CeO2·ZnO@biomass-derived carbon nanocomposite-based electrochemical sensor for efficient detection of ascorbic acid.

Ascorbic acid (AA), a prominent antioxidant commonly found in human blood serum, serves as a biomarker for assessing oxidative stress levels. Therefore, precise detection of AA is crucial for swiftly diagnosing conditions arising from abnormal AA levels. Consequently, the primary aim of this research is to develop a sensitive and selective electrochemical sensor for accurate AA determination. To accomplish this aim, we used a novel nanocomposite comprised of CeO2-doped ZnO adorned on biomass-derived carbon (CeO2·ZnO@BC) as the active nanomaterial, effectively fabricating a glassy carbon electrode (GCE). Various analytical techniques were employed to scrutinize the structure and morphology features of the CeO2·ZnO@BC nanocomposite, ensuring its suitability as the sensing nanomaterial. This innovative sensor is capable of quantifying a wide range of AA concentrations, spanning from 0.5 to 1925 µM in a neutral phosphate buffer solution. It exhibits a remarkable sensitivity of 0.2267 µA µM-1cm-2 and a practical detection limit of 0.022 µM. Thanks to its exceptional sensitivity and selectivity, this sensor enables highly accurate determination of AA concentrations in real samples. Moreover, its superior reproducibility, repeatability, and stability underscore its reliability and robustness for AA quantification.

MutLα suppresses error-prone DNA mismatch repair and preferentially protects noncoding DNA from mutations.

The DNA mismatch repair (MMR) system promotes genome stability and protects humans from certain types of cancer. Its primary function is the correction of DNA polymerase errors. MutLα is an important eukaryotic MMR factor. We have examined the contributions of MutLα to maintaining genome stability. We show here that loss of MutLα in yeast increases the genome-wide mutation rate by ∼130-fold and generates a genome-wide mutation spectrum that consists of small indels and base substitutions. We also show that loss of yeast MutLα leads to error-prone MMR that produces T > C base substitutions in 5'-ATA-3' sequences. In agreement with this finding, our examination of human whole-genome DNA sequencing data has revealed that loss of MutLα in induced pluripotent stem cells triggers error-prone MMR that leads to the formation of T > C mutations in 5'-NTN-3' sequences. Our further analysis has shown that MutLα-independent MMR plays a role in suppressing base substitutions in N3 homopolymeric runs. In addition, we describe that MutLα preferentially protects noncoding DNA from mutations. Our study defines the contributions of MutLα-dependent and independent mechanisms to genome-wide MMR.

MutLα suppresses error-prone DNA mismatch repair and preferentially protects noncoding DNA from mutations.

The DNA mismatch repair (MMR) system promotes genome stability and protects humans from certain types of cancer. Its primary function is the correction of DNA polymerase errors. MutLα is an important eukaryotic MMR factor. We have examined the contributions of MutLα to maintaining genome stability. We show here that loss of MutLα in yeast increases the genome-wide mutation rate by ~130-fold and generates a genome-wide mutation spectrum that consists of small indels and base substitutions. We also show that loss of yeast MutLα leads to error-prone MMR that produces T>C base substitutions in 5'-ATA-3' sequences. In agreement with this finding, our examination of human whole genome DNA sequencing data has revealed that loss of MutLα in induced pluripotent stem cells triggers error-prone MMR that leads to the formation of T>C mutations in 5'-NTN-3' sequences. Our further analysis has shown that MutLα-independent MMR plays a role in suppressing base substitutions in N3 homopolymeric runs. In addition, we describe that MutLα preferentially defends noncoding DNA from mutations. Our study defines the contributions of MutLα-dependent and independent mechanisms to genome-wide MMR.

Evaluation of cellular viability in chitosan/L-arginine hydrogels.

