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Recent advancements in the treatment of melanoma are encouraging, but there remains a need to identify additional therapeutic targets. We identify a role for microsomal glutathione transferase 1 (MGST1) in biosynthetic pathways for melanin and as a determinant of tumor progression. Knockdown (KD) of MGST1 depleted midline-localized, pigmented melanocytes in zebrafish embryos, while in both mouse and human melanoma cells, loss of MGST1 resulted in a catalytically dependent, quantitative, and linear depigmentation, associated with diminished conversion of L-dopa to dopachrome (eumelanin precursor). Melanin, especially eumelanin, has antioxidant properties, and MGST1 KD melanoma cells are under higher oxidative stress, with increased reactive oxygen species, decreased antioxidant capacities, reduced energy metabolism and ATP production, and lower proliferation rates in 3D culture. In mice, when compared to nontarget control, Mgst1 KD B16 cells had less melanin, more active CD8+ T cell infiltration, slower growing tumors, and enhanced animal survival. Thus, MGST1 is an integral enzyme in melanin synthesis and its inhibition adversely influences tumor growth.
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Glutationa Transferase , Melaninas , Melanoma , Animais , Humanos , Camundongos , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Melaninas/biossíntese , Melanoma/genética , Melanoma/imunologia , Melanoma/fisiopatologia , Peixe-Zebra/metabolismo , Oxirredução , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral , Proliferação de Células/genéticaRESUMO
In the LY.17 randomized phase II clinical trial, adults with relapsed and refractory diffuse large B-cell lymphoma treated with ibrutinib-R-GDP (IR-GDP) for up to three cycles had more documented bacterial and fungal infections, without improvement in overall response, compared with R-GDP. CR, complete response; DLBCL, diffuse large B-cell lymphoma; PD, progressive disease; PR, partial response; R/R, relapsed/refractory; SD, stable disease.
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Most vegetable crops are severely affected by the uptake of heavy metals from the soil. Heavy metals in vegetable bodies generate reactive oxygen species (ROS) that unbalance the antioxidant defense system. This study was initiated to determine the physiological and biochemical characteristics of spinach plants grown on soil contaminated with heavy metals and responding to Bacillus cereus and Bacillus aerius were isolated from soil contaminated with heavy metals. Heavy metal contamination led to a significant reduction in seed germination, seedling biomass, protein, and total nitrogen content of spinach plants grown in contaminated soils compared to control soils. In contrast, a significant increase in the content of metallothioneins and antioxidant enzymes was observed. Plants inoculated with B. cereus and B. aerius significantly reduced the oxidative stress induced by heavy metals by improving seed germination (%), seedling growth, nitrogen, and protein content. The content of metallothioneins and the activities of antioxidant enzymes were reduced in spinach plants grown from seeds inoculated with bacterial strains. In addition, plants inoculated with, B. cereus and B. aerius showed greater stomata opening than plants grown on soil contaminated with heavy metals, whose stomata were almost closed. These results suggested that both bacterial strains enhanced plant growth by reducing oxidative stress caused by metals.
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Loratadina/análogos & derivados , Metais Pesados , Poluentes do Solo , Spinacia oleracea , Antioxidantes/metabolismo , Metais Pesados/toxicidade , Estresse Oxidativo , Bactérias/metabolismo , Solo/química , Plantas/metabolismo , Nitrogênio/metabolismo , Poluentes do Solo/toxicidade , Poluentes do Solo/metabolismoRESUMO
AIMS: To create and validate a weakly supervised artificial intelligence (AI) model for detection of abnormal colorectal histology, including dysplasia and cancer, and prioritise biopsies according to clinical significance (severity of diagnosis). MATERIALS AND METHODS: Triagnexia Colorectal, a weakly supervised deep learning model, was developed for the classification of colorectal samples from haematoxylin and eosin (H&E)-stained whole slide images. The model was trained on 24 983 digitised images and assessed by multiple pathologists in a simulated digital pathology environment. The AI application was implemented as part of a point and click graphical user interface to streamline decision-making. Pathologists assessed the accuracy of the AI tool, its value, ease of use and integration into the digital pathology workflow. RESULTS: Validation of the model was conducted on two cohorts: the first, on 100 single-slide cases, achieved micro-average model specificity of 0.984, micro-average model sensitivity of 0.949 and micro-average model F1 score of 0.949 across all classes. A secondary multi-institutional validation cohort, of 101 single-slide cases, achieved micro-average model specificity of 0.978, micro-average model sensitivity of 0.931 and micro-average model F1 score of 0.931 across all classes. Pathologists reflected their positive impressions on the overall accuracy of the AI in detecting colorectal pathology abnormalities. CONCLUSIONS: We have developed a high-performing colorectal biopsy AI triage model that can be integrated into a routine digital pathology workflow to assist pathologists in prioritising cases and identifying cases with dysplasia/cancer versus non-neoplastic biopsies.
