Preparation and assessment of agar/TEMPO-oxidized bacterial cellulose cryogels for hemostatic applications.

In this work, we have demonstrated agar and oxidized bacterial cellulose cryogels as a potential hemostatic dressing material. TEMPO-oxidized bacterial cellulose (OBC) was incorporated into the agar matrix, improving its mechanical and hemostatic properties. The oxidation of bacterial cellulose (BC) was evidenced by chemical characterization studies, confirming the presence of carboxyl groups. The in vitro blood clotting test conducted on agar/OBC composite cryogels demonstrated complete blood clotting within 90 seconds, indicating their excellent hemostatic efficacy. The cryogels exhibited superabsorbent properties with a swelling degree of 4200%, enabling them to absorb large amounts of blood. Moreover, the compressive strength of the composite cryogels was appreciably improved compared to pure agar, resulting in a more stable physical structure. The platelet adhesion test proved the significant ability of the composite cryogels to adhere to and aggregate platelets. Hemocompatibility and cytocompatibility tests have verified the safety of these cryogels for hemostatic applications. Finally, the material exhibited remarkable in vivo hemostatic performance, achieving clotting times of 64 seconds and 35 seconds when tested in the rat tail amputation model and the liver puncture model, respectively. The experiment results were compared with those of commercial hemostat, Axiostat, and Surgispon, affirming the potential of agar/OBC composite cryogel as a hemostatic dressing material.

Identification of ethyl-6-bromo-2((phenylthio)methyl)imidazo[1,2-a]pyridine-3-carboxylate as a narrow spectrum inhibitor of Streptococcus pneumoniae and its FtsZ.

Filamentous temperature-sensitive mutant Z (FtsZ) is a key cell-division protein recognized as an important target for anti-bacterial drug discovery, especially in the context of rising multi-drug resistance. A respiratory pathogen, Streptococcus pneumoniae, is rapidly evolving antibiotic resistance, thus posing a clinical risk in the developing world. Inhibiting the conserved protein FtsZ, leading to the arrest of cell division, is an attractive alternative strategy for inhibiting S. pneumoniae. Previously, Vitamin K3 was identified as an FtsZ-targeting agent against S. pneumoniae. In the present work, docking studies were used to identify potential anti-FtsZ agents that bind to the Vitamin K3-binding region of a homology model generated for S. pneumoniae FtsZ. Compounds with imidazo[1,2-a]pyridine-3-carboxylate core were synthesized and screened for their anti-proliferative activity against S. pneumoniae. Remarkably, the hit compound IP-01 showed anti-bacterial action against S. pneumoniae without any activity on other bacteria. In S. pneumoniae, IP-01 showed similar inhibitory action on FtsZ and cell division as Vitamin K3. Sequence alignment identified three unique residues within S. pneumoniae FtsZ that IP-01 binds to, providing a structural basis for the observed specificity. IP-01 is one of the first narrow-spectrum agents identified against S. pneumoniae that targets FtsZ, and we present it as a promising lead for the design of narrow-spectrum anti-FtsZ anti-pneumococcal compounds.

Sulfur functionalized biocarbon sorbents for low-concentration mercury isolation.

Sulfur functionalized biocarbons were prepared from naturally abundant lignin alkali with sodium thiocyanate as an activation agent and a sulfur source. The resultant biocarbon sorbents showed a high mercury isolation ability from aqueous solutions, where high surface area and doping of sulfur significantly aid the uptake of mercury, i.e., 0.05 g of biocarbon sorbent removed 99% of mercury from 250 mL of simulated wastewater with an initial concentration of mercury of 10 mg L-1.

Effects of the Grapevine Biochar on the Properties of PLA Composites.

This study found that biochar made from grapevines (GVC), an agricultural waste product, can be used as a nucleating agent to promote the crystallization of polylactic acid (PLA). Differential scanning calorimetry (DSC) analysis of GVC/PLA composites showed that different particle sizes (200 and 100 mesh size) and amounts (1 wt%, 10 wt%) of biochar affect the re-crystallization of PLA, with 200 mesh GVC in the amount of 10 wt% being the most significant. In addition, it was found that there were two peaks related to imperfect and perfect crystals in the Tm part for GVC/PLA composites. TGA analysis showed that adding GVC tends to lower the maximum decomposition temperature of PLA, revealing that GVC may accelerate the degradation reaction of PLA. This research also studied the effects of GVC in various particle sizes and amounts on the mechanical properties and degradation of PLA. The results revealed that the tensile and impact strengths of GVC/PLA composite could reach 79.79 MPa and 22.67 J/m, respectively, and the increments were 41.4% and 32.1%, greater than those of pristine PLA. Moreover, the molecular weight of PLA decreased as the amount of GVC increased. Therefore, GVC particles can be used as reinforcing fillers for PLA to improve its mechanical properties and adjust its molecular weight. These agricultural-waste-reinforced biocomposites can reduce both greenhouse gas (GHG) emissions and the cost of biodegradable polymers and achieve the goals of a circular economy.

Mechanistic insights into granule-bound starch synthase I (GBSSI.L539P) allele in high amylose starch biosynthesis in wheat (Triticum aestivum L.).

