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1.
J Clin Lipidol ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38485619

RESUMO

OBJECTIVE: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.

2.
iScience ; 27(1): 108664, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38226165

RESUMO

The 5'-deoxyadenosine deaminase (DADD), a member of the amidohydrolase family regulates biological purine metabolism. In this study, bioinformatic analysis, overexpression and knockdown of GhdadD gene were detected to identify its potential role in drought and salt stress tolerance. The results revealed that GhdadD was induced by ABA, Auxin, MBS and light responsive elements. In transgenic Arabidopsis, seed germination rate and root length were increased under drought or salt stress. GhdadD overexpressed seedlings resulted in higher plant height, less leaf damage and lower ion permeability. The expression of osmotic stress and ABA-responsive genes were up regulated. While in GhdadD-silenced cotton seedlings, CAT, SOD activity and soluble sugar content were reduced, MDA content was increased, and the stoma opening was depressed under drought or salt stress. Some osmics stress marker genes were also up regulated. These data indicating that GhdadD enhanced plant resistance to drought and salt stress through ABA pathways.

4.
Heliyon ; 10(1): e23391, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192751

RESUMO

In the present study we have presented the notion of FUZZY BAYESIAN DECISION TECHNIQUE and combined the idea of the Fuzzy TOPSIS technique and entropy. We define the new ideas of fuzzy TOPSIS technique and entropy. So, we introduce the TOPSIS method and entropy, and the weights of the DMs are used. We proposed an MCDM technique based on TOPSIS and entropy. We focus on parameter different solutions of Fuzzy TOPSIS Positive ideal and Negative ideal solutions efficient decision making. Also, we provide a numerical example to elucidate the proposed technique stage by stage. Lastly, we compare the explanations of the current problem with the many existing MCGDM approaches to deliver the skills and rationality of the offered technique. We also provide a sensitivity study by shifting the entropy to establish the weights of the criteria underneath the dominant entropy measure meaning.

5.
Sci Total Environ ; 917: 170417, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38280611

RESUMO

Drought is a potent abiotic stressor that arrests crop growth, significantly affecting crop health and yields. The arbuscular mycorrhizal fungi (AMF), and plant growth-promoting rhizobacteria (PGPR) can offer to protect plants from stressful environments through improving water, and nutrient use efficiency by strengthening plant root structure and harnessing favorable rhizosphere environments. When Acaulospora laevis (AMF) and Bacillus subtilus (PGPR) are introduced in combination, enhanced root growth and beneficial microbial colonization can mitigate drought stress. To assess this potential, a pot experiment was done with maize (Zea mays L.) to explore the effects of A. laevis and B. subtilus under different water levels (well-watered = 80 %; moderate water stress = 55 %; and severe water stress = 35 %) on maize yield, soil microbial activities, nutrients contents, root, and leaf functioning. Plants exposed to severe drought stress hampered their root and leaf functioning, and reduced grain yield compared with control plants. Combined use of AMF and PGPR increased root colonization (104.6 %-113.2 %) and microbial biomass carbon (36.38 %-40.23 %) under moderate to severe drought conditions over control. Higher root colonization was strongly linked with elevated ACC (aminocyclopropane-1-carboxylic acid) production, subsequently enhancing water use efficiency (21.62 %-12.77 %), root hydraulic conductivity (1.9 %-1.4 %) and root nutrient uptake under moderate to severe drought conditions. Enhanced nutrient uptake further promoted leaf photosynthetic rate by 27.3 %-29.8 % under moderate and severe drought stress. Improving leaf and root physiological functioning enhanced maize grain yield under stressful environments. Furthermore, co-inoculation with AMF-PGPR reduced cellular damage by lowering oxidative enzyme levels and increasing antioxidative enzyme activities, improving plant performance and grain yield under stressful environments. Conclusively, the synergistic interaction of AMF with PGPR ensured plant stress tolerance by reducing cellular injury, facilitating root-leaf functioning, enhancing nutrient-water-use-efficiencies, and increasing yield under drought stress.