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Urease-producing bacteria (UPB) provide inorganic nitrogen for primary producers by hydrolyzing urea, and play an important role in marine nitrogen cycle. However, there is still an incomplete understanding of UPB and their ecological functions in the cultivation environment of the red macroalgae Gracilariopsis lemaneiformis. This study comprehensively analyzed the diversity of culturable UPB and explored their effects on urea uptake by G. lemaneiformis. A total of 34 isolates belonging to four main bacterial phyla i.e. (Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria) were identified through 16S rRNA sequencing and were screened for UPB by urea agar chromogenic medium assay and ureC gene cloning. Our data revealed that only 8 strains contained urease. All of these UPB exhibited different urease activities, which were determined by the Berthelot reaction colorimetry assay. Additionally, the UPB strain (G13) isolated from G. lemaneiformis with higher urease activity was selected for co-culture with G. lemaneiformis to explore its role in promoting or inhibiting nitrogen uptake by macroalgae. The results showed a significant increase in urea consumption in the culture medium and the total cellular nitrogen in G. lemaneiformis in the UPB-co culture group compared to the sterile group. This suggests that the selected UPB strain positively influences nitrogen uptake by G. lemaneiformis. Similarly, isotopic assays revealed that the δ15N content of G. lemaneiformis was significantly higher in the UPB-co culture than in the control group, where δ15N-urea was the only nitrogen source in the culture medium. This indicates that the UPB helped G. lemaneiformis to absorb more nitrogen from urea. Moreover, the highest content of δ15N was found in G. lemaneiformis with epiphytic bacteria compared to sterilized (i.e. control), showing that epiphytic bacteria, along with UPB, have a compound effect in helping G. lemaneiformis absorb more nitrogen from urea. Taken together, these results provide unique insight into the ecological role of UPB and suggest that urease from macroalgae environment-associated bacteria might be an important player in marine nitrogen cycling.
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Alga Marinha , Urease , RNA Ribossômico 16S/genética , Bactérias/genética , Nitrogênio , UreiaRESUMO
BACKGROUND: Hepatitis C virus (HCV) antibody self-testing (HCVST) may help expand screening access and support HCV elimination efforts. Despite potential benefits, HCVST is not currently implemented in Pakistan. This study aimed to assess the usability and acceptability of HCVST in a high HCV prevalence informal settlement in Karachi, Pakistan. METHODS: We performed a cross-sectional study in a hepatitis C clinic from April through June 2023. Participants were invited to perform a saliva-based HCVST (OraSure Technologies, USA) while following pictorial instructions. A study member evaluated test performance using a standardized checklist and provided verbal support if a step could not be completed. Perceived usability and acceptability were assessed using a semi-structured questionnaire. The HCVST was considered successful if the participant was able to complete all steps and correctly interpret test results. Overall concordance and positive and negative agreement were estimated in comparison with the HCVST result read by the study member (inter-reader concordance and agreement) and result of a second rapid HCV test (Abbott Diagnostics Korea Inc, South Korea) performed by a trained user (inter-operator concordance and agreement). RESULTS: The study included 295 participants of which 97 (32%) were illiterate. In total, 280 (95%, 95% CI 92-97%) HCVSTs were successful. Overall, 38 (13%) people performed the HCVST without verbal assistance, 67 (23%) needed verbal assistance in one step, 190 (64%) in two or more. Assistance was most often needed in managing the test buffer and test reading times. The inter-reader concordance was 96% and inter-operator concordance 93%. Inter-reader and inter-operator positive percent agreement were 84 and 70%, respectively. All participants reported they would use HCVST again and would recommend it to friends and family. CONCLUSION: Saliva-based HCVST was very well accepted in this clinic-based setting. However, many people requested verbal support in several steps, highlighting the need for clear instructions for use and test devices that are simple to use, particularly in low literacy settings. Moderately low positive percent agreement with the results of a rapid test performed by a trained user highlights potential uncertainty in the accuracy of HCVST in the hands of lay users.
