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The best environment for plant growth and development contains certain essential metabolites. A broad category of metabolites known as "plant biostimulants" (PBs) includes biomolecules such as proteins, carbohydrates, lipids, and other secondary metabolites related to groups of terpenes, specific nitrogen-containing compounds, and benzene ring-conjugated compounds. The formation of biomolecules depends on both biotic and abiotic factors, such as the release of PB by plants, animals, and microorganisms, or it can result from the control of temperature, humidity, and pressure in the atmosphere, in the case of humic substances (HSs). Understanding the genomic outputs of the concerned organism (may be plants or others than them) becomes crucial for identifying the underlying behaviors that lead to the synthesis of these complex compounds. For the purposes of achieving the objectives of sustainable agriculture, detailed research on PBs is essential because they aid in increasing yield and other growth patterns of agro-economic crops. The regulation of homeostasis in the plant-soil-microbe system for the survival of humans and other animals is mediated by the action of plant biostimulants, as considered essential for the growth of plants. The genomic size and gene operons for functional and regulation control have so far been revealed through technological implementations, but important gene annotations are still lacking, causing a delay in revealing the information. Next-generation sequencing techniques, such as nanopore, nanoball, and Illumina, are essential in troubleshooting the information gaps. These technical advancements have greatly expanded the candidate gene openings. The secondary metabolites being important precursors need to be studied in a much wider scale for accurate calculations of biochemical reactions, taking place inside and outside the synthesized living cell. The present review highlights the sequencing techniques to provide a foundation of opportunity generation for agricultural sustainability.
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Acquired chemoresistance remains a significant challenge in the clinics as most of the treated cancers eventually emerge as hard-to-treat phenotypes. Therefore, identifying chemoresistance targets is highly warranted to manage the disease better. In this study, we employed a label-free LC-MS/MS-based quantitative proteomics analysis to identify potential targets and signaling pathways underlying acquired chemoresistance in a sub-cell line (A549DR) derived from the parental lung adenocarcinoma cells (A549) treated with gradually increasing doses of doxorubicin (DOX). Our proteomics analysis identified 146 upregulated and 129 downregulated targets in A549DR cells. The KEGG pathway and Gene ontology (GO) analysis of differentially expressed upregulated and downregulated proteins showed that most abundant upregulated pathways were related to metabolic pathways, cellular senescence, cell cycle, and p53 signaling. Meanwhile, the downregulated pathways were related to spliceosome, nucleotide metabolism, DNA replication, nucleotide excision repair, and nuclear-cytoplasmic transport. Further, STRING analysis of upregulated biological processes showed a protein-protein interaction (PPI) between CDK1, AKT2, SRC, STAT1, HDAC1, FDXR, FDX1, NPC1, ALDH2, GPx1, CDK4, and B2M, proteins. The identified proteins in this study might be the potential therapeutic targets for mitigating DOX resistance.
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Background: End-of-life care (EOLC) is a critical aspect of healthcare, yet accessing reliable information remains challenging, particularly in culturally diverse contexts like India. Objective: This study investigates the potential of artificial intelligence (AI) in addressing the informational gap by analyzing patient information leaflets (PILs) generated by AI chatbots on EOLC. Methodology: Using a comparative research design, PILs generated by ChatGPT and Google Gemini were evaluated for readability, sentiment, accuracy, completeness, and suitability. Readability was assessed using established metrics, sentiment analysis determined emotional tone, accuracy, and completeness were rated by subject experts, and suitability was evaluated using the Patient Education Materials Assessment Tool (PEMAT). Results: Google Gemini PILs exhibited superior readability and actionability compared to ChatGPT PILs. Both conveyed positive sentiments and high levels of accuracy and completeness, with Google Gemini PILs showing slightly lower accuracy scores. Conclusion: The findings highlight the promising role of AI in enhancing patient education in EOLC, with implications for improving care outcomes and promoting informed decision-making in diverse cultural settings. Ongoing refinement and innovation in AI-driven patient education strategies are needed to ensure compassionate and culturally sensitive EOLC. How to cite this article: Gondode PG, Khanna P, Sharma P, Duggal S, Garg N. End-of-life Care Patient Information Leaflets-A Comparative Evaluation of Artificial Intelligence-generated Content for Readability, Sentiment, Accuracy, Completeness, and Suitability: ChatGPT vs Google Gemini. Indian J Crit Care Med 2024;28(6):561-568.