BACKGROUND: There is a lack of studies evaluating the toxicity of nitric oxide (NO) precursors in chitosan/L-arginine hydrogels and their topical administration. However, clarifying the characteristics of these elements is essential for their possible use in non-surgical techniques of tooth movement acceleration. Such characteristics include interaction with different cell types, metabolism and drug safety. OBJECTIVES: This in vitro study aimed to assess the cytotoxicity of chitosan hydrogels on human HeLa cells using different concentrations of L-arginine. MATERIAL AND METHODS: The hydrogels were synthesized in a materials engineering laboratory, with a controlled environment, using 4 different L-arginine concentrations of 0%, 10%, 15%, and 20%. Once the hydrogels were prepared, their physical and chemical properties were characterized, and viability analysis was performed using 2 different methods, including a 48-h assay with Artemia salina nauplii and a 24-h cell culture with human HeLa cells followed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation assay. Data analysis was performed using a Mann-Whitney U test to evaluate positive and negative controls in the cell culture, with a significance level of 0.01. A Wilcoxon paired test contrasted the 24-h compared to 48-h Artemia salina assays, with a Kruskal-Wallis and post hoc Dunn test used to compare groups using a significance level of 0.05. RESULTS: In the more viscous hydrogels, Artemia salina nauplii decreased drastically in 24 h, while the 15% and 20% hydrogels had no statistical differences from the negative control. The 10% and 20% hydrogels were statistically different from the negative control when comparing cell culture data. CONCLUSIONS: Our findings suggest that chitosan/L-arginine hydrogels could be used in humans without toxic effects. However, more trials and tests are needed to evaluate tooth movement rate during orthodontic treatment.

Una educación para la vida: resignificación de proyectos educativos integrales / integralesAn Education for Life: Re-meaning of Integral Education ProjectsUma / Uma educação para a vida: ressignificação de projetos educativos complementares

El proyecto de resignificación educativa busca la forma-ción permanente del docente que piensa en la educación como proceso, para transformar el espacio educativo tradicional en un espacio democrático y participativo, con proyectos cooperativos e interdisciplinarios. Duran-te seis meses se trabajó desde la Investigación Acción Educativa (iae) (Elliot, 1998), por lo que los temas del programa se establecieron de acuerdo con los intereses y necesidades de los profesores y directores de la escuela. La implementación se realizó con la comunidad edu-cativa de una institución rural de São Paulo, en la cual se desarrollaron talleres semanales alrededor de las preguntas: ¿Cuáles serían las propuestas de trabajo di-recto con los estudiantes?, ¿qué cambios afectarían las concepciones y prácticas pedagógicas de los maestros y las relaciones entre todos los miembros de la comuni-dad escolar (estudiantes, maestros, empleados, familia, etc.)? Con los 217 estudiantes, de 4 a 11 años de esta institución, se trabajaron guiones de estudio basados en sus intereses. Los resultados preliminares de estos proyectos han demostrado que es posible construir la educación para la ciudadanía y la conciencia ambiental a través de acciones que tengan sentido para la comu-nidad escolar

The Educational Resignification Project seeks the per-manent training of the teacher who thinks of education as a process, to transform the traditional educational space into a democratic and participatory space, with cooperative and interdisciplinary projects. Work was carried out for six months using the Educational Action Research-iae (Elliot, 1998); therefore, the topics of the program were established according to the interests and needs of the teachers and school directors. The implemen-tation was conducted with the educational community of a rural institution in São Paulo, where weekly workshops were developed around the questions: What would be the proposals for direct work with students? and What changes would affect pedagogical conceptions and practices of teachers and the relationships between all members of the school community (students, teachers, employees, family, etc.)? With the 217 students from 04 to 11 years old at this school, study scripts were developed based on their interests. The preliminary projects' results showed it is possible to build education for citizenship and environmental awareness through actions that make sense for the school community.

