Your browser doesn't support javascript.
loading
Montrer: 20 | 50 | 100
Résultats 1 - 20 de 683
Filtrer
1.
ChemSusChem ; : e202401111, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38954154

RÉSUMÉ

Due to the active unstable nature of carbon anions, it is challenging to develop carbanion-functionalized ionic liquids (ILs) for efficient and reversible carbon dioxide (CO2) capture. Here, a series of carbanion-based ILs with large conjugated structures were designed and a promising system was achieved through tuning the nucleophilicity of carbanions and screening the cation. The ideal carbanion-functionalized IL trihexyl(tetradecyl)phosphonium N,N-diethycyanoacetoamide ([P66614][DECA]) showed equimolar chemisorption of CO2 (up to 0.98 mol CO2 /mol IL) under ambient pressure and excellent absorption rate. What's more, the combined CO2 can be released easily, leading to excellent reversibility due to high stability of anion conjugated structures. More importantly, the presence of water had negligible effect on the absorption capacity, which makes it potential to be applied to the CO2 capture in industrial flue gas. The chemisorption mechanism of the carbanion and CO2 was confirmed by spectroscopic investigations and DFT calculations, where carboxylic acid product was formed through proton transfer after the carbanions reacted with CO2. Considering that high capacity, quick rate as well as excellent reversibility, these carbanion-functionalized IL should certainly represent competitive candidates for further scale up and practical application in CO2 capture.

2.
J Pers Assess ; : 1-13, 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38959132

RÉSUMÉ

Although many studies have attempted to validate grit scales because of the construct's popularity, most have considered the shorter rather than the longer Original Grit Scale (Grit-O). We examined the Grit-O's construct validity, longitudinal measurement invariance, incremental validity for academic performance, and longitudinal predictive validity for subjective well-being among young Chinese. We used a cross-sectional sample of 3,322 college students and a longitudinal sample of 1,884 college students, tested twice over 10 months. The first-order factor model fit the data better than other models and showed partial configural and metric measurement invariance over time. Grit and its two facets longitudinally predicted subjective well-being (i.e., life satisfaction, happiness, positive affect, negative affect, and depression) but had negligible incremental validity for two semesters' grades after controlling for conscientiousness. So, while the Grit-O could be a useful construct for young adults, its predictive value overlaps with a better-established construct, conscientiousness.

3.
J Evid Based Med ; 2024 Jul 08.
Article de Anglais | MEDLINE | ID: mdl-38975690

RÉSUMÉ

OBJECTIVE: Skeletal muscle catabolism supports multiple organs and systems during severe trauma and infection, but its role in COVID-19 remains unclear. This study investigates the interactions between skeletal muscle and COVID-19. METHODS: The PubMed, EMbase, and The Cochrane Library databases were systematically searched from January 2020 to August 2023 for cohort studies focusing on the impact of skeletal muscle on COVID-19 prevalence and outcomes, and longitudinal studies examining skeletal muscle changes caused by COVID-19. Skeletal muscle quantity (SMQN) and quality (SMQL) were assessed separately. The random-effect model was predominantly utilized for statistical analysis. RESULTS: Seventy studies with moderate to high quality were included. Low SMQN/SMQL was associated with an increased risk of COVID-19 infection (OR = 1.62, p < 0.001). Both the low SMQN and SMQL predicted COVID-19-related mortality (OR = 1.53, p = 0.016; OR = 2.18, p = 0.001, respectively). Mortality risk decreased with increasing SMQN (OR = 0.979, p = 0.009) and SMQL (OR = 0.972, p = 0.034). Low SMQN and SMQL were also linked to the need for intensive care unit/mechanical ventilation, increased COVID-19 severity, and longer hospital stays. Significant skeletal muscle wasting, characterized by reduced volume and strength, was observed during COVID-19 infection and the pandemic. CONCLUSIONS: This study reveals a detrimental vicious circle between skeletal muscle and COVID-19. Effective management of skeletal muscle could be beneficial for treating COVID-19 infections and addressing the broader pandemic. These findings have important implications for the management of future virus pandemics. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023395476.

