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Ulcerative colitis (UC) is a prominent category of disease that is associated with bowel inflammation, it can occur at any period of life and is prevalently rising on a global scale. Dextran sulfate sodium (DSS) has been extensively used to develop colitis due to its ability to mimic human UC, providing consistent and reproducible inflammation, ulceration, and disruption of the epithelial barrier in the colon. Chronic inflammation in the gut can lead to alterations in the gut-liver axis, potentially impacting liver function over time, while direct evidence linking diversion colitis to liver damage is limited. Thus, the present study aims to assess the gut and liver damage against DSS and the possible molecular mechanisms. Forty-seven animals were randomly assigned to six groups. Ulcerative colitis was induced using 2.5% w/v DSS in three alternate cycles, each lasting 7 days, with 1-week remission periods in between. SOV (5 and 10 mg/kg, orally) and the standard drug 5-aminosalicylic acid (100 mg/kg, orally) were administered from the start of the 2nd DSS cycle until the end of the experiment. Biochemical parameters, ELISA, histopathological, and immunohistochemical analyses have been conducted to assess damage in the colon and liver. SOV significantly reduced colitis severity by lowering the DAI score, oxidative stress markers (LPS, IL-1ß, MPO, nitrite), and restoring liver biomarkers (SGPT, SGOT). Histopathological findings supported these protective benefits in the liver and gut. Moreover, immunohistochemical analysis showed SOV enhanced the expression of the cytoprotective mediator Nrf2/Keap-1 and reduced the expression of inflammatory mediators NF-κB and IL-6. Present findings concluded that SOV demonstrated a dose-dependent effect against UC through anti-inflammatory and antioxidant pathways, with the highest dose of SOV 10 mg/kg having more significant (p < 0.001) results than the low dose of 5 mg/kg.
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Mesoporous silica nanoparticles (MSNPs) are inorganic nanoparticles that have been comprehensively investigated and are intended to deliver therapeutic agents. MSNPs have revolutionized the therapy for various conditions, especially cancer and infectious diseases. In this article, the viability of MSNPs' administration for lung cancer therapy has been reviewed. However, certain challenges lay ahead in the successful translation such as toxicology, immunology, large-scale production, and regulatory matters have made it extremely difficult to translate such discoveries from the bench to the bedside. This review highlights recent developments, characteristics, mechanism of action and customization for targeted delivery. This review also covers the most recent data that sheds light on MSNPs' extraordinary therapeutic potential in fighting lung cancer as well as future hurdles.
[Box: see text].
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Neoplasias Pulmonares , Nanopartículas , Dióxido de Silício , Dióxido de Silício/química , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Porosidade , Portadores de Fármacos/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Sistemas de Liberação de Medicamentos/métodosRESUMO
The integrated application of inorganic fertilizers, organic fertilizers, and biofertilizers helps sustain the nutrient pool and benefits the soil quality, thereby boosting plant health. The effect of different combinations of biofertilizers (consortium biofertilizer [CBF]-non-rhizobial PGPR), inorganic fertilizers, and organic fertilizers on soil health, growth, and yield of cowpea was evaluated by conducting a field experiment. The application of N100 FYM + CBF resulted in significantly higher populations of bacteria, fungi, PSB, and diazotroph, as well as soil dehydrogenase and alkaline phosphatase enzyme activities. However, the application of N100 FYM recorded a significantly higher actinomycetes population. The application of N100 FYM + CBF resulted in significantly higher soil OC, available nitrogen, phosphorus, and potassium. The soil pH was recorded to be highest in control, and soil EC was recorded to be lowest in control. The plant uptake of nitrogen, phosphorus, and potassium was significantly higher with N50 FYM + NP50 + CBF. The root-shoot biomass, number of leaves, nodules/plant, number of pods/plants, pod biomass, pod length, and pod width were significantly higher in treatment having N50 FYM + NP50 + CBF. However, the height of the plant, number of branches, and biomass of leaves were highest in treatment with N25 FYM + NP75 + CBF. The pod and stover yield were significantly higher in treatment with N50 FYM + NP50 + CBF. The results showed that the integrated application of non-rhizobial PGPR along with organic and inorganic fertilizer helps to improve overall soil health, quality, and plant growth of forage cowpea contributing to an increase in crop yield.