O Projeto de Ressignificação Educacional busca a for-mação permanente do professor que pensa a educação como um processo, para transformar o espaço educa-cional tradicional em um espaço democrático e partici-pativo, com projetos cooperativos e interdisciplinares. Trabalhamos por seis meses a partir da Pesquisa-Ação Educacional (pae) (Elliot, 1998), de modo que os te-mas do programa foram estabelecidos de acordo com os interesses e necessidades dos professores e direto-res escolares. A implementação foi realizada com a comunidade educativa de uma instituição rural de São Paulo, onde foram desenvolvidas oficinas semanais em torno das questões: "Quais seriam as propostas de tra-balho direto com os alunos?"; "Que mudanças afetariam as concepções e práticas pedagógicas dos professores e as relações entre todos os membros da comunidade escolar (alunos, professores, funcionários, família, etc.)?". Com os 217 alunos de 04 a 11 anos desta escola, foram trabalhados roteiros de estudo baseados em seus in-teresses. Os resultados preliminares desses projetos mostraram que é possível construir educação para a cidadania e consciência ambiental por meio de ações que façam sentido para a comunidade escolar.

Occurrence, characteristics, and microbial community of microplastics in anaerobic sludge of wastewater treatment plants.

Wastewater treatment plants (WWTPs) usually contain microplastics (MPs) due to daily influents of domestic and municipal wastewater. Thus, the WWTPs act as a point source of MPs distribution in the environment due to their incapability to remove MPs completely. In this study, MPs occurrence and distribution in anaerobic sludge from WWTPs in different regions (Kaifeng "KHP", Jinan "JSP", and Lanzhou "LGP") were studied. Followed by MPs identification by microscopy and Fourier transform infrared (FTIR) spectrum. The microbial communities associated with anaerobic sludge and MPs were also explored. The results showed that MPs concentrations were 16.5, 38.5, and 17.2 particles/g of total solids (TS) and transparent MPs accounted for 49.1%, 58.5%, and 48.3% in KHP, JSP, and LGP samples, respectively. Fibers represented the most common shape of MPs in KHP (49.1%), JSP (56.0%), and LGP (69.0%). The FTIR spectroscopy indicated the predominance of polyethylene polymer in 1-5 mm MPs. The Proteobacteria, Chloroflexi, Actinobacteria, Bacteroidetes, and Planctomycetes were the abundant phyla in all anaerobic sludge. The bacterial genera in KHP and LGP were similar, in which Caldilinea (>23%), Terrimonas (>10%), and Ferruginibacter (>7%) formed the core bacterial genera. While Rhodococcus (15.3%) and Rhodoplanes (10.9%) were dominating in JSP. The archaeal genera Methanosaeta (>69%) and Methanobrevibacter (>10%) were abundant in KHP and LGP sludge. While Methanomethylovorans accounted for 90% of JSP. Acetyltransferase and hydratase were the major bacterial enzymes, while reductase was the key archaeal enzyme in all anaerobic sludge. This study provided the baseline for MPs distribution, characterization, and MPs associated microbes in WWTPs.

Metabolic Profiling, GC-MS, LC-ESI-MS/MS Analysis, Phenolics Isolation and Biological Evaluation of the Aerial Parts Extracts of Felicia abyssinica L.

Felicia abyssinica L., family Asteraceae, is widely used in folk medicine. This represents the first study to investigate its phytoconstituents and pharmacological effects. Phytoconstituents identified by GC-MS, LC-ESI-MS/MS-based metabolomics, and NMR (1D & 2D). GC-MS of the (FAMEs) revealed mainly the identification of 55 fatty acids. LC-ESI-MS/MS analysis resulted in the tentative identity of 13 compounds representing flavonoids, phenolics, and fatty acids. Ethyl acetate fraction exhibited the highest total flavonoids 66.19 mg/mL Rutin equivalent, while the methanolic fraction showed the highest phenolics 87.70 mg/mL gallic acid equivalent, and the total condensed tannins were 64.35 µg CE/mg catechins equivalent. A flavonoid and a cinnamic acid derivative were identified as quercetin 3-O-(2'''-O-acetyl) rutinoside (Mumikotin A) (1) and Methyl sinapate (2). Biological evaluation of antioxidant and cytotoxic activities was carried out. Cytotoxicity was examined on HepG-2 cell lines where the average cell viability was 91.42 % and 52.48 % for concentrations 10 and 100 µg/mL respectively. Methylene chloride and methanolic fractions showed the highest antioxidant activity 225 µg/mL Ascorbic acid equivalents. It is hypothesized that high phenolics, flavonoid content, and oxygenated identified compounds contribute to the antioxidant activity and can be regarded as a promising species for nutraceuticals active antioxidants with potential value for remedy.

