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BACKGROUND: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. METHODS: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. FINDINGS: The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]). INTERPRETATION: In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. FUNDING: Stryker Neurovascular.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Isquemia Encefálica/terapia , Isquemia Encefálica/tratamiento farmacológico , Resultado del Tratamiento , Procedimientos Endovasculares/métodos , Trombectomía/métodos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/cirugía , Alberta , Fibrinolíticos/uso terapéuticoRESUMEN
BACKGROUND: Existing data and clinical trials could not determine whether faster intravenous thrombolytic therapy (IVT) translates into better long-term functional outcomes after acute ischemic stroke among those treated with endovascular thrombectomy (EVT). Patient-level national data can provide the required large population to study the associations between earlier IVT, versus later, with longitudinal functional outcomes and mortality in patients receiving IVT+EVT combined treatment. METHODS: This cohort study included older US patients (age ≥65 years) who received IVT within 4.5 hours or EVT within 7 hours after acute ischemic stroke using the linked 2015 to 2018 Get With The Guidelines-Stroke and Medicare database (38 913 treated with IVT only and 3946 with IVT+EVT). Primary outcome was home time, a patient-prioritized functional outcome. Secondary outcomes included all-cause mortality in 1 year. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the associations between door-to-needle (DTN) times and outcomes. RESULTS: Among patients treated with IVT+EVT, after adjusting for patient and hospital factors, including onset-to-EVT times, each 15-minute increase in DTN times for IVT was associated with significantly higher odds of zero home time in a year (never discharged to home) (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]), less home time among those discharged to home (adjusted odds ratio, 0.93 per 1% of 365 days [95% CI, 0.89-0.98]), and higher all-cause mortality (adjusted hazard ratio, 1.07 [95% CI, 1.02-1.11]). These associations were also statistically significant among patients treated with IVT but at a modest degree (adjusted odds ratio, 1.04 for zero home time, 0.96 per 1% home time for those discharged to home, and adjusted hazard ratio 1.03 for mortality). In the secondary analysis where the IVT+EVT group was compared with 3704 patients treated with EVT only, shorter DTN times (≤60, 45, and 30 minutes) achieved incrementally more home time in a year, and more modified Rankin Scale 0 to 2 at discharge (22.3%, 23.4%, and 25.0%, respectively) versus EVT only (16.4%, P<0.001 for each). The benefit dissipated with DTN>60 minutes. CONCLUSIONS: Among older patients with stroke treated with either IVT only or IVT+EVT, shorter DTN times are associated with better long-term functional outcomes and lower mortality. These findings support further efforts to accelerate thrombolytic administration in all eligible patients, including EVT candidates.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Anciano , Estados Unidos/epidemiología , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/terapia , Estudios de Cohortes , Isquemia Encefálica/tratamiento farmacológico , Resultado del Tratamiento , Medicare , Fibrinolíticos/uso terapéutico , Terapia Trombolítica/efectos adversos , Trombectomía/efectos adversos , Procedimientos Endovasculares/efectos adversosRESUMEN
BACKGROUND: Salt Overly Sensitive 1 (SOS1), a plasma membrane Na+/H+ exchanger, is essential for plant salt tolerance. Salt damage is a significant abiotic stress that impacts plant species globally. All living organisms require copper (Cu), a necessary micronutrient and a protein cofactor for many biological and physiological processes. High Cu concentrations, however, may result in pollution that inhibits the growth and development of plants. The function and production of mangrove ecosystems are significantly impacted by rising salinity and copper contamination. RESULTS: A genome-wide analysis and bioinformatics techniques were used in this study to identify 20 SOS1 genes in the genome of Kandelia obovata. Most of the SOS1 genes were found on the plasma membrane and dispersed over 11 of the 18 chromosomes. Based on phylogenetic analysis, KoSOS1s can be categorized into four groups, similar to Solanum tuberosum. Kandelia obovata's SOS1 gene family expanded due to tandem and segmental duplication. These SOS1 homologs shared similar protein structures, according to the results of the conserved motif analysis. The coding regions of 20 KoSOS1 genes consist of amino acids ranging from 466 to 1221, while the exons include amino acids ranging from 3 to 23. In addition, we found that the 2.0 kb upstream promoter region of the KoSOS1s gene contains several cis-elements associated with phytohormones and stress responses. According to the expression experiments, seven randomly chosen genes experienced up- and down-regulation of their expression levels in response to copper (CuCl2) and salt stressors. CONCLUSIONS: For the first time, this work systematically identified SOS1 genes in Kandelia obovata. Our investigations also encompassed physicochemical properties, evolution, and expression patterns, thereby furnishing a theoretical framework for subsequent research endeavours aimed at functionally characterizing the Kandelia obovata SOS1 genes throughout the life cycle of plants.