Assuntos
Micorrizas , Micorrizas/fisiologia , Zea mays , Solo , Raízes de Plantas/microbiologia , Retroalimentação , Desidratação
6.
Nucleic Acids Res ; 52(D1): D174-D182, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37962376

RESUMO

JASPAR (https://jaspar.elixir.no/) is a widely-used open-access database presenting manually curated high-quality and non-redundant DNA-binding profiles for transcription factors (TFs) across taxa. In this 10th release and 20th-anniversary update, the CORE collection has expanded with 329 new profiles. We updated three existing profiles and provided orthogonal support for 72 profiles from the previous release's UNVALIDATED collection. Altogether, the JASPAR 2024 update provides a 20% increase in CORE profiles from the previous release. A trimming algorithm enhanced profiles by removing low information content flanking base pairs, which were likely uninformative (within the capacity of the PFM models) for TFBS predictions and modelling TF-DNA interactions. This release includes enhanced metadata, featuring a refined classification for plant TFs' structural DNA-binding domains. The new JASPAR collections prompt updates to the genomic tracks of predicted TF binding sites (TFBSs) in 8 organisms, with human and mouse tracks available as native tracks in the UCSC Genome browser. All data are available through the JASPAR web interface and programmatically through its API and the updated Bioconductor and pyJASPAR packages. Finally, a new TFBS extraction tool enables users to retrieve predicted JASPAR TFBSs intersecting their genomic regions of interest.


Assuntos
Bases de Dados Genéticas , Ligação Proteica , Fatores de Transcrição , Animais , Humanos , Camundongos , Bases de Dados Genéticas/normas , Bases de Dados Genéticas/tendências , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Plantas/genética
7.
Heliyon ; 9(11): e21726, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027754

RESUMO

This study is confined to the numerical evaluation of variable density and magnetohydrodynamics influence on Williamson Sakiadis flow in a porous space. In this study, Joule heating, dissipation, heat generation effect on optically dense gray fluid is encountered. The inclined moving surface as flow geometry is considered to induce the fluid flow. A proposed phenomenon is given a mathematical structure in partial differential equations form. These partial differential equations are then made dimensionless using dimensionless variables. The obtained dimensionless model in partial differential equations is then changed to ordinary differential equations via stream function formulation. A set of transformed equations has been solved with bvp4c solver. The numerical fallout of velocity field, temperature field, skin friction, and heat transfer rate are illustrated in graphs and tables with flow parametric variations. Conclusion is drawn that mounting values of density variation parameter confirm the reduction in velocity field and augmentation in temperature of the fluid. When Williamson fluid parameter enhances, both fluid velocity and temperature are rising correspondingly. Growing magnitudes of the magnetic number, radiation parameter, heat generation, and Eckert number rise the temperature of the fluid. A rise in a porous medium parameter weakens the fluid velocity. Skin friction is reducing as radiation parameter and density variation parameter are increased. The present solutions are compared to those that have already been published in order to validate the current model. The comparison leads to the conclusion that the two outcomes are in excellent agreement, endorsing the veracity of the current answers.

