Congenital heart disease (CHD) affects almost one percent of all live births. Despite diagnostic and surgical reparative advances, the causes and mechanisms of CHD are still primarily unknown. The extracellular matrix plays a large role in cell communication, function, and differentiation, and therefore likely plays a role in disease development and pathophysiology. Cell adhesion and gap junction proteins, such as integrins and connexins, are also essential to cellular communication and behavior, and could interact directly (integrins) or indirectly (connexins) with the extracellular matrix. In this work, we explore disparities in the expression and spatial patterning of extracellular matrix, adhesion, and gap junction proteins between wild type and Nkx2-5 +/R52G mutant mice. Decellularization and proteomic analysis, Western blotting, histology, immunostaining, and mechanical assessment of embryonic and neonatal wild type and Nkx2-5 mutant mouse hearts were performed. An increased abundance of collagen IV, fibronectin, and integrin β-1 was found in Nkx2-5 mutant neonatal mouse hearts, as well as increased expression of connexin 43 in embryonic mutant hearts. Furthermore, a ventricular noncompaction phenotype was observed in both embryonic and neonatal mutant hearts, as well as spatial disorganization of ECM proteins collagen IV and laminin in mutant hearts. Characterizing such properties in a mutant mouse model provides valuable information that can be applied to better understanding the mechanisms of congenital heart disease.

Olfactory dysfunction (OD) has been reported in coronavirus disease 2019 (COVID-19). However, there are knowledge gaps about the severity, prevalence, etiology, and duration of OD in COVID-19 patients.

The immune regulation of cancer growth and regression has been underscored by the recent success of immunotherapy. The possibility that immune microenvironmental factors may impact on clinical outcome and treatment response still requires intense investigations. Hereby, supporting data of the research article "Integrated CT Imaging and Tissue Immune Features Disclose a Radio-Immune Signature with High Prognostic Impact on Surgically Resected NSCLC" [1], are presented. With the ultimate aim to provide non-invasive prognostic scores, we report on our approach to correlate different Tumor Immune Microenvironment (TIME) profiles with CT imaging-derived qualitative (semantic, CT-SFs) and quantitative (radiomic, CT-RFs) features in a cohort of 60 surgically resected NSCLC. The renowned characterization of TIME, essentially based on the score evaluation of Programme Death Ligand-1 (PD-L1) and Tumor Infiltrating Lymphocytes (TILs), was implemented here by the assessment of effector and suppressor phenotypes including the analysis of Programme Death receptor 1 (PD-1). Thus, we defined two main TIME categories: hot inflamed (PD-L1high, CD8/CD3high and PD-1/CD8low) as opposed to cold inactive (PD-L1low, CD8/CD3lowand PD-1/CD8high). Importantly, as reported in the extended publication [1], these distinctive immune contextures identified different prognostic classes and were decoded by radiomics. To corroborate our radiomic approach, a comparative estimation of CT-RFs extracted from 60 NSCLC and 13 non neoplastic tissues was undertaken, documenting high discrimination ability. Moreover, we tested the potential association of qualitative radiologic features with clinico-pathological and TIME parameters. Taken together, our findings suggest that CT-SFs and CT-RFs may underlay specific patterns of lung cancer.

It has been reported that environmental factors such as hypoxia could contribute to the pathogenesis of Alzheimer's disease (AD). Therapeutics like hyperbaric oxygen treatment, which improves tissue oxygen supply and ameliorates hypoxic conditions in the brain, may be an alternative therapy for AD and amnestic mild cognitive impairment (aMCI). The present work aims to investigate the potential therapeutic effect of hyperbaric oxygen treatment for AD and aMCI.

The frequently used Cox regression applies two critical assumptions, which might not hold for all predictors. In this study, the results from a Cox regression model (CM) and a generalized Cox regression model (GCM) are compared.

Primary graft dysfunction, infections, and acute rejection (AR) worsen lung transplantation (LTx) outcome and patient survival. Despite significant efforts, reliable biomarkers of acute lung allograft dysfunction are lacking. To address this issue, we profiled the bronchoalveolar lavage (BAL) miRNome in LTx patients.

Human technology is characterized by cumulative cultural knowledge gain, yet researchers have limited knowledge of the mix of copying and innovation that maximizes progress. Here, we analyze a unique large-scale dataset originating from collaborative online programming competitions to investigate, in a setting of real-world complexity, how individual differences in innovation, social-information use, and performance generate technological progress. We find that cumulative knowledge gain is primarily driven by pragmatists, willing to copy, innovate, explore, and take risks flexibly, rather than by pure innovators or habitual copiers. Our study also reveals a key role for prestige in information transfer.