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Cobre , Filogenia , Proteínas de Plantas , Rhizophoraceae , Cobre/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Rhizophoraceae/genética , Rhizophoraceae/fisiología , Estrés Salino/genética , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Familia de Multigenes , Estrés Fisiológico/genética , Genes de Plantas , Tolerancia a la Sal/genética , Proteína SOS1/genética , Proteína SOS1/metabolismoRESUMEN
BACKGROUND: Soil salinity is one of the major menaces to food security, particularly in dealing with the food demand of the ever-increasing global population. Production of cereal crops such as wheat is severely affected by soil salinity and improper fertilization. The present study aimed to examine the effect of selected microbes and poultry manure (PM) on seedling emergence, physiology, nutrient uptake, and growth of wheat in saline soil. A pot experiment was carried out in research area of Institute of Soil and Environmental Sciences, University of Agriculture, Faisalabad, Pakistan. Saline soil (12 dS m- 1 w/w) was developed by spiking using sodium chloride, and used in experiment along with two microbial strains (i.e., Alcaligenes faecalis MH-2 and Achromobacter denitrificans MH-6) and PM. Finally, wheat seeds (variety Akbar-2019) were sown in amended and unamended soil, and pots were placed following a completely randomized design. The wheat crop was harvested after 140 days of sowing. RESULTS: The results showed a 10-39% increase (compared to non-saline control) in agronomic, physiological, and nutritive attributes of wheat plants when augmented with PM and microbes. Microbes together with PM significantly enhanced seedling emergence (up to 38%), agronomic (up to 36%), and physiological (up to 33%) in saline soil as compared to their respective unamended control. Moreover, the co-use of microbes and PM also improved soil's physicochemical attributes and enhanced N (i.e., 21.7%-17.1%), P (i.e., 24.1-29.3%), and K (i.e., 28.7%-25.3%) availability to the plant (roots and shoots, respectively). Similarly, the co-use of amendments also lowered the Na+ contents in soil (i.e., up to 62%) as compared to unamended saline control. This is the first study reporting the effects of the co-addition of newly identified salt-tolerant bacterial strains and PM on seedling emergence, physiology, nutrient uptake, and growth of wheat in highly saline soil. CONCLUSION: Our findings suggest that co-using a multi-trait bacterial culture and PM could be an appropriate option for sustainable crop production in salt-affected soil.
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Estiércol , Aves de Corral , Salinidad , Suelo , Triticum , Triticum/crecimiento & desarrollo , Suelo/química , Animales , Microbiología del Suelo , Plantones/crecimiento & desarrollo , Fertilizantes/análisis , Alcaligenes faecalis/crecimiento & desarrolloRESUMEN
Salinity stress is a significant challenge in agricultural production. When soil contains high salts, it can adversely affect plant growth and productivity due to the high concentration of soluble salts in the soil water. To overcome this issue, foliar applications of methyl jasmonate (MJ) and gibberellic acid (GA3) can be productive amendments. Both can potentially improve the plant's growth attributes and flowering, which are imperative in improving growth and yield. However, limited literature is available on their combined use in canola to mitigate salinity stress. That's why the current study investigates the impact of different levels of MJ (at concentrations of 0.8, 1.6, and 3.2 mM MJ) and GA3 (0GA3 and 5 mg/L GA3) on canola cultivated in salt-affected soils. Applying all the treatments in four replicates. Results indicate that the application of 0.8 mM MJ with 5 mg/L GA3 significantly enhances shoot length (23.29%), shoot dry weight (24.77%), number of leaves per plant (24.93%), number of flowering branches (26.11%), chlorophyll a (31.44%), chlorophyll b (20.28%) and total chlorophyll (27.66%) and shoot total soluble carbohydrates (22.53%) over control. Treatment with 0.8 mM MJ and 5 mg/L GA3 resulted in a decrease in shoot proline (48.17%), MDA (81.41%), SOD (50.59%), POD (14.81%) while increase in N (10.38%), P (15.22%), and K (8.05%) compared to control in canola under salinity stress. In conclusion, 0.8 mM MJ + 5 mg/L GA3 can improve canola growth under salinity stress. More investigations are recommended at the field level to declare 0.8 mM MJ + 5 mg/L GA3 as the best amendment for alleviating salinity stress in different crops.