9.
Front Plant Sci ; 14: 1225939, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719208

RESUMO

Introduction: Low agricultural nutrient input efficiency remains a significant impediment for crop production globally. To address this issue in cotton agroecosystems, there is a need to develop sustainable crop nutrient management strategies to achieve high crop yields. We hypothesized that organic liquid fertilizer (OF) combined with reduced chemical fertilizer (CF) would enhance cotton yield by improving leaf functioning and soil properties. However, the underlying mechanism and its related process is poorly understood. Methods: This study explored the effects of OF combined with reduced CF on cotton yield, physiology and soil properties. Treatments included a single application of CF (CF: N, P2O5 and K2O applied at 228, 131 and 95 kg ha-1) and combined applications of OF and CF (OF0.6-OF1.4) in the following ratios: OF0.6, OF+60% CF; OF0.8, OF+80% CF; OF1.0, OF+100% CF; OF1.2, OF+120% CF; OF1.4, OF+140% CF. Results and discussion: The result showed that compared with CF, OF0.8, OF1.0 and OF1.2 increased soil organic matter (SOM) content by 9.9%, 16.3% and 23.7%, respectively. Compared with CF, the OF0.6, OF0.8, OF1.0, and OF1.2 treatments increased leaf area (LA) by 10.6-26.1%, chlorophyll content (Chl content) by 6.8-39.6%, and the efficiency of photosystem II (PSII) light energy (Y(II)), electron transfer rate of PSII (ETR) and photochemical quenching (qP) by 3.6-26.3%, 4.7-15.3% and 4.3-9.8%, respectively. The OF0.8 treatment increased net photosynthetic rate (P n), stomatal conductance (G s) and transpiration rate (E) by 22.0%, 27.4% and 26.8%, respectively, resulting in higher seed cotton yield. The seed cotton yield and economic coefficient were positively correlated with P n, E, G s and Y(II) from the full boll stage to the boll opening stage. In summary, the OF0.8 treatment can maintain a high SOM content and photosynthetic performance with reduced chemical fertilizer input without sacrificing yield. The integration of OF+80% CF (OF0.8) is a promising nutrient management strategy for highly efficient cotton production under mulch drip irrigation systems.

10.
Water Res ; 245: 120581, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37703757

RESUMO

Polyethylene film mulching is a key technology for soil water retention in dryland agriculture, but the aging of the films can generate a large number of microplastics with different shapes. There exists a widespread misunderstanding that the concentrations of microplastics might be the determinant affecting the diversity and assembly of soil bacterial communities, rather than their shapes. Here, we examined the variations of soil bacteria community composition and functioning under two-year field incubation by four shapes (ball, fiber, fragment and powder) of microplastics along the concentration gradients (0.01%, 0.1% and 1%). Data showed that specific surface area of microplastics was significantly positively correlated with the variations of bacterial community abundance and diversity (r=0.505, p<0.05). The fragment- and fiber-shape microplastics displayed more pronounced interfacial continuity with soil particles and induced greater soil bacterial α-diversity, relative to the powder- and ball-shape ones. Strikingly, microplastic concentrations were not significantly correlated with bacterial community indices (r=0.079, p>0.05). Based on the variations of the ßNTI, bacterial community assembly actually followed both stochastic and deterministic processes, and microplastic shapes significantly modified soil biogeochemical cycle and ecological functions. Therefore, the shapes of microplastics, rather than the concentration, significantly affected soil bacterial community assembly, in association with microplastic-soil-water interfaces.

12.
Sci Total Environ ; 900: 165814, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37517723

RESUMO

The primary utilization strategy for meadow grasslands on the Qinghai-Tibet Plateau (QTP) is livestock grazing. This practice is considered as one of the major drivers of plant-associated bacterial community construction and changes in soil properties. The species of Kobresia humilis is considered as the most dominant one in grasslands. However, how different grazing practices affect the phyllosphere and rhizosphere bacterial communities of K. humilis is unknown. To address this issue, the effects of the grazing enclosure (GE), single-species grazing (YG and SG, representing yak only and sheep only, respectively), and different ratios of grazing (ratio of yak to sheep is 1:2, 1:4, and 1:6, represented by MG1:2, MG1:4, and MG1:6, respectively) on the dominant plant of K. humilis, it's phyllosphere and rhizosphere bacteria, and soil properties were investigated using artificially controlled grazing and grazing enclosure. Our data showed that grazing enclosure enhanced vegetation coverage, and rhizosphere bacterial richness and diversity, while reduced plant number and bacterial network stability of K. humilis. The NO3--N, K+, and Cl- concentrations were lower under grazing compared to GE. SG reduced the concentration of NH4+-N, TN, K+, and Na+ compared to YG. Moderate grazing intensity had a lower relative abundance of the r-strategists (Bacteroidota and Gammaproteobacteria) with higher bacterial network stability. Yak and sheep grazing showed reversed impacts on the bacterial network stability between the phyllosphere and rhizosphere of K. humilis. Proteobacteria and Actinobacteriota were identified in the molecular ecological network analysis as keystone taxa in the phyllosphere and rhizosphere networks, respectively, under all treatments. This study explained why sheep grazing has more adverse effects on grazing-tolerant grass species, K. humilis, than yak grazing, and will contribute to a better understanding of the impacts of different grazing practices and grazing enclosure on alpine grassland ecosystems on the QTP.


