Analysis of the growth and physicochemical properties of the newly developed stilbazolium derivative 4-N,N-dimethylamino-4-N-methyl stilbazolium 2-formyl benzene sulfonate (DSFS) single crystal: an effective material for nonlinear optical applications.

A novel ionic stilbazolium derivative single crystal of 4-N,N-dimethylamino-4-N-methyl stilbazolium 2-formyl benzene sulfonate (DSFS) was successfully cultivated with methanol as the solvent by using the slow evaporation technique. Structural confirmation was done using single-crystal X-ray diffraction (SCXRD), and the obtained results reveal that the DSFS crystal crystallized in a centrosymmetric pattern with P1̄ space group. The presence of different vibrational modes in the DSFS crystal is affirmed via Fourier transform infrared (FTIR) spectroscopy. Linear optical constants such as cut-off wavelength, bandgap, extinction coefficient, Urbach energy, electrical conductivity and optical conductivity of the titular crystal were found from ultraviolet-visible-near infra-red spectroscopy (UV-Vis-NIR). The emission wavelength of the title crystal lies in the red region (620 nm), which was confirmed from the photoluminescence spectroscopy (PL). The surface nature of the grown ionic crystal was examined through the etching and atomic force microscopy (AFM) technique. With a He-Ne laser as the source, Z scan analysis was carried out to study the third-order nonlinear properties of the DSFS crystal.

Unleashing a novel function of Endonuclease G in mitochondrial genome instability.

Having its genome makes the mitochondrion a unique and semiautonomous organelle within cells. Mammalian mitochondrial DNA (mtDNA) is a double-stranded closed circular molecule of about 16 kb coding for 37 genes. Mutations, including deletions in the mitochondrial genome, can culminate in different human diseases. Mapping the deletion junctions suggests that the breakpoints are generally seen at hotspots. '9 bp deletion' (8271-8281), seen in the intergenic region of cytochrome c oxidase II/tRNALys, is the most common mitochondrial deletion. While it is associated with several diseases like myopathy, dystonia, and hepatocellular carcinoma, it has also been used as an evolutionary marker. However, the mechanism responsible for its fragility is unclear. In the current study, we show that Endonuclease G, a mitochondrial nuclease responsible for nonspecific cleavage of nuclear DNA during apoptosis, can induce breaks at sequences associated with '9 bp deletion' when it is present on a plasmid or in the mitochondrial genome. Through a series of in vitro and intracellular studies, we show that Endonuclease G binds to G-quadruplex structures formed at the hotspot and induces DNA breaks. Therefore, we uncover a new role for Endonuclease G in generating mtDNA deletions, which depends on the formation of G4 DNA within the mitochondrial genome. In summary, we identify a novel property of Endonuclease G, besides its role in apoptosis and the recently described 'elimination of paternal mitochondria during fertilisation.

COVID-19 impacts and adaptations in Asia and Africa's aquatic food value chains.

The COVID-19 pandemic is a shock affecting all areas of the global food system. We tracked the impacts of COVID-19 and associated policy responses on the availability and price of aquatic foods and production inputs during 2020, using a high frequency longitudinal survey of 768 respondents in Bangladesh, Egypt, India, Myanmar, Nigeria. We found the following: (1) Aquatic food value chains were severely disrupted but most effects on the availability and accessibility of aquatic foods and production inputs were short-lived. (2) Impacts on demand for aquatic foods, production inputs, and labor have been longer lasting than impacts on their supply. (3) Retail prices of aquatic foods spiked briefly during March-May 2020 but trended down thereafter, whereas prices of production inputs rose. These trends suggest a deepening 'squeeze' on the financial viability of producers and other value chain actors. (4) Survey respondents adapted to the challenges of COVID-19 by reducing production costs, sourcing alternative inputs, diversifying business activities, leveraging social capital, borrowing, seeking alternative employment, and reducing food consumption. Many of these coping strategies are likely to undermine well-being and longer-term resilience, but we also find some evidence of proactive strategies with potential to strengthen business performance. Global production of aquatic food likely contracted significantly in 2020. The importance of aquatic food value chains in supporting livelihoods and food and nutrition security in Asia and Africa makes their revitalization essential in the context of COVID-19 recovery efforts. We outline immediate and longer-term policies and interventions to support this goal.

Biopolymer and Synthetic Polymer-Based Nanocomposites in Wound Dressing Applications: A Review.