Artificial tongues have been receiving increasing attention for the perception of five basic tastes. However, it is still challenging to fully mimic human tongue-like performance for tastes such as astringency. Mimicking the mechanism of astringency perception on the human tongue, we use a saliva-like chemiresistive ionic hydrogel anchored to a flexible substrate as a soft artificial tongue. When exposed to astringent compounds, hydrophobic aggregates form inside the microporous network and transform it into a micro/nanoporous structure with enhanced ionic conductivity. This unique human tongue-like performance enables tannic acid to be detected over a wide range (0.0005 to 1 wt %) with high sensitivity (0.292 wt %-1) and fast response time (~10 s). As a proof of concept, our sensor can detect the degree of astringency in beverages and fruits using a simple wipe-and-detection method, making a powerful platform for future applications involving humanoid robots and taste monitoring devices.

The huntingtin gene (HTT) pathogenic cytosine-adenine-guanine (CAG) repeat expansion responsible for Huntington disease (HD) is phased with single nucleotide polymorphisms (SNPs), providing targets for allele-selective treatments.

The presented analysis of multisite, multiplatform clinical oncology trial data sought to enhance quantitative utility of the apparent diffusion coefficient (ADC) metric, derived from diffusion-weighted magnetic resonance imaging, by reducing technical interplatform variability owing to systematic gradient nonlinearity (GNL). This study tested the feasibility and effectiveness of a retrospective GNL correction (GNC) implementation for quantitative quality control phantom data, as well as in a representative subset of 60 subjects from the ACRIN 6698 breast cancer therapy response trial who were scanned on 6 different gradient systems. The GNL ADC correction based on a previously developed formalism was applied to trace-DWI using system-specific gradient-channel fields derived from vendor-provided spherical harmonic tables. For quantitative DWI phantom images acquired in typical breast imaging positions, the GNC improved interplatform accuracy from a median of 6% down to 0.5% and reproducibility of 11% down to 2.5%. Across studied trial subjects, GNC increased low ADC (<1 µm2/ms) tumor volume by 16% and histogram percentiles by 5%-8%, uniformly shifting percentile-dependent ADC thresholds by ∼0.06 µm2/ms. This feasibility study lays the grounds for retrospective GNC implementation in multiplatform clinical imaging trials to improve accuracy and reproducibility of ADC metrics used for breast cancer treatment response prediction.

Scarcity in studies defining the precise three-dimensional structure of approved drugs has led to an abandoning of their use for other therapeutic indications. In this manuscript, we solely focus on studying computationally the anticancer drug "Nocodazole" as a model compound for anthelmintic drugs -due to structural similarity- proven to exert anticancer activity such as Mebendazole and Albendazole. Computations on Nocodazole structures deposited in the Protein Data Bank (PDB) revealed possible existence of at least 6 conformers of Nocodazole. By combining the reported experimental UV-Vis data with our calculations, two conformers were assigned as the predominant structures of Nocodazole. In addition, td-DFT calculations revealed that the conformational flexibility of Nocodazole results in significant changes in atomic and molecular charge densities. The results have ramifications in identification of possible conformers of carbendazim-based drugs for repurposing in oncology through giving deep insights in understanding the spatial and electronic changes upon drug binding to anticancer targets.

Rice bran arabinoxylan compound (RBAC) is a nutraceutical for enhancing a depleted immune system during and after cancer treatment. This pilot feasibility trial aims to evaluate the effects of RBAC on cancer patients' quality of life during active treatment, compared to placebo, using a validated questionnaire. Other outcome measures include changes in inflammatory and nutritional status, cytokine profile, and gut microbiota.

About 21.4% of India's population uses smokeless tobacco products (SLT), yet limited data are available on their microbial contamination. To understand the potential microbiological risks associated with SLT use, the present study aims to investigate bacterial contamination of tobacco and the types of microbes that could be cultured from SLT products.