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Acetatos , Antioxidantes , Brassica napus , Ciclopentanos , Giberelinas , Oxilipinas , Reguladores del Crecimiento de las Plantas , Suelo , Ciclopentanos/farmacología , Oxilipinas/farmacología , Brassica napus/crecimiento & desarrollo , Brassica napus/efectos de los fármacos , Brassica napus/metabolismo , Giberelinas/metabolismo , Giberelinas/farmacología , Antioxidantes/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/metabolismo , Acetatos/farmacología , Suelo/química , Clorofila/metabolismo , Estrés Salino/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Nutrientes/metabolismoRESUMEN
Bacterial canker disease caused by Clavibacter michiganensis is a substantial threat to the cultivation of tomatoes, leading to considerable economic losses and global food insecurity. Infection is characterized by white raised lesions on leaves, stem, and fruits with yellow to tan patches between veins, and marginal necrosis. Several agrochemical substances have been reported in previous studies to manage this disease but these were not ecofriendly. Thus present study was designed to control the bacterial canker disease in tomato using green fabricated silver nanoparticles (AgNps). Nanosilver particles (AgNPs) were synthesized utilizing Moringa oleifera leaf extract as a reducing and stabilizing agent. Synthesized AgNPs were characterized using UV-visible spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive X-ray (EDX), and Fourier transform infrared spectrometry (FTIR). FTIR showed presence of bioactive compounds in green fabricated AgNPs and UV-visible spectroscopy confirmed the surface plasmon resonance (SPR) band in the range of 350 nm to 355 nm. SEM showed the rectangular segments fused together, and XRD confirmed the crystalline nature of the synthesized AgNPs. The presence of metallic silver ions was confirmed by an EDX detector. Different concentrations (10, 20, 30, and 40 ppm) of the green fabricated AgNPs were exogenously applied on tomato before applying an inoculum of Clavibacter michigensis to record the bacterial canker disease incidence at different day intervals. The optimal concentration of AgNPs was found to be 30 µg/mg that exhibited the most favorable impact on morphological (shoot length, root length, plant fresh and dry weights, root fresh and dry weights) and physiological parameters (chlorophyll contents, membrane stability index, and relative water content) as well as biochemical parameters (proline, total soluble sugar and catalase activity). These findings indicated a noteworthy reduction in biotic stress through the increase of both enzymatic and non-enzymatic activities by the green fabricated AgNPs. This study marks a first biocompatible approach in assessing the potential of green fabricated AgNPs in enhancing the well-being of tomato plants that affected with bacterial canker and establishing an effective management strategy against Clavibacter michiganensis. This is the first study suggests that low concentration of green fabricated nanosilvers (AgNPs) from leaf extract of Moringa oleifera against Clavibacter michiganensis is a promisingly efficient and eco-friendly alternative approach for management of bacterial canker disease in tomato crop.
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Nanopartículas del Metal , Enfermedades de las Plantas , Plata , Solanum lycopersicum , Solanum lycopersicum/microbiología , Plata/farmacología , Nanopartículas del Metal/química , Enfermedades de las Plantas/microbiología , Clavibacter , Moringa oleifera/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Tecnología Química Verde , Hojas de la Planta/microbiologíaRESUMEN
TGF-ß supergene family has a wide range of physiological functions including cell adhesion, motility, proliferation, apoptosis, and differentiation. We systematically analyzed and characterized the TGF-ß gene superfamily from the whole blue whale (Balaenoptera musculus) genome, using comparative genomic and evolutionary analysis. We identified 30 TGF-ß genes and were split into two subgroups, BMP-like and TGF-like. All TGF-ß proteins demonstrating a basic nature, with the exception of BMP1, BMP2, BMP10, GDF2, MSTN, and NODAL modulator, had acidic characteristics. All the blue whale (B. musculus) TGF-ß proteins, excluding BMP1, are thermostable based on aliphatic index. The instability index showed all proteins except the NODAL modulator was unstable. TGF-ß proteins showed a hydrophilic character, with the exception of GDF1 and INHBC. Moreover, all the detected TGF-ß genes showed evolutionary conserved nature. A segmental duplication was indicated by TGF-ß gene family, and the Ka/Ks ratio showed that the duplicated gene pairs were subjected to selection pressure, indicating both purifying and positive selection pressure. Two possible recombination breakpoints were also predicted. This study provides insights into the genetic characterization and evolutionary aspects of the TGF-ß superfamily in blue whales (B. musculus).
