Extracting lignin from sugarcane bagasse for methylene blue and hexavalent chromium adsorption in textile wastewater: a facile, green, and sustainable approach.

This study presents the process of extracting lignin from sugarcane bagasse collected in the Mekong Delta, Vietnam by the alkali method. NaOH has been used as an effective, environmentally friendly chemical to enhance the extraction process. The obtained lignin was applied for methylene blue (MB) and hexavalent chromium (Cr(vi)) removal. Factors influencing lignin extraction and adsorption processes of MB and Cr(vi) were investigated, showcasing the sustainable reusability of lignin extracted from sugarcane bagasse. Lignin characterization was also carried out by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) techniques. The results showed that the extracted lignin content reached 38.61% under optimal conditions (NaOH concentration of 10%, reaction temperature of 90 °C and reaction time of 90 min). The adsorption efficiency and capacity of lignin reached 90.90% and 9.09 mg g-1 for MB and 80.10% and 28.04 mg g-1 for Cr(vi), respectively, under optimum adsorption conditions (pH, adsorption time, initial methylene blue concentration, and used lignin content). The adsorption process obeyed Langmuir adsorption and was principally physical adsorption. These findings prove sugarcane bagasse based lignin as a cheap and efficient adsorbent for MB and Cr(vi) removal, which contributes to the utilization of the abundant agricultural by-product for wastewater treatment.

Rational design of novel diaryl ether-linked benzimidazole derivatives as potent and selective BACE1 inhibitors.

Due to the large size and high flexibility of the catalytic active site of BACE1 enzyme, the development of nonpeptide inhibitors with optimal pharmacological properties is still highly demanding. In this work, we have discovered 2-aminobenzimidazole-containg ether scaffolds having potent and selective inhibitory potentials against BACE1 enzyme. We have synthesized novel 29 compounds and optimization of aryl linker region resulted in highly potent BACE1 inhibitory activities with EC50 values of 0.05-2.71 µM. The aryloxy-phenyl analogs 20j showed the EC50 value as low as 0.07 µM in the enzyme assay, whereas, the benzyloxyphenyl dervative 24b was comparatively less effective in the enzyme assay. But interestingly the latter was more effective in the cell assay (EC50 value 1.2 µM). While comparing synthesized derivatives in the cell assay using PC12-APPSW cell, compound 27f appeared as the most potent BACE1 inhibitor having EC50 value 0.7 µM. This scaffold also showed high selectivity over BACE2 enzyme and cathepsin D. Furthermore, the research findings were bolstered through the incorporation of molecular docking, molecular dynamics, and DFT studies. We firmly believe that these discoveries will pave the way for the development of a novel class of small-molecule selective BACE1 inhibitors.

ZIKV Inhibitors Based on Pyrazolo[3,4-d]pyridazine-7-one Core: Rational Design, In Vitro Evaluation, and Theoretical Studies.

The Zika virus (ZIKV) is believed to cause birth defects, and no anti-ZIKV drugs have been approved by medical organizations to date. Starting from antimicrobial lead compounds with a pyrazolo[3,4-d]pyridazine-7-one scaffold, we synthesized 16 derivatives and screened their ability to interfere with ZIKV infection utilizing a cell-based phenotypic assay. Of these, five compounds showed significant inhibition of ZIKV with a selective index value greater than 4.6. In particular, compound 9b showed the best anti-ZIKV activity with a selectivity index of 22.4 (half-maximal effective concentration = 25.6 µM and 50% cytotoxic concentration = 572.4 µM). Through the brine shrimp lethality bioassay, 9b, 10b, 12, 17a, and 19a showed median lethal dose values in a range of 87.2-100.3 µg/mL. Compound 9b was also targeted to the NS2B-NS3 protease of ZIKV using molecular docking protocols, in which it acted as a noncompetitive inhibitor and strongly bound to five key amino acids (His51, Asp75, Ser135, Ala132, Tyr161). Utilizing the pharmacophore model of 9b, the top 20 hits were identified as prospective inhibitors of NS2B-NS3 protease, and six of them were confirmed for their stability with the protease via redocking and molecular dynamics simulations.

Anti-multiple myeloma potential of resynthesized belinostat derivatives: an experimental study on cytotoxic activity, drug combination, and docking studies.

Multiple myeloma is a deadly cancer that is a complex and multifactorial disease. In the present study, 12 belinostat derivatives (four resynthesized and eight new), HDAC inhibitors, were resynthesized via either Knoevenagel condensation, or Wittig reaction, or Heck reaction. Then an evaluation of the antiproliferative activities against myeloma cells MOPC-315 was carried out. Amongst them, compound 7f was the most bioactive compound with an IC50 of 0.090 ± 0.016 µM, being 3.5-fold more potent than the reference belinostat (IC50 = 0.318 ± 0.049 µM). Furthermore, we also confirmed the inhibitory activity of 7f in a cellular model. Additionally, we found that the inhibitory activity of 7f against histone deacetylase 6 catalytic activity (HDAC6) is more potent than that of belinostat. Finally, we observed the strong synergistic interaction between the derivative 7f and the proteasome bortezomib inhibitor (CI = 0.26), while belinostat and bortezomib showed synergism with a CI value of 0.36. Taken together, the above results suggest that 7f is a promising HDAC inhibitor deserving further investigation.