4.
Int J Biol Macromol ; : 133351, 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38945713

RÉSUMÉ

The current food packaging films can be preservative but lack the function of combining antibacterial and sterilization which lead to films can not maximize prolong shelf life of perishable foods. This study provided a new strategy to realize prolonging shelf life of perishable foods by integrating antibacterial and sterilization which focused on applying photodynamic inactivation to films with continuous activity, where curcumin (CUR) and sodium copper chlorophyll (SCC) were loaded into chitosan (CS) films. Compared to pure CS films, the barrier capacity (oxygen permeability and water vapor permeability) and mechanical properties of composite films were improved by introducing CUR and SCC. In addition, the composite film can effectively against food-borne pathogenic bacteria and significantly prolong the shelf life of cherries and pork. The provided strategy has potential application prospects in food preservation packaging.

5.
SLAS Technol ; : 100152, 2024 May 31.
Article de Anglais | MEDLINE | ID: mdl-38823582

RÉSUMÉ

Coronary microcirculation dysfunction (CMD) is one of the main causes of cardiovascular disease. Traditional treatment methods lack specificity, making it difficult to fully consider the differences in patient conditions and achieve effective treatment and intervention. The complexity and diversity of CMD require more standardized diagnosis and treatment plans to clarify the best treatment strategy and long-term outcomes. The existing treatment measures mainly focus on symptom management, including medication treatment, lifestyle intervention, and psychological therapy. However, the efficacy of these methods is not consistent for all patients, and the long-term efficacy is not yet clear. GSEA is a bioinformatics method used to interpret gene expression data, particularly for identifying the enrichment of predefined gene sets in gene expression data. In order to achieve personalized treatment and improve the quality and effectiveness of interventions, this article combined GSEA (Gene Set Enrichment Analysis) technology to conduct in-depth research on potential drug targets and their interaction networks in coronary microcirculation dysfunctions. This article first utilized the Coremine medical database, GeneCards, and DrugBank public databases to collect gene data. Then, filtering methods were used to preprocess the data, and GSEA was used to analyze the preprocessed gene expression data to identify and calculate pathways and enrichment scores related to CMD. Finally, protein sequence features were extracted through the calculation of autocorrelation features. To verify the effectiveness of GSEA, this article conducted experimental analysis from four aspects: precision, receiver operating characteristic (ROC) curve, correlation, and potential drug targets, and compared them with Gene Regulatory Networks (GRN) and Random Forest (RF) methods. The results showed that compared to the GRN and RF methods, the average precision of GSEA improved by 0.11. The conclusion indicated that GSEA helped identify and explore potential drug targets and their interaction networks, providing new ideas for personalized quality of CMD.

6.
Nat Methods ; 2024 Jun 07.
Article de Anglais | MEDLINE | ID: mdl-38849569

RÉSUMÉ

The Long-read RNA-Seq Genome Annotation Assessment Project Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. Using different protocols and sequencing platforms, the consortium generated over 427 million long-read sequences from complementary DNA and direct RNA datasets, encompassing human, mouse and manatee species. Developers utilized these data to address challenges in transcript isoform detection, quantification and de novo transcript detection. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. Incorporating additional orthogonal data and replicate samples is advised when aiming to detect rare and novel transcripts or using reference-free approaches. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.

7.
Aesthet Surg J ; 2024 Jun 17.
Article de Anglais | MEDLINE | ID: mdl-38885307

RÉSUMÉ

BACKGROUND: Capsular contracture is a significant complication following mammaplasty, with varying incidence rates and symptoms. The etiology of capsular contracture is multifactorial, with postoperative hematoma being recognized as a potential contributing factor. OBJECTIVES: The study aimed to investigate the impact of postoperative hematoma on capsular contracture following mammaplasty, utilizing pig models and modified biomechanical testing. It sought to compare the severity of capsular contracture between smooth and textured implants in the presence of hematoma, assess the biomechanical properties of the capsules, and explore the histological and molecular changes associated with the condition. METHODS: The study involved five female miniature pigs, implanted with both smooth and textured implants. Hematoma models were established, and various methods were employed to evaluate the impact of the prosthesis surface and hematoma on capsular contracture, including ultrasound assessment, biomechanical tests, scanning electron microscopy, histological analysis, and transcriptome sequencing. RESULTS: Capsules in hematoma groups were classified as Baker III/IV, with significantly unfavorable thickness, elastic modulus, and relaxation/creep amounts compared to non-hematoma groups. Smooth implants under hematoma conditions exhibited increased muscle content and biomechanical strength of the capsule. Transcriptomic analysis highlighted differential gene expression related to muscle development and contraction in smooth implants with hematomas. CONCLUSIONS: Hematomas increase the risk of capsular contracture, with smooth implants exacerbating this effect by enhancing pathways related to muscle development and contraction. This underscores the importance of hematoma prevention and treatment strategies, particularly when using smooth implants, to minimize the occurrence of capsular contracture. The study provides insights into the mechanisms underlying capsular contracture and offers evidence to guide surgical and postoperative management strategies.