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Hepatite C , Autoteste , Humanos , Paquistão/epidemiologia , Masculino , Feminino , Estudos Transversais , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Adulto , Pessoa de Meia-Idade , Prevalência , Hepacivirus/isolamento & purificação , Programas de Rastreamento/métodos , Anticorpos Anti-Hepatite C/sangue , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , População Urbana , Inquéritos e Questionários , Adulto Jovem , Saliva/virologiaRESUMO
BACKGROUND: It is well-known that serum uric acid (SUA) can increase the risk of hypertension, diabetes, obesity and dyslipidemia. However, its independent association with the risk of cardiovascular diseases (CVD) is controversial particularly in different populations. Hence, this study was aimed to assess an independent association of SUA with CVD risk in a Punjabi Pakistani cohort. METHODS: This is a retrospective observational study in which 502 human subjects having CVD, hypertension and/or diabetes were grouped based on SUA levels as normouricemia (n = 266) and hyperuricemia (n = 236). Role of SUA was assessed in increasing the risk of CVD independent of other key confounding factors (i.e. age, gender, dyslipidemia, hypertension, diabetes, dietary and life-style habits). All clinical and biochemical data were analyzed in SPSS (ver. 20). RESULTS: Subjects aged 55 ± 13 years were of both genders (males: 52%). SUA levels were significantly different among clinical subtypes of CVD [i.e. acute coronary syndrome (ACS), myocardial infarction (MI) and heart failure (HF)]. Spearman correlation showed a significantly positive association between CVD and SUA (rho = 0.149, p < 0.001). Multivariate logistic regression of SUA quartiles showed that hyperuricemia is associated with CVD [3rd quartile: OR: 1.78 (CI: 1.28-2.48), p = 0.001 and 4th quartile: OR: 2.37 (CI: 1.72-3.27), p < 0.001]. Moreover, this association remained significant even after adjusting for confounding factors. CONCLUSION: This study showed that SUA is positively associated with CVD, thus it can act as an independent risk factor for CVD.
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Biomarcadores , Doenças Cardiovasculares , Hiperuricemia , Ácido Úrico , Humanos , Masculino , Ácido Úrico/sangue , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hiperuricemia/sangue , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Paquistão/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Adulto , Biomarcadores/sangue , Idoso , Medição de Risco , Fatores de Risco de Doenças Cardíacas , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Fatores de RiscoRESUMO
In this paper, we examine intraspecific variation in the quantity of alkaloid chemical defence in field collected individuals of the polymorphic ladybird beetle Adalia decempunctata (10-spot ladybird). Like its more widely studied relative Adalia bipunctata (2-spot ladybird), A. decempunctata possesses the alkaloids adaline and adalinine, which are, respectively, the major and minor alkaloids of A. bipunctata. We focused especially on alkaloid concentration in relation to colour pattern morph, sex, and the relationship between female and egg parameters. There was a marked sexual dimorphism in the balance of the two alkaloids, with adaline predominating in females and adalinine predominating in males: in males, on average, over 70% of total alkaloid was adalinine. Females had a lower proportion of adalinine (< 10%) than their eggs (> 15%) and relationships between egg alkaloid and female alkaloid or fecundity were weak or non-existent. Colour pattern morph had a borderline (although not) significant relationship with adaline concentration and total alkaloid concentration, which could be further explored with laboratory reared individuals. The sexual dimorphism in alkaloid content, which seems likely due to differences in synthesis, might be related to their relative costs to the two sexes and might provide insight into the evolution of alkaloid diversity in ladybirds.