Evaluation of an automatized AMBU ESSI-1 INC designed at the Instituto Nacional de Cardiología Ignacio Chávez / Evaluación del AMBU automatizado ESSI-1 INC diseñado en el Instituto Nacional de Cardiología Ignacio Chávez

Abstract Objective: The objectives of this study were to evaluate an automated device for ventilatory support based on AMBU manufactured in March 2020. Methods: The ESSI-1 INC was evaluated through pulmonary mechanics and physiology parameters through compensatory spirometer tests (TISSOTs), and an artificial lung Model5600i Dual Adult PNEU VIEW SYSTEM; it was also compared to the anesthetic ventilatory support equipment (AEONMED 7500) in porcine models, measuring ventilatory, hemodynamic and gasometric parameters. Results: This equipment (ESSI-1 INC) was successfully tested by mechanical and biological models, such as pigs in which its performance was evaluated in terms of variability of tidal volume, ventilation frequency, and I/E relationship versus the manual performance of two medical interns. All the results turned out as expected and were satisfactory. Conclusions: It is safe and effective equipment and should be tested and used in diverse clinical conditions to standardize the ventilatory safety and care of patients who require it.

Resumen Objetivo: Evaluar un dispositivo automatizado para la asistencia ventilatoria basado en un AMBU manufacturado en Marzo del 2020. Métodos: El ESSI-1 INC fue evaluado por medio de parámetros fisiológicos y mecánica pulmonar a través de pruebas de espirómetro compensatorios (TISSOT); pulmón artificial (Modelo 5600i Dual Adult PNEU VIEW SYSTEM); así como su desempeño comparado a la máquina de anestesia (AEONMED 7500) en modelos porcinos, midiendo criterios ventilatorios, hemodinámicos y gasométricos. Resultados: Este equipo (ESSI-1 INC) fue exitosamente probado por modelos mecánicos y biológicos, tales como cerdos donde su desempeño fue evaluado en términos de la variabilidad del volumen tidal, frecuencia ventilatoria, y relación I/E versus el desempeño manual de dos médicos. Todos los resultados finalizaron como se esperaba de forma satisfactoria. Conclusiones: Es un equipo seguro y efectivo, el cual debería ser probado y usado en distintas condiciones clínicas para estandarizar la seguridad ventilatoria y cuidado de pacientes que lo requieran.

Evaluation of an automatized AMBU ESSI-1 INC designed at the Instituto Nacional de Cardiología Ignacio Chávez.

OBJECTIVE: The objectives of this study were to evaluate an automated device for ventilatory support based on AMBU manufactured in March 2020. METHODS: The ESSI-1 INC was evaluated through pulmonary mechanics and physiology parameters through compensatory spirometer tests (TISSOTs), and an artificial lung Model5600i Dual Adult PNEU VIEW SYSTEM; it was also compared to the anesthetic ventilatory support equipment (AEONMED 7500) in porcine models, measuring ventilatory, hemodynamic and gasometric parameters. RESULTS: This equipment (ESSI-1 INC) was successfully tested by mechanical and biological models, such as pigs in which its performance was evaluated in terms of variability of tidal volume, ventilation frequency, and I/E relationship versus the manual performance of two medical interns. All the results turned out as expected and were satisfactory. CONCLUSIONS: It is safe and effective equipment and should be tested and used in diverse clinical conditions to standardize the ventilatory safety and care of patients who require it.

