Targeting Myeloid Differentiation Primary Response Protein 88 (MyD88) and Galectin-3 to Develop Broad-Spectrum Host-Mediated Therapeutics against SARS-CoV-2.

Nearly six million people worldwide have died from the coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although COVID-19 vaccines are largely successful in reducing the severity of the disease and deaths, the decline in vaccine-induced immunity over time and the continuing emergence of new viral variants or mutations underscore the need for an alternative strategy for developing broad-spectrum host-mediated therapeutics against SARS-CoV-2. A key feature of severe COVID-19 is dysregulated innate immune signaling, culminating in a high expression of numerous pro-inflammatory cytokines and chemokines and a lack of antiviral interferons (IFNs), particularly type I (alpha and beta) and type III (lambda). As a natural host defense, the myeloid differentiation primary response protein, MyD88, plays pivotal roles in innate and acquired immune responses via the signal transduction pathways of Toll-like receptors (TLRs), a type of pathogen recognition receptors (PRRs). However, recent studies have highlighted that infection with viruses upregulates MyD88 expression and impairs the host antiviral response by negatively regulating type I IFN. Galectin-3 (Gal3), another key player in viral infections, has been shown to modulate the host immune response by regulating viral entry and activating TLRs, the NLRP3 inflammasome, and NF-κB, resulting in the release of pro-inflammatory cytokines and contributing to the overall inflammatory response, the so-called "cytokine storm". These studies suggest that the specific inhibition of MyD88 and Gal3 could be a promising therapy for COVID-19. This review presents future directions for MyD88- and Gal3-targeted antiviral drug discovery, highlighting the potential to restore host immunity in SARS-CoV-2 infections.

Physiological Mechanisms by Which the Functional Ingredients in Beer Impact Human Health.

Nutritional therapy, for example through beer, is the best solution to human chronic diseases. In this article, we demonstrate the physiological mechanisms of the functional ingredients in beer with health-promoting effects, based on the PubMed, Google, CNKI, and ISI Web of Science databases, published from 1997 to 2024. Beer, a complex of barley malt and hops, is rich in functional ingredients. The health effects of beer against 26 chronic diseases are highly similar to those of barley due to the physiological mechanisms of polyphenols (phenolic acids, flavonoids), melatonin, minerals, bitter acids, vitamins, and peptides. Functional beer with low purine and high active ingredients made from pure barley malt, as well as an additional functional food, represents an important development direction, specifically, ginger beer, ginseng beer, and coix-lily beer, as consumed by our ancestors ca. 9000 years ago. Low-purine beer can be produced via enzymatic and biological degradation and adsorption of purines, as well as dandelion addition. Therefore, this review paper not only reveals the physiological mechanisms of beer in overcoming chronic human diseases, but also provides a scientific basis for the development of functional beer with health-promoting effects.

Investigating the confinement effects on masonry behavior based on friction interface.

As a material masonry is anisotropic in nature as it is constituted of various components that differ each other in many ways. Though, the ideas of modeling of concrete are also valid for masonry, still there are difficulties in determining the exact behavior of masonry. The micro modeling (simplified) approach has been adopted in this study for modeling masonry samples subjected to various nature of loadings. The brick masonry units were modeled as discrete elements and linked together by interface element. The coulomb friction model was used to describe the interface element as mortar joint. Damage was assumed to be governed by the compressive strength of both the constituents i.e., mortar and brick. The mechanical properties of the masonry samples were determined by means of variety of tests and those properties then served as input parameters in the constitutive model. The results clearly indicate that numerical model predicted the behavior of the experimentally tested samples, in compression as well as tension prims for both unconfined and confined cases. The proposed model is suitable for modeling any type of brick masonry walls.

Design and analysis of virtual impedance control scheme based on MESOGI for improving harmonic sharing of nonlinear loads.

Under the presence of nonlinear load, the most existing virtual impedance (VI) methods-based control solution performs poorly in reactive power sharing among droop-operated VSIs in microgrids (MGs). This may be due to the involved estimation techniques for extracting the current harmonics at selected frequencies, which suffer from either poor accuracy of the harmonic estimation and/or the effect of DC offset in the measurements. Such an issue may affect the performance of the virtual impedance control, hence, the system stability. To bridge this gap, the implementation of the virtual impedance based on multiple enhanced second-order generalized integrator (MESOGI) suitable for harmonics and DC-offset estimation/rejection, is proposed in this paper. The MESOGI can offer an accurate estimation of the current quadrature components free from DC offset at selected frequencies, required to implement the virtual impedance control. Therefore, it makes the designed virtual impedance-based control scheme robust to voltage distortions, immune to DC disturbance, and capable of sharing properly the power harmonics. As a result, this may contribute to improving the reactive and harmonic power-sharing between droop-controlled VSIs within an islanded MG. The modeling of the MESOGI scheme and its performance investigation is carried out. In addition, the mathematical model of the implemented virtual impedance is derived. Further, analysis based on the obtained model of the equivalent output impedance including virtual impedance is established to study its effect. Simulation and experimental tests are performed to prove the effectiveness of the control proposal in improving the reactive power sharing under nonlinear load operating conditions.