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Herein, we investigated the stereochemical effects of 4'-methyl substitution on A3 adenosine receptor (A3AR) ligands by synthesizing and evaluating a series of truncated 4'-thioadenosine derivatives featuring 4'-α-methyl, 4'-ß-methyl, and 4',4'-dimethyl substitutions. We successfully synthesized these derivatives, using the stereoselective addition of an organometallic reagent, KSAc-mediated sulfur cyclization, and Vorbrüggen condensation. Binding assays demonstrated that the 4'-ß-methyl substitution conferred the highest affinity for A3AR, with compound 1 h exhibiting a Ki = 3.5 nM, followed by the 4',4'-dimethyl and 4'-α-methyl substitutions. Notably, despite the absence of the 5'-OH group, compound 1 h unexpectedly displayed partial agonism. Computational docking studies indicated that compound 1 h, the ß-methyl derivative, adopted a South conformation and maintained strong interactions within the receptor, including a critical interaction with Thr94, a residue known to be notable for agonistic effects. Conversely, compound 2 h, the α-methyl derivative, also adopted a South conformation but resulted in a flattened structure that hindered interactions with Thr94 and Asn250. The dimethyl derivative 3 h exhibited steric clashes with Thr94, contributing to a reduction in binding affinity. However, the docking results for 3 h indicated a North conformation, suggesting that the change in sugar conformation due to the additional 4'-methyl group altered the angle between the α-methyl group and the sugar plane, enabling binding despite the increased steric bulk. These findings suggest that not only do the substituents and their stereochemistry influence receptor-ligand interactions, but the conformation and the resulting spatial orientation of the substituents also play a crucial role in modulating receptor-ligand interaction. This stereochemical insight offers a valuable framework for the design of new, selective, and potent A3AR ligands, potentially facilitating the development of novel therapeutics for A3AR-related diseases such as glaucoma, inflammation, and cancer.
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The current investigation examines the effectiveness of various approaches in predicting the soil texture class (clay, silt, and sand contents) of the Rawalpindi district, Punjab province, Pakistan. The employed techniques included artificial neural networks (ANNs), kriging, co-kriging, and inverse distance weighting (IDW). A total of 44 soil specimens from depths of 10-15 cm were gathered, and then the hydrometer method was adopted to measure their texture. The map of soil grain sets was formulated in the ArcGIS environment, utilizing distinct interpolation approaches. The MATLAB software was used to evaluate soil texture. The gradient fraction, latitude and longitude, elevation, and soil texture fragments of points were proposed to an ANN. Several statistical values, such as correlation coefficient (R), geometric mean error ratios (GMER), and root mean square error (RMSE), were utilized to evaluate the precision of the intended techniques. In assessing grain size and spatial dissemination of clay, silt, and sand, the effectiveness and precision of ANN were superior compared to kriging, co-kriging, and inverse distance weighting. Still, less than a 50% correlation was observed using the ANN. In this examination, the IDW had inferior precision compared to the other approaches. The results demonstrated that the practices produced acceptable results and can be used for future research. Soil texture is among the most central variables that can manipulate agriculture plans. The prepared maps exhibiting the soil texture groups are imperative for crop yield and pastoral scheduling.
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Areia , Solo , Argila , Monitoramento Ambiental/métodos , AgriculturaRESUMO
INTRODUCTION AND HYPOTHESIS: The objective was to investigate the relationship between mesh exposure and persistent stress urinary incontinence (SUI) post-midurethral sling (MUS) surgery. METHODS: Extensive data collection including patient demographics, obstetric history, existing medical conditions, previous surgeries, and surgical outcomes, encompassing both perioperative and postoperative complications. RESULTS: Out of 456 patients who underwent the MUS procedure within the specified period, the persistence of SUI was noted in 6.4% of cases. Mesh exposure was observed in 8.8% of these cases. Notably, 25% of patients with mesh exposure suffered from persistent SUI, in stark contrast to 4.6% of those without mesh exposure (p < 0.0001). Further, multivariate analysis indicated that patients with mesh exposure had an approximately 6.5-fold increased likelihood (95% CI: 2.71-15.44) of experiencing persistent SUI compared with those without mesh exposure. CONCLUSIONS: Mesh exposure is a significant independent risk factor for persistent SUI post-MUS surgery. Patients with mesh exposure are about 6.5 times more prone to persistent SUI than those without. Although mesh exposure is typically managed with expectant measures, vaginal estrogen or mesh excision, current evidence does not support surgical revision of MUS affected by mesh exposure or additional incontinence procedures during mesh excision.
