kinetic resolution of sulfoximines, providing chiral benzothiadiazine-1-oxides and recovered chiral sulfoximines with moderate to good enantioselectivities (s factors up to 36.6).

13.
Science ; 384(6698): eadi5199, 2024 May 24.
Article de Anglais | MEDLINE | ID: mdl-38781369

RÉSUMÉ

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.


Sujet(s)
Encéphale , Réseaux de régulation génique , Troubles mentaux , Analyse sur cellule unique , Humains , Vieillissement/génétique , Encéphale/métabolisme , Communication cellulaire/génétique , Chromatine/métabolisme , Chromatine/génétique , Génomique , Troubles mentaux/génétique , Cortex préfrontal/métabolisme , Cortex préfrontal/physiologie , Locus de caractère quantitatif
14.
Int J Biol Macromol ; 271(Pt 2): 132742, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38821297

RÉSUMÉ

Injectable hydrogels, offering adaptable drug delivery of growth factors (GFs), hold promise for treating bone defects. To optimize osteogenic efficacy, the release of GFs should mirror the natural bone healing. We developed an injectable thermo-responsive hydrogel/microgels platform for dual GF delivery for bone regeneration. Stromal cell-derived factor-1 alpha (SDF-1a) and the Methacrylate Gelatin (GelMA) microgels which encapsulated insulin-like growth factor-1 (IGF-1) loaded liposomes (Ls) were introduced into Poloxamer 407 (P407) hydrogel matrix. This system achieved the biomimetic release profile of SDF-1a and IGF-1, which covered the early stage from day 1 to 7 and the continuous stage from day 5 to 21, respectively. In vitro study confirmed the enhanced migration, osteogenic biomarker expression, and matrix mineralization of the bone marrow mesenchymal stem cells (BMSCs) co-cultivated with the dual GFs delivering hydrogel/microgels. Transcriptome sequencing revealed that the potential mechanism was associated with mitogen-activated protein kinase (MAPK) signaling activation and its downstream ribosomal protein S6 kinase 2 (RSK2) upregulation. In a critical-sized calvarial defect model in Sprague-Dawley (SD) rats, the injectable hydrogel/microgels system promoted significant bone regeneration. Collectively, our study suggested the current hydrogel/microgels system with the biomimetic release of SDF-1a and IGF-1 efficiently promoted bone regeneration, informing the future development of GF delivery systems intended for bone regeneration therapies.


Sujet(s)
Régénération osseuse , Chimiokine CXCL12 , Gélatine , Hydrogels , Facteur de croissance IGF-I , Poloxamère , Animaux , Régénération osseuse/effets des médicaments et des substances chimiques , Facteur de croissance IGF-I/pharmacologie , Chimiokine CXCL12/pharmacologie , Chimiokine CXCL12/administration et posologie , Gélatine/composition chimique , Hydrogels/composition chimique , Poloxamère/composition chimique , Rats , Cellules souches mésenchymateuses/effets des médicaments et des substances chimiques , Cellules souches mésenchymateuses/métabolisme , Rat Sprague-Dawley , Méthacrylates/composition chimique , Ostéogenèse/effets des médicaments et des substances chimiques , Matériaux biomimétiques/composition chimique , Matériaux biomimétiques/pharmacologie , Libération de médicament , Injections , Mâle
15.
Ageing Res Rev ; 98: 102323, 2024 07.
Article de Anglais | MEDLINE | ID: mdl-38734147

RÉSUMÉ

Oxidative stress is one of the main driving mechanisms of intervertebral disc degeneration(IDD). Oxidative stress has been associated with inflammation in the intervertebral disc, cellular senescence, autophagy, and epigenetics of intervertebral disc cells. It and the above pathological mechanisms are closely linked through the common hub reactive oxygen species(ROS), and promote each other in the process of disc degeneration and promote the development of the disease. This reveals the important role of oxidative stress in the process of IDD, and the importance and great potential of IDD therapy targeting oxidative stress. The efficacy of traditional therapy is unstable or cannot be maintained. In recent years, due to the rise of materials science, many bioactive functional materials have been applied in the treatment of IDD, and through the combination with traditional drugs, satisfactory efficacy has been achieved. At present, the research review of antioxidant bioactive materials in the treatment of IDD is not complete. Based on the existing studies, the mechanism of oxidative stress in IDD and the common antioxidant therapy were summarized in this paper, and the strategies based on emerging bioactive materials were reviewed.


Sujet(s)
Antioxydants , Dégénérescence de disque intervertébral , Stress oxydatif , Stress oxydatif/physiologie , Stress oxydatif/effets des médicaments et des substances chimiques , Humains , Dégénérescence de disque intervertébral/métabolisme , Dégénérescence de disque intervertébral/thérapie , Dégénérescence de disque intervertébral/traitement médicamenteux , Antioxydants/usage thérapeutique , Antioxydants/pharmacologie , Animaux , Espèces réactives de l'oxygène/métabolisme , Disque intervertébral/métabolisme , Disque intervertébral/effets des médicaments et des substances chimiques
16.
PLoS One ; 19(5): e0300741, 2024.
Article de Anglais | MEDLINE | ID: mdl-38771856

RÉSUMÉ

With the increasing importance of the stock market, it is of great practical significance to accurately describe the systemic risk of the stock market and conduct more accurate early warning research on it. However, the existing research on the systemic risk of the stock market lacks multi-dimensional factors, and there is still room for improvement in the forecasting model. Therefore, to further measure the systemic risk profile of the Chinese stock market, establish a risk early warning system suitable for the Chinese stock market, and improve the risk management awareness of investors and regulators. This paper proposes a combination model of EEMD-LSTM, which can describe the complex nonlinear interaction. Firstly, 35 stock market systemic risk indicators are selected from the perspectives of macroeconomic operation, market cross-contagion and the stock market itself to build a comprehensive indicator system that conforms to the reality of China. Furthermore, based on TEI@I complex system methodology, an EEMD-LSTM model is proposed. The EEMD method is adopted to decompose the composite index sequence into intrinsic mode function components (IMF) of different scales and one trend term. Then the LSTM algorithm is used to predicted and model the decomposed sub-sequences. Finally, the forecast result of the composite index is obtained through integration. The empirical results show that the stock market systemic risk index constructed in this paper can effectively identify important risk events within the sample period. In addition, compared with the benchmark model, the EEMD-LSTM model constructed in this paper shows a stronger early warning ability for systemic financial risks in the stock market.