OBJETIVO: Evaluar un dispositivo automatizado para la asistencia ventilatoria basado en un AMBU manufacturado en Marzo del 2020. MÉTODOS: El ESSI-1 INC fue evaluado por medio de parámetros fisiológicos y mecánica pulmonar a través de pruebas de espirómetro compensatorios (TISSOT); pulmón artificial (Modelo 5600i Dual Adult PNEU VIEW SYSTEM); así como su desempeño comparado a la máquina de anestesia (AEONMED 7500) en modelos porcinos, midiendo criterios ventilatorios, hemodinámicos y gasométricos. RESULTADOS: Este equipo (ESSI-1 INC) fue exitosamente probado por modelos mecánicos y biológicos, tales como cerdos donde su desempeño fue evaluado en términos de la variabilidad del volumen tidal, frecuencia ventilatoria, y relación I/E versus el desempeño manual de dos médicos. Todos los resultados finalizaron como se esperaba de forma satisfactoria. CONCLUSIONES: Es un equipo seguro y efectivo, el cual debería ser probado y usado en distintas condiciones clínicas para estandarizar la seguridad ventilatoria y cuidado de pacientes que lo requieran.

Supplementation of micro-nutrients to growth media of microalgae-induced biomass and fatty acids composition for clean energy generation.

The presence of harmful heavy metals (HMs) in the aquatic environment can damage the environment and threaten human health. Traditional remediation techniques can have secondary impacts. Thus, more sustainable approaches must be developed. Microalgae have biological properties (such as high photosynthetic efficiency and growth), which are of great advantage in the HMs removal. In this study, the effect of various concentrations (2×, 4×, and 6×) of copper (Cu), cobalt (Co), and zinc (Zn) on microalgae (C. sorokiniana GEEL-01, P. kessleri GEEL-02, D. asymmetricus GEEL-05) was investigated. The microalgal growth kinetics, HMs removal, total nitrogen (TN), total phosphor (TP), and fatty acids (FAs) compositions were analyzed. The highest growth of 1.474 OD680nm and 1.348 OD680nm was obtained at 2× and 4×, respectively, for P. kessleri GEEL-02. P. kessleri GEEL-02 showed high removal efficiency of Cu, Co, and Zn (38.92-55.44%), (36.27-68.38%), and (32.94-51.71%), respectively. Fatty acids (FAs) analysis showed that saturated FAs in C. sorokiniana GEEL-01 and P. kessleri GEEL-02 increased at 2× and 4× concentrations while decreasing at 6×. For P. kessleri GEEL-02, the properties of biodiesel including the degree of unsaturation (UD) and cetane value (CN) increased at 2×, 4×, and 6× as compared to the control. Thus, this study demonstrated that the three microalgae (particularly P. kessleri GEEL-02) are more suitable for nutrient and HMs removal coupled with biomass/biodiesel production.

3-Acetyl-11-keto-ß-boswellic Acid-Based Hybrids Alleviate Acetaminophen-Induced Hepatotoxicity in HepG2 by the Regulation of Inflammatory and Oxidative Stress Pathways: An Integrated Approach.

In an effort to develop new compounds for managing drug-induced liver injury, we prepared 23 novel hybrids based on 3-acetyl-11-keto-ß-boswellic acid (AKBA) using various biocompatible linkers. A bioguided approach was employed to identify the most promising hybrid. Eight compounds exhibited superior anti-inflammatory activity compared to the parent compound. Two of these hybrids (5b and 18) were able to reduce gene expression of TNF-α in LPS-induced inflammation in RAW 264.7 cells, similar to dexamethasone. Subsequently, the hepatoprotective potential of these hybrids was evaluated against acetaminophen (APAP) toxicity in HepG2 cells at doses of 1 and 10 µM. Both hybrids effectively restored cytokine levels, which had been elevated by APAP, to normal levels. Furthermore, they normalized depleted superoxide dismutase and reduced glutathione levels while significantly reducing malondialdehyde (MDA) levels. Network pharmacology analysis suggested that AKBA-based hybrids exert their action by regulating PI3K and EGFR pathways, activating anti-inflammatory mechanisms, and initiating tissue repair and regeneration. Molecular docking studies provided insights into the interaction of the hybrids with PI3K. Additionally, the hybrids demonstrated good stability at different pH levels, following first-order kinetics, with relatively long half-lives, suggesting potential for absorption into circulation without significant degradation.