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Thiacloprid, a hazardous neonicotinoid insecticide, prevalent in daily agricultural practices, raises concerns due to the harmful effects of its residues on food items, and on unintended organisms poses a significant threat to human health. Introduced in 1990, Thiacloprid have gained popularity for its perceived effectiveness and reduced risks to non-target animals. However, emerging research in recent years reports significant toxic effects of Thiacloprid on non-target species, spanning neurotoxicity, immunotoxicity, hepatotoxicity, nephrotoxicity, and reproductive issues. Mammalian studies, particularly involving rodents, reveal cognitive impairment, hippocampal damage, and hepatic abnormalities upon Thiacloprid exposure. Reproductive toxicity and DNA damage are imminent concerns, disrupting gestational epigenetic reprogramming and suggesting persistent effects on future generations. Genotoxic effects, Embryotoxic, and observed reproductive toxicity accentuate the need for caution in the utilization of Thiacloprid. This review highlights reported toxic effects produced by Thiacloprid in recent years, challenging the initial belief in its lower toxicity for vertebrates.
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First examples of covalently linked triphyrin(2.1.1)-triphyrin(2.1.1) homo dimers connected via flexible alkoxy linkers at ß-pyrrole positions were synthesized in 28-30% yields by reacting 2-bromo triphyrin(2.1.1) with three different alkane diols such as 1,2-ethanediol, 1,4-butanediol and 1,6-hexanediol in toluene under Pd2(dba)3/DPEphos catalyzed conditions by refluxing for 12-20 h. One of the free base triphyrin-triphyrin homo dimers was metallated by treating the homo dimer with Re(CO)5Cl in toluene under reflux and afforded bis-Re(I) homo dimer complex in 53% yield. Three free base homo dimers and one bis-Re(I) homo dimer complex were thoroughly characterized and studied using HR-MS, 1D and 2D NMR, absorption spectroscopy, cyclic voltammetry and DFT calculations. Our attempts to obtain the X-ray structure of homo dimers were not successful. However, DFT studies revealed that homo dimers prefer to exist in anti-conformation rather than syn-conformation and both triphyrin macrocycles in homo dimers were similar in terms of the deviation of pyrrole rings from the mean plane defined by the four meso carbons of the respective triphyrin unit. Absorption spectra of homo dimers showed similar absorption features such as in triphyrin(2.1.1) with slight changes in their absorption peak maxima. Electrochemical studies revealed that the homo dimers were electron rich, whereas the bis-Re(I) complex was electron deficient in nature.
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Bovine Herpes Virus (BHV-1) is a virus prevalent among cattle and buffaloes which accounts for considerable reproductive failures. This study was undertaken with the objective of studying the prevalence of BHV-1 in reproductive tract infections of cattle and buffaloes in Punjab region in India. A total of 70 reproductive tract samples (like vaginal mucous, cervical mucous, uterine discharges, uterine pus and aborted materials like placenta, caruncles, foetal stomach contents, amniotic fluid and placental fluid) were taken from cattle and buffaloes from various areas of Punjab which were suffering from different reproductive disorders. The samples were screened for the presence of genome of BHV-1using PCR targeting gE gene. Out of 70 samples screened, only one sample was positive for the presence of BHV-1 genome which had an amplicon size of 468 bp, specific to the targeted gene. The study concluded that BHV-1 has very low prevalence among reproductive disorders in cattle and buffaloes in Punjab region, but has increased over last few years, particularly in female cattle and buffaloes.
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Antibacterial photodynamic therapy (APDT) has received increased attention as a treatment for multidrug-resistant bacterial infections caused by antibiotic abuse. However, photosensitizers used in APDT have disadvantages such as water insolubility, self-aggregation, and photobleaching. To address these limitations, metal complexes have been explored. However, the use of such complexes tends to confine their antibacterial effectiveness specific bacterial strains. In this study, we report iron (Fe)- and copper (Cu)-based metallosurfactants as unique moieties for antibacterial photodynamic therapy (PDT) under the illumination of visible light. Briefly, our formulated Fe and Cu metallosurfactants, when combined with a fluorescein photosensitizer, exhibit nearly 100% antibacterial efficacy. This high efficiency is primarily attributed to the enhanced generation of singlet oxygen using FL in the presence of metallosurfactants when targeting bacteria such as Escherichia coli and Staphylococcus aureus under laser light. In vitro experiments further confirmed the superior antimicrobial activity of these metallosurfactants against a diverse range of microbial cultures, encompassing Gram-negative and Gram-positive bacteria as well as fungi. This performance outpaces conventional surfactants like cetyltrimethylammonium chloride and cetylpyridinium chloride. The compelling results from MTT assays and flow cytometry endorsed the substantial enhancement in antimicrobial properties achieved through Fe and Cu doping, all without the need for additional secondary agents. Notably, this synergistic antibacterial approach using metallosurfactants in PDT holds significant promise for the elimination of various bacteria in vivo, with the added advantage of mitigating the emergence of multidrug resistance.