Antibacterial resistance remains a major global problem due to frequent prescriptions, leading to significant toxicities. To overcome the limitations of antibiotic therapy, it is highly desirable to provide site-specific delivery of drugs with controlled release. Inspired by the biocompatible, biodegradable, and site-specific mimicking behavior of poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL), we developed vancomycin-PEG-PCL-PEG conjugates to maximize the pharmacological effects and minimize the side effects. Drug-loaded vancomycin-PEG-PCL-PEG conjugates are influenced by size, shape, surface area, encapsulation efficiency, in vitro drug release, hemolysis assay, cytotoxicity, and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and bacterial kill kinetics. The results demonstrated that vancomycin (VCM) release from PEG-PCL-PEG triblock revealed a biphasic manner. Hemolysis assay showed the nonprescription nature of VCM-PEG-PCL-PEG. Cytotoxicity studies confirmed the biocompatibility of VCM-PEG-PCL-PEG. The in vitro antibacterial results showed enhance activity with minimum inhibitory concentration compared to bare VCM. Molecular dynamics simulation study revealed that binding between VCM and PEG-PCL-PEG by hydrophobic interactions offers molecular encapsulation and steric barrier to drug degradation. This newly developed therapeutic delivery system can offer to enhance activity and delivery VCM against MRSA.

Silver nanoparticles (AgNPs) are the most used nanomaterials worldwide due to their excellent antibacterial, antiviral, and antitumor activities, among others. However, there is scarce information regarding their genotoxic potential measured using human peripheral blood lymphocytes. In this work, we present the cytotoxic and genotoxic behavior of two commercially available poly(vinylpyrrolidone)-coated silver nanoparticle (PVP-AgNPs) formulations that can be identified as noncytotoxic and nongenotoxic by just evaluating micronuclei (MNi) induction and the mitotic index, but present enormous differences when other parameters such as cytostasis, apoptosis, necrosis, and nuclear damage (nuclear buds (NBUDs) and nucleoplasmic bridges (NPBs)) are analyzed. The results show that Argovit (35 nm PVP-AgNPs) and nanoComposix (50 nm PVP-AgNPs), at concentrations from 0.012 to 12 μg/mL, produce no changes in the nuclear division index (NDI) or micronuclei (MNi) frequency compared with the values found on control cultures of human blood peripheral lymphocytes from a healthy donor. Still, 50 nm PVP-AgNPs significantly decrease the replication index and significantly increase cytostasis, apoptosis, necrosis, and the frequencies of nuclear buds (NBUDs) and nucleoplasmic bridges (NPBs). These results provide evidence that the cytokinesis-block micronucleus (CBMN) assay using human lymphocytes and evaluating the eight parameters provided by the technique is a sensitive, fast, accurate, and inexpensive detection tool to support or discard AgNPs or other nanomaterials, which is worthwhile for continued testing of their effectiveness and toxicity for biomedical applications. In addition, it provides very important information about the role played by the [coating agent]/[metal] ratio in the design of nanomaterials that could reduce adverse effects as much as possible while retaining their therapeutic capabilities.

The conventional use of antibiotics for the treatment of infectious keratitis currently faces two major challenges: poor drug penetration and the emergence of antibiotic resistance in microbial strains. Cell-penetrating peptides (CPPs) with antimicrobial properties have the potential to address these challenges. However, their mode of action, mechanism of uptake, and interaction potential have not been explored in detail. In this study, we probed the mechanism of uptake and interaction potential of our previously designed peptides (VRF005 and VRF007). Our results showed that VRF005 undergoes direct translocation and induces a rough membrane surface, whereas VRF007 undergoes clathrin-mediated endocytic uptake. The gel shift assay showed that VRF005 is bound to genomic DNA, whereas VRF007 is bound to chitin and β-d-glucan. Gene expression studies revealed the effect of peptide VRF005 on Candida albicans transcription. Molecular docking and simulations showed that VRF005 forms noncovalent interactions (such as H-bonding and water bridges) with natamycin. It exhibited synergistic antifungal activity in the colony-forming assay. VRF005, functionalized in the polycaprolactone fiber matrix, showed sustained delivery and antifungal activity.