Theophylline-based hybrids as acetylcholinesterase inhibitors endowed with anti-inflammatory activity: synthesis, bioevaluation, in silico and preliminary kinetic studies.

In this study, we investigated the conjugation of theophylline with different compounds of natural origin hoping to construct new hybrids with dual activity against cholinergic and inflammatory pathways as potential agents for the treatment of Alzheimer's disease (AD). Out of 28 tested hybrids, two hybrids, acefylline-eugenol 6d and acefylline-isatin 19, were able to inhibit acetylcholinesterase (AChE) at low micromolar concentration displaying IC50 values of 1.8 and 3.3 µM, respectively, when compared to the galantamine standard AChE inhibitor. Moreover, the prepared hybrids exhibited a significant anti-inflammatory effect against lipopolysaccharide induced inflammation in RAW 264.7 and reduced nitric oxide (NO), tumor necrosis alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) levels in a dose dependent manner. These hybrids demonstrated significant reductions in nitric oxide (NO), tumor necrosis alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) levels in RAW 264.7 cells induced by lipopolysaccharide (LPS). The findings of this study were further explained in light of network pharmacology analysis which suggested that AChE and nitric oxide synthase were the main targets of the most active compounds. Molecular docking studies revealed their ability to bind to the heme binding site of nitric oxide synthase 3 (NOS-3) and effectively occupy the active site of AChE, interacting with both the peripheral aromatic subsite and catalytic triad. Finally, the compounds demonstrated stability in simulated gastric and intestinal environments, suggesting potential absorption into the bloodstream without significant hydrolysis. These findings highlight the possible therapeutic potential of acefylline-eugenol 6d and acefylline-isatin 19 hybrids in targeting multiple pathological mechanisms involved in AD, offering promising avenues for further development as potential treatments for this devastating disease.

Antibacterial conductive self-healing hydrogel wound dressing with dual dynamic bonds promotes infected wound healing.

In clinical applications, there is a lack of wound dressings that combine efficient resistance to drug-resistant bacteria with good self-healing properties. In this study, a series of adhesive self-healing conductive antibacterial hydrogel dressings based on oxidized sodium alginate-grafted dopamine/carboxymethyl chitosan/Fe3+ (OSD/CMC/Fe hydrogel)/polydopamine-encapsulated poly(thiophene-3-acetic acid) (OSD/CMC/Fe/PA hydrogel) were prepared for the repair of infected wound. The Schiff base and Fe3+ coordination bonds of the hydrogel structure are dynamic bonds that can be repaired automatically after the hydrogel network is disrupted. Macroscopically, the hydrogel exhibits self-healing properties, allowing the hydrogel dressing to adapt to complex wound surfaces. The OSD/CMC/Fe/PA hydrogel showed good conductivity and photothermal antibacterial properties under near-infrared (NIR) light irradiation. In addition, the hydrogels exhibit tunable rheological properties, suitable mechanical properties, antioxidant properties, tissue adhesion properties and hemostatic properties. Furthermore, all hydrogel dressings improved wound healing in the infected full-thickness defect skin wound repair test in mice. The wound size repaired by OSD/CMC/Fe/PA3 hydrogel + NIR was much smaller (12%) than the control group treated with Tegaderm™ film after 14 days. In conclusion, the hydrogels have high antibacterial efficiency, suitable conductivity, great self-healing properties, good biocompatibility, hemostasis and antioxidant properties, making them promising candidates for wound healing dressings for the treatment of infected skin wounds.

Identification of sulphonamide-tethered N-((triazol-4-yl)methyl)isatin derivatives as inhibitors of SARS-CoV-2 main protease.

SARS-CoV-2 pandemic in the end of 2019 led to profound consequences on global health and economy. Till producing successful vaccination strategies, the healthcare sectors suffered from the lack of effective therapeutic agents that could control the spread of infection. Thus, academia and the pharmaceutical sector prioritise SARS-CoV-2 antiviral drug discovery. Here, we exploited previous reports highlighting the anti-SARS-CoV-2 activities of isatin-based molecules to develop novel triazolo-isatins for inhibiting main protease (Mpro) of the virus, a crucial enzyme for its replication in the host cells. Particularly, sulphonamide 6b showed promising inhibitory activity with an IC50= 0.249 µM. Additionally, 6b inhibited viral cell proliferation with an IC50 of 4.33 µg/ml, and was non-toxic to VERO-E6 cells (CC50 = 564.74 µg/ml) displaying a selectivity index of 130.4. In silico analysis of 6b disclosed its ability to interact with key residues in the enzyme active site, supporting the obtained in vitro findings.

