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1.
Eur J Med Res ; 29(1): 284, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745261

RESUMO

BACKGROUND: The Berlin definition of acute respiratory distress syndrome (ARDS) includes only clinical characteristics. Understanding unique patient pathobiology may allow personalized treatment. We aimed to define and describe ARDS phenotypes/endotypes combining clinical and pathophysiologic parameters from a Canadian ARDS cohort. METHODS: A cohort of adult ARDS patients from multiple sites in Calgary, Canada, had plasma cytokine levels and clinical parameters measured in the first 24 h of ICU admission. We used a latent class model (LCM) to group the patients into several ARDS subgroups and identified the features differentiating those subgroups. We then discuss the subgroup effect on 30 day mortality. RESULTS: The LCM suggested three subgroups (n1 = 64, n2 = 86, and n3 = 30), and 23 out of 69 features made these subgroups distinct. The top five discriminating features were IL-8, IL-6, IL-10, TNF-a, and serum lactate. Mortality distinctively varied between subgroups. Individual clinical characteristics within the subgroup associated with mortality included mean PaO2/FiO2 ratio, pneumonia, platelet count, and bicarbonate negatively associated with mortality, while lactate, creatinine, shock, chronic kidney disease, vasopressor/ionotropic use, low GCS at admission, and sepsis were positively associated. IL-8 and Apache II were individual markers strongly associated with mortality (Area Under the Curve = 0.84). PERSPECTIVE: ARDS subgrouping using biomarkers and clinical characteristics is useful for categorizing a heterogeneous condition into several homogenous patient groups. This study found three ARDS subgroups using LCM; each subgroup has a different level of mortality. This model may also apply to developing further trial design, prognostication, and treatment selection.


Assuntos
Medicina de Precisão , Síndrome do Desconforto Respiratório , Humanos , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Medicina de Precisão/métodos , Idoso , Biomarcadores/sangue , Adulto , Fenótipo , Canadá/epidemiologia , Estudos de Coortes
2.
Artigo em Inglês | MEDLINE | ID: mdl-38698530

RESUMO

Condensation of 5-benzyl-3-hydrazino-1,2,4-triazino[5,6-b]indole with various sugar aldoses or ketoses gave the corresponding sugar hydrazones as single geometrical isomer or exist in E/Z tautomeric isomers. The hydrazones underwent heterocyclization with Fe(Ш)Cl3 to give the N2-adduct acyclo C-nucleosides: 3-(alditol-1yl)-10-benzyl-1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indoles rather than the N4-adduct: 10-(alditol-1-yl)-3-benzyl-1,2,4-triazolo[3,4-c]1,2,4-triazino[5,6-b] indoles on the basis of chemical and UV spectral proofs. Conformational analysis of their polyacetates were studied. The new acyclo C-nucleosides were evaluated for antimicrobial activity.

4.
Mikrochim Acta ; 191(6): 299, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709371

RESUMO

Gold nanoclusters are a smart platform for sensing potassium ions (K+). They have been synthesized using bovine serum albumin (BSA) and valinomycin (Val) to protect and cap the nanoclusters. The nanoclusters (Val-AuNCs) produced have a red emission at 616 nm under excitation with 470 nm. In the presence of K+, the valinomycin polar groups switch to the molecule's interior by complexing with K+, forming a bracelet structure, and being surrounded by the hydrophobic exterior conformation. This structure allows a proposed fluorometric method for detecting K+ by switching between the Val-AuNCs' hydrophilicity and hydrophobicity, which induces the aggregation of gold nanoclusters. As a result, significant quenching is seen in fluorescence after adding K+. The quenching in fluorescence in the presence of K+ is attributed to the aggregation mechanism. This sensing technique provides a highly precise and selective sensing method for K+ in the range 0.78 to 8 µM with LOD equal to 233 nM. The selectivity of Val-AuNCs toward K+ ions was investigated compared to other ions. Furthermore, the Val-AuNCs have novel possibilities as favorable sensor candidates for various imaging applications. Our detection technique was validated by determining K+ ions in postmortem vitreous humor samples, which yielded promising results.