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Slings Suburetrais , Telas Cirúrgicas , Incontinência Urinária por Estresse , Humanos , Incontinência Urinária por Estresse/cirurgia , Incontinência Urinária por Estresse/etiologia , Feminino , Pessoa de Meia-Idade , Slings Suburetrais/efeitos adversos , Telas Cirúrgicas/efeitos adversos , Fatores de Risco , Idoso , Adulto , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologiaRESUMO
AIM: Growth reference values about mid-upper arm circumference (MUAC) are vital for assessing children's nutritional status. However, Pakistan lacks these reference values and growth charts. This study aims to develop these for children aged 6-60 months and compare them with global standards. METHODS: The data were acquired from the 2018 National Nutrition Survey of Pakistan, which was conducted by the United Nations Children's Fund (UNICEF) during 2018-2019. The final study cohort comprised 57 285 children, with 51% being boys. Percentile values and charts for MUAC-for-age were developed using generalised additive models for location, scale and shape with the Box-Cox power exponential distribution. RESULTS: The mean MUAC was 14.21 cm (±2.07 cm) and 14.13 cm (±2.12 cm) for the boys and girls, respectively. At 60 months of age, the P3 and P97 percentiles for girls were slightly higher than those for boys. The median percentiles of Pakistani children were smaller than the World Health Organisation 2007 standards and with international references. CONCLUSION: We observed disparities in MUAC-for-age growth references among Pakistani children compared to global standards, highlighting regional, age and gender variations. This underscores the need for developing countries like Pakistan to establish their growth references.
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Braço , Gráficos de Crescimento , Humanos , Masculino , Paquistão , Feminino , Lactente , Braço/anatomia & histologia , Pré-Escolar , Valores de Referência , AntropometriaRESUMO
The objective is to determine if the timing of midurethral sling (MUS) placement has an impact on the recurrence rate of stress urinary incontinence. We conducted a retrospective cohort study of patients who underwent robot sacrocolpopexy (RSC) with MUS placement at a large community hospital. Our data demonstrated that there was no significant difference in stress urinary incontinence recurrence when the MUS was placed before or after the RSC (15% vs. 11%, P = 0.41, respectively). We concluded that physician preference may dictate surgical approach to sequence of retropubic MUS placement at the time of RSC.
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Slings Suburetrais , Incontinência Urinária por Estresse , Humanos , Feminino , Estudos Retrospectivos , Incontinência Urinária por Estresse/cirurgia , Pessoa de Meia-Idade , Idoso , Prolapso de Órgão Pélvico/cirurgia , Recidiva , Procedimentos Cirúrgicos em Ginecologia/métodos , Procedimentos Cirúrgicos RobóticosRESUMO
Control charts, used in healthcare operations to monitor process stability and quality, are essential for ensuring patient safety and improving clinical outcomes. This comprehensive research study aims to provide a thorough understanding of the role of control charts in healthcare quality monitoring and future perspectives by utilizing a dual methodology approach involving a systematic review and a pioneering bibliometric analysis. A systematic review of 73 out of 223 articles was conducted, synthesizing existing literature (1995-2023) and revealing insights into key trends, methodological approaches, and emerging themes of control charts in healthcare. In parallel, a bibliometric analysis (1990-2023) on 184 articles gathered from Web of Science and Scopus was performed, quantitatively assessing the scholarly landscape encompassing control charts in healthcare. Among 25 countries, the USA is the foremost user of control charts, accounting for 33% of all applications, whereas among 14 health departments, epidemiology leads with 28% of applications. The practice of control charts in health monitoring has increased by more than one-third during the last 3 years. Globally, exponentially weighted moving average charts are the most popular, but interestingly the USA remained the top user of Shewhart charts. The study also uncovers a dynamic landscape in healthcare quality monitoring, with key contributors, research networks, research hotspot tendencies, and leading countries. Influential authors, such as J.C. Benneyan, W.H. Woodall, and M.A. Mohammed played a leading role in this field. In-countries networking, USA-UK leads the largest cluster, while other clusters include Denmark-Norway-Sweden, China-Singapore, and Canada-South Africa. From 1990 to 2023, healthcare monitoring evolved from studying efficiency to focusing on conditional monitoring and flowcharting, with human health, patient safety, and health surveys dominating 2011-2020, and recent years emphasizing epidemic control, COronaVIrus Disease of 2019 (COVID-19) statistical process control, hospitals, and human health monitoring using control charts. It identifies a transition from conventional to artificial intelligence approaches, with increasing contributions from machine learning and deep learning in the context of Industry 4.0. New researchers and journals are emerging, reshaping the academic context of control charts in healthcare. Our research reveals the evolving landscape of healthcare quality monitoring, surpassing traditional reviews. We uncover emerging trends, research gaps, and a transition in leadership from established contributors to newcomers amidst technological advancements. This study deepens the importance of control charts, offering insights for healthcare professionals, researchers, and policymakers to enhance healthcare quality. Future challenges and research directions are also provided.