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Antibacterianos , Cobre , Luz , Testes de Sensibilidade Microbiana , Fotoquimioterapia , Fármacos Fotossensibilizantes , Tensoativos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Tensoativos/química , Tensoativos/farmacologia , Tensoativos/síntese química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Cobre/química , Cobre/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Teste de Materiais , Staphylococcus aureus/efeitos dos fármacos , Tamanho da Partícula , Escherichia coli/efeitos dos fármacos , Estrutura Molecular , Ferro/química , Ferro/farmacologia , HumanosRESUMO
Autophagy is a fundamental pillar of cellular resilience, indispensable for maintaining cellular health and vitality. It coordinates the meticulous breakdown of cytoplasmic macromolecules as a guardian of cell metabolism, genomic integrity, and survival. In the complex play of biological warfare, autophagy emerges as a firm defender, bravely confronting various pathogenic, infectious, and cancerous adversaries. Nevertheless, its role transcends mere defense, wielding both protective and harmful effects in the complex landscape of disease pathogenesis. From the onslaught of infectious outbreaks to the devious progression of chronic lifestyle disorders, autophagy emerges as a central protagonist, convolutedly shaping the trajectory of cellular health and disease progression. In this article, we embark on a journey into the complicated web of molecular and immunological mechanisms that govern autophagy's profound influence over disease. Our focus sharpens on dissecting the impact of various autophagy-associated proteins on the kaleidoscope of immune responses, spanning the spectrum from infectious outbreaks to chronic lifestyle ailments. Through this voyage of discovery, we unveil the vast potential of autophagy as a therapeutic linchpin, offering tantalizing prospects for targeted interventions and innovative treatment modalities that promise to transform the landscape of disease management.
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Morphine addiction poses a significant challenge to global healthcare. Current opioid substitution therapies, such as buprenorphine, naloxone and methadone are effective but often lead to dependence. Thus, exploring alternative treatments for opioid addiction is crucial. We have developed a novel vaccine that presents morphine and Pam3Cys (a TLR-2 agonist) on the surface of Acr1 nanoparticles. This vaccine has self-adjuvant properties and targets TLR-2 receptors on antigen-presenting cells, particularly dendritic cells. Our vaccination strategy promotes the proliferation and differentiation of morphine-specific B-cells and Acr1-reactive CD4 T-cells. Additionally, the vaccine elicited the production of high-affinity anti-morphine antibodies, effectively eliminating morphine from the bloodstream and brain in mice. It also reduced the expression of addiction-associated µ-opioid receptor and dopamine genes. The significant increase in memory CD4 T-cells and B-cells indicates the vaccine's ability to induce long-lasting immunity against morphine. This vaccine holds promise as a prophylactic measure against morphine addiction.
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Células Dendríticas , Morfina , Nanovacinas , Receptor 2 Toll-Like , Animais , Camundongos , Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Morfina/farmacologia , Dependência de Morfina/imunologia , Dependência de Morfina/tratamento farmacológico , Nanovacinas/imunologia , Receptores Opioides mu/imunologia , Receptores Opioides mu/metabolismo , Receptor 2 Toll-Like/metabolismoRESUMO
Genetic and epigenetic variations produced via cell and tissue culture open up new sources of variability intra-species which can be used to improve crops. The use of in vitro generated somaclonal variations for selecting novel variants aids in the development of novel genotypes having desirable agronomic traits that can be released as varieties or utilized for breeding purposes. Horticultural crops give higher yield and productivity per unit area than other crops, as well as provide good economic returns which have led to an increase in their potential benefits throughout time. The last three to four decades have seen the selection and release of a number of valuable somaclonal variants, many of which possess remarkable features including disease resistance, high yield, improved nutritional quality and abiotic stress tolerance. Generating somaclonal variations has given breeders a novel alternative option for obtaining genetic diversity in horticultural crops and without advanced technologies. The variations introduced through tissue culture process, methods to determine and validate genetic changes in vitro regenerated plantlets, along with prospective application of such variations in horticultural crops' improvement are reviewed in the present work.