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Tilletia indica Mitra causes Karnal bunt (KB) in wheat by pathogenic dikaryophase. The present study is the first to provide the draft genomes of the dikaryon (PSWKBGD-3) and its two monosporidial lines (PSWKBGH-1 and 2) using Illumina and PacBio reads, their annotation and the comparative analyses among the three genomes by extracting polymorphic SSR markers. The trancriptome from infected wheat grains of the susceptible wheat cultivar WL711 at 24 h, 48h, and 7d after inoculation of PSWKBGH-1, 2 and PSWKBGD-3 were also isolated. Further, two transcriptome analyses were performed utilizing T. indica transcriptome to extract dikaryon genes responsible for pathogenesis, and wheat transcriptome to extract wheat genes affected by dikaryon involved in plant-pathogen interaction during progression of KB in wheat. A total of 54, 529, and 87 genes at 24hai, 48hai, and 7dai, respectively were upregulated in dikaryon stage while 21, 35, and 134 genes of T. indica at 24hai, 48hai, and 7dai, respectively, were activated only in dikaryon stage. While, a total of 23, 17, and 52 wheat genes at 24hai, 48hai, and 7dai, respectively were upregulated due to the presence of dikaryon stage only. The results obtained during this study have been compiled in a web resource called TiGeR ( http://backlin.cabgrid.res.in/tiger/ ), which is the first genomic resource for T. indica cataloguing genes, genomic and polymorphic SSRs of the three T. indica lines, wheat and T. indica DEGs as well as wheat genes affected by T. indica dikaryon along with the pathogenecity related proteins of T. indica dikaryon during incidence of KB at different time points. The present study would be helpful to understand the role of dikaryon in plant-pathogen interaction during progression of KB, which would be helpful to manage KB in wheat, and to develop KB-resistant wheat varieties.
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Basidiomycota , Doenças das Plantas , Transcriptoma , Triticum , Triticum/genética , Triticum/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Basidiomycota/patogenicidade , Basidiomycota/fisiologia , Perfilação da Expressão Gênica , Genoma Fúngico , Interações Hospedeiro-Patógeno/genéticaRESUMO
Bifurcations are a common site for saccular aneurysms, but rarely can be a site for dissecting aneurysms. Identification of these aneurysms is extremely important because the management plan depends on it. We describe a rare case of a ruptured dissecting aneurysm at the right ICA bifurcation in a pre-teen child which posed a diagnostic dilemma but ultimately was successfully managed with flow diversion.
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Dissecção Aórtica , Humanos , Diagnóstico Diferencial , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Masculino , Angiografia Cerebral , Criança , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Dissecação da Artéria Carótida Interna/diagnóstico por imagem , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS). DESIGN: Prospective, placebo-controlled, double-blind, cross-over study. METHODS: Setting- A tertiary eye care center. Patients- Cases of idiopathic INS with and without abnormal head posture aged ≥10 years who had not received previous treatment for nystagmus. Intervention- Patients were randomized into two groups. Group 1 was given placebo for 3 months, and after a washout period of 7 days started on topical brinzolamide for the next 3 months. In group 2, the order was reversed. The drops were administered topically three times (every 8 hours) in both eyes. Outcome measure- Binocular best corrected visual acuity (BCVA) using the ETDRS chart, eXpanded nystagmus acuity function (NAFX) score and INS waveforms obtained from eye movement recordings, intraocular pressure (IOP) by Goldmann applanation tonometer, near stereopsis by TNO stereo test, and change in abnormal head posture before and after intervention in the null position. RESULTS: A total of 29 cases completed the study (23 with abnormal head posture; 6 without abnormal head posture).A significant improvement was noted in INS waveform characteristics, mean NAFX score (P < 0.001), and mean binocular visual acuity (P < 0.001) with topical brinzolamide in comparison to baseline as well as placebo. No significant change in head position and stereopsis was noted. No side effects were reported with 3 months of brinzolamide therapy. CONCLUSIONS: While brinzolamide shows improvement in visual acuity and NAFX score in idiopathic INS, its clinical significance needs further evidence.