8.
Molecules ; 29(11)2024 May 29.
Article de Anglais | MEDLINE | ID: mdl-38893429

RÉSUMÉ

In recent years, 2D materials and their heterostructures have started to offer an ideal platform for high-performance photodetection devices. In this work, a highly responsive, self-powered photodetector based on PtSe2/MoS2 van der Waals heterostructure is demonstrated. The device achieves a noteworthy wide band spectral response from visible (405 nm) range to the near infrared region (980 nm). The remarkable photoresponsivity and external quantum efficiency up to 4.52 A/W, and 1880% are achieved, respectively, at 405 nm illumination with fast response time of 20 ms. In addition, the photodetector exhibits a decent photoresponsivity of 33.4 mA/W at zero bias, revealing the photodetector works well in the self-driven mode. Our work suggests that a PtSe2/MoS2 heterostructure could be a potential candidate for the high-performance photodetection applications.

9.
J Environ Manage ; 365: 121512, 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38897083

RÉSUMÉ

The construction of ecological networks within the context of urbanization is an effective approach to cope with the challenges of urban biodiversity decline, representing a crucial goal in urban planning and development. However, existing studies often overlook the richness and uniqueness within species communities by homogenizing traits of species in the same class. This study proposes a framework for constructing and optimizing ecological networks focused on differential conservation within the same class. By classifying birds into three groups (specialists of water, forest or urban areas) based on their ecological requirements and urbanization tolerance, we constructed an ecological network tailored to their distinct migratory dispersal patterns. We then identified strategic areas including pinch points, barriers, and breakpoints specific to each bird group. Our findings reveal notable variations in suitable habitat distribution among different bird groups in urban environments. Corridor layouts varied according to habitat preferences and migratory dispersal patterns. Despite these differences, urban built-up areas persist as central hubs for the distribution of suitable habitats for 75% of bird species, with peripheral mountain-plain transition areas constituting 63% of crucial dispersal corridors. This emphasizes the critical role of urban built-up areas in maintaining biodiversity and ecological connectivity. Prioritizing connectivity between central urban areas and distant natural spaces is imperative. Our approach innovatively classifies and constructs networks to identify strategic areas with diverse species-specific attributes, providing valuable spatial information for land planning and guiding solutions to enhance target species. While the primary focus is on bird conservation in Beijing, our framework is broadly applicable to global biodiversity management and green planning under urbanization challenges. Overall, this study offers innovative insights for urban planning development and serves as decision support for prioritizing urban actions.

10.
ACS Synth Biol ; 13(6): 1737-1749, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38845097

RÉSUMÉ

Genome editing is the basis for the modification of engineered microbes. In the process of genome editing, the design of editing sequences, such as primers and sgRNA, is very important for the accurate positioning of editing sites and efficient sequence editing. The whole process of genome editing involves multiple rounds and types of editing sequence design, while the development of related whole-workflow design tools for high-throughput experimental requirements lags. Here, we propose AutoESDCas, an online tool for the end-to-end editing sequence design for microbial genome editing based on the CRISPR/Cas system. This tool facilitates all types of genetic manipulation covering diverse experimental requirements and design scenarios, enables biologists to quickly and efficiently obtain all editing sequences needed for the entire genome editing process, and empowers high-throughput strain modification. Notably, with its off-target risk assessment function for editing sequences, the usability of the design results is significantly improved. AutoESDCas is freely available at https://autoesdcas.biodesign.ac.cn/with the source code at https://github.com/tibbdc/AutoESDCas/.