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Human noroviruses (HuNoVs) are a significant cause of both epidemic and sporadic acute gastroenteritis worldwide. The lack of a reproducible culture system for HuNoVs was a major obstacle in studying virus replication and pathogenesis for almost a half-century. This barrier was overcome with our successful cultivation of multiple HuNoV strains in human intestinal enteroids (HIEs), which has significantly advanced HuNoV research. We previously optimized culture media conditions and generated genetically-modified HIE cultures to enhance HuNoV replication in HIEs. Building upon these achievements, we now present additional advancements to this culture system, which involve testing different media, unique HIE lines, and additional virus strains. HuNoV infectivity was evaluated and compared in new HIE models, including HIEs generated from different intestinal segments of individual adult organ donors, HIEs made from human embryonic stem cell-derived human intestinal organoids that were transplanted into mice (H9tHIEs), genetically-engineered (J4 FUT2 knock-in [ KI ], J2 STAT1 knock-out [ KO ]) HIEs, as well as HIEs derived from a patient with common variable immunodeficiency (CVID) and from infants. Our findings reveal that small intestinal HIEs, but not colonoids, from adults, H9tHIEs, HIEs from a CVID patient, and HIEs from infants support HuNoV replication with segment and strain-specific differences in viral infection. J4 FUT2-KI HIEs exhibit the highest susceptibility to HuNoV infection, allowing the cultivation of a broader range of GI and GII HuNoV strains than previously reported. Overall, these results contribute to a deeper understanding of HuNoVs and highlight the transformative potential of HIE cultures in HuNoV research. Importance: Human noroviruses (HuNoVs) are very contagious and cause significant acute gastroenteritis globally, but studying them has been hindered by the lack of a reproducible culture system for nearly 50 years. This barrier was overcome by successfully cultivating multiple HuNoV strains in human intestinal enteroids (HIEs), advancing HuNoV research. We previously optimized culture conditions and developed genetically modified HIEs to enhance HuNoV replication. In this study, we tested different media, unique HIE lines, and additional virus strains, evaluating HuNoV infectivity in new HIE models. These models include HIEs from various intestinal segments of adult donors, human embryonic stem cell-derived HIEs transplanted into mice (H9tHIEs), genetically-engineered HIEs (J4 FUT2 knock-in [ KI ], J2 STAT1 knock-out [ KO ]), HIEs from a common variable immunodeficiency (CVID) patient, and from infants. Our findings show that adult small intestinal HIEs, H9tHIEs, CVID patient HIEs, and infant HIEs support HuNoV replication with segment and strain-specific differences. J4 FUT2-KI HIEs exhibited the highest susceptibility, allowing cultivation of a broader range of HuNoV strains. These results enhance the understanding of HuNoVs and highlight the transformative potential of HIE cultures in HuNoV research.
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Lead halide perovskites (LHPs) have gained prominence for their exceptional photophysical properties, holding promise for applications in high-end optoelectronic devices. However, the presence of lead is one of the major obstacles to the commercialization of LHPs in the field of photovoltaics. To address this, researchers have explored environment friendly lead-free perovskite solar cells by investigating non-toxic perovskite materials. This study explores the enhancement of photophysical properties through chemical engineering, specifically cation exchange, focusing on the crucial photophysical process of hot carrier cooling. Employing femtosecond transient absorption spectroscopy and optical pump terahertz probe spectroscopy, we have probed the carrier relaxation dynamics in A3Sb2I9 with cesium and rubidium cations. This study unravels that the carrier relaxation is found to be slower in Rb3Sb2I9; along with this, the transient mobility decay is found to be retarded. Overall, this study suggests that an antimony-based Rb3Sb2I9 perovskite could be a substantial lead-free perovskite in photovoltaics. These findings provide valuable insights into cation engineering strategies, aiming to improve the overall performance of lead-free-based photovoltaic devices.