Assuntos
Carex (Planta) , Ecossistema , Animais , Ovinos , Pradaria , Rizosfera , Tibet , Bactérias , Solo
13.
Sci Total Environ ; 899: 165688, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37490947

RESUMO

The rise of plasticulture as mulching material in farming systems has raised concerns about microplastics (MPs) in the agricultural landscape. MPs are emerging pollutants in croplands and water systems with significant ecological risks, particularly over the long term. In the soil systems, MPs polymer type, thinness, shape, and size induces numerous effects on soil aggregates, dissolved organic carbon (C), rapidly oxidized organic C, microbial biomass C, microbial biomass nitrogen (N), microbial immobilization, degradation of organic matter, N cycling, and production of greenhouse gas emissions (GHGs), thereby posing a significant risk of impairing soil physical and biochemical properties over time. Further, toxic chemicals released from polyethylene mulching (PMs) might indirectly harm plant growth by affecting soil wetting-drying cycles, releasing toxic substances that interact with soil matrix, and suppressing soil microbial activity. In the environment, accumulation of MPs poses a risk to human health by accelerating emissions of GHGs, e.g., methane and carbon dioxide, or directly releasing toxic substances such as phthalic acid esters (PAEs) into the soils. Also, larger sizes MPs can adhere to root surface and block stomata could significantly change the shape of root epidermal cells resulting in arrest plant growth and development by restricting water-nutrient uptake, and gene expression and altering the biodiversity of the soil pollutants. In this review, we systematically analyzed the potential risks of MPs to the soil-plant and human body, their occurrence, abundance, and migration in agroecosystems. Further, the impacts of MPs on soil microbial function, nutrient cycling, soil C, and GHGs are mechanistically reviewed, with emphasis on potential green solutions such as organic materials amendments along with future research directions for more eco-friendly and sustainable plastic management in agroecosystems.


Assuntos
Poluentes Ambientais , Microplásticos , Humanos , Microplásticos/toxicidade , Plásticos , Solo/química , Agricultura , Ecossistema
14.
Eur Heart J Digit Health ; 4(3): 145-154, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37265867

RESUMO

Aims: Clinical differentiation of acute myocardial infarction (MI) from unstable angina and other presentations mimicking acute coronary syndromes (ACS) is critical for implementing time-sensitive interventions and optimizing outcomes. However, the diagnostic steps are dependent on blood draws and laboratory turnaround times. We tested the clinical feasibility of a wrist-worn transdermal infrared spectrophotometric sensor (transdermal-ISS) in clinical practice and assessed the performance of a machine learning algorithm for identifying elevated high-sensitivity cardiac troponin-I (hs-cTnI) levels in patients hospitalized with ACS. Methods and results: We enrolled 238 patients hospitalized with ACS at five sites. The final diagnosis of MI (with or without ST elevation) and unstable angina was adjudicated using electrocardiography (ECG), cardiac troponin (cTn) test, echocardiography (regional wall motion abnormality), or coronary angiography. A transdermal-ISS-derived deep learning model was trained (three sites) and externally validated with hs-cTnI (one site) and echocardiography and angiography (two sites), respectively. The transdermal-ISS model predicted elevated hs-cTnI levels with areas under the receiver operator characteristics of 0.90 [95% confidence interval (CI), 0.84-0.94; sensitivity, 0.86; and specificity, 0.82] and 0.92 (95% CI, 0.80-0.98; sensitivity, 0.94; and specificity, 0.64), for internal and external validation cohorts, respectively. In addition, the model predictions were associated with regional wall motion abnormalities [odds ratio (OR), 3.37; CI, 1.02-11.15; P = 0.046] and significant coronary stenosis (OR, 4.69; CI, 1.27-17.26; P = 0.019). Conclusion: A wrist-worn transdermal-ISS is clinically feasible for rapid, bloodless prediction of elevated hs-cTnI levels in real-world settings. It may have a role in establishing a point-of-care biomarker diagnosis of MI and impact triaging patients with suspected ACS.