Sujet(s)
Systèmes CRISPR-Cas , Internet , Logiciel , Systèmes CRISPR-Cas/génétique , Génome microbien/génétique , Édition de gène/méthodes
11.
J Colloid Interface Sci ; 671: 751-769, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-38824748

RÉSUMÉ

Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor's adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG's efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.


Sujet(s)
Antibactériens , Antinéoplasiques , Catéchine , Cuivre , Nanocomposites , Antibactériens/pharmacologie , Antibactériens/composition chimique , Cuivre/composition chimique , Cuivre/pharmacologie , Nanocomposites/composition chimique , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Animaux , Souris , Humains , Catéchine/composition chimique , Catéchine/pharmacologie , Catéchine/analogues et dérivés , Tests de sensibilité microbienne , Résistance bactérienne aux médicaments/effets des médicaments et des substances chimiques , Photothérapie dynamique , Infection de plaie/traitement médicamenteux , Infection de plaie/anatomopathologie , Infection de plaie/microbiologie , Tests de criblage d'agents antitumoraux , Staphylococcus aureus/effets des médicaments et des substances chimiques , Thérapie photothermique , Taille de particule , Escherichia coli/effets des médicaments et des substances chimiques , Survie cellulaire/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale , Propriétés de surface , Prolifération cellulaire/effets des médicaments et des substances chimiques
12.
Opt Express ; 32(12): 21629-21642, 2024 Jun 03.
Article de Anglais | MEDLINE | ID: mdl-38859512

RÉSUMÉ

Precisely sensing the light field direction information plays the essential role in the fields of three-dimensional (3D) imaging, light field sensing, target positioning and tracking, remote sensing, etc. It is thrilling to find that the optical fiber can be used as a sensing component due to its high sensitivity, compact size, and strong resistance to electromagnetic interference. According to the core principle that the few-mode fiber output speckle pattern is sensitive to the change of incident light field direction, the variation characteristics is further investigated in this research study. Based on the simulation and analysis of the fiber transmission characteristics, the output speckle corresponding to the incident light field with the direction in the range of ±6° horizontally and vertically are calculated. Furthermore, a deep convolutional neural network (CNN): fiber speckle demodulation network (FSDNET) is proposed and constructed to establish what we believe to be a novel way to reveal and identify the mapping relationship between the light field direction and the output speckle. The theoretical simulation shows that the mean absolute error (MAE) between the perceived light field directions and the true directions is 0.01°. Then, a light field direction sensing system based on the few-mode fiber is developed. Regarding to the performance of the sensing system, the MAE of the FSDNET for the light field directions that have appeared in the training set is 0.0389°, and for testing set of the unknown directions that have not appeared in the training set, the MAE is 0.0570°. Therefore, the simulation and experimental results prove that high performance sensing of light field direction can be achieved by the proposed few-mode fiber sensing system and the FSDNET.

13.
J Med Chem ; 2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-38920289

RÉSUMÉ

Developing therapies for the activated B-cell like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL) remains an area of unmet medical need. A subset of ABC DLBCL tumors is driven by activating mutations in myeloid differentiation primary response protein 88 (MYD88), which lead to constitutive activation of interleukin-1 receptor associated kinase 4 (IRAK4) and cellular proliferation. IRAK4 signaling is driven by its catalytic and scaffolding functions, necessitating complete removal of this protein and its escape mechanisms for complete therapeutic suppression. Herein, we describe the identification and characterization of a dual-functioning molecule, KT-413 and show it efficiently degrades IRAK4 and the transcription factors Ikaros and Aiolos. KT-413 achieves concurrent degradation of these proteins by functioning as both a heterobifunctional degrader and a molecular glue. Based on the demonstrated activity and safety of KT-413 in preclinical studies, a phase 1 clinical trial in B-cell lymphomas, including MYD88 mutant ABC DLBCL, is currently underway.