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Administração Tópica , Inibidores da Anidrase Carbônica , Estudos Cross-Over , Soluções Oftálmicas , Sulfonamidas , Tiazinas , Acuidade Visual , Humanos , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/uso terapêutico , Método Duplo-Cego , Masculino , Feminino , Acuidade Visual/fisiologia , Estudos Prospectivos , Tiazinas/administração & dosagem , Sulfonamidas/administração & dosagem , Criança , Adulto , Soluções Oftálmicas/administração & dosagem , Adolescente , Nistagmo Congênito/tratamento farmacológico , Nistagmo Congênito/fisiopatologia , Nistagmo Congênito/diagnóstico , Resultado do Tratamento , Adulto Jovem , Seguimentos , Pessoa de Meia-Idade , Movimentos Oculares/fisiologia , Movimentos Oculares/efeitos dos fármacos , Visão Binocular/fisiologiaRESUMO
Aim: Currently, we have limited armamentarium of antifungal agents against Mucorales. There is an urgent need to discover novel antifungal agents that are effective, safe and affordable. Materials & methods: In this study, the anti-Mucorale action of native lactoferrin (LF) and its functional fragments CLF, RR6 and LFcin against three common Mucorale species are reported. The synergistic action of LF with antifungal agents like amphotericin B, isavuconazole and posaconazole was analyzed using checkerboard technique. Results: All the three mucor species showed inhibition when treated with fragments. The checkerboard assay confirmed that native LF showed the best synergistic action against Mucorales in combination with Amphotericin B. Conclusion: These results highlight the potential therapeutic value of native LF against Mucorales.
Black fungus, or 'mucormycosis', is a dangerous fungal infection. Normally, it affects people with a weakened immune system. It is only treatable when diagnosed early. It spreads by breathing the fungus in, eating contaminated food or direct contact with an infected wound. There are not many medicines that can treat this type of fungus, so it is important to find new ones. In this study, we tested a natural protein called lactoferrin and some of its building blocks, called peptides, to see if they could stop the fungus from growing. Lactoferrin and its peptides could stop the fungus from growing, especially when used with a medicine called amphotericin B. This means that lactoferrin could potentially be a helpful treatment for this fungal infection.