15.
Nature ; 618(7964): 383-393, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37258665

RESUMO

The earliest events during human tumour initiation, although poorly characterized, may hold clues to malignancy detection and prevention1. Here we model occult preneoplasia by biallelic inactivation of TP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over 2 years. TP53 loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders. Longitudinal single-cell sequencing of TP53-deficient gastric organoids similarly indicates progression towards malignant transcriptional programmes. Moreover, high-throughput lineage tracing with expressed cellular barcodes demonstrates reproducible dynamics whereby initially rare subclones with shared transcriptional programmes repeatedly attain clonal dominance. This powerful platform for experimental evolution exposes stringent selection, clonal interference and a marked degree of phenotypic convergence in premalignant epithelial organoids. These data imply predictability in the earliest stages of tumorigenesis and show evolutionary constraints and barriers to malignant transformation, with implications for earlier detection and interception of aggressive, genome-instable tumours.


Assuntos
Transformação Celular Neoplásica , Evolução Clonal , Lesões Pré-Cancerosas , Seleção Genética , Neoplasias Gástricas , Humanos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Evolução Clonal/genética , Instabilidade Genômica , Mutação , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Organoides/metabolismo , Organoides/patologia , Aneuploidia , Variações do Número de Cópias de DNA , Análise de Célula Única , Proteína Supressora de Tumor p53/deficiência , Proteína Supressora de Tumor p53/genética , Progressão da Doença , Linhagem da Célula
16.
Chemosphere ; 329: 138602, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37028722

RESUMO

Plastic film residuals are increasingly remaining in cultivated lands. However, it is a critical issue how residual plastic type and thickness affect soil properties and crop yield. To address this issue, in situ landfill was conducted using thick polyethylene (PEt1), thin polyethylene (PEt2), thick biodegradable (BIOt1), thin biodegradable (BIOt2) residues, and CK (control) with no residues landfill in a semiarid maize field. The findings demonstrated that the impact of various treatments on soil characteristics and maize yield varied considerably. Soil water content decreased by 24.82% in PEt1 and 25.43% in PEt2, compared to BIOt1 and BIOt2, respectively. BIOt2 treatment increased soil bulk density by 1.31 g cm-3 and lowered soil porosity by 51.11%, respectively; it also elevated the silt/clay proportion by 49.42% relative to CK. In contrast, microaggregate composition in PEt2 was higher (43.02%). Moreover, BIOt2 lowered soil nitrate (NO3-) and ammonium (NH4+) content. Compared with other treatments, BIOt2 resulted in significantly higher soil total nitrogen (STN) and lower SOC/STN. Finally, BIOt2 exhibited the lowest water use efficiency (WUE) (20.57 kg ha-1 mm-1) and yield (6896 kg ha-1) among all the treatments. Therefore, BIO film residues exhibited detrimental impacts on soil quality and maize productivity compared to PE film ones. Considering film thickness, thin residual films more evidently influenced soil quality and maize productivity than thick film ones.