Low Overpotential Amperometric Sensor Using Yb2O3.CuO@rGO Nanocomposite for Sensitive Detection of Ascorbic Acid in Real Samples.

The ultimate objective of this research work is to design a sensitive and selective electrochemical sensor for the efficient detection of ascorbic acid (AA), a vital antioxidant found in blood serum that may serve as a biomarker for oxidative stress. To achieve this, we utilized a novel Yb2O3.CuO@rGO nanocomposite (NC) as the active material to modify the glassy carbon working electrode (GCE). The structural properties and morphological characteristics of the Yb2O3.CuO@rGO NC were investigated using various techniques to ensure their suitability for the sensor. The resulting sensor electrode was able to detect a broad range of AA concentrations (0.5-1571 µM) in neutral phosphate buffer solution, with a high sensitivity of 0.4341 µAµM-1cm-2 and a reasonable detection limit of 0.062 µM. The sensor's great sensitivity and selectivity allowed it to accurately determine the levels of AA in human blood serum and commercial vitamin C tablets. It demonstrated high levels of reproducibility, repeatability, and stability, making it a reliable and robust sensor for the measurement of AA at low overpotential. Overall, the Yb2O3.CuO@rGO/GCE sensor showed great potential in detecting AA from real samples.

Microbial Transformation of the Sesquiterpene Lactone, Vulgarin, by Aspergillus niger.

The biotransformation of vulgarin (1), an eudesmanolides-type sesquiterpene lactone obtained from Artemisia judaica, by the microorganism, Aspergillus niger, was carried out to give three more polar metabolites; 1-epi-tetrahydrovulgarin (1α,4α-dihydroxy-5αH,6,11ßH-eudesman-6,12-olide (2), 20% yield, 1α,4α-dihydroxyeudesm-2-en-5αH,6,11ßH-6,12-olide (3a), 10% yield, and C-1 epimeric mixture (3a, b), 4% yield, in a ratio of 4:1, 3a/3b. The structures of vulgarin and its metabolites were elucidated by 1 and 2D NMR spectroscopy in conjunction with HRESIMS. Metabolites (3a) and (3b) are epimers, and they are reported here for the first time as new metabolites obtained by biotransformation by selective reduction at C-1. Vulgarin and its metabolites were evaluated as anti-inflammatory agents using the human cyclooxygenase (COX) inhibitory assay. The obtained data showed that (1) exhibited a good preferential inhibitory activity towards COX-2 (IC50 = 07.21 ± 0.10) and had a moderate effect on COX-1 (IC50 = 11.32 ± 0.24). Meanwhile, its metabolite (3a) retained a selective inhibitory activity against COX-1 (IC50 = 15.70 ± 0.51). In conclusion, the results of this study revealed the necessity of the presence α, ß unsaturated carbonyl group in (1) for better COX-2 inhibitory activity. On the other hand, the selectivity of (1) as COX-1 inhibitor may be enhanced via the reduction of C-1 carbonyl group.

Nano-Silica Bubbled Structure Based Durable and Flexible Superhydrophobic Electrospun Nanofibrous Membrane for Extensive Functional Applications.