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Balaenoptera , Evolución Molecular , Familia de Multigenes , Filogenia , Factor de Crecimiento Transformador beta , Animales , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Balaenoptera/genética , Genómica , Genoma/genética , Selección Genética , Duplicación de GenRESUMEN
PURPOSE: Neurodevelopmental disorders exhibit clinical and genetic heterogeneity, ergo manifest dysfunction in components of diverse cellular pathways; the precise pathomechanism for the majority remains elusive. METHODS: We studied 5 affected individuals from 3 unrelated families manifesting global developmental delay, postnatal microcephaly, and hypotonia. We used exome sequencing and prioritized variants that were subsequently characterized using immunofluorescence, immunoblotting, pulldown assays, and RNA sequencing. RESULTS: We identified biallelic variants in ZFTRAF1, encoding a protein of yet unknown function. Four affected individuals from 2 unrelated families segregated 2 homozygous frameshift variants in ZFTRAF1, whereas, in the third family, an intronic splice site variant was detected. We investigated ZFTRAF1 at the cellular level and signified it as a nucleocytoplasmic protein in different human cell lines. ZFTRAF1 was completely absent in the fibroblasts of 2 affected individuals. We also identified 110 interacting proteins enriched in mRNA processing and autophagy-related pathways. Based on profiling of autophagy markers, patient-derived fibroblasts show irregularities in the protein degradation process. CONCLUSION: Thus, our findings suggest that biallelic variants of ZFTRAF1 cause a severe neurodevelopmental disorder.
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Mutación con Pérdida de Función , Microcefalia , Hipotonía Muscular , Trastornos del Neurodesarrollo , Linaje , Humanos , Microcefalia/genética , Microcefalia/patología , Hipotonía Muscular/genética , Hipotonía Muscular/patología , Masculino , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/patología , Femenino , Preescolar , Mutación con Pérdida de Función/genética , Alelos , Niño , Lactante , Secuenciación del Exoma , Fibroblastos/metabolismo , Fibroblastos/patología , Autofagia/genéticaRESUMEN
BACKGROUND: Device-assisted enteroscopy (DAE) has become a well-established diagnostic and therapeutic tool for the management of small-bowel pathology. We aimed to evaluate the performance measures for DAE across the UK against the quality benchmarks proposed by the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We retrospectively collected data on patient demographics and DAE performance measures from electronic endoscopy records of consecutive patients who underwent DAE for diagnostic and therapeutic purposes across 12 enteroscopy centers in the UK between January 2017 and December 2022. RESULTS: A total of 2005 DAE procedures were performed in 1663 patients (median age 60 years; 53% men). Almost all procedures (98.1%) were performed for appropriate indications. Double-balloon enteroscopy was used for most procedures (82.0%), followed by single-balloon enteroscopy (17.2%) and spiral enteroscopy (0.7%). The estimated depth of insertion was documented in 73.4% of procedures. The overall diagnostic yield was 70.0%. Therapeutic interventions were performed in 42.6% of procedures, with a success rate of 96.6%. Overall, 78.0% of detected lesions were marked with a tattoo. Patient comfort was significantly better with the use of deep sedation compared with conscious sedation (99.7% vs. 68.5%; P<0.001). Major adverse events occurred in only 0.6% of procedures. CONCLUSIONS: Performance measures for DAE in the UK meet the ESGE quality benchmarks, with high diagnostic and therapeutic yields, and a low incidence of major adverse events. However, there is room for improvement in optimizing sedation practices, standardizing the depth of insertion documentation, and adopting marking techniques to aid in the follow-up of detected lesions.
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Enfermedades Intestinales , Masculino , Humanos , Persona de Mediana Edad , Femenino , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/terapia , Estudios Retrospectivos , Mejoramiento de la Calidad , Endoscopía Gastrointestinal/métodos , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/patología , Enteroscopía de Doble Balón/métodosRESUMEN
BACKGROUND: Cyanidin-3-O-glucoside (C3G), is an anthocyanin mainly found in berries, and can also be produced by microorganisms. It has been traditionally used as a natural coloring agent for decades. Recently, it has been investigated for its high antioxidant activity and anti-cancer attributes. C3G has low bioavailability and is sensitive to oxidation and gastric pH; therefore, it is encapsulated in nanoliposomes to enhance its bio-availability, targeted delivery- and efficacy against chronic disease. SCOPE AND APPROACH: In this review, the role of C3G nanoliposomes against major chronic diseases has been discussed. The focus was on research findings and the mechanism of action to affect the proliferation of cancer, neuro disease and cardiovascular problems. It also discussed the formulation of nanoliposomes, their role in nutraceutical delivery and enhancement in C3G bioavailability. KEY FINDINGS AND CONCLUSIONS: Data suggested that nanoliposomes safeguard C3G, enhance bioavailability, and ensure safe, adequate and targeted delivery. It can reduce the impact of cancer and inflammation by inhibiting the ß-catenin/O6-methylguanine-DNA methyltransferase (MGMT) pathway and upregulating miR-214-5p. Formation of C3G nanoliposomes significantly enhances the nutraceutical efficacy of C3G against major chronic disease therefore, C3G nanoliposomes might be a future-based nutraceutical to treat major chronic diseases, including cancer, neuro problems and CVD, but challenges remain in finding correct dose and techniques to maximize its efficacy.