Assuntos
Corantes Fluorescentes , Ouro , Nanopartículas Metálicas , Potássio , Soroalbumina Bovina , Valinomicina , Ouro/química , Valinomicina/química , Potássio/análise , Potássio/química , Nanopartículas Metálicas/química , Soroalbumina Bovina/química , Corantes Fluorescentes/química , Espectrometria de Fluorescência/métodos , Limite de Detecção , Animais , Interações Hidrofóbicas e Hidrofílicas , Bovinos
5.
Mol Biol Rep ; 51(1): 608, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704766

RESUMO

BACKGROUND: Tacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims to investigate the effect of linagliptin (Lina) on TAC-induced renal injury and its underlying mechanisms. METHODS AND RESULTS: Thirty-two Sprague Dawley rats were treated with TAC (1.5 mg/kg/day, subcutaneously) and/or Lina (5 mg/kg/day, orally) for 4 weeks. Histological examination was conducted, and serum and urinary biomarkers were measured to assess kidney function and integrity. Furthermore, ELISA, Western blot analysis and immunohistochemical assay were employed to determine signaling molecules of oxidative stress, profibrogenic, hypoxic, and apoptotic proteins. Tacrolimus caused renal dysfunction and histological deterioration evidenced by increased serum creatinine, blood urea nitrogen (BUN), urinary cystatin C, and decreased serum albumin as well as elevated tubular injury and interstitial fibrosis scores. Additionally, TAC significantly increased the expression of collagen type-1, alpha-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta1 (TGF-ß1) renal content. Moreover, TAC decreased the expression of nuclear factor erythroid-2-related factor2 (Nrf2), heme oxygenase 1 (HO-1), and mitochondrial superoxide dismutase (SOD2). In addition, TAC increased protein expression of hypoxia-inducible factor1-alpha (HIF-1α), connective tissue growth factor (CTGF), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), as well as nitric oxide (NO), 4-hydroxynonenal, caspase-3 and Bax renal contents. Furthermore, TAC decreased Bcl-2 renal contents. The Lina administration markedly attenuated these alterations. CONCLUSION: Lina ameliorated TAC-induced kidney injury through modulation of oxidative stress, hypoxia, and apoptosis related proteins.


Assuntos
Fator de Crescimento do Tecido Conjuntivo , Subunidade alfa do Fator 1 Induzível por Hipóxia , Rim , Linagliptina , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Ratos Sprague-Dawley , Tacrolimo , Animais , Tacrolimo/farmacologia , Ratos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Linagliptina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Masculino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Transdução de Sinais/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Imunossupressores/farmacologia
6.
BMC Chem ; 18(1): 92, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702832

RESUMO

The simultaneous assay of duloxetine hydrochloride (DLX) and avanafil (AVN) in their pure forms, synthetic mixtures, and spiked human plasma was achieved using a novel, eco-friendly, sensitive, and specific HPTLC methodology that have been established and validated. Measuring the levels of co-administered antidepressants and sexual stimulants in biological fluids is an important step for individuals with depression and sexual problems. Separation was performed successfully using pre-coated silica gel 60-F254 as a stationary phase and a mobile phase composed of methanol, acetone, and 33% ammonia (8:2:0.05, v/v/v). Compact bands were produced by the optimized mobile phase that was chosen for development (Rf values were 0.23 and 0.75 for DLX and AVN, individually) after dual-wavelength detection for DLX and AVN at 232 and 253 nm, respectively. The results of polynomial regression analysis were exceptional (r = 0.9999 for both medicines) over concentration ranges of 5-800 and 10-800ng/spot for DLX and AVN, respectively. The quantitation limits were 4.69 and 9.53 ng/spot (0.31 and 0.94 µg/mL), whereas the detection limits were 1.55 and 3.15 ng/spot (0.63 and 1.91 µg/mL), for DLX and AVN, respectively. The International Council for Harmonization (ICH) criteria served as the basis for validating the established approach. Moreover, the proposed technique was evaluated in terms of greenness using four contemporary ecological metrics: The Analytical Greenness software (AGREE), the Green Analytical Procedure Index (GAPI), Eco-Scale, and the National Environmental Method Index (NEMI). Additionally, the Blue Applicability Grade Index (BAGI), a newly developed tool for evaluating the practicality (blueness) of procedures, was taken into consideration when evaluating the sustainability levels of the established approach.