14.
J Transl Med ; 22(1): 577, 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38890669

RÉSUMÉ

BACKGROUND: Inherited variations in DNA double-strand break (DSB) repair pathway are known to influence ovarian cancer occurrence, progression and treatment response. Despite its significance, survival-associated genetic variants within the DSB pathway remain underexplored. METHODS: In the present study, we performed a two-phase analysis of 19,290 single-nucleotide polymorphisms (SNPs) in 199 genes in the DSB repair pathway from a genome-wide association study (GWAS) dataset and explored their associations with overall survival (OS) in 1039 Han Chinese epithelial ovarian carcinoma (EOC) patients. After utilizing multivariate Cox regression analysis with bayesian false-discovery probability for multiple test correction, significant genetic variations were identified and subsequently underwent functional prediction and validation. RESULTS: We discovered a significant association between poor overall survival and the functional variant GEN1 rs56070363 C > T (CT + TT vs. TT, adjusted hazard ratio (HR) = 2.50, P < 0.001). And the impact of GEN1 rs56070363 C > T on survival was attributed to its reduced binding affinity to hsa-miR-1287-5p and the resultant upregulation of GEN1 mRNA expression. Overexpression of GEN1 aggregated EOC cell proliferation, invasion and migration presumably by influencing the expression of immune inhibitory factors, thereby elevating the proportion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and then constructing an immunosuppressive tumor microenvironment. CONCLUSIONS: In conclusion, GEN1 rs56070363 variant could serve as a potential predictive biomarker and chemotherapeutic target for improving the survival of EOC patients.


Sujet(s)
Carcinome épithélial de l'ovaire , Holliday junction resolvases , Tumeurs de l'ovaire , Polymorphisme de nucléotide simple , Femelle , Humains , Adulte d'âge moyen , Carcinome épithélial de l'ovaire/génétique , Carcinome épithélial de l'ovaire/mortalité , Lignée cellulaire tumorale , Mouvement cellulaire , Prolifération cellulaire , Chine , Peuples d'Asie de l'Est/génétique , Régulation de l'expression des gènes tumoraux , Étude d'association pangénomique , Estimation de Kaplan-Meier , microARN/génétique , Invasion tumorale , Tumeurs de l'ovaire/génétique , Tumeurs de l'ovaire/mortalité , Pronostic , Analyse de survie , Holliday junction resolvases/génétique
15.
Cancer Med ; 13(12): e7388, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38924330

RÉSUMÉ

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.


Sujet(s)
Antigènes glycanniques associés aux tumeurs , Tumeurs des voies biliaires , Marqueurs biologiques tumoraux , Courbe ROC , Humains , Mâle , Femelle , Adulte d'âge moyen , Tumeurs des voies biliaires/diagnostic , Tumeurs des voies biliaires/sang , Antigènes glycanniques associés aux tumeurs/sang , Marqueurs biologiques tumoraux/sang , Sujet âgé , Carcinome hépatocellulaire/diagnostic , Carcinome hépatocellulaire/sang , Tumeurs du foie/diagnostic , Tumeurs du foie/sang , Cholangiocarcinome/diagnostic , Cholangiocarcinome/sang , Antigène CA 19-9/sang , Études rétrospectives , Sensibilité et spécificité
16.
Cancer Lett ; 597: 217068, 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38901665

RÉSUMÉ

With the widespread use of anti-androgen therapy, such as abiraterone and enzalutamide, the incidence of neuroendocrine prostate cancer (NEPC) is increasing. NEPC is a lethal form of prostate cancer (PCa), with a median overall survival of less than one year after diagnosis. In addition to the common bone metastases seen in PCa, NEPC exhibits characteristics of visceral metastases, notably liver metastasis, which serves as an indicator of a poor prognosis clinically. Key factors driving the neuroendocrine plasticity of PCa have been identified, yet the underlying mechanism behind liver metastasis remains unclear. In this study, we identified PROX1 as a driver of neuroendocrine plasticity in PCa, responsible for promoting liver metastases. Mechanistically, anti-androgen therapy alleviates transcriptional inhibition of PROX1. Subsequently, elevated PROX1 levels drive both neuroendocrine plasticity and liver-specific transcriptional reprogramming, promoting liver metastases. Moreover, liver metastases in PCa induced by PROX1 depend on reprogrammed lipid metabolism, a disruption that effectively reduces the formation of liver metastases.