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Direct combustion of sulfur-enriched liquid fuel oil causes sulfur oxide emission, which is one of the main contributors to air pollution. Biodesulfurization is a promising and eco-friendly method to desulfurize a wide range of thiophenic compounds present in fuel oil. Previously, numerous bacterial strains from genera such as Rhodococcus, Corynebacterium, Gordonia, Nocardia, Mycobacterium, Mycolicibacterium, Paenibacillus, Shewanella, Sphingomonas, Halothiobacillus, and Bacillus have been reported to be capable of desulfurizing model thiophenic compounds or fossil fuels. In the present study, we report a new desulfurizing bacterium, Tsukamurella sp. 3OW, capable of desulfurization of dibenzothiophene through the carbon-sulfur bond cleavage 4S pathway. The bacterium showed a high affinity for the hydrocarbon phase and broad substrate specificity towards various thiophenic compounds. The overall genome-related index analysis revealed that the bacterium is closely related to Tsukamurella paurometabola species. The genomic pool of strain 3OW contains 57 genes related to sulfur metabolism, including the key dszABC genes responsible for dibenzothiophene desulfurization. The DBT-adapted cells of the strain 3OW displayed significant resilience and viability in elevated concentrations of crude oil. The bacterium showed a 19 and 37% reduction in the total sulfur present in crude and diesel oil, respectively. Furthermore, FTIR analysis indicates that the oil's overall chemistry remained unaltered following biodesulfurization. This study implies that Tsukamurella paurometabola species, previously undocumented in the context of biodesulfurization, has good potential for application in the biodesulfurization of petroleum oils.
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Under changing climatic conditions, plants are simultaneously facing conflicting stresses in nature. Plants can sense different stresses, induce systematic ROS signals, and regulate transcriptomic, hormonal, and stomatal responses. We performed transcriptome analysis to reveal the integrative stress response regulatory mechanism underlying heavy metal stress alone or in combination with heat and drought conditions in pitaya (dragon fruit). A total of 70 genes were identified from 31,130 transcripts with conserved differential expression. Furthermore, weighted gene co-expression network analysis (WGCNA) identified trait-associated modules. By integrating information from three modules and protein-protein interaction (PPI) networks, we identified 10 interconnected genes associated with the multifaceted defense mechanism employed by pitaya against co-occurring stresses. To further confirm the reliability of the results, we performed a comparative analysis of 350 genes identified by three trait modules and 70 conserved genes exhibiting their dynamic expression under all treatments. Differential expression pattern of genes and comparative analysis, have proven instrumental in identifying ten putative structural genes. These ten genes were annotated as PLAT/LH2, CAT, MLP, HSP, PB1, PLA, NAC, HMA, and CER1 transcription factors involved in antioxidant activity, defense response, MAPK signaling, detoxification of metals and regulating the crosstalk between the complex pathways. Predictive analysis of putative candidate genes, potentially governing single, double, and multifactorial stress response, by several signaling systems and molecular patterns. These findings represent a valuable resource for pitaya breeding programs, offering the potential to develop resilient "super pitaya" plants.