Biopolymers are materials obtained from a natural origin, such as plants, animals, microorganisms, or other living beings; they are flexible, elastic, or fibrous materials. Polysaccharides and proteins are some of the natural polymers that are widely used in wound dressing applications. In this review paper, we will provide an overview of biopolymers and synthetic polymer-based nanocomposites, which have promising applications in the biomedical research field, such as wound dressings, wound healing, tissue engineering, drug delivery, and medical implants. Since these polymers have intrinsic biocompatibility, low immunogenicity, non-toxicity, and biodegradable properties, they can be used for various clinical applications. The significant advancements in materials research, drug development, nanotechnology, and biotechnology have laid the foundation for changing the biopolymeric structural and functional properties. The properties of biopolymer and synthetic polymers were modified by blending them with nanoparticles, so that these materials can be used as a wound dressing application. Recent wound care issues, such as tissue repairs, scarless healing, and lost tissue integrity, can be treated with blended polymers. Currently, researchers are focusing on metal/metal oxide nanomaterials such as zinc oxide (ZnO), cerium oxide (CeO2), silver (Ag), titanium oxide (TiO2), iron oxide (Fe2O3), and other materials (graphene and carbon nanotubes (CNT)). These materials have good antimicrobial properties, as well as action as antibacterial agents. Due to the highly antimicrobial properties of the metal/metal oxide materials, they can be used for wound dressing applications.

Microhomology-mediated end joining is the principal mediator of double-strand break repair during mitochondrial DNA lesions.

Mitochondrial DNA (mtDNA) deletions are associated with various mitochondrial disorders. The deletions identified in humans are flanked by short, directly repeated mitochondrial DNA sequences; however, the mechanism of such DNA rearrangements has yet to be elucidated. In contrast to nuclear DNA (nDNA), mtDNA is more exposed to oxidative damage, which may result in double-strand breaks (DSBs). Although DSB repair in nDNA is well studied, repair mechanisms in mitochondria are not characterized. In the present study, we investigate the mechanisms of DSB repair in mitochondria using in vitro and ex vivo assays. Whereas classical NHEJ (C-NHEJ) is undetectable, microhomology-mediated alternative NHEJ efficiently repairs DSBs in mitochondria. Of interest, robust microhomology-mediated end joining (MMEJ) was observed with DNA substrates bearing 5-, 8-, 10-, 13-, 16-, 19-, and 22-nt microhomology. Furthermore, MMEJ efficiency was enhanced with an increase in the length of homology. Western blotting, immunoprecipitation, and protein inhibition assays suggest the involvement of CtIP, FEN1, MRE11, and PARP1 in mitochondrial MMEJ. Knockdown studies, in conjunction with other experiments, demonstrated that DNA ligase III, but not ligase IV or ligase I, is primarily responsible for the final sealing of DSBs during mitochondrial MMEJ. These observations highlight the central role of MMEJ in maintenance of mammalian mitochondrial genome integrity and is likely relevant for deletions observed in many human mitochondrial disorders.

Simultaneous determination of carisoprodol and aspirin in human plasma using liquid chromatography-tandem mass spectrometry in polarity switch mode: application to a human pharmacokinetic study.

A simple, sensitive and rapid LC-MS/MS-ESI method has been developed and validated for simultaneous quantification of the carisoprodol and aspirin in human plasma. Carisoprodol was detected in positive ion mode, whereas aspirin was detected in negative ion mode. Carbamazepine and furosemide were used as internal standards (IS) for quantification of carisoprodol and aspirin, respectively. The extraction procedure involves a liquid-liquid extraction method with ter-butyl methyl ether. Chromatographic separation was achieved on a Zorbax XDB-Phenyl (4.6 × 75 mm, 3.5 µm) column using an isocratic mobile phase (5 mm ammonium acetate:methanol, 20:80, v/v) at a flow rate of 0.8 mL/min with a total run time of 2.2 min. A detailed method validation was performed as per the FDA guidelines. The standard curves found to be linear in the range of 25.5-4900 and 15.3-3000 ng/mL for carisoprodol and aspirin, respectively. The results met the acceptance criteria. Carisoprodol and aspirin were found to be stable in various stability studies. The validated method was successfully applied to a pharmacokinetic study following co-administration of carisoprodol (250 mg) and aspirin (75 mg) tablets by oral route to human volunteers.

A rapid and sensitive liquid chromatography-tandem mass spectrometric assay for duloxetine in human plasma: Its pharmacokinetic application.