17.
Nucleic Acids Res ; 52(W1): W299-W305, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38769057

RÉSUMÉ

A key challenge in pathway design is finding proper enzymes that can be engineered to catalyze a non-natural reaction. Although existing tools can identify potential enzymes based on similar reactions, these tools encounter several issues. Firstly, the calculated similar reactions may not even have the same reaction type. Secondly, the associated enzymes are often numerous and identifying the most promising candidate enzymes is difficult due to the lack of data for evaluation. Thirdly, existing web tools do not provide interactive functions that enable users to fine-tune results based on their expertise. Here, we present REME (https://reme.biodesign.ac.cn/), the first integrated web platform for reaction enzyme mining and evaluation. Combining atom-to-atom mapping, atom type change identification, and reaction similarity calculation enables quick ranking and visualization of reactions similar to an objective non-natural reaction. Additional functionality enables users to filter similar reactions by their specified functional groups and candidate enzymes can be further filtered (e.g. by organisms) or expanded by Enzyme Commission number (EC) or sequence homology. Afterward, enzyme attributes (such as kcat, Km, optimal temperature and pH) can be assessed with deep learning-based methods, facilitating the swift identification of potential enzymes that can catalyze the non-natural reaction.


Sujet(s)
Enzymes , Logiciel , Enzymes/composition chimique , Enzymes/métabolisme , Fouille de données/méthodes , Internet , Apprentissage profond , Biocatalyse
18.
Technol Cancer Res Treat ; 23: 15330338241257490, 2024.
Article de Anglais | MEDLINE | ID: mdl-38803001

RÉSUMÉ

Objectives: This study aimed to investigate the effect of specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1)-mediated deSUMOylation on the malignant behavior of glioma stem cells (GSCs) under hypoxia conditions and evaluate the clinical value of prevention in glioma patients. Introductions: Under hypoxic conditions, upregulated hypoxia-inducible factor 1α (HIF1α) expression in GSCs activates Wnt/ß-catenin signaling pathways, which provide rich nutritional support for glioblastoma (GBM). SENP1-mediated deSUMOylation stabilizes the expression of HIF1α and ß-catenin, leading to the occurrence of GSCs-initiated tumorigenesis. Targeting SENP1-mediated deSUMOylation may suppress the malignancy of GSCs and disrupt GBM progression. Methods: The expression of SENP1 in different World Health Organization grades was observed by immunohistochemistry and western blot. Lentivirus-packaged SENP1shRNA downregulated the expression of SENP1 in GSCs, and the downregulated results were verified by western blotting and polymerase chain reaction. The effects of LV-SENP1shRNA on the migration and proliferation of GSCs were detected by scratch and cloning experiments. The effect of LV-SENP1shRNA on the tumor formation ability of GSCs was observed in nude mice. Immunoprecipitation clarified the mechanism of SENP1 regulating the malignant behavior of GSCs under hypoxia. The correlation between the expression level of SENP1 and the survival of glioma patients was determined by statistical analysis. Results: SENP1 expression in GSCs derived from clinical samples was upregulated in GBM. SUMOylation was observed in GSCs in vitro, and deSUMOylation, accompanied by an increase in SENP1 expression, was induced by hypoxia. SENP1 expression was downregulated in GSCs with lentivirus-mediated stable transfection, which attenuated the proliferation and differentiation of GSCs, thus diminishing tumorigenesis. Mechanistically, HIF1α induced activation of Wnt/ß-catenin, which depended on SENP1-mediated deSUMOylation, promoting GSC-driven GBM growth under the hypoxia microenvironment. Conclusion: Our findings indicate that SENP1-mediated deSUMOylation as a feature of GSCs is essential for GBM maintenance, suggesting that targeting SENP1 against GSCs may effectively improve GBM therapeutic efficacy.


Sujet(s)
Prolifération cellulaire , Cysteine endopeptidases , Gliome , Cellules souches tumorales , Sumoylation , Humains , Animaux , Cysteine endopeptidases/métabolisme , Cysteine endopeptidases/génétique , Cellules souches tumorales/métabolisme , Cellules souches tumorales/anatomopathologie , Souris , Gliome/anatomopathologie , Gliome/métabolisme , Gliome/génétique , Sous-unité alpha du facteur-1 induit par l'hypoxie/métabolisme , Sous-unité alpha du facteur-1 induit par l'hypoxie/génétique , Lignée cellulaire tumorale , Régulation de l'expression des gènes tumoraux , Tumeurs du cerveau/métabolisme , Tumeurs du cerveau/anatomopathologie , Tumeurs du cerveau/génétique , Voie de signalisation Wnt , Femelle , Mâle , Mouvement cellulaire/génétique , Souris nude , Hypoxie cellulaire , Tests d'activité antitumorale sur modèle de xénogreffe
19.
World Neurosurg ; 2024 May 23.
Article de Anglais | MEDLINE | ID: mdl-38796152