Assuntos
Solo , Zea mays , Solo/química , Agricultura/métodos , Polietileno , Plásticos , Água/análise , Nitrogênio/análise , China
17.
bioRxiv ; 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36993286

RESUMO

Cancer represents a broad spectrum of molecularly and morphologically diverse diseases. Individuals with the same clinical diagnosis can have tumors with drastically different molecular profiles and clinical response to treatment. It remains unclear when these differences arise during disease course and why some tumors are addicted to one oncogenic pathway over another. Somatic genomic aberrations occur within the context of an individual's germline genome, which can vary across millions of polymorphic sites. An open question is whether germline differences influence somatic tumor evolution. Interrogating 3,855 breast cancer lesions, spanning pre-invasive to metastatic disease, we demonstrate that germline variants in highly expressed and amplified genes influence somatic evolution by modulating immunoediting at early stages of tumor development. Specifically, we show that the burden of germline-derived epitopes in recurrently amplified genes selects against somatic gene amplification in breast cancer. For example, individuals with a high burden of germline-derived epitopes in ERBB2, encoding human epidermal growth factor receptor 2 (HER2), are significantly less likely to develop HER2-positive breast cancer compared to other subtypes. The same holds true for recurrent amplicons that define four subgroups of ER-positive breast cancers at high risk of distant relapse. High epitope burden in these recurrently amplified regions is associated with decreased likelihood of developing high risk ER-positive cancer. Tumors that overcome such immune-mediated negative selection are more aggressive and demonstrate an "immune cold" phenotype. These data show the germline genome plays a previously unappreciated role in dictating somatic evolution. Exploiting germline-mediated immunoediting may inform the development of biomarkers that refine risk stratification within breast cancer subtypes.

18.
Am Heart J ; 256: 128-138, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36780372

RESUMO

BACKGROUND: The role of percutaneous coronary interventions (PCI) in patients with diabetes mellitus and multi-vessel disease has been questioned by the results of the FREEDOM trial, which showed superiority of coronary artery bypass graft(CABG) over first generation drug-eluting stents (DES) including a reduction in mortality. In the light of safer and more efficacious stents and significantly better medical management, those results that date back to 2012 need to be revisited. TUXEDO-2 is a study designed to compare two contemporary stents in Indian diabetic patients with multi-vessel disease. AIMS: The primary objective of the TUXEDO-2 study is to compare the clinical outcomes of PCI with ultra-thin Supraflex Cruz vs Xience when combined with contemporary optimal medical therapy (OMT) in diabetic patients with multi-vessel disease. The secondary objective is to compare clinical outcomes between a pooled cohort from both arms of the study (Supraflex Cruz + Xience; PCI arm) vs CABG based on a performance goal derived from the CABG arm of the FREEDOM trial (historical cohort). The tertiary objective is a randomized comparison of ticagrelor vs prasugrel in addition to aspirin for the composite of ischemic and bleeding events. METHODS: In this prospective, open-label, multi-centre, 2 × 2 factorial, randomized, controlled study, 1,800 patients with diabetes mellitus and multi-vessel disease (inclusion criteria similar to FREEDOM trial) with indication for coronary revascularization will be randomly assigned to Supraflex Cruz or Xience stents and also to ticagrelor- or prasugrel- based antiplatelet strategies. All patients will receive guideline directed OMT and optimal PCI including image- and physiology-guided complete revascularization where feasible. The patients will be followed through five years to assess their clinical status and major clinical events. The primary endpoint is a non-inferiority comparison of target lesion failure at one-year for Supraflex Cruz vs Xience (primary objective) with an expected event rate of 11% and a non-inferiority margin of 4.5%. For PCI vs CABG (secondary objective), the primary endpoint is major adverse cardiac events (MACE), defined as a composite of all cause death, nonfatal myocardial infarction, or stroke at one-year and yearly up to five years, with a performance goal of 21.6%. For ticagrelor vs prasugrel (tertiary objective), the primary endpoint is composite of death, myocardial infarction, stroke, and major bleeding as per the Bleeding Academic Research Consortium (BARC) at one-year with expected event rate of 15% and a non-inferiority margin of 5%. CONCLUSIONS: The TUXEDO-2 study is a contemporary study involving state-of-the-art PCI combined with guideline directed OMT in a complex subset of patients with diabetes mellitus and multi-vessel disease. The trial will answer the question as to whether a biodegradable polymer coated ultra-thin Supraflex Cruz stent is an attractive option for PCI in diabetic patients with multi-vessel disease. It will also help address the question whether the results of FREEDOM trial would have been different in the current era of safer and more efficacious stents and modern medical therapy. In addition, the comparative efficacy and safety of ticagrelor vs prasugrel in addition to aspirin will be evaluated. (CTRI/2019/11/022088).