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Frutas , Regulación de la Expresión Génica de las Plantas , Redes Reguladoras de Genes , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Redes Reguladoras de Genes/efectos de los fármacos , Frutas/genética , Frutas/efectos de los fármacos , Frutas/metabolismo , Vanadio/farmacología , Estrés Fisiológico/genética , Caragana/genética , Caragana/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mapas de Interacción de Proteínas , Perfilación de la Expresión Génica , Sequías , Transcriptoma/genética , Transcriptoma/efectos de los fármacos , CactaceaeRESUMEN
BACKGROUND: Autosomal Recessive Primary Microcephaly (MCPH) is a rare, neurodevelopmental disorder associated with mild to severe mental retardation. It is characterized by reduced cerebral cortex that ultimately leads to reduction in skull size less than - 3 S.D below the mean for normal individuals having same age and sex. Till date, 30 known loci have been reported for MCPH. METHODS: In the present study, Sanger sequencing was performed followed by linkage analysis to validate the mutation in ASPM gene of the consanguineous Pakistani clans. Bioinformatics tools were also used to confirm the pathogenicity of the diseased variant in the gene. MRI scan was used to compare the brain structure of both the affected individuals (Aslam et al. in Kinnaird's 2nd International Conference on Science, Technology and Innovation, Lahore, 2023). RESULTS: Our study described a consanguineous family with two patients with a known ASPM (MCPH5) variant c.8508_8509delGA causing a frameshift mutation in exon 18 which located in calmodulin-binding IQ domain of the ASPM protein. The salient feature of this study is that a single variant led to significantly distinct changes in the architecture of brain of both siblings which is further confirmed by MRI results. The computation analysis showed that the change in the conservation of this residue cause this variant highly pathogenic. Carrier screening and genetic counselling were also remarkable features of this study (Aslam et al. in Kinnaird's 2nd International Conference on Science, Technology and Innovation, Lahore, 2023). CONCLUSION: This study explores the extraordinary influence of a single ASPM variant on divergent brain structure in consanguineous siblings and enable us to reduce the incidence of further microcephalic cases in this Pakistani family (Aslam et al. in Kinnaird's 2nd International Conference on Science, Technology and Innovation, Lahore, 2023).
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Encéfalo , Hermanos , Humanos , Consanguinidad , Pakistán , Encéfalo/diagnóstico por imagen , Proteínas del Tejido NerviosoRESUMEN
BACKGROUND: Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental and genetically heterogeneous disorder, characterized by small cranium size (> - 3 SD below mean) and often results in varying degree of intellectual disability. Thirty genes have been identified for the etiology of this disorder due to its clinical and genetic heterogeneity. METHODS AND RESULTS: Here, we report two consanguineous Pakistani families affected with MCPH exhibiting mutation in WDR62 gene. The investigation approach involved Next Generation Sequencing (NGS) gene panel sequencing coupled with linkage analysis followed by validation of identified variants through automated Sanger sequencing and Barcode-Tagged (BT) sequencing. The molecular genetic analysis revealed one novel splice site variant (NM_001083961.2(WDR62):c.1372-1del) in Family A and one known exonic variant NM_001083961.2(WDR62):c.3936dup (p.Val1313Argfs*18) in Family B. Magnetic Resonance Imaging (MRI) scans were also employed to gain insights into the structural architecture of affected individuals. Neurological assessments showed the reduced gyral and sulcal patterns along with normal corpus callosum in affected individuals harboring novel variant. In silico assessments of the identified variants were conducted using different tools to confirm the pathogenicity of these variants. Through In silico analyses, both variants were identified as disease causing and protein modeling of exonic variant indicates subtle conformational alterations in prophesied protein structure. CONCLUSION: This study identifies a novel variant (c.1372-1del) and a recurrent pathogenic variant c.3936dup (p.Val1313Argfs*18) in the WDR62 gene among the Pakistani population, expanding the mutation spectrum for MCPH. These findings emphasize the importance of genetic counseling and awareness to reduce consanguinity and address the burden of this disorder.