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Bibliometria , Qualidade da Assistência à Saúde , Humanos , Segurança do PacienteRESUMO
Water contamination with metals poses significant environmental challenges. The occurrence of heavy metals (HMs) prompts modifications in plant structures, emphasizing the necessity of employing focused safeguarding measures. Cadmium (Cd), lead (Pb), and chromium (Cr) emerge as particularly menacing toxins due to their high accumulation potential. Increasing the availability of organic acids is crucial for optimizing toxic metal removal via phytoremediation. This constructed wetland system (CWs) was used to determine how oxalic acid (OA) treatments of textile wastewater (WW) effluents affected morpho-physiological characteristics, antioxidant enzyme activity, oxidative stress, and HM concentrations in Phragmites australis. Multiple treatments, comprising the application of OA at a concentration of 10 mM and WW at different dilutions (25%, 50%, 75%, and 100%), were employed, with three replications of each treatment. WW stress decreased chlorophyll and carotenoid content, and concurrently enhanced HMs adsorption and antioxidant enzyme activities. Furthermore, the application of WW was found to elevate oxidative stress levels, whereas the presence of OA concurrently mitigated this oxidative stress. Similarly, WW negatively affected soil-plant analysis development (SPAD) and the total soluble proteins (SP) in both roots and shoots. Conversely, these parameters showed improvement with OA treatments. P. australis showed the potential to enhance HM accumulation under 100% WW stress. Specifically, there is an increase in root SP ranging from 9% to 39%, an increase in shoot SP from 6% to 91%, and an elevation in SPAD values from 4% to 64% compared to their respective treatments lacking OA inclusion. The OA addition resulted in decreased EL contents in the root and shoot by 10%-19% and 13%-15%, MDA by 9%-14% and 9%-20%, and H2O2 by 14%-21% and 9%-17%, in comparison to the respective treatments without OA. Interestingly, the findings further revealed that the augmentation of OA also contributed to an increased accumulation of Cr, Cd, and Pb. Specifically, at 100% WW with OA (10 mM), the concentrations of Cr, Pb, and Cd in leaves rose by 164%, 447%, and 350%, in stems by 213%, 247%, and 219%, and in roots by 155%, 238%, and 195%, respectively. The chelating agent oxalic acid effectively alleviated plant toxicity induced by toxins. Overall, our findings demonstrate the remarkable tolerance of P. australis to elevated concentrations of WW stress, positioning it as an eco-friendly candidate for industrial effluent remediation. This plant exhibits efficacy in restoring contaminants present in textile effluents, and notably, oxalic acid emerges as a promising agent for the phytoextraction of HMs.
HMs stress decreased the physiology and morphology of Phragmites australis L.OA improved the photosynthetic pigments and antioxidant enzymesHMs accumulation and bioavailability increased under OAPhragmites australis L. showed higher efficacy for textile effluent treatment under OA.