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Anfotericina B , Antifúngicos , Sinergismo Farmacológico , Lactoferrina , Testes de Sensibilidade Microbiana , Mucormicose , Lactoferrina/farmacologia , Lactoferrina/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Anfotericina B/farmacologia , Humanos , Triazóis/farmacologia , Triazóis/uso terapêutico , Mucorales/efeitos dos fármacos , Mucor/efeitos dos fármacos , Piridinas/farmacologia , Piridinas/uso terapêutico , Nitrilas/farmacologia , Nitrilas/uso terapêuticoRESUMO
Extensive global dependency on rice and wheat crops has necessitated the adoption of intensive cultivation practices, thereby compelling to closely monitor the potential yield-limiting factors, among which, boron (B) deficiency stands out to be a prime concern. The present study explores the effects of B fertilization strategies within the Rice-Wheat Cropping System (RWCS) in the Tarai region of North-West India. A comprehensive six-year field experiment was conducted (2013-2019) at G.B. Pant University of Agriculture and Technology, Uttarakhand, India. The experiment tested graded B doses (0.5, 1.0, 1.5, and 2.0 kg ha-1) at varied frequencies (single, alternate, and annual) in a factorial design. The study revealed significant impacts of alternate B application at 1.5 kg ha-1 on crop yields and the Sustainable Yield Index (SYI). The System Rice Equivalent Yield (SREY) exhibited an increase of 6.7% with B supplementation over B-deprived plots, highlighting the pivotal role of B fertilizer in enhancing productivity within the RWCS. The economic optimum B dose was found to be 1.422 kg ha-1 using a linear plus plateau model, resulting in a calculated annual SREY of 9.73 t ha-1 when applied alternately to the cropping system. Continuous application and higher B rates demonstrated substantial increases in various B fractions, while the mobility factor remained within 10%, depicting safe ecological limits. The distribution of fractions in B-treated plots on average followed the order: residual B > organically-bound B > oxide bound B > specifically adsorbed B > readily soluble B. Similarities in the distribution patterns of B fractions between B-treated plots and the control indicated potential influence of biotic or abiotic processes on B fraction dynamics, even in the absence of external B application. To sum up, B application in alternate years at 1.5 kg ha-1 was most sustainable in enhancing the SREY, SYI, available soil B, and B fractions and lowering the environmental hazards.
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Agricultura , Boro , Produtos Agrícolas , Fertilizantes , Oryza , Triticum , Oryza/crescimento & desenvolvimento , Triticum/crescimento & desenvolvimento , Índia , Agricultura/métodos , Produtos Agrícolas/crescimento & desenvolvimento , Solo/químicaRESUMO
Our cohort study aimed to compare serum C-reactive protein (CRP) and procalcitonin (PCT) levels in children with community-acquired pneumonia defined by WHO. The former differentiated between pneumonia and severe pneumonia while the latter was better for the outcome of pneumonia.
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Biomarcadores , Proteína C-Reativa , Infecções Comunitárias Adquiridas , Pneumonia , Pró-Calcitonina , Índice de Gravidade de Doença , Humanos , Pró-Calcitonina/sangue , Proteína C-Reativa/análise , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Biomarcadores/sangue , Masculino , Feminino , Pré-Escolar , Pneumonia/sangue , Pneumonia/diagnóstico , Criança , Lactente , Estudos de Coortes , Valor Preditivo dos TestesRESUMO
Mucormycosis, a rare but deadly fungal infection, was an epidemic during the COVID-19 pandemic. The rise in cases (COVID-19-associated mucormycosis, CAM) is attributed to excessive steroid and antibiotic use, poor hospital hygiene, and crowded settings. Major contributing factors include diabetes and weakened immune systems. The main manifesting forms of CAMâcutaneous, pulmonary, and the deadliest, rhinocerebralâand disseminated infections elevated mortality rates to 85%. Recent focus lies on small-molecule inhibitors due to their advantages over standard treatments like surgery and liposomal amphotericin B (which carry several long-term adverse effects), offering potential central nervous system penetration, diverse targets, and simpler dosing owing to their small size, rendering the ability to traverse the blood-brain barrier via passive diffusion facilitated by the phospholipid membrane. Adaptation and versatility in mucormycosis are facilitated by a multitude of virulence factors, enabling the pathogen to dynamically respond to various environmental stressors. A comprehensive understanding of these virulence mechanisms is imperative for devising effective therapeutic interventions against this highly opportunistic pathogen that thrives in immunocompromised individuals through its angio-invasive nature. Hence, this Review delineates the principal virulence factors of mucormycosis, the mechanisms it employs to persist in challenging host environments, and the current progress in developing small-molecule inhibitors against them.