7.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612799

RESUMO

EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naïve patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.


Assuntos
Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Pirimidinas , Masculino , Humanos , Feminino , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Éxons
8.
A A Pract ; 18(4): e01778, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38572887

RESUMO

Even though epidural blood patch (EBP) is thought to be the definitive treatment for severe cases of postdural puncture headache (PDPH), it may be accompanied by complications like adhesion arachnoiditis, and cauda equina syndrome, especially if the injection is repeated. The sphenopalatine ganglion (SPG) block is a new minimally invasive technique for the treatment of PDPH, with variable results according to the clinical situation and deployed approach. We describe a case of PDPH resistant to EBP in which we successfully managed symptoms using ultrasound-guided suprazygomatic SPG block to deliver local anesthetic directly into pterygopalatine fossa, thus avoiding a second EBP.


Assuntos
Cefaleia Pós-Punção Dural , Bloqueio do Gânglio Esfenopalatino , Humanos , Cefaleia Pós-Punção Dural/terapia , Cefaleia Pós-Punção Dural/etiologia , Placa de Sangue Epidural/métodos , Bloqueio do Gânglio Esfenopalatino/métodos , Anestésicos Locais , Ultrassonografia de Intervenção/efeitos adversos
9.
Environ Sci Pollut Res Int ; 31(18): 27465-27484, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38512572

RESUMO

Microorganisms are cost-effective and eco-friendly alternative methods for removing heavy metals (HM) from contaminated agricultural soils. Therefore, this study aims to identify and characterize HM-tolerant (HMT) plant growth-promoting rhizobacteria (PGPR) isolated from industry-contaminated soils to determine their impact as bioremediators on HM-stressed pepper plants. Four isolates [Pseudomonas azotoformans (Pa), Serratia rubidaea (Sr), Paenibacillus pabuli (Pp) and Bacillus velezensis (Bv)] were identified based on their remarkable levels of HM tolerance in vitro. Field studies were conducted to evaluate the growth promotion and tolerance to HM toxicity of pepper plants grown in HM-polluted soils. Plants exposed to HM stress showed improved growth, physio-biochemistry, and antioxidant defense system components when treated with any of the individual isolates, in contrast to the control group that did not receive PGPR. The combined treatment of the tested HMT PGPR was, however, relatively superior to other treatments. Compared to no or single PGPR treatment, the consortia (Pa+Sr+Pp+Bv) increased the photosynthetic pigment contents, relative water content, and membrane stability index but lowered the electrolyte leakage and contents of malondialdehyde and hydrogen peroxide by suppressing the (non) enzymatic antioxidants in plant tissues. In pepper, Cd, Cu, Pb, and Ni contents decreased by 88.0-88.5, 63.8-66.5, 66.2-67.0, and 90.2-90.9% in leaves, and 87.2-88.1, 69.4-70.0%, 80.0-81.3, and 92.3%% in fruits, respectively. Thus, these PGPR are highly effective at immobilizing HM and reducing translocation in planta. These findings indicate that the application of HMT PGPR could be a promising "bioremediation" strategy to enhance growth and productivity of crops cultivated in soils contaminated with HM for sustainable agricultural practices.


Assuntos
Capsicum , Metais Pesados , Poluentes do Solo , Capsicum/microbiologia , Metais Pesados/toxicidade , Poluentes do Solo/toxicidade , Biodegradação Ambiental , Bacillus , Microbiologia do Solo
10.
BMC Psychol ; 12(1): 145, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481329