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Biodegradação Ambiental , Metais Pesados , Ácido Oxálico , Poaceae , Águas Residuárias , Poluentes Químicos da Água , Áreas Alagadas , Ácido Oxálico/metabolismo , Poaceae/metabolismo , Metais Pesados/metabolismo , Poluentes Químicos da Água/metabolismo , Eliminação de Resíduos Líquidos/métodos , Resíduos Industriais , Indústria Têxtil , Estresse OxidativoRESUMO
Eukaryotic cells contain membrane-bound and membrane-less organelles that are often in contact with each other. How the interface properties of membrane-less organelles regulate their interactions with membranes remains challenging to assess. Here, we employ graphene-based sensors to investigate the electrostatic properties of synapsin 1, a major synaptic phosphoprotein, either in a single phase or after undergoing phase separation to form synapsin condensates. Using these graphene-based sensors, we discover that synapsin condensates generate strong electrical responses that are otherwise absent when synapsin is present as a single phase. By introducing atomically thin dielectric barriers, we show that the electrical response originates in an electric double layer whose formation governs the interaction between synapsin condensates and graphene. Our data indicate that the interface properties of the same protein are substantially different when the protein is in a single phase versus within a biomolecular condensate, unraveling that condensates can harbor ion potential differences at their interface.
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Condensados Biomoleculares , Grafite , Grafite/metabolismo , Sinapsinas , Proteínas , OrganelasRESUMO
Anthocyanin accumulation is regulated by specific genes during fruit ripening. Currently, peel coloration of mango fruit in response to exogenous ethylene and the underlying molecular mechanism remain largely unknown. The role of MiMYB8 on suppressing peel coloration in postharvest 'Guifei' mango was investigated by physiology detection, RNA-seq, qRT-PCR, bioinformatics analysis, yeast one-hybrid, dual-luciferase reporter assay, and transient overexpression. Results showed that compared with the control, low concentration of exogenous ethylene (ETH, 500 mg·L-1) significantly promoted peel coloration of mango fruit (cv. Guifei). However, a higher concentration of ETH (1000 mg·L-1) suppressed color transformation, which is associated with higher chlorophyll content, lower a* value, anthocyanin content, and phenylalanine ammonia-lyase (PAL) activity of mango fruit. M. indica myeloblastosis8 MiMYB8 and MiPAL1 were differentially expressed during storage. MiMYB8 was highly similar to those found in other plant species related to anthocyanin biosynthesis and was located in the nucleus. MiMYB8 suppressed the transcription of MiPAL1 by binding directly to its promoter. Transient overexpression of MiMYB8 in tobacco leaves and mango fruit inhibited anthocyanin accumulation by decreasing PAL activity and down-regulating the gene expression. Our observations suggest that MiMYB8 may act as repressor of anthocyanin synthesis by negatively modulating the MiPAL gene during ripening of mango fruit, which provides us with a theoretical basis for the scientific use of exogenous ethylene in practice.
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Antocianinas , Etilenos , Frutas , Regulação da Expressão Gênica de Plantas , Mangifera , Proteínas de Plantas , Fatores de Transcrição , Mangifera/metabolismo , Mangifera/genética , Etilenos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Frutas/metabolismo , Frutas/genética , Antocianinas/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Fenilalanina Amônia-Liase/genética , Pigmentação/genética , Clorofila/metabolismoRESUMO
The auxin/indoleacetic acid (Aux/IAA) family plays a central role in regulating gene expression during auxin signal transduction. Nonetheless, there is limited knowledge regarding this gene family in sugarcane. In this study, 92 members of the IAA family were identified in Saccharum spontaneum, distributed on 32 chromosomes, and classified into three clusters based on phylogeny and motif compositions. Segmental duplication and recombination events contributed largely to the expansion of this superfamily. Additionally, cis-acting elements in the promoters of SsIAAs involved in plant hormone regulation and stress responsiveness were predicted. Transcriptomics data revealed that most SsIAA expressions were significantly higher in stems and basal parts of leaves, and at nighttime, suggesting that these genes might be involved in sugar transport. QRT-PCR assays confirmed that cold and salt stress significantly induced four and five SsIAAs, respectively. GFP-subcellular localization showed that SsIAA23 and SsIAA12a were localized in the nucleus, consistent with the results of bioinformatics analysis. In conclusion, to a certain extent, the functional redundancy of family members caused by the expansion of the sugarcane IAA gene family is related to stress resistance and regeneration of sugarcane as a perennial crop. This study reveals the gene evolution and function of the SsIAA gene family in sugarcane, laying the foundation for further research on its mode of action.