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Lead-free double perovskite nanocrystals (A2B'(III)Bâ³(I)X6 NCs) address the instability and toxicity concerns of lead-based counterparts, but their device performance is limited by subpar absorption and unexplored carrier dynamics. Impurity ion doping offers a route to tune electrical conductivity and charge carrier transport. Herein, we synthesized Cu-doped Cs2AgBiBr6 (CABB) nanocrystals using a hot-injection approach and investigated the charge carrier's dynamics through ultrafast pump-probe spectroscopy. Copper introduction into the CABB lattice enhanced absorption in the near-infrared region and introduced sub-band gap defect states in CABB NCs. The transient absorption study revealed a faster bleach decay with increased copper doping, as a result of charge transfer from the conduction band to copper defect states. Also, an optical pump terahertz probe study displays higher photoconductivity and mobility in Cu-doped CABB NCs. Slower mobility decay in Cu-doped systems was attributed to the charge carrier's entrapment at the defect state. These findings suggest that copper-doped CABB is a superior contender for optoelectronic applications over conventional CABB.
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Sterol derivatives are a crucial part of liposomes, as their concentration and nature can induce significant alternations in their characteristic features. For natural liposomal-based (phospholipid-based) studies, the bulk literature is already present depicting the role of the concentration or nature of different sterol derivatives in modulation of membrane properties. However, the studies aiming at evaluating the effect of sterol derivatives on synthetic liposomal assemblies are limited to cholesterol (Chl), and a comparative effect with other sterol derivatives, such as ergosterol (Erg), has never been studied. To fill this research gap, through this work, we intend to provide insights into the concentration-dependent effect of two sterol derivatives (Chl and Erg) on a synthetic liposomal assembly (i.e., metallosomes) prepared via thin film hydration route using a double-tailed metallosurfactant fabricated by modifying cetylpyridinium chloride with cobalt (Co) (i.e., Co:CPC II). The morphological evaluations with cryogenic-transmission electron microscopy (cryo-TEM), atomic force microscopy (AFM), and field emission-scanning electron microscopy (FE-SEM) indicated that metallosomes retained their spherical morphology irrespective of the nature and concentration of sterol derivatives. However, the size, ζ-potential, and lamellar width values were significantly modified with the incorporation of sterol derivatives in a concentration-dependent manner. In-depth studies affirmed that the extent of modulation of the bilayer in terms of hydrophobicity, fluidity, and rigidity was more severe with Chl than Erg. Such differences in the membrane properties lead to their contrasting behavior in the delivery of the broad-spectrum active compound "curcumin". From entrapment to in vitro behavior, the metallosomes demonstrated dissimilar behavior as even though Erg-modified metallosomes (at higher concentrations of Erg) exhibited low entrapment efficiency, they still could easily release >80% of the entrapped drug. In vitro studies conducted with Staphylococcus aureus bacterial cultures further revealed an interesting pattern of activity as the incorporation of Chl reduced the toxicity of the self-assembly, whereas their Erg-modified counterparts yielded slightly augmented toxicity toward these bacterial cells. Furthermore, Chl- and Erg-modified assemblies also exhibited contrasting behavior in their interaction studies with bacterial DNA.
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Colesterol , Cobalto , Ergosterol , Bicamadas Lipídicas , Lipossomos , Ergosterol/química , Cobalto/química , Lipossomos/química , Colesterol/química , Bicamadas Lipídicas/química , Microscopia de Força AtômicaRESUMO
In this study, two novel chalcone-derived 1,2,3-triazole-appended positional isomers (probe 6 and probe 9) were synthesized via the 'CuAAC' (Cu(i) - catalysed alkyne azide cycloaddition) methodology for the purpose of metal ion detection. The synthesized probes underwent characterization utilizing standard spectroscopic methodologies including FTIR, NMR (1H and 13C), and mass spectrometry. Subsequently, the sensing capabilities of these probes were explored using UV-Vis and fluorescence spectroscopy, wherein their selective recognition potential was established for Pb(ii) and Cu(ii), both of which can pose serious health hazards when prevalent in the environment above permissible limits. Both the probes exhibited fairly low limits of detection (LoD), determined as 5.69 µM and 6.55 µM in the case of probe 6 for Pb(ii) and Cu(ii) respectively; whereas the probe 9 exhibited an LoD of 5.06 µM and 7.52 µM for Pb(ii) and Cu(ii), respectively. The job's plot for the probe demonstrates the formation of a 1 : 1 complex between the metal and ligand. Furthermore, the interaction of the free probes with the metal ions in the metal-ligand complex was elucidated through 1H NMR analysis and validated theoretically using Density Functional Theory (DFT) simulations with the B3LYP/6-311G++(d,p) and B3LYP/LANL2DZ basis sets for geometry optimization of the probes and their corresponding metal complexes. These findings offer a reliable approach to Cu(ii) and Pb(ii) ion detection and can be further used for the potential applications in environmental monitoring and analytical chemistry.