RESUMO

This research investigated the impact of planning time, working memory (WM), and cognitive styles on language learning outcomes within the framework of Task-Based Language Teaching (TBLT). Drawing on a diverse sample of language learners, the study employed a pretest-posttest control group quasi-experiment to examine the effects of providing pre-task planning time on language performance. Participants engaged in communicative tasks, with a focus on vocabulary acquisition and task complexity, while their cognitive processes were assessed through measures of WM and cognitive styles. The findings revealed significant interactions between planning time and cognitive styles, particularly field dependence, influencing language production and proficiency such that learners with planning time outperformed learners without planning time; high-WM learners outperformed their low-WM peers, and field independent learners outstripped their field-dependent counterparts. Moreover, the study contributes to the broader understanding of the nuanced relationship between planning time, WM, and cognitive styles in the context of TBLT. The implications of these findings for language teachers, materials developers, syllabus designers, curriculum developers, and policymakers are discussed, offering insights into the design of effective language learning environments. Despite certain limitations, the study provides a foundation for further research exploring cross-cultural variations, longitudinal effects, and the integration of technology in language education, with the aim of advancing pedagogical practices tailored to diverse learner profiles.


Assuntos
Multilinguismo , Vocabulário , Humanos , Memória de Curto Prazo , Idioma , Desenvolvimento da Linguagem
11.
Curr Med Chem ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38500276

RESUMO

AIM: In this study, a neoteric and expedient oxidation method is applied for a variety of Hantzsch 1,4-dihydropyridine derivatives such as 1,4-dihydro- 2,6-dimethyl-3,5-diacetylpyridine, 3,5-bis-hydrazono--2,6-dimethyl-1,4-dihydropyridine, and 3,5-bis-thiazoly-2,6-dimethyl-1,4-dihydro pyridine. METHOD: This simple oxidation is based upon the in situ generation of nitrous acid from an aqueous sodium nitrite and acetic acid mixture and could be used to downgrade costs, sustain resources, and minimize chemical wastes. Also, a molecular modeling strategy was used to study the mechanism of action for various derivatives of bis-hydrazinylidene- thiazole as the protein Vascular Endothelial Growth Factor Receptor Tyrosine Kinase (VEGFR TK) inhibitor through evaluating their binding scores and modes compared with Sorafenib as a reference standard. RESULT: The results revealed that the interaction of hydrazinylidene and thiazole as an anticancer Tyrosine Kinase inhibitor has been improved. CONCLUSION: Additionally, the compounds exhibiting the highest activity were assessed for their potential anticancer effects against HepG-2, MCF-7, and WI-38 cells, and the outcomes demonstrated encouraging activity against cancer.

12.
BMC Psychol ; 12(1): 148, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486343

RESUMO

This study investigates the impact of Philosophy-Based Language Teaching (PBLT) on the critical thinking skills and learner engagement of English as a Foreign Language (EFL) students. A concurrent mixed-methods approach, including semi-structured interviews, document analysis, and academic achievement tests, was employed with an experimental group (EG) exposed to PBLT and a control group (CG) receiving traditional instruction. The results reveal a substantial positive effect of PBLT on the critical thinking abilities of EFL learners, as evidenced by thematic analyses of interviews and document content. Themes include heightened critical thinking awareness, collaborative knowledge construction, and increased learner engagement. Academic achievement tests further demonstrate significant improvement in the experimental group's performance. A comparison with existing literature underscores the novelty of our mixed-methods approach. Implications for language teachers, materials developers, syllabus designers, and policy-makers are discussed, highlighting the potential of PBLT in cultivating critical thinking and learner engagement.


Assuntos
Sucesso Acadêmico , Humanos , Idioma , Estudantes , Filosofia , Pensamento
13.
RSC Adv ; 14(12): 8283-8292, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38469194

RESUMO

A green-complied spectrofluorimetric approach for quantification of the antidepressant, fluvoxamine, has been established. The method that has been suggested relies on the development of an association complex between fluvoxamine and erythrosine B in an acetate buffer solution. After being excited at 530 nm, the quenching in erythrosine B's native fluorescence caused by complex formation with fluvoxamine was detected at a wavelength of 552 nm. The values of fluorescence quenching at the most optimal reaction conditions were rectilinear at the concentration range of 0.2-2.0 µg mL-1, with a good correlation coefficient (r = 0.9998). The detection limit for the method was 0.03 µg mL-1 while the quantitation limit was 0.09 µg mL-1. The suggested approach has been validated according to the ICH. The established approach was effectively used to determine the drug under study in its dosage form with an average percent recovery of 98.92 ± 0.87 (n = 5), with no effect caused by the existing excipients. The proposed approach was also successfully used for the content uniformity test.