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Antifúngicos , Inteligência Artificial , COVID-19 , Mucormicose , Fatores de Virulência , Mucormicose/tratamento farmacológico , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fatores de Virulência/antagonistas & inibidores , Fatores de Virulência/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidadeRESUMO
Introduction: Heat stress at terminal stage of wheat is critical and leads to huge yield losses worldwide. microRNAs (miRNAs) play significant regulatory roles in gene expression associated with abiotic and biotic stress at the post-transcriptional level. Methods: In the present study, we carried out a comparative analysis of miRNAs and their targets in flag leaves as well as developing seeds of heat tolerant (RAJ3765) and heat susceptible (HUW510) wheat genotypes under heat stress and normal conditions using small RNA and degradome sequencing. Results and discussion: A total of 84 conserved miRNAs belonging to 35 miRNA families and 93 novel miRNAs were identified in the 8 libraries. Tae-miR9672a-3p, tae-miR9774, tae-miR9669-5p, and tae-miR5048-5p showed the highest expression under heat stress. Tae-miR9775, tae-miR9662b-3p, tae-miR1120a, tae-miR5084, tae-miR1122a, tae-miR5085, tae-miR1118, tae-miR1130a, tae-miR9678-3p, tae-miR7757-5p, tae-miR9668-5p, tae-miR5050, tae-miR9652-5p, and tae-miR9679-5p were expressed only in the tolerant genotype, indicating their role in heat tolerance. Comparison between heat-treated and control groups revealed that 146 known and 57 novel miRNAs were differentially expressed in the various tissues. Eight degradome libraries sequence identified 457 targets of the differentially expressed miRNAs. Functional analysis of the targets indicated their involvement in photosynthesis, spliceosome, biosynthesis of nucleotide sugars and protein processing in the endoplasmic reticulum, arginine and proline metabolism and endocytosis. Conclusion: This study increases the number of identified and novel miRNAs along with their roles involved in heat stress response in contrasting genotypes at two developing stages of wheat.
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Phosphopantetheine adenylyltransferase (EC. 2.7.7.3, PPAT) catalyzes the penultimate step of the multistep reaction in the coenzyme A (CoA) biosynthesis pathway. In this step, an adenylyl group from adenosine triphosphate (ATP) is transferred to 4'-phosphopantetheine (PNS) yielding 3'-dephospho-coenzyme A (dpCoA) and pyrophosphate (PPi). PPAT from strain C3 of Klebsiella pneumoniae (KpPPAT) was cloned, expressed and purified. It was crystallized using 0.1 M HEPES buffer and PEG10000 at pH 7.5. The crystals belonged to tetragonal space group P41212 with cell dimensions of a = b = 72.82 Å and c = 200.37 Å. The structure was determined using the molecular replacement method and refined to values of 0.208 and 0.255 for Rcryst and Rfree factors, respectively. The structure determination showed the presence of three crystallographically independent molecules A, B and C in the asymmetric unit. The molecules A and B are observed in the form of a dimer in the asymmetric unit while molecule C belongs to the second dimer whose partner is related by crystallographic twofold symmetry. The polypeptide chain of KpPPAT folds into a ß/α structure. The conformations of the side chains of several residues in the substrate binding site in KpPPAT are significantly different from those reported in other PPATs. As a result, the modes of binding of substrates, phosphopantetheine (PNS) and adenosine triphosphate (ATP) differ considerably. The binding studies using fluorescence spectroscopy indicated a KD value of 3.45 × 10-4 M for ATP which is significantly lower than the corresponding values reported for PPAT from other species.