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BACKGROUND: Cholera outbreaks are on the rise globally, with conflict-affected settings particularly at risk. Case-area targeted interventions (CATIs), a strategy whereby teams provide a package of interventions to case and neighboring households within a predefined "ring," are increasingly employed in cholera responses. However, evidence on their ability to attenuate incidence is limited. METHODS AND FINDINGS: We conducted a prospective observational cohort study in 3 conflict-affected states in Nigeria in 2021. Enumerators within rapid response teams observed CATI implementation during a cholera outbreak and collected data on household demographics; existing water, sanitation, and hygiene (WASH) infrastructure; and CATI interventions. Descriptive statistics showed that CATIs were delivered to 46,864 case and neighbor households, with 80.0% of cases and 33.5% of neighbors receiving all intended supplies and activities, in a context with operational challenges of population density, supply stock outs, and security constraints. We then applied prospective Poisson space-time scan statistics (STSS) across 3 models for each state: (1) an unadjusted model with case and population data; (2) an environmentally adjusted model adjusting for distance to cholera treatment centers and existing WASH infrastructure (improved water source, improved latrine, and handwashing station); and (3) a fully adjusted model adjusting for environmental and CATI variables (supply of Aquatabs and soap, hygiene promotion, bedding and latrine disinfection activities, ring coverage, and response timeliness). We ran the STSS each day of our study period to evaluate the space-time dynamics of the cholera outbreaks. Compared to the unadjusted model, significant cholera clustering was attenuated in the environmentally adjusted model (from 572 to 18 clusters) but there was still risk of cholera transmission. Two states still yielded significant clusters (range 8-10 total clusters, relative risk of 2.2-5.5, 16.6-19.9 day duration, including 11.1-56.8 cholera cases). Cholera clustering was completely attenuated in the fully adjusted model, with no significant anomalous clusters across time and space. Associated measures including quantity, relative risk, significance, likelihood of recurrence, size, and duration of clusters reinforced the results. Key limitations include selection bias, remote data monitoring, and the lack of a control group. CONCLUSIONS: CATIs were associated with significant reductions in cholera clustering in Northeast Nigeria despite operational challenges. Our results provide a strong justification for rapid implementation and scale-up CATIs in cholera-response, particularly in conflict settings where WASH access is often limited.
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Cólera , Saneamento , Humanos , Nigéria/epidemiologia , Cólera/epidemiologia , Cólera/prevenção & controle , Estudos Prospectivos , Masculino , Higiene , Feminino , Adulto , Epidemias/prevenção & controle , Incidência , Surtos de Doenças/prevenção & controle , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , CriançaRESUMO
Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of polycarbonate plastics and epoxy resins, found in numerous consumer products. Despite its widespread use, its potential adverse health effects have raised significant concerns. This review explores the molecular mechanisms and evidence-based literature underlying BPA-induced toxicities and its implications for human health. BPA is an endocrine-disrupting chemical (EDC) which exhibits carcinogenic properties by influencing various receptors, such as ER, AhR, PPARs, LXRs, and RARs. It induces oxidative stress and contributes to cellular dysfunction, inflammation, and DNA damage, ultimately leading to various toxicities including but not limited to reproductive, cardiotoxicity, neurotoxicity, and endocrine toxicity. Moreover, BPA can modify DNA methylation patterns, histone modifications, and non-coding RNA expression, leading to epigenetic changes and contribute to carcinogenesis. Overall, understanding molecular mechanisms of BPA-induced toxicity is crucial for developing effective strategies and policies to mitigate its adverse effects on human health.