Sujet(s)
Investissements , Modèles économiques , Chine , Algorithmes , Humains , Appréciation des risques/méthodes , Gestion du risque , Prévision/méthodes
17.
Front Plant Sci ; 15: 1374912, 2024.
Article de Anglais | MEDLINE | ID: mdl-38751843

RÉSUMÉ

Prunella vulgaris is an important material for Chinese medicines with rosmarinic acid (RA) as its index component. Based on the chromosome-level genome assembly we obtained recently, 51 RA biosynthesis-related genes were identified. Sequence feature, gene expression pattern and phylogenetic relationship analyses showed that 17 of them could be involved in RA biosynthesis. In vitro enzymatic assay showed that PvRAS3 catalyzed the condensation of p-coumaroyl-CoA and caffeoyl-CoA with pHPL and DHPL. Its affinity toward p-coumaroyl-CoA was higher than caffeoyl-CoA. PvRAS4 catalyzed the condensation of p-coumaroyl-CoA with pHPL and DHPL. Its affinity toward p-coumaroyl-CoA was lower than PvRAS3. UPLC and LC-MS/MS analyses showed the existence of RA, 4-coumaroyl-3',4'-dihydroxyphenyllactic acid, 4-coumaroyl-4'-hydroxyphenyllactic acid and caffeoyl-4'-hydroxyphenyllactic acid in P. vulgaris. Generation and analysis of pvras3 homozygous mutants showed significant decrease of RA, 4-coumaroyl-3',4'-dihydroxyphenyllactic acid, 4-coumaroyl-4'-hydroxyphenyllactic acid and caffeoyl-4'-hydroxyphenyllactic acid and significant increase of DHPL and pHPL. It suggests that PvRAS3 is the main enzyme catalyzing the condensation of acyl donors and acceptors during RA biosynthesis. The role of PvRAS4 appears minor. The results provide significant information for quality control of P. vulgaris medicinal materials.

18.
bioRxiv ; 2024 Mar 30.
Article de Anglais | MEDLINE | ID: mdl-38562822

RÉSUMÉ

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet, little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

19.
Langmuir ; 40(16): 8409-8417, 2024 Apr 23.
Article de Anglais | MEDLINE | ID: mdl-38588456

RÉSUMÉ

Understanding the mechanics of blisters confined by two-dimensional (2D) materials is of great importance for either fundamental studies or for their practical applications. In this work, we investigate the mechanical properties of nanoscale 2D material blisters using contact-resonance atomic force microscopy (CR-AFM). From the measurement results at the blister centers, the blisters' internal pressures are characterized, which are shown to be inversely proportional to the blisters' sizes. Our measurements agree considerably well with values predicted by theoretical mechanic analyses of the blisters. In addition, high-resolution mechanical mapping with CR-AFM reveals fine, complex ridge patterns of the blisters' confining membranes, which can hardly be distinguished from their topographies. The pattern complexity of a blister system is shown to increase with an increase in its bendability.

20.
Chemosphere ; 358: 142157, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38679181

RÉSUMÉ

Microbial electrosynthesis (MES) is an electrically driven technology that can be used for converting CO/CO2 into chemicals. The unique electronic and substrate properties of CO make it an important research target for MES. However, CO can poison the cathode and increase the overpotential of hydrogen evolution reaction (HER), thus reducing the electron transfer rate via H2. This work evaluated the effect of an anti-CO HER catalyst on the performance of MES for CO/CO2 conversion. ZnMo-metal-organic framework (MOF) materials with different calcination temperatures were synthesized. ZnMo-MOF-800 with Mo2C nanoparticles as active centers exhibited excellent resistance to CO toxicity. It also obtained the highest hydrogen evolution and enhanced electron transfer rate in CO atmosphere. MES with ZnMo-MOF-800 cathode and Clostridium ljungdahlii as biocatalyst obtained 0.31 g L-1 d-1 acetate yield, 0.1 g L-1 d-1 butyrate yield, and 0.09 g L-1 d-1 2,3-butanediol yield in CO/CO2, while Pt/C only get 0.076 g L-1 d-1 acetate yield, 0.05 g L-1 d-1 butyrate yield and 0.02 g L-1 d-1 2,3-butanediol yield. ZnMo-MOF-800 was conducive to biofilm formation, enabling it to better resist CO toxicity. This work provides new opportunities for constructing a highly efficient cathode with an anti-CO hydrogen evolution catalyst to enhance CO/CO2 conversion in MES.


Sujet(s)
Dioxyde de carbone , Monoxyde de carbone , Hydrogène , Réseaux organométalliques , Hydrogène/métabolisme , Hydrogène/composition chimique , Dioxyde de carbone/composition chimique , Catalyse , Réseaux organométalliques/composition chimique , Électrodes , Clostridium/métabolisme , Techniques électrochimiques , Molybdène/composition chimique , Zinc/composition chimique
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