Correction: Synthesis of CuSe/PVP/GO and CuSe/MWCNTs for their applications as nonenzymatic electrochemical glucose biosensors.

[This corrects the article DOI: 10.1039/D3RA06713K.].

Synthesis of CuSe/PVP/GO and CuSe/MWCNTs for their applications as nonenzymatic electrochemical glucose biosensors.

Copper selenide (CuSe) is an inorganic binary compound which exhibits metallic behavior with zero band gap. CuSe has multiple applications in electrocatalysis, photothermal therapy, flexible electronic and solar cells. In the current study, copper selenide based nanocomposites CuSe/PVP/GO and CuSe/MWCNTs were synthesized by using the sol-gel method for application as a non-enzymatic glucose biosensor. Different characterization methods were employed, such as X-ray diffraction (XRD), photoluminescence (PL), Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible (UV-Vis) spectroscopy, and photoluminescence for determining various aspects of CuSe/PVP/GO and CuSe/MWCNTs nanocomposites including phase formation, functional group analysis, band gaps and morphology. Electrochemical impedance spectroscopy (EIS) showed that the resistances of modified electrode/bare electrode were 12.3 kΩ/17.3 kΩ and 6.3 kΩ/17.3 kΩ for CuSe/PVP/GO and CuSe/MWCNTs nanocomposites, respectively. Cyclic voltammetry showed that both CuSe/PVP/GO and CuSe/MWCNTs nanocomposites are promising biosensors for detection and monitoring of the glucose level in an analyte. The sensitivity and limit of detection are 2328 µA mM-1 cm-2/0.2 µM and 4157 µA mM-1 cm-2/0.3 µM for CuSe/PVP/GO and CuSe/MWCNTs, respectively. Chronoamperometry confirmed that our nanocomposite was the best sensor for glucose even in the presence of other interferents like ascorbic acid (AA), uric acid (UA) and dopamine (DA).

Unveiling Oxidative Stress-Induced Genotoxicity and Its Alleviation through Selenium and Vitamin E Therapy in Naturally Infected Cattle with Lumpy Skin Disease.

Lumpy skin disease (LSD) is a contagious infection of cattle caused by a virus of the Poxviridae family, genus Capripoxvirus. In Pakistan, recent outbreaks have resulted in significant nationwide mortality and economic losses. A 20-day prospective cohort study was performed on sixty infected cattle with the aim to evaluate LSD-induced oxidative stress's genotoxic role and to determine the ameliorative effect of antioxidant therapy using principal component analysis (PCA) and a multivariable ordinal logistic regression model. LSDV was identified from scab samples and nodular lesions using RPO30-specific gene primers. The infected cattle were divided into control and treated groups. The animals were observed initially and finally on day 20 to evaluate the homeostatic, oxidative, and genotoxic changes. The animals in the treated group were administered a combination of selenium (Se) and vitamin E at the standard dose rate for five consecutive days. A substantial (p < 0.05) improvement in the hematological indices was observed in the treated group. The treated group also showed a significant (p < 0.05) reduction in levels of serum nitric oxide (NO) and malondialdehyde (MDA) post-therapy. The PCA at the final sampling data of the treated group showed that Principal Component (PC1 eigenvalue 1.429) was influenced by superoxide dismutase (SOD; 0.3632), catalase (CAT; 0.2906), and glutathione (GSH; 0.0816) and PC2 (eigenvalue 1.200) was influenced by CAT (0.4362), MDA (0.2056), and NO (0.0693). A significant correlation between serum NO (76%) and MDA levels (80%) was observed with genetic damage index (GDI) scores. The ordinal logistic regression model regarding the use of antioxidant therapy revealed 73.95-times (95%CI; 17.36-314.96) improvement in the GDI in treated animals. The multivariable ordinal logistic regression showed that each unit increase in NO and MDA resulted in a 13% increase in genotoxicity in infected individuals. In conclusion, our study revealed that LSD-induced oxidative stress and lipid peroxidation product causes genotoxicity in affected animals. Furthermore, the combined Se and vitamin E therapy significantly alleviated oxidative stress and genotoxicity in LSD-affected cattle.

Patterns of Common Dermatological Conditions among Children and Adolescents in Pakistan.