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Compostos Benzidrílicos , Disruptores Endócrinos , Fenóis , Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Humanos , Disruptores Endócrinos/toxicidade , Animais , Estresse Oxidativo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Poluentes Ambientais/toxicidadeRESUMO
One of the serious challenges facing modern point-of-care (PoC) molecular diagnostic platforms relate to reliable detection of low concentration biomarkers such as nucleic acids or proteins in biological samples. Non-specific analyte-receptor interactions due to competitive binding in the presence of abundant molecules, inefficient mass transport and very low number of analyte molecules in sample volume, in general pose critical hurdles for successful implementation of such PoC platforms for clinical use. Focusing on these specific challenges, this work reports a unique PoC biosensor that combines the advantages of nanoscale biologically-sensitive field-effect transistor arrays (BioFET-arrays) realized in a wafer-scale top-down nanofabrication as high sensitivity electrical transducers with that of sophisticated molecular programs (MPs) customized for selective recognition of analyte miRNAs and amplification resulting in an overall augmentation of signal transduction strategy. The MPs realize a programmable universal molecular amplifier (PUMA) in fluidic matrix on chip and provide a biomarker-triggered exponential release of small nucleic acid sequences easily detected by receptor-modified BioFETs. A common miRNA biomarker LET7a was selected for successful demonstration of this novel biosensor, achieving limit of detection (LoD) down to 10 fM and wide dynamic ranges (10 pM-10 nM) in complex physiological solutions. As the determination of biomarker concentration is implemented by following the electrical signal related to analyte-triggered PUMA in time-domain instead of measuring the threshold shifts of BioFETs, and circumvents direct hybridization of biomarkers at transducer surface, this new strategy also allows for multiple usage (>3 times) of the biosensor platform suggesting exceptional cost-effectiveness for practical use.
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Técnicas Biossensoriais , Desenho de Equipamento , Limite de Detecção , MicroRNAs , Técnicas Biossensoriais/instrumentação , MicroRNAs/análise , Humanos , Biomarcadores , Transistores Eletrônicos , Sistemas Automatizados de Assistência Junto ao Leito , Dispositivos Lab-On-A-ChipRESUMO
Polyelectrolyte complexes (PECs) formed by the interaction between oppositely charged polymers have emerged as promising carriers for accomplishing colon-specific release. In this study, we have explored the potential of polyelectrolyte complexes between a succinate derivative of Leucaena leucocephala galactomannan and cationic guar gum for colon delivery of synbiotic. The PECs were prepared using a polyelectrolyte complexation method and characterized. The PECs exhibited excellent stability, with high encapsulation efficiency for both probiotics (95.53 %) and prebiotics (83.33 %). In vitro studies demonstrated enhanced survivability and proliferation of the encapsulated probiotics in the presence of prebiotics (93.29 %). The SEM images revealed a smooth and firm structure with reduced number of pores when both prebiotic and probiotic were encapsulated together. The treatment with synbiotic PECs in acetic acid induced IBD rats significantly relieves colitis symptoms as was evident from colon/body ratio, DAI score and histopathology studies. An increase in the protein and reduced glutathione levels and reduction in superoxide dismutase activity was observed in colitic rats that received synbiotic treatment as compared to colitic rats. Overall, this study highlights the potential of Leucaena leucocephala succinate-cationic guar gum PECs as a promising system for colon-specific synbiotic delivery, with implications for improved gut health and the treatment of various gastrointestinal disorders.
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Cover crops (CC) can improve phosphorus (P) cycling by reducing water related P losses and contributing to P nutrition of a rotational crop. This is particularly important in claypan soils with freeze-thaw cycles in early spring in the Midwest U.S. This 4-year study (2019-2022) examined the impact of CC monoculture and mix of CC species on P losses from a fertilizer application, and determined the P balance in soil compared to no cover crop (noCC). The CC mix consisted of wheat (Triticum aestivum L.), radish (Raphanus raphanistrum subsp. Sativus), and turnip (Brassica rapa subsp. Rapa) (3xCCmix) in 2019 and 2021 before corn, and cereal rye (Secale cereale L.) was planted as monoculture before soybean in 2020 and 2022. The 3xCCmix had no effect on total phosphorus (TP) and dissolved reactive phosphorus (PO4-P) concentration or load in 2019 and 2021. Cereal rye reduced TP and PO4-P load 70% and 73%, respectively, compared to noCC. The variation in soil moisture, temperature, and net precipitation from fertilizer application until CC termination affected available soil P pools due to variability in CC species P uptake, residue decomposition, and P loss in surface water runoff. Overall, the P budget calculations showed cereal rye had 2.4 kg ha-1 greater P uptake compared to the 3xCCmix species which also reduced P loss in water and had greater differences in soil P status compared to noCC. This study highlights the benefit of CCs in reducing P loss in surface runoff and immobilizing P through plant uptake. However, these effects were minimal with 3xCCmix species and variability in crop residue decomposition from different CC species could affect overall P-soil balance.