Regulating the states of hydrogen bonds in ionic liquids (ILs) is an effective way to improve their catalytic performance. In this paper, disulfonic-functionalized acidic ionic liquids (DSFAILs) were synthesized successfully, including novel SO3H-functionalized binuclear IL (bis[3-(CH2)3SO3H-1-(CH2)2-Im][HSO4]2). For the biodiesel synthesis, compared with the traditional ILs catalysts, DSFAILs bis[(3-(CH2)3SO3H-1-(CH2)2-Im][HSO4]2, [Im(N (CH2)3SO3H)2][HSO4]) had higher catalytic activity even under mild reaction conditions. Using the density functional theory (DFT) method, the role of hydrogen bonds in different SO3H-functionalized acidic ionic liquids (SFAILs) was explored. The forms of hydrogen bonds existing in different ILs directly determine their acidity. It suggested that the forming status of the active sites (hydrogen bonds) were diverse in different SFAILs. Also, deep ionization of the hydrogen atoms from the cation-anion strong interaction could increase the acidity and catalytic performance of SFAILs. From this, the structure-activity relationship between the SFAILs structures and the catalytic activity of methyl oleate synthesis was proposed. Besides, the experimental results also showed that bis[3-(CH2)3SO3H-1-(CH2)2-Im][HSO4]2 catalyst had a high catalytic activity to obtain methyl oleate and the catalyst could be separated easily owing to its larger molecular weight. However, [Im(N(CH2)3SO3H)2][HSO4] had a stronger acidity and a lower steric hindrance and thus a higher catalytic activity and was the optimal catalyst for the methyl oleate synthesis. In the presence of a small amount of catalyst (6 wt %) and at low reaction temperature (353 K), the methyl oleate yield could reach up to 93%. After six recycles of the catalyst, the methyl oleate yield remained at 90%.

Direct visualization of soft organic molecules like cellulose is extremely challenging under a high-energy electron beam. Herein, we adopt two ionization damage extenuation strategies to visualize the lattice arrangements of the β-(1→4)-d-glucan chains in carboxylated nanocellulose fibers (C-NCFs) having cellulose II crystalline phase using high-resolution transmission electron microscopy. Direct imaging of individual nanocellulose fibrils with high-resolution and least damage under high-energy electron beam is achieved by employing reduced graphene oxide, a conducting material with high electron transmittance and Ag+ ions, with high electron density, eliminating the use of sample-specific, toxic staining agents, or other advanced add-on techniques. Furthermore, the imaging of cellulose lattices in a C-NCF/TiO2 nanohybrid system is accomplished in the presence of Ag+ ions in a medium revealing the mode of association of C-NCFs in the system, which validates the feasibility of the presented strategy. The methods adopted here can provide further understanding of the fine structures of carboxylated nanocellulose fibrils for studying their structure-property relationship for various applications.

Efforts to enhance the transformative potential of biofuels is an important step to achieving an environment-friendly and sustainable energy source. Fremyella diplosiphon is an ideal third-generation biofuel agent due to its ability to produce lipids and desirable essential fatty acids. In this study, the impact of Nanofer 25s nanoscale zero-valent iron nanoparticles (nZVIs) on total lipid content and fatty acid composition of F. diplosiphon strains SF33 and B481 was investigated. We observed significant increases (P < 0.05) in the growth of F. diplosiphon treated with 0.2-1.6 mg L-1 Nanofer 25s, indicating that trace concentrations of nZVIs were not toxic to the organism. Chlorophyll a, carotenoids, and phycobiliprotein levels were not altered in F. diplosiphon treated with nZVIs ranging from 0.4 to 1.6 mg L-1, confirming that these concentrations did not negatively impact photosynthetic efficacy. In addition, Nanofer 25s ranging from 0.2 to 1.6 mg L-1 had an optimal impact on SF33 and B481 total lipid content. We identified significant increases in unsaturated fatty acid methyl esters (FAMEs) from F. diplosiphon Nanofer 25s-treated transesterified lipids. Theoretical chemical and physical biofuel properties revealed a product with elevated cetane number and oxidative stability for both strains. Scanning electron microscopy and energy-dispersive X-ray spectroscopy validated the localization of nZVIs. Our findings indicate that Nanofer 25s nZVIs significantly enhance F. diplosiphon total lipid content and essential FAMEs, thus offering a promising approach to augment the potential of the cyanobacterium as a large-scale biofuel agent.

This study aims to investigate how the morphology of cellulose influences the hydrolysis and carbonization during hydrothermal treatment at temperatures between 180 and 240 °C. The morphology of cellulose, especially different crystallinities and degrees of polymerization, is represented by microcrystalline cellulose and α-cellulose. Kinetic analysis is considered a tool to allow the determination of the mechanisms of the two types of cellulose during the hydrothermal process. A kinetic model, in which cellulose is assumed to be hydrolyzed to a limited extent, is proposed. Five scenarios are used as models for pyrolysis of nonhydrolyzed cellulose that forms primary char, along with reaction pathways of hydrolyzable cellulose and its derivatives that latterly form secondary char. The morphologies of solid products are in good agreement with the results of the proposed model.