14.
RSC Adv ; 14(11): 7797-7805, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38444975

RESUMO

Prucalopride (PCP) is one of the recent drugs used for the regulation of gastrointestinal tract motility and the treatment of constipation. A new, highly sensitive and fast resonance Rayleigh scattering (RRS) approach was suggested for PCP determination. The approach was based on its reaction of PCP with eosin Y in buffered medium (pH 3.5) to form an ion pair association complex which had a significant enhancement in RRS compared to that of eosin Y or PCP alone. The enhancement of RRS intensity had straight correlation to PCP concentration ranging from 150 to 2000 ng mL-1 with 38 ng mL-1 as LOD and 125 ng mL-1 as LOQ. The measurements were done at a wavelength of 365 nm that provided the maximum sensitivity. All the experimental parameters were studied carefully and optimized via Box-Behnken experimental design. The International Council for Harmonization (ICH) guidelines were employed to validate the suggested method and the obtained results proved the appropriate method performance. The method was efficiently utilized to determine PCP in pure form, pharmaceutical tablets and spiked urine samples with no interferences from the surrounding matrices. Furthermore, the greenness of the suggested procedure was confirmed using different green metric approaches.

15.
Environ Sci Pollut Res Int ; 31(16): 24235-24249, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38436856

RESUMO

Coastal aquifer vulnerability assessment (CAVA) studies are essential for mitigating the effects of seawater intrusion (SWI) worldwide. In this research, the vulnerability of the coastal aquifer in the Lahijan region of northwest Iran was investigated. A vulnerability map (VM) was created applying hydrogeological parameters derived from the original GALDIT model (OGM). The significance of OGM parameters was assessed using the mean decrease accuracy (MDA) method, with the current state of SWI emerging as the most crucial factor for evaluating vulnerability. To optimize GALDIT weights, we introduced the biogeography-based optimization (BBO) and gray wolf optimization (GWO) techniques to obtain to hybrid OGM-BBO and OGM-GWO models, respectively. Despite considerable research focused on enhancing CAVA models, efforts to modify the weights and rates of OGM parameters by incorporating deep learning algorithms remain scarce. Hence, a convolutional neural network (CNN) algorithm was applied to produce the VM. The area under the receiver-operating characteristic curves for OGM-BBO, OGM-GWO, and VMCNN were 0.794, 0.835, and 0.982, respectively. According to the CNN-based VM, 41% of the aquifer displayed very high and high vulnerability to SWI, concentrated primarily along the coastline. Additionally, 32% of the aquifer exhibited very low and low vulnerability to SWI, predominantly in the southern and southwestern regions. The proposed model can be extended to evaluate the vulnerability of various coastal aquifers to SWI, thereby assisting land use planers and policymakers in identifying at-risk areas. Moreover, deep-learning-based approaches can help clarify the associations between aquifer vulnerability and contamination resulting from SWI.


Assuntos
Aprendizado Profundo , Água Subterrânea , Monitoramento Ambiental/métodos , Água do Mar , Algoritmos
16.
Mikrochim Acta ; 191(4): 199, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483615

RESUMO

An innovative triple optical sensor is presented that utilizes gold nanoclusters (GNCs) stabilized with ciprofloxacin (CIP) and bovine serum albumin (BSA). The sensor is designed to identify three critical metal ions, namely Cu2+, Al3+, and Hg2+. Under 360 nm excitation, the synthesized CIP-BSA-GNCs demonstrate dual fluorescence emission with peaks at 448 nm (blue) and 612 nm (red). The red emission is associated with the interior of the CIP-BSA-GNCs, whereas the blue emission results from the surface-bound CIP molecules. The sensitive and selective fluorescent nanosensor CIP-BSA-GNCs were employed to detect Cu2+, Al3+, and Hg2+ ions. Cu2+ effectively quenched the fluorescence intensity of the CIP-BSA-GNCs at both peaks via the internal charge transfer mechanism (ICT). Cu2+ could be detected within the concentration range 1.13 × 10-3 to 0.05 µM, with a detection limit of 0.34 nM. Al3+ increased the intensity of CIP fluorescence at 448 nm via the chelation-induced fluorescence enhancement mechanism. The fluorescence intensity of the core CIP-BSA-GNCs at 612 nm was utilized as a reference signal. Thus, the ratiometric detection of Al3+ succeeded with a limit of detection of 0.21 nM within the dynamic range 0.69 × 10-3 to 0.07 µM. Hg2+ effectively quenched the fluorescence intensity of the CIP-BSA-GNCs at 612 nm via the metallophilic interaction mechanism. The fluorescence intensity of CIP molecules at 448 nm was utilized as a reference signal. This allowed for the ratiometric detection of Hg2+ with a detection limit of 0.7 nM within the concentration range 2.3 × 10-3 to 0.1 µM.