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Consanguinidad , Microcefalia , Mutación , Proteínas del Tejido Nervioso , Linaje , Humanos , Microcefalia/genética , Femenino , Masculino , Pakistán , Mutación/genética , Proteínas del Tejido Nervioso/genética , Neuroimagen/métodos , Niño , Imagen por Resonancia Magnética/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Preescolar , Adolescente , Proteínas de Ciclo CelularRESUMEN
The cultivation of forage crops on wastewater-irrigated soils, while common in many developing countries, poses significant risks due to heavy metal pollution, particularly Lead (Pb) and Nickel (Ni). This practice, aimed at addressing water scarcity challenges and providing affordable irrigation, was investigated for its ecological and human health implications across three diverse sites (site A, site B, and site C). Our study unveiled increases in Pb concentrations in contaminated soil, cultivated with Sesbania bispinosa showing the highest Pb accumulation. The Ni concentrations ranged from 5.34 to 10.43 across all forage crop samples, with S. fruticosa from site C displaying the highest Ni concentration and S. bicolor from site A exhibiting the lowest. Trace element concentrations in the specimens were determined using an atomic absorption spectrophotometer. The Pb levels in the blood, hair, and feces of farm ruminants (cows, buffaloes, and sheep) varied across the sites, with buffaloes consistently displaying the highest Pb levels. Insights into daily Pb intake by ruminant's highlighted variations influenced by plant species, animal types, and sites, with site C, the cows exhibiting the highest Health Risk Index (HRI) associated with lead exposure from consuming forage crops. Soil and forage samples showed Pb concentrations ranging from 8.003 to 12.29â¯mg/kg and 6.69-10.52â¯mg/kg, respectively, emphasizing the severe health risks associated with continuous sewage usage. Variations in Ni concentrations across animal blood, hair, and feces samples underscored the importance of monitoring Ni exposure in livestock, with sheep at site B consistently showing the highest Ni levels. These findings highlight the necessity of vigilance in monitoring trace element (Pb and Ni) exposure in forage crops and livestock, to mitigate potential health risks associated with their consumption, with variations dependent on species, site, and trace element concentrations.
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An experiment was carried out to explore the impact of petroleum hydrocarbons (PHs)-degrading microbial consortium (MC) on phytoremediation ability and growth of water hyacinth (WH) plants in water contaminated with lead (Pb) and PHs. Buckets (12-L capacity) were filled with water and WH plants, PHs (2,400 mg L-1) and Pb (10 mg L-1) in respective buckets. Plants were harvested after 30 days of transplanting and results showed that PHs and Pb substantially reduced the agronomic (up to 62%) and physiological (up to 49%) attributes of WH plants. However, the application of MC resulted in a substantial increase in growth (38%) and physiology (22%) of WH plants over uninoculated contaminated control. The WH + MC were able to accumulate 93% Pb and degrade/accumulate 72% of PHs as compared to initial concentration. Furthermore, combined use of WH plants and MC in co-contamination of PHs and Pb, reduced Pb and PHs contents in water by 74% and 68%, respectively, than that of initially applied concentration. Our findings suggest that the WH in combination with PHs-degrading MC could be a suitable nature-based water remediation technology for organic and inorganic contaminants and in future it can be used for decontamination of mix pollutants from water bodies.
Phytoremediation by aquatic macrophytes is a promising technique for the cleanup of environmental toxins from wastewater. To our knowledge, this is the first study reporting the integrated use of water hyacinth (WH) plants and a newly developed multi-trait microbial consortium for the simultaneous remediation of organic (i.e., petroleum hydrocarbons) and inorganic (i.e., lead) pollutants from the contaminated water. Findings of this study provide the basic but important information on the combined use of WH and microbes for remediation of mix pollution from water bodies.
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Eichhornia , Petróleo , Contaminantes del Suelo , Biodegradación Ambiental , Plomo , Hidrocarburos , Plantas , Contaminantes del Suelo/análisis , SueloRESUMEN
Glyphosate (Gly) and its formulations are broad-spectrum herbicides globally used for pre- and post-emergent weed control. Glyphosate has been applied to terrestrial and aquatic ecosystems. Critics have claimed that Gly-treated plants have altered mineral nutrition and increased susceptibility to plant pathogens because of Gly ability to chelate divalent metal cations. Still, the complete resistance of Gly indicates that chelation of metal cations does not play a role in herbicidal efficacy or have a substantial impact on mineral nutrition. Due to its extensive and inadequate use, this herbicide has been frequently detected in soil (2 mg kg-1, European Union) and in stream water (328 µg L-1, USA), mostly in surface (7.6 µg L-1, USA) and groundwater (2.5 µg L-1, Denmark). International Agency for Research on Cancer (IARC) already classified Gly as a category 2 A carcinogen in 2016. Therefore, it is necessary to find the best degradation techniques to remediate soil and aquatic environments polluted with Gly. This review elucidates the effects of Gly on humans, soil microbiota, plants, algae, and water. This review develops deeper insight toward the advances in Gly biodegradation using microbial communities. This review provides a thorough understanding of Gly interaction with mineral elements and its limitations by interfering with the plants biochemical and morphological attributes.
Glyphosate (Gly) contamination in water, soil, and crops is an eminent threat globally. Various advanced and integrated approaches have been reported to remediate Gly contamination from the water-soil-crop system. This review elucidates the effects of Gly on human health, soil microbial communities, plants, algae, and water. This review develops deeper insight into the advances in Gly biodegradation using microbial communities, particularly soil microbiota. This review provides a brief understanding of Gly interaction with mineral elements and its limitations in interfering with the plants biochemical and morphological attributes.