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Trifosfato de Adenosina , Klebsiella pneumoniae , Nucleotidiltransferases , Klebsiella pneumoniae/metabolismo , Cristalografia por Raios X , Coenzima A/química , Coenzima A/metabolismoRESUMO
Despite significant efforts, currently, there is no particular drug available to treat Zika virus (ZIKV) infection, highlighting the urgent need for effective therapeutic interventions. To identify putative inhibitors of the ZIKV RdRp protein's RNA binding function, the present study applied an extensive in-silico drug discovery methodology. The initial phase involved virtual screening using Lipinski's rule of five as a filter, ensuring the selection of molecules with favorable pharmacokinetic properties. This process yielded 238 compounds with promising docking scores, ranging from -6.0 to -7.48 kcal/mol, indicative of their potential binding affinity to the ZIKV RdRp. To refine the selection, these compounds underwent a re-docking process, comparing their binding energies with a reference molecule known for its inhibitory action against RdRp. Remarkably, five compounds, labeled CMNPD30598, CMNPD27464, CMNPD25971, CMNPD27444, and CMNPD16599, demonstrated superior re-docking energies compared to the reference, suggesting a stronger interaction with the RdRp allosteric site. Subsequent molecular dynamics (MD) simulations provided insights into the stability of these complexes over time, reinforcing their potential as RdRp inhibitors. Additionally, the calculation of free binding energies and principal component analysis (PCA) of the free energy landscape offered a deeper understanding of the binding dynamics and energetics. This study not only highlights the utility of marine fungi compounds in antiviral drug discovery but also showcases the power of computational tools in identifying novel therapeutics. The identified compounds represent promising candidates for further experimental validation and development as ZIKV RdRp inhibitors.Communicated by Ramaswamy H. Sarma.
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PURPOSE: To evaluate the effect of weight reduction on the structural and functional parameters of the optic nerve in established cases of papilledema in Idiopathic Intracranial Hypertension (IIH). METHODS: A prospective observational study in early and established cases of papilledema in IIH presenting from December 2019 to February 2021. Functional parameters (visual acuity, contrast sensitivity, mean deviation, VER), structural parameters (RNFL, GCL-IPL, and optic disc height), and clinical grading of papilledema were measured at baseline and every 6 weeks for 6 months. All patients underwent medical (oral acetazolamide) and diet therapy. RESULTS: Mean body mass index (BMI) at presentation was 26.32 ± 3.52â kg/m² and the mean change in BMI over 6 months was 1.27 ± 0.50â kg/m². 67% of eyes had papilledema of grades 2-3 at the presentation. At the end of 6 months, 75% of eyes had grade 1 papilledema while 13% showed complete resolution. A reduction of 5.32 ± 3.58 in mean deviation (r = 0.316; p-value 0.01) and gain in VER P100 amplitude of 4.2 ± 2.7â µV (r = 0.40; p-value 0.003) were noted over 6 months with reduction in BMI over 6 months. A statistically significant reduction in optic disc height (ODH) was noticed with BMI reduction over 6 months (p = 0.0007; r = 0.45).A reduction of 1.72 ± 0.90â kg/m² (equivalent to 6.53% weight loss) in BMI was associated with a four-grade change in clinical grading of papilledema. CONCLUSION: Reduction in BMI had a significant impact on both structural and functional parameters of the optic nerve in IIH. The involvement of a well-certified dietician should be an integral part of treatment in IIH.
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OBJECTIVES: Inflammatory disorders including periodontitis have been investigated for their impact on systemic inflammation and bone health. The present study was conducted with an aim to evaluate impact of control of periodontal inflammation through subgingival instrumentation on serum interleukin 6 and serum C-terminal telopeptide of type I collagen (CTX) in premenopausal females with stage II and III periodontitis. METHOD AND MATERIALS: In this single-arm prospective study, periodontal parameters, serum interleukin 6, serum CTX, and hematologic parameters (total leukocyte count, differential leukocyte count, platelet count, mean platelet volume, and platelet distribution width) were assessed at baseline. Subgingival instrumentation was done, and oral hygiene instructions were given. At week 4, professional plaque control was performed, and oral hygiene instructions were reinforced. Serum and hematologic parameters were reassessed at 8 weeks after subgingival instrumentation, in individuals meeting the clinical endpoints (ie, bleeding on probing < 10%). RESULTS: There was significant reduction in serum interleukin 6 of 0.168 ± 0.164 pg/mL (P = .000), and serum CTX of 17.459 ± 4.363 pg/mL (P = .000) at 8 weeks after subgingival instrumentation. There was significant decrease in eosinophil count (P = .018) and mean platelet volume (P = .016) at 8 weeks after subgingival instrumentation; however, no significant change was found in other hematologic parameters. CONCLUSION: Following subgingival instrumentation, biomarkers of both systemic inflammation (interleukin 6) and bone turnover (CTX) were observed to reduce significantly. This finding hints towards a positive impact of periodontal intervention on bone health.