Assuntos
Mercúrio , Nanopartículas Metálicas , Ouro , Ciprofloxacina , Espectrometria de Fluorescência/métodos , Corantes Fluorescentes , Soroalbumina Bovina , Íons
17.
Diabetologia ; 67(6): 1079-1094, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38512414

RESUMO

AIMS/HYPOTHESIS: Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly connected 'hub' cells, important for the propagation of intercellular Ca2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood. Changes at the level of the epigenome provide one such possibility, which we explore here by focusing on the imprinted gene Nnat (encoding neuronatin [NNAT]), which is required for normal insulin synthesis and secretion. METHODS: Single-cell RNA-seq datasets were examined using Seurat 4.0 and ClusterProfiler running under R. Transgenic mice expressing enhanced GFP under the control of the Nnat enhancer/promoter regions were generated for FACS of beta cells and downstream analysis of CpG methylation by bisulphite sequencing and RNA-seq, respectively. Animals deleted for the de novo methyltransferase DNA methyltransferase 3 alpha (DNMT3A) from the pancreatic progenitor stage were used to explore control of promoter methylation. Proteomics was performed using affinity purification mass spectrometry and Ca2+ dynamics explored by rapid confocal imaging of Cal-520 AM and Cal-590 AM. Insulin secretion was measured using homogeneous time-resolved fluorescence imaging. RESULTS: Nnat mRNA was differentially expressed in a discrete beta cell population in a developmental stage- and DNA methylation (DNMT3A)-dependent manner. Thus, pseudo-time analysis of embryonic datasets demonstrated the early establishment of Nnat-positive and -negative subpopulations during embryogenesis. NNAT expression is also restricted to a subset of beta cells across the human islet that is maintained throughout adult life. NNAT+ beta cells also displayed a discrete transcriptome at adult stages, representing a subpopulation specialised for insulin production, and were diminished in db/db mice. 'Hub' cells were less abundant in the NNAT+ population, consistent with epigenetic control of this functional specialisation. CONCLUSIONS/INTERPRETATION: These findings demonstrate that differential DNA methylation at Nnat represents a novel means through which beta cell heterogeneity is established during development. We therefore hypothesise that changes in methylation at this locus may contribute to a loss of beta cell hierarchy and connectivity, potentially contributing to defective insulin secretion in some forms of diabetes. DATA AVAILABILITY: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD048465.


Assuntos
Ilhas de CpG , Metilação de DNA , Células Secretoras de Insulina , Células Secretoras de Insulina/metabolismo , Animais , Camundongos , Ilhas de CpG/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Transgênicos , DNA Metiltransferase 3A/metabolismo , Humanos , Insulina/metabolismo , Secreção de Insulina/fisiologia
18.
J Econ Entomol ; 117(2): 618-628, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38377139

RESUMO

Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae) is a major economic pest attacking a variety of crops in Egypt and other Mediterranean countries. S. littoralis has developed resistance to both traditional and novel insecticides. The current study investigated S. littoralis resistance to indoxacarb regarding inheritance mode, realized heritability (h2), and fitness costs. An indoxacarb-resistant strain (Indoxa-SEL) was obtained by selecting a field strain with indoxacarb. Indoxa-SEL strain outperformed the susceptible one (Indoxa-S) by 29.77-fold after 16 consecutive generations of selection. Based on the LC50 values of the progenies of reciprocal crosses F1 (R♂ × S♀) and F1' (R♀ × S♂), S. littoralis resistance to indoxacarb was found to be autosomal and partially recessive. Chi-square tests for goodness-of-fit between observed and expected mortalities of self-bred F1 and resistant strain reciprocal crosses revealed that the resistance was controlled by multiple genes. The resistant strain had a relative fitness of 0.80, with significantly increased total preovipositional period of females, egg, larvae, pupae, preadult, adult, and total longevity period. The estimated realized heritability value in the Indoxa-SEL strain was 0.21. The current study will contribute to sustaining indoxacarb efficacy and designing effective resistance management programs against S. littoralis.