Background and Objectives: Dermatological disorders are highly prevalent among children in Pakistan. The present cross-sectional study aims to identify the spectrum of dermatological conditions among children and adolescents in Pakistan. Materials and Methods: A total of 582 patients (50.9% males; 49.1% females) were included in the study based on their age (5.7 ± 4.1 years), dermatological condition, and epidemiology. The youngest patient was aged ten days, whereas the eldest was seventeen. Age criteria were further stratified into three categories: infants and toddlers (≤5 years), children (≥5 to <12 years), and adolescents (≥12 to <18 years). Amongst them, the majority was from Punjab (81.6%), while the other regions included were Azad Jammu and Kashmir (14.4%), Islamabad (3.3%), and Khyber Pakhtunkhwa (0.7%). Results: Scabies was the highest reported skin condition with 281 (45.55%) patients, followed by 114 (19.6%) with eczema, 60 (10.3%) with dermatitis, 33 (5.7%) with tinea capitis, 17 (2.9%) with tinea corporis, 16 (2.7%) with impetigo, and 15 (2.6%) with folliculitis. Other conditions include urticaria, burns, infections, pediculosis, tinea inguinalis, tinea faciei, nappy rashes, alopecia, warts, tinea incognito, tinea cruris, and acne vulgaris. The chi-squared test showed a high prevalence of tinea corporis and acne among adolescents (12-17 years), whereas eczema, dermatitis, and impetigo were more prevalent among infants and toddlers. Conclusions: Pets or livestock and poor hygiene were found to be highly reported risk factors for many dermatological conditions like scabies and fungal infections. Dermatological conditions are common in younger individuals, but unfortunately, many children do not receive the desired medical assistance.

Facile synthesis of a CuSe/PVP nanocomposite for ultrasensitive non-enzymatic glucose biosensing.

Non-enzymatic glucose biosensors show high sensitivity, lower response time, wide linear range and low cost. Copper based composites show excellent electrocatalytic tunability and lead to a better charge transfer in electrochemical non-enzymatic glucose biosensors. In this work, a nanocomposite of polyvinylpyrrolidone (PVP) and copper selenide was synthesized by a facile one pot sol gel method. Synthesized nanomaterials were characterized by XRD, FTIR, UV-visible spectroscopy, SEM, EDS and XPS techniques. Electrochemical behavior was analyzed by cyclic voltammetry (CV), electrochemical impendence (EIS) and chronoamperometry techniques. XRD analysis revealed a hexagonal structure and crystalline nature of CuSe/PVP. FTIR spectra depicted C-N bonding at 1284 cm-1 and C[double bond, length as m-dash]O stretching at 1634 cm-1, which indicated the presence of PVP in the nanocomposite. Stretching at 823 cm-1 was attributed to the presence of copper selenide. UV-visible absorption indicated the bandgap of copper selenide/PVP at 2.7 eV. SEM analysis revealed a flake like morphology of CuSe/PVP. EDS and XPS analysis confirmed the presence of copper and selenium in the prepared nanocomposite. Prior to employing for biosensing applications, it is important to evaluate the antibacterial activity of nanomaterials for long term use in biological in vitro testing. These materials have shown an efficient inhibition zone of 26 mm against Gram negative Pseudomonas at 50 µg ml-1 and MIC value of 10 µg ml-1. Cyclic voltammetry shows that CuSe/PVP is a promising biosensor for monitoring glucose levels in a wide linear range of 0.5 mM to 3 mM at an excellent sensitivity of 13 450 µA mM-1 cm-2 with an LOD of 0.223 µM. Chronoamperometry measurements revealed a selective behavior of CuSe/PVP for glucose biosensing amongst ascorbic acid and dopamine as common interfering molecules. The nanocomposite was stable after 8 repeated cycles with 92% retention for glucose sensing capacity. This is attributed to the stable nature of the CuSe/PVP nanocomposite as well as higher surface area of available active sites. Herein the CuSe/PVP nanocomposite offered reasonable selectivity, high sensitivity wide linear range with very low LOD, as well as being abundant in nature, this Cu based biosensor has promising applications for future point of care tests (POCT).

Comparing the Positive Impacts and Stress Induction by Polyethylene Glycol (PEG 6000) Variable Levels on Canola (Brassica napus L.) Growth, Yield, and Oil Contents.

Seed quality (i.e., emergence energy, viability, physical purity, size, weight) is a critical factor that influences the yield of crops. Poor seed quality can lead to reduced germination rates, lower plant populations, and, ultimately, lower crop yields. On the other hand, seed priming is suggested to be an effective technique for improving seeds germination and plant population. In this study, we investigated the effect of seed priming with polyethylene glycol (PEG) on the germination, growth, and yield of two varieties of canola, super canola, and sandal canola. The treatment plan includes five concentrations of PEG (i.e., 5, 10, 15, 20%), distilled water priming, and control (no priming). All of the treatments were applied in 3 replications following a completely randomized design. Our results showed that seed priming with 5%PEG (T2) significantly improved radicle length (50 and 36%), plant height (43 and 34%), chlorophyll a (44 and 43%), chlorophyll b (120 and 208%), and total chlorophyll (83 and 111%) compared to control in super canola and sandal canola, respectively. In particular, seed priming with 5%PEG resulted in the highest increase in protein contents (25 and 1.40%), oleic acid (26 and 40%), and linolenic acid (6 and 6%) compared to control in super canola and sandal canola, respectively. It is concluded that seed priming with 5%PEG is an effective treatment to improve the performance of canola crops in terms of seedling growth, yield, chlorophyll, protein, and oil content. More investigations are recommended as future perspectives using other canola varieties to declare 5% PEG as an effective treatment for canola for improvement in growth, oil, protein, and chlorophyll contents.