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Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos , Família Multigênica , Filogenia , Proteínas de Plantas , Saccharum , Saccharum/genética , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Genoma de Planta , Regiões Promotoras Genéticas , Cromossomos de Plantas/genética , Perfilação da Expressão Gênica , Reguladores de Crescimento de Plantas/metabolismoRESUMO
BACKGROUND: The emergence of deep learning (DL) techniques has revolutionized tumor detection and classification in medical imaging, with multimodal medical imaging (MMI) gaining recognition for its precision in diagnosis, treatment, and progression tracking. OBJECTIVE: This review comprehensively examines DL methods in transforming tumor detection and classification across MMI modalities, aiming to provide insights into advancements, limitations, and key challenges for further progress. METHODS: Systematic literature analysis identifies DL studies for tumor detection and classification, outlining methodologies including convolutional neural networks (CNNs), recurrent neural networks (RNNs), and their variants. Integration of multimodality imaging enhances accuracy and robustness. RESULTS: Recent advancements in DL-based MMI evaluation methods are surveyed, focusing on tumor detection and classification tasks. Various DL approaches, including CNNs, YOLO, Siamese Networks, Fusion-Based Models, Attention-Based Models, and Generative Adversarial Networks, are discussed with emphasis on PET-MRI, PET-CT, and SPECT-CT. FUTURE DIRECTIONS: The review outlines emerging trends and future directions in DL-based tumor analysis, aiming to guide researchers and clinicians toward more effective diagnosis and prognosis. Continued innovation and collaboration are stressed in this rapidly evolving domain. CONCLUSION: Conclusions drawn from literature analysis underscore the efficacy of DL approaches in tumor detection and classification, highlighting their potential to address challenges in MMI analysis and their implications for clinical practice.
Assuntos
Aprendizado Profundo , Imagem Multimodal , Neoplasias , Humanos , Imagem Multimodal/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/classificação , Redes Neurais de ComputaçãoRESUMO
Simple and sensitive electrochemical sensors were fabricated from cerium oxide (CeO2) and copper-benzene tricarboxylic acid-modified cerium oxide (CeO2-Cu-BTC) materials for differential pulse voltammetric analysis of toxic cadmium (Cd) ions in aqueous solutions. The materials were prepared by hydrothermal method and structurally characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy with energy-dispersive X-ray (SEM-EDX), thermogravimetric analysis (TGA), and X-ray diffraction analysis (XRD). The CeO2-modified carbon paste electrode (CeCPE) and the CeO2-Cu-BTC-modified carbon paste electrode (CeBCPE) were electrochemically characterized by their cyclic voltammetry and electrochemical impedance study in standard K3[Fe(CN)6] single-electron redox process. Their electrochemical surface areas, electrode surface coverages, and charge transfer resistances were calculated to be 1.46 cm2, 2.338 × 10-5 molâcm-2, and 2790 Ω and 5.48 cm2, 2.476 × 10-5 molâcm-2, and 1254.65 Ω for CeCPE and CeBCPE, respectively. These fabricated electrodes were used as electrochemical sensors for cadmium ion estimation by optimizing the experimental parameters through differential pulse voltammetry. The optimized conditions included 10% modifier for CeCPE and 5% modifier for CeBCPE in 0.12 M HCl solution of pH 5 as supporting electrolyte at - 1.2 V deposition for 30 s in 0.01 to 10 mg L-1 linear cadmium solution range. Under these conditions, the limit of quantification (LOQ) of 0.368 mg L-1 and 0.005 mg L-1 was calculated for CeCPE and CeBCPE electrodes, respectively. The limit of detection (LOD) was calculated to be 0.121 mg L-1 and 0.002 mg L-1 for CeCPE and CeBCPE, respectively. All the experimental results indicated that electrodes fabricated from CeO2-Cu-BTC show better performance as compared to CeO2-based electrodes. Both these types of electrochemical sensors presented good repeatability and performance in the presence of interfering ions as well. From these findings, it can also be inferred that these electrochemical sensors can provide a simple and very sensitive method for approximation of toxic cadmium ions in aqueous solutions.