Nanoscale surface roughness has conventionally been induced by using complicated approaches; however, the homogeneity of superhydrophobic surface and hazardous pollutants continue to have existing challenges that require a solution. As a prospective solution, a novel bubbled-structured silica nanoparticle (SiO2) decorated electrospun polyurethane (PU) nanofibrous membrane (SiO2@PU-NFs) was prepared through a synchronized electrospinning and electrospraying process. The SiO2@PU-NFs nanofibrous membrane exhibited a nanoscale hierarchical surface roughness, attributed to excellent superhydrophobicity. The SiO2@PU-NFs membrane had an optimized fiber diameter of 394 ± 105 nm and was fabricated with a 25 kV applied voltage, 18% PU concentration, 20 cm spinning distance, and 6% SiO2 nanoparticles. The resulting membrane exhibited a water contact angle of 155.23°. Moreover, the developed membrane attributed excellent mechanical properties (14.22 MPa tensile modulus, 134.5% elongation, and 57.12 kPa hydrostatic pressure). The composite nanofibrous membrane also offered good breathability characteristics (with an air permeability of 70.63 mm/s and a water vapor permeability of 4167 g/m2/day). In addition, the proposed composite nanofibrous membrane showed a significant water/oil separation efficiency of 99.98, 99.97, and 99.98% against the water/xylene, water/n-hexane, and water/toluene mixers. When exposed to severe mechanical stresses and chemicals, the composite nanofibrous membrane sustained its superhydrophobic quality (WCA greater than 155.23°) up to 50 abrasion, bending, and stretching cycles. Consequently, this composite structure could be a good alternative for various functional applications.

Non-Infectious Complications in B-Lymphopenic Common Variable Immunodeficiency.

BACKGROUND AND OBJECTIVE: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, non-infectious complications are also a major challenge among CVID patients. METHODS: All registered CVID patients in the national database were included in this retrospective cohort study. Patients were divided into two groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, non-infectious organ involvements, autoimmunity, and lymphoproliferative diseases were evaluated. RESULTS: Among 387 enrolled patients, 66.4% were diagnosed with non-infectious complications; however, 33.6% had only infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly higher among patients with B-cell lymphopenia. Among organ involvement, dermatologic, endocrine and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher compared to other types of autoimmunity independent from the B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were slightly introduced as the most common type of malignancy. Meanwhile, the mortality rate was 24.5%, and respiratory failure and malignancies were reported as the most common cause of death in our patients without significant differences between the two groups. CONCLUSION: Considering that some of the non-infectious complications might be associated with B-cell lymphopenia, therefore, regular patient monitoring and follow-up along with proper medications (besides immunoglobulins replacement therapy) are highly recommended to prevent further sequels and increase the patients' quality of life.

Genome-wide contributions of the MutSα- and MutSß-dependent DNA mismatch repair pathways to the maintenance of genetic stability in Saccharomyces cerevisiae.

The DNA mismatch repair (MMR) system is a major DNA repair system that suppresses both inherited and sporadic cancers in humans. In eukaryotes, the MutSα-dependent and MutSß-dependent MMR pathways correct DNA polymerase errors. Here, we investigated these two pathways on a whole genome level in Saccharomyces cerevisiae. We found that inactivation of MutSα-dependent MMR increases the genome-wide mutation rate by ∼17-fold and loss of MutSß-dependent MMR elevates the genome-wide mutation rate by ∼4-fold. We also found that MutSα-dependent MMR does not show a preference for protecting coding or noncoding DNA from mutations, whereas MutSß-dependent MMR preferentially protects noncoding DNA from mutations. The most frequent mutations in the msh6Δ strain are C>T transitions, whereas 1- to 6-bp deletions are the most common genetic alterations in the msh3Δ strain. Strikingly, MutSα-dependent MMR is more important than MutSß-dependent MMR for protection from 1-bp insertions, while MutSß-dependent MMR has a more critical role in the defense against 1-bp deletions and 2- to 6-bp indels. We also determined that a mutational signature of yeast MSH6 loss is similar to mutational signatures of human MMR deficiency. Furthermore, our analysis showed that compared to other 5'-NCN-3' trinucleotides, 5'-GCA-3' trinucleotides are at the highest risk of accumulating C>T transitions at the central position in the msh6Δ cells and that the presence of a G/A base at the -1 position is important for the efficient MutSα-dependent suppression of C>T transitions. Our results highlight key differences between the roles of the MutSα-dependent and MutSß-dependent MMR pathways.