Assuntos
Inseticidas , Mariposas , Feminino , Animais , Spodoptera/genética , Resistência a Inseticidas/genética , Mariposas/genética , Oxazinas/farmacologia , Larva/genética , Inseticidas/farmacologia
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 311: 123986, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38335587

RESUMO

Tolterodine tartrate (TTD) was the first antimuscarinic medication developed exclusively for the treatment of overactive bladder syndrome and was approved by the FDA in 1998. As a result of the drug's extensive utilization within the local community following its authorization, there is a pressing need to develop and validate a spectrofluorometric method that is economically efficient, easily reproducible, environmentally sustainable, and possesses high sensitivity. The developed approach relies on enhancing the fluorescence intensity of TTD to reach a level 720 % higher than its initial value, achieved through the application of an aqueous sodium dodecyl sulfate (SDS) solution. A strong correlation was observed with a correlation coefficient of 0.9998 between the concentration of TTD and the fluorescence intensity within the range of 25.0-500.0 ng mL-1. This approach could be employed to quantify TTD in its pure form and to examine pharmaceutical tablets for the purposes of verifying uniform content. Additionally, it was utilized for the evaluation of TTD concentrations in spiked human plasma.


Assuntos
Bexiga Urinária Hiperativa , Humanos , Tartarato de Tolterodina , Bexiga Urinária Hiperativa/tratamento farmacológico , Espectrometria de Fluorescência/métodos , Antagonistas Muscarínicos/uso terapêutico , Dodecilsulfato de Sódio
20.
Sci Total Environ ; 920: 171006, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38369137

RESUMO

Understanding the patterns and controls regulating nitrogen (N) transformation and its response to N enrichment is critical to re-evaluating soil N limitation or availability and its environmental consequences. Nevertheless, how climatic conditions affect nitrate dynamics and the response of gross N cycling rates to N enrichment in forest soils is still only rudimentarily known. Through collecting and analyzing 4426-single and 769-paired observations from 231 15N labeling studies, we found that nitrification capacity [the ratio of gross autotrophic nitrification (GAN) to gross N mineralization (GNM)] was significantly lower in tropical/subtropical (19%) than in temperate (68%) forest soils, mainly due to the higher GNM and lower GAN in tropical/subtropical regions resulting from low C/N ratio and high precipitation, respectively. However, nitrate retention capacity [the ratio of dissimilatory nitrate reduction to ammonium (DNRA) plus gross nitrate immobilization (INO3) to gross nitrification] was significantly higher in tropical/subtropical (86%) than in temperate (54%) forest soils, mainly due to the higher precipitation and GNM of tropical/subtropical regions, which stimulated DNRA and INO3. As a result, the ratio of GAN to ammonium immobilization (INH4) was significantly higher in temperate than in tropical/subtropical soils. Climatic rather than edaphic factors control heterotrophic nitrification rate (GHN) in forest soils. GHN significantly increased with increasing temperature in temperate regions and with decreasing precipitation in tropical/subtropical regions. In temperate forest soils, gross N transformation rates were insensitive to N enrichment. In tropical/subtropical forests, however, N enrichment significantly stimulated GNM, GAN and GAN to INH4 ratio, but inhibited INH4 and INO3 due to reduced microbial biomass and pH. We propose that temperate forest soils have higher nitrification capacity and lower nitrate retention capacity, implying a higher potential risk of N losses. However, tropical/subtropical forest systems shift from a conservative to a leaky N-cycling system in response to N enrichment.


Assuntos
Compostos de Amônio , Nitrogênio , Nitrogênio/análise , Nitratos/análise , Solo , Florestas
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