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Herbicidas , Microbiota , Humanos , Glifosato , Suelo , Glicina/metabolismo , Biodegradación Ambiental , Herbicidas/metabolismo , Cationes , MineralesRESUMEN
Under paddy soil conditions, rice plants are vulnerable to arsenic (As) accumulation, thus causing potential threat to human health. Here we investigated the influence of foliar-applied phosphorus (P: 10 and 20 mg L-1), silicon (Si: 0.6 and 1.5 g L-1) and selenium (Se: 5 and 10 mg L-1) on As accumulation, morphological and physiological attributes of two contrasting rice genotypes (KSK-133 and Super Basmati) under As stress (25 mg kg-1 as arsenate). Silicon foliar dressing significantly (p < 0.05) reduced grain As uptake (up to 67%) and improved rice growth and chlorophyll content (28-66%) in both rice genotypes over their controls. Phosphorus foliar application resulted in a notable decrease (17%) in grain As uptake of coarse rice genotype (KSK-133), while it slightly increased grain As uptake in the fine one (Super Basmati; 6%) compared to controls. However, foliar-applied Se did not show significant effects on rice plants growth attributes and As uptake in both genotypes. Similarly, biochemical and enzymatic attributes (i.e., lipid peroxidation, electrolyte leakage, peroxidase and catalase) were improved with Si application in rice plants, except for P treatment that was only effective for coarse one. Foliar-applied Si also resulted in reduced cancer risk and hazard quotient (< 0.10) for both rice genotypes. This study advances our understanding on critical role of different foliar-applied nutrients and rice genotypes, which is imperative to develop effective As remediation and management strategies in coarse and fine rice genotypes and protect human health.
This study provided new insights on the significance of foliar-applied phosphorus, silicon and selenium for the management and remediation of arsenic in fine (Super Basmati) and coarse (KSK-133) rice genotypes. Foliar-applied silicon was the most promising strategy to mitigate arsenic uptake and minimizing health risk in rice grain of both genotypes, while phosphorus was effective only for coarse one, thus showing a genotype dependent response. Interestingly, selenium foliar application had no significant effect on arsenic accumulation in both rice genotypes.
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Arsénico , Oryza , Selenio , Contaminantes del Suelo , Humanos , Silicio/análisis , Silicio/farmacología , Fósforo , Oryza/genética , Contaminantes del Suelo/análisis , Biodegradación Ambiental , Suelo/química , Genotipo , Grano Comestible/químicaRESUMEN
Wastewater contamination with heavy metal(loids)s has become a worldwide environmental and public health problem due to their toxic and non-degradable nature. Different methods and technologies have been applied for water/wastewater treatment to mitigate heavy metal(loid)-induced toxicity threat to humans. Among various treatment methods, adsorption is considered the most attractive method because of its high ability and efficiency to remove contaminants from wastewater. Agricultural waste-based adsorbents have gained great attention because of high efficiency to heavy metal(loids)s removal from contaminated water. Chemically modified biosorbents can significantly enhance the stability and adsorption ability of the sorbents. The two mathematical models of sorption, Freundlich and Langmuir isotherm models, have mostly been studied. In kinetic modeling, pseudo-second-order model proved better in most of the studies compared to pseudo-first-order model. The ion exchange and electrostatic attraction are the main mechanisms for adsorption of heavy metal(loid)s on biosorbents. The regeneration has allowed various biosorbents to be recycled and reused up to 4-5 time. Most effective eluents used for regeneration are dilute acids. For practical perspective, biosorbent removal efficiency has been elucidated using various types of wastewater and economic analysis studies. Economic analysis of adsorption process using agricultural waste-based biosorbents proved this approach cheaper compared to traditional commercial adsorbents, such as chemically activated carbon. The review also highlights key research gaps to advance the scope and application of waste peels for the remediation of heavy metal(loid)s-contaminated wastewater.
This review provides new information and insights on the potential utilization of agriculture-based biosorbents for the removal of contaminants, especially heavy metal(loid)s from toxic water/wastewater, as well as their mechanisms, adsorption efficiency, and regeneration ability. For practical perspective, biosorbent adsorption efficiency was elucidated by using various types of wastewater and economic analysis studies.
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Metales Pesados , Contaminantes Químicos del Agua , Humanos , Aguas Residuales , Biodegradación Ambiental , Modelos Teóricos , Adsorción , Cinética , AguaRESUMEN
Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.