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Reabsorção Óssea , Periodontite , Humanos , Feminino , Estudos Prospectivos , Bolsa Periodontal , Interleucina-6 , Raspagem Dentária , Periodontite/terapia , InflamaçãoRESUMO
Epigenetic modifications act as conductors of inheritable alterations in gene expression, all while keeping the DNA sequence intact, thereby playing a pivotal role in shaping plant growth and development. This review article presents an overview of techniques employed to investigate and manipulate epigenetic diversity in crop plants, focusing on both naturally occurring and artificially induced epialleles. The significance of epigenetic modifications in facilitating adaptive responses is explored through the examination of how various biotic and abiotic stresses impact them. Further, environmental chemicals are explored for their role in inducing epigenetic changes, particularly focusing on inhibitors of DNA methylation like 5-AzaC and zebularine, as well as inhibitors of histone deacetylation including trichostatin A and sodium butyrate. The review delves into various approaches for generating epialleles, including tissue culture techniques, mutagenesis, and grafting, elucidating their potential to induce heritable epigenetic modifications in plants. In addition, the ground breaking CRISPR/Cas is emphasized for its accuracy in targeting specific epigenetic changes. This presents a potent tools for deciphering the intricacies of epigenetic mechanisms. Furthermore, the intricate relationship between epigenetic modifications and non-coding RNA expression, including siRNAs and miRNAs, is investigated. The emerging role of exo-RNAi in epigenetic regulation is also introduced, unveiling its promising potential for future applications. The article concludes by addressing the opportunities and challenges presented by these techniques, emphasizing their implications for crop improvement. Conclusively, this extensive review provides valuable insights into the intricate realm of epigenetic changes, illuminating their significance in phenotypic plasticity and their potential in advancing crop improvement.
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Epigênese Genética , MicroRNAs , Epigênese Genética/genética , Plantas , Metilação de DNA , Mutagênese , MicroRNAs/genéticaRESUMO
Key components of the RNA interference (RNAi) pathway include the Dicer-like (DCL), Argonaute (AGO), and RNA-dependent RNA polymerase (RDR) gene families. While these components have been studied in various plant species, their functional validation in wheat remains unexplored particularly under heat stress. In this study, a comprehensive genome-wide analysis to identify, and characterize DCL, AGO, and RDR genes in wheat and their expression patterns was carried out. Using phylogenetic analysis with orthologous genes from Arabidopsis and rice, we identified a total of 82 AGO, 31 DCL, and 31 RDR genes distributed across the 21 chromosomes of wheat. To understand the regulatory network, a network analysis of miRNAs that target RNA-silencing genes was performed. Our analysis revealed that 13 miRNAs target AGO genes, 8 miRNAs target DCL genes, and 10 miRNAs target RDR genes at different sites, respectively. Additionally, promoter analysis of the RNA-silencing genes was done and identified the presence of 132 cis-elements responsive to stress and phytohormones. To examine their expression patterns, we performed RNA-seq analysis in the flag leaf samples of wheat exposed to both normal and heat stress conditions. To understand the regulation of RNA silencing, we experimentally analysed the transcriptional changes in response to gradient heat stress treatments. Our results showed constitutive expression of the AGO1, AGO9, and DCL2 gene families, indicating their importance in the overall biological processes of wheat. Notably, RDR1, known to be involved in small interfering RNA (siRNA) biogenesis, exhibited higher expression levels in wheat leaf tissues. These findings suggest that these genes may play a role in responses to stress in wheat, highlighting their significance in adapting to environmental challenges. Overall, our study provides additional knowledge to understand the mechanisms underlying heat stress responses and emphasizes the essential roles of these gene families in wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01362-0.
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BACKGROUND: Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism. OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge. METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined. RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy. CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.