RÉSUMÉ

OBJECTIVE: This study analyzed and explored the relationship between isthmic spondylolisthesis and disc degeneration by comparing the degree of disc degeneration in patients with isthmic spondylolisthesis, lumbar disc herniation, and asymptomatic healthy individuals. METHODS: This study included a total of 138 cases, consisting of L5-S1 single segment lesion patients and a normal lumbar spine population. The cases were divided into 3 groups based on the type of disease: fifty eight cases in the isthmic spondylolisthesis (IS) group, 50 cases in the lumbar disc herniation (LDH) group, and 30 cases in the normal lumbar vertebrae (NLV) group. RESULTS: The research findings indicate that the proportion of intervertebral disc degeneration in the LDH group is significantly higher than that in the IS group and NLV group (65.3% vs. 33.3% vs. 25.8%, P < 0.05). The Pfirrmann grades of lumbar intervertebral discs (L1-L4) in the LDH group are significantly higher than those in the IS group and NLV group (P < 0.05), and the intervertebral height index (IHI) (L1-L4) of lumbar vertebrae in the LDH group is significantly lower than that in the IS group and NLV group (P < 0.05). CONCLUSIONS: The results showed that the degree of intervertebral disc degeneration in patients with isthmic spondylolisthesis was lighter than that in patients with LDH, and even similar to that in healthy individuals. The occurrence of IS may have slowed down the degeneration of nonaffected segment intervertebral discs through certain factors.

20.
Plant Cell Rep ; 43(6): 136, 2024 May 06.
Article de Anglais | MEDLINE | ID: mdl-38709311

RÉSUMÉ

KEY MESSAGE: In our study, we discovered a fragment duplication autoregulation mechanism in 'ZS-HY', which may be the reason for the phenotype of red foliage and red flesh in grapes. In grapes, MYBA1 and MYBA2 are the main genetic factors responsible for skin coloration which are located at the color loci on chromosome 2, but the exact genes responsible for color have not been identified in the flesh. We used a new teinturier grape germplasm 'ZhongShan-HongYu' (ZS-HY) which accumulate anthocyanin both in skin and flesh as experimental materials. All tissues of 'ZS-HY' contained cyanidin 3-O-(6″-p-coumaroyl glucoside), and pelargonidins were detected in skin, flesh, and tendril. Through gene expression analysis at different stage of flesh, significant differences in the expression levels of VvMYBA1 were found. Gene amplification analysis showed that the VvMYBA1 promoter is composed of two alleles, VvMYBA1a and 'VvMYBA1c-like'. An insertion of a 408 bp repetitive fragment was detected in the allele 'VvMYBA1c-like'. In this process, we found the 408 bp repetitive fragment was co-segregated with red flesh and foliage phenotype. Our results revealed that the 408 bp fragment replication insertion in promoter of 'VvMYBA1c-like' was the target of its protein, and the number of repeat fragments was related to the increase of trans-activation of VvMYBA1 protein. The activation of promoter by VvMYBA1 was enhanced by the addition of VvMYC1. In addition, VvMYBA1 interacted with VvMYC1 to promote the expression of VvGT1 and VvGST4 genes in 'ZS-HY'. The discovery of this mutation event provides new insights into the regulation of VvMYBA1 on anthocyanin accumulation in red-fleshed grape, which is of great significance for molecular breeding of red-fleshed table grapes.


Sujet(s)
Anthocyanes , Régulation de l'expression des gènes végétaux , Phénotype , Protéines végétales , Régions promotrices (génétique) , Facteurs de transcription , Vitis , Vitis/génétique , Vitis/métabolisme , Régions promotrices (génétique)/génétique , Protéines végétales/génétique , Protéines végétales/métabolisme , Facteurs de transcription/génétique , Facteurs de transcription/métabolisme , Anthocyanes/métabolisme , Anthocyanes/génétique , Pigmentation/génétique , Fruit/génétique , Fruit/métabolisme , Allèles
SÉLECTION CITATIONS
DÉTAIL DE RECHERCHE
...