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus , Infarto do Miocárdio , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Humanos , Everolimo/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Intervenção Coronária Percutânea/métodos , Ticagrelor , Estudos Prospectivos , Infarto do Miocárdio/etiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Aspirina/uso terapêutico , Resultado do Tratamento , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia
19.
BMC Plant Biol ; 23(1): 14, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609252

RESUMO

BACKGROUND: Current climate change scenarios are posing greater threats to the growth and development of plants. Thus, significant efforts are required that can mitigate the negative effects of drought on the cotton plant. GDSL esterase/lipases can offer an imperative role in plant development and stress tolerance. However, thesystematic and functional roles of the GDSL gene family, particularly in cotton under water deficit conditions have not yet been explored. RESULTS: In this study, 103, 103, 99, 198, 203, 239, 249, and 215 GDSL proteins were identified in eight cotton genomes i.e., Gossypium herbaceum (A1), Gossypium arboretum (A2), Gossypium raimondii (D5), Gossypium hirsutum (AD1), Gossypium barbadense (AD2), Gossypium tomentosum (AD3), Gossypium mustelinum (AD4), Gossypium darwinii (AD5), respectively. A total of 198 GDSL genes of Gossypium hirsutum were divided into eleven clades using phylogenetic analysis, and the number of GhirGDSL varied among different clades. The cis-elements analysis showed that GhirGDSL gene expression was mainly related to light, plant hormones, and variable tense environments. Combining the results of transcriptome and RT-qPCR, GhirGDSL26 (Gh_A01G1774), a highly up-regulated gene, was selected for further elucidating its tole in drought stress tolerance via estimating physiological and biochemical parameters. Heterologous expression of the GhirGDSL26 gene in Arabidopsis thaliana resulted in a higher germination and survival rates, longer root lengths, lower ion leakage and induced stress-responsive genes expression under drought stress. This further highlighted that overexpressed plants had a better drought tolerance as compared to the wildtype plants. Moreover, 3, 3'-diaminobenzidine (DAB) and Trypan staining results indicated reduced oxidative damage, less cell membrane damage, and lower ion leakage in overexpressed plants as compared to wild type. Silencing of GhirGDSL26 in cotton via VIGS resulting in a susceptible phenotype, higher MDA and H2O2 contents, lower SOD activity, and proline content. CONCLUSION: Our results demonstrated that GhirGDSL26 plays a critical role in cotton drought stress tolerance. Current findings enrich our knowledge of GDSL genes in cotton and provide theoretical guidance and excellent gene resources for improving drought tolerance in cotton.


Assuntos
Arabidopsis , Gossypium , Secas , Peróxido de Hidrogênio/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas
20.
STAR Protoc ; 4(1): 101927, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36586123

RESUMO

A common technique for uncovering intra-tumor genomic heterogeneity (ITH) is variant detection. However, it can be challenging to reliably characterize ITH given uneven sample quality (e.g., depth of coverage, tumor purity, and subclonality). We describe a protocol for calling point mutations and copy number alterations using sequencing of multiple related clinical patient samples across diverse tissue, optimizing for sensitivity with specificity. The ith.Variant pipeline can be run on single- or multi-region whole-genome and whole-exome sequencing. For complete details on the use and execution of this protocol, please refer to Sun et al. (2017).1.


Assuntos
Genômica , Neoplasias , Humanos , Genômica/métodos , Neoplasias/diagnóstico , Neoplasias/genética , Variações do Número de Cópias de DNA/genética , Exoma
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