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Antineoplásicos , Neoplasias , Humanos , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Neoplasias/metabolismo , Transporte Biológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/metabolismoRESUMO
Salt stress affects plant growth and development, resulting in the loss of crop yield across the world, and sodium-proton antiporters (NHXs) are one of the genes known to promote salt tolerance in transgenic plants. In this study, we conducted a comprehensive genome-wide analysis and expression profile of NHX genes in wheat under salinity stress. We identified 30 TaNHX genes in wheat based on the Na+/H+ exchanger domain, with all genes containing an amiloride motif except one, a known for inhibiting Na+ ions in plants. Phylogenetic analysis classified these genes into three classes with subfamilies: 12 were localized in vacuoles, while 18 were in the endoplasmic reticulum and plasma membrane. Promoter analysis revealed stress-related cis-acting elements, indicating their potential role in abiotic stress tolerance. The non-synonymous (Ka)/synonymous (Ks) ratios highlighted that the majority of TaNHX genes experienced robust purifying selection throughout their evolutionary history. Transcriptomis data analysis and qRT-PCR demonstrated distinct expression patterns for TaNHX genes across various tissues when subjected to salt stress. Additionally, we predicted 20 different miRNA candidates targeting the identified TaNHX genes. Protein-protein interaction prediction revealed NHX6's involvement in the SOS1 pathway, while NHX1 gene exhibit proton antiporter activity. Molecular dynamics (MD) simulations were also conducted to examine the interactions of TaNHX1, TaNHX2, and TaNHX3. These results represent a significant advancement in our understanding of the molecular mechanisms governing Na+ transporters. This may also offer promising avenues for future studies aimed at unraveling the intricate details of their biological roles and applications.
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Septage refers to the semi-liquid waste material that accumulates in septic tanks and other onsite sanitation systems. It is composed of a complex mixture of human excreta, wastewater, and various solid particles. Septage is a potential source of water pollution owing to presence of high organic content, significant pathogen concentrations, and a range of nutrients like nitrogen and phosphorus. The harmful impacts of septage pollution poses significant risks to public health through the contamination of drinking water sources, eutrophication of water bodies and spread of water borne diseases. Conventional septage treatment technologies often face limitations such as high operational costs, energy requirements, and the need for extensive infrastructure. Therefore, with an aim to treat septage through an alternative cost effective and energy-efficient technology, a laboratory-scale constructed wetland (CW) system (0.99 m2) consisting of a sludge drying bed and a vertical flow wetland bed was utilized for the treatment of septage. The sludge drying bed and vertical flow beds were connected in series and filled with a combination of gravel with varying sizes (ranging from 5 to 40 mm) and washed sand. Canna indica plants were cultivated on both beds to facilitate phytoremediation process. The system was operated with intermittent dosing of 30 Ltrs of septage every day for 2 months. The HRT of the system was fixed at 48 h. The average inlet loads of Biochemical Oxygen Demand (BOD5), Chemical Oxygen Demand (COD), and Total Suspended Solids (TSS) were measured as 150 ± 65.7 g m-2 day-1, 713 ± 443.9 g m-2 day-1, and 309 ± 66.3 g m-2 day-1, respectively. After treatment, the final effluent had an average load of 6 g m-2 day-1 for BOD5, 15 g m-2 day-1 for COD, and 51 g m-2 day-1 for TSS, indicating that the CW system achieved an average removal efficiency of 88% for BOD, 87% for COD, and 65% for TSS. The average load of total coliforms and helminthes eggs in the influent was recorded as 4 × 108 Colony-Forming Units (CFU) m-2 day-1 and 3 × 107 eggs m-2 day-1, respectively. However, the CW system demonstrated significant effectiveness in reducing microbial contamination, with an average removal efficiency of 99% for both total coliforms and helminthes eggs. The vertical flow constructed wetland system, equipped with pretreatment by sludge drying bed, has proven to be efficient in treatment of septage.