Inhibition of α-Glucosidase, Acetylcholinesterase, and Nitric Oxide Production by Phytochemicals Isolated from Millettia speciosa-In Vitro and Molecular Docking Studies.

The phytochemical constituents from the roots of Millettia speciosa were investigated by chromatographic isolation, and their chemical structures were characterized using the MS and NMR spectroscopic methods. A total of 10 compounds, including six triterpenoids, two flavonoids, and two phenolic compounds, were identified from the roots of M. speciosa. Out of the isolated compounds, eight showed inhibitory effects on NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, with IC50 values ranging from 43.9 to 449.5 µg/mL. Ursane-type triterpenes significantly suppressed NO production compared to the remaining compounds. In addition, these compounds also exhibited remarkable inhibitory effects on α-glucosidase. Among the tested compounds, 4, 5, and 10 exhibited excellent α-glucosidase inhibition, with IC50 values ranging from 1.1 to 2.2 µg/mL. Almost all of the test compounds showed little or no acetylcholinesterase inhibition, except for 5, which showed moderate anti-acetylcholinesterase activity in vitro. The molecular docking study of α-glucosidase inhibition by 3-5 and 10 was conducted to observe the interactions of these molecules with the enzyme. Compounds 4, 5, and 10 exhibited a better binding affinity toward the targeted receptor and the H-bond interactions located at the entrance of the enzyme active site pocket in comparison to those of 3 and the positive control acarbose. Our findings evidence the pharmacological potential of this species and suggest that the phytochemicals derived from the roots of M. speciosa may be promising lead molecules for further studies on the development of anti-inflammatory and anti-diabetes drugs.

Longitudinal Monitoring of Biofilm Formation via Robust Surface-Enhanced Raman Scattering Quantification of Pseudomonas aeruginosa-Produced Metabolites.

Detection of bacterial metabolites at low concentrations in fluids with complex background allows for applications ranging from detecting biomarkers of respiratory infections to identifying contaminated medical instruments. Surface-enhanced Raman scattering (SERS) spectroscopy, when utilizing plasmonic nanogaps, has the relatively unique capacity to reach trace molecular detection limits in a label-free format, yet large-area device fabrication incorporating nanogaps with this level of performance has proven difficult. Here, we demonstrate the advantages of using chemical assembly to fabricate SERS surfaces with controlled nanometer gap spacings between plasmonic nanospheres. Control of nanogap spacings via the length of the chemical crosslinker provides uniform SERS signals, exhibiting detection of pyocyanin, a secondary metabolite of Pseudomonas aeruginosa, in aqueous media at concentration of 100 pg·mL-1. When using machine learning algorithms to analyze the SERS data of the conditioned medium from a bacterial culture, having a more complex background, we achieve 1 ng·mL-1 limit of detection of pyocyanin and robust quantification of concentration spanning 5 orders of magnitude. Nanogaps are also incorporated in an in-line microfluidic device, enabling longitudinal monitoring of P. aeruginosa biofilm formation via rapid pyocyanin detection in a medium effluent as early as 3 h after inoculation and quantification in under 9 h. Surface-attached bacteria exposed to a bactericidal antibiotic were differentially less susceptible after 10 h of growth, indicating that these devices may be useful for early intervention of bacterial infections.

The Interferon-Signature of Sjögren's Syndrome: How Unique Biomarkers Can Identify Underlying Inflammatory and Immunopathological Mechanisms of Specific Diseases.

Innate immune responses direct the nature and specificity of downstream adaptive responses in autoimmune diseases. One of the strongest markers of innate immunity is the up-regulated expression of interferon (IFN) and IFN-responsive/stimulated genes (IRGs/ISGs). While multiple IRGs are induced during the innate phase of host responses, transcriptome data suggest unique IRG-signatures for different diseases. Sjögren's syndrome (SjS) is characterized by chronic immune attacks against exocrine glands leading to exocrine dysfunction, plus strong up-regulated expressions of IFN IRG transcripts. Genome-wide transcriptome analyses indicate that differentially expressed IRGs are restricted during disease development and therefore define underlying etiopathological mechanisms. Here we review the innate immune-associated IFN-signature of SjS and show how differential gene expressions of IRG/ISG sets interact molecularly and biologically to identify critical details of SjS etiopathogenesis.

Sjögren's syndrome (SjS)-like disease of mice: the importance of B lymphocytes and autoantibodies.

Sjögren's syndrome (SjS) is a systemic autoimmune disease in which an immunological attack against the salivary and lacrimal glands results, respectively, in severe dry mouth and dry eye diseases. Although a CD4+ T lymphocyte population is an integral component in the pathogenesis of SjS, recent studies have focused on the importance the B lymphocyte plays in both the pre-clinical and clinical phases of the disease process. To understand the molecular and cellular mechanisms involved in SjS, numerous mouse models that mimic major clinical manifestations of the human disease have been developed. Studies have begun to define the genetics, the nature of the autoimmune response towards the salivary and lacrimal glands, as well as the possible mechanisms for effecting glandular dysfunction, thereby establishing insights to new intervention therapies. Not surprising, the B cell is taking center stage. Here, we present an in-depth discussion of how B cell populations may be involved in orchestrating or determining exocrine gland dysfunction.