Amylose fraction of grain starch is correlated with a type of resistant starch with better nutritional quality. Granule-bound starch synthase I (GBSSI) is the known starch synthase, responsible for elongation of linear amylose chains. GBSSI expression, activity, and binding to starch and other proteins are the key factors that can affect amylose content. Previously, a QTL, qhams7A.1 carrying GBSSI mutant allele, was identified through QTL mapping using F2 population of the high amylose mutant line, 'TAC 75'. This high amylose mutant line has >2-fold higher amylose content than wild variety 'C 306'. In this study, we characterized this novel mutant allele, GBSSI.L539P. In vitro starch synthase activity of GBSSI.L539P showed improved activity than the wild type (GBSSI-wt). When expressed in yeast glycogen synthase mutants (Δgsy1gsy2), GBSSI-wt and GBSSI.L539P partially complemented the glycogen synthase (gsy1gsy2) activity in yeast. Structural analysis by circular dichroism (CD) and homology modelling showed no significant structural distortion in the mutant enzyme. Molecular docking studies suggested that the residue Leu539 is distant from the catalytic active site (ADP binding pocket) and had no detectable conformational changes in active site. Both wild and mutant enzymes were assayed for starch binding in vitro, and demonstrating higher affinity of the GBSSI.L539P mutant for starch than the wild type. The present study indicated that distant residue (L539P) influenced GBSSI activity by affecting its starch-binding ability. Therefore, it may be a potential molecular target for enhanced amylose content in grain.

Base-Mediated Anti-Markovnikov Hydroamidation of Vinyl Arenes with Arylamides.

We investigated a base-promoted protocol for the intermolecular anti-Markovnikov hydroamidation of vinyl arenes with arylamides to furnish the arylethylbenzamides with excellent chemo- and regioselectivity. The reaction tolerates an extensive variety of functional groups and has been successfully extended with electronically varied handles, aminobenzamides, electron-rich/electron-deficient heterocyclic amides, and vinyl arenes to afford the hydroamidated products. Excellent chemoselectivity was observed for the amide group over amine. The proposed mechanism and vital role of the solvent was well supported by deuterium labeling studies and control experiments.

Mechanistic studies on the drug metabolism and toxicity originating from cytochromes P450.

Cytochromes P450 are oxidizing enzymes; a few families of cytochromes P450 are implicated in drug metabolism. These enzymatic reactions involve many processes including (i) prodrug to drug conversion, (ii) easy excretion of drug, (iii) generation of reactive metabolites, many of which cause toxicity. In this review, the fundamental biochemical mechanisms associated with the conversion of drugs into the useful or toxic metabolites have been discussed. The mechanisms can be established with the help of many experimental methods like mass spectral analysis, NMR and in vitro analysis etc. Computational methods provide detailed atomic level information, which is generally not available from experimental studies. Thus, the in silico efforts in elucidating the molecular mechanisms are complementary to the known experimental methods and are often clearer (especially in providing 3D information about the metabolites and their reactions). Quantum chemical methods and molecular docking become especially very useful. This review includes five case studies, which explain how the atomic level details were obtained to explore the reaction mechanisms of drug metabolism by cytochromes P450.

Novel Furan-2-yl-1H-pyrazoles Possess Inhibitory Activity against α-Synuclein Aggregation.

A series of novel furan-2-yl-1H-pyrazoles and their chemical precursors were synthesized and evaluated for their effectiveness at disrupting α-synuclein (α-syn) aggregation in vitro. The compounds were found to inhibit α-syn aggregation with efficacy comparable to the promising drug candidate anle138b. The results of this study indicate that compounds 8b, 8l, and 9f may qualify as secondary leads for the structure-activity relationship studies aimed to identify the suitable compounds for improving the modulatory activity targeted at α-syn self-assembly related to Parkinson's disease.

Crosslinking of agar by diisocyanates.

In the present study, crosslinking of agar using diisocyanate (DI) was demonstrated to limit the high water absorption property of agar. In addition, the efficacy of aromatic diisocyanate, DDI (4, 4 diphenyl diisocyanate) and aliphatic diisocyanate, HDI (1, 6 hexamethylene diisocyanate) on crosslinked agar properties was compared. The water uptake was successfully reduced by crosslinking and its minimum values observed for DDI and HDI crosslinked agar was 33.6% and 43.6%, respectively in comparison to agar (206%). The maximum tensile strength was observed for DDI crosslinked agar (45.3 MPa) which was higher than HDI crosslinked agar (30.6 MPa) and agar (31.7 MPa). The aromatic diisocyanates crosslinked agar showed better thermal resistance at higher temperature. It was observed that aromatic diisocyanate crosslinked agar more effectively than the aliphatic diisocyanate due to the higher reactivity. The crosslinked agar samples were hemocompatible and show non-toxic nature for cell proliferation.

Nongassing long-lasting electro-osmotic pump with polyaniline-wrapped aminated graphene electrodes.

An efficient nongassing electro-osmotic pump (EOP) with long-lasting electrodes and exceptionally stable operation is developed by using novel flow-through polyaniline (PANI)-wrapped aminated graphene (NH2-G) electrodes. The NH2-G/PANI electrode combines the excellent oxidation/reduction capacity of PANI with the exceptional conductivity and inertness of NH2-G. The flow rate varies linearly with voltage but is highly dependent on the electrode composition. The flow rates at a potential of 5 V for pristine NH2-G and PANI electrodes are 71 and 100 µL min(-1) cm(-2), respectively, which increase substantially by the use of NH2-G/PANI electrode. It increased from 125 to 182 µL min(-1) cm(-2) as the fraction of aniline increased from 66.63 to 90.90%. The maximum flux obtained is 40 µL min(-1) V(-1) cm(-2) with NH2-G/PANI-90.9 electrodes. The assembled EOP remained exceptionally stable until the electrode columbic capacity was fully utilized. The prototype shown here delivered 8.0 µL/min at a constant applied voltage of 2 V for over 7 h of continuous operation. The best EOP produces a maximum stall pressure of 3.5 kPa at 3 V. These characteristics make it suitable for a variety of microfluidic/device applications.