This paper describes a simple, rapid and sensitive liquid chromatography-tandem mass spectrometry assay for the determination of duloxetine in human plasma. A duloxetine stable labeled isotope (duloxetine d5) was used as an internal standard. Analyte and the internal standard were extracted from 100 µL of human plasma via solid phase extraction technique using Oasis HLB cartridges. The chromatographic separation was achieved on a C18 column by using a mixture of acetonitrile-5 mM ammonium acetate buffer (83:17, v/v) as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear (r2≥0.99) over the concentration range of 0.05-101 ng/mL. Multiple-reaction monitoring mode (MRM) was used for quantification of ion transitions at m/z 298.3/154.1 and 303.3/159.1 for the drug and the internal standard, respectively. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.

Design and evaluation of oral bioadhesive controlled release formulations of miglitol, intended for prolonged inhibition of intestinal alpha-glucosidases and enhancement of plasma glucagon like peptide-1 levels.

Alpha-glucosidase enzyme is present ubiquitously throughout the lumen of the small intestine. It is responsible for the breakdown of complex into simple carbohydrates. alpha-Glucosidase inhibitors such as miglitol, are drugs that have greater affinity towards this enzyme in comparison to carbohydrates. Miglitol regulates the postprandial glucose levels directly by inhibiting the enzyme reversibly and also indirectly by including the secretion of glucagon like peptide-1 (GLP-1). The aims of this study were (i) to design a controlled release (CR) mucoadhesive (in the intestine) formulation of miglitol which would inhibit the alpha-glucosidase enzyme for a longer duration of time (in comparison to the non-controlled release (IR) formulation) thus reducing the dosing frequency, and also controlling the postprandial glucose levels more effectively over a longer period of time; (ii) to assess the effect of different formulation parameters on the release of miglitol in vitro from the CR pellets; (iii) to evaluate the mucoadhesion of pellets in the intestine ex vivo; (iv) to study the effect of formulation parameters on plasma GLP-1 levels; and (v) to find out the effect of formulations on postprandial glucose levels. The data obtained was analysed to find out whether there was a correlation between these different parameters. Four controlled release formulations (CR1, CR2, CR3 and CR4) of miglitol comprising of multilayered pellets were designed successfully. The CR4 formulation containing 30% of 20 cps of ethyl cellulose (the retarding layer of the formulation) displayed slowest release of miglitol in vitro in comparison to other formulations. We designed an ex vivo experimental setup for studying the mucoadhesion of the pellets in the lumen of the intestine. Results indicated that amongst all of the adherent pellets, 5% were found to be adhering in the duodenal region, 61% in the jejunum, 32% in the ileum and 2% in the colon. Two of the controlled release formulations CR1 and CR4 were evaluated in vivo in dogs. Both the formulations displayed significantly higher and more prolonged (greater AUC) levels of GLP-1 in comparison to either the placebo or the immediate release (IR) formulations. They even displayed a significantly better control of postprandial glucose in comparison to either placebo or IR formulations. However, a comparison between the two controlled release formulations (CR1 and CR4) revealed that the plasma GLP-1 (AUC by CR1=63.1+/-1.32 and CR4=66.2+/-0.82) and postprandial glucose values due to both the formulations were rather similar despite their differences in in vitro release as well as pharmacokinetic profiles (plasma miglitol AUC of CR1=16.17+/-4.11 and CR4=27.17+/-4.33).

Detection of Laem-Singh virus in cultured Penaeus monodon shrimp from several sites in the Indo-Pacific region.

Laem-Singh virus (LSNV) is a positive-sense single-stranded RNA (ssRNA) virus that was recently identified in Penaeus monodon shrimp in Thailand displaying signs of slow growth syndrome. A total of 326 shrimp collected between 1998 and 2007 from countries in the Indo-Pacific region were tested by RT-PCR for evidence of LSNV infection. The samples comprised batches of whole postlarvae, and lymphoid organ, gill, muscle or pleopod tissue of juvenile, subadult and adult shrimp. LSNV was not detected in 96 P. monodon, P. japonicus or P. merguiensis from Australia or 16 P. monodon from Fiji, Philippines, Sri Lanka and Mozambique. There was no evidence of LSNV infection in 73 healthy juvenile P. vannamei collected during 2006 from ponds at 9 locations in Thailand. However, LNSV was detected in each of 6 healthy P. monodon tested from Malaysia and Indonesia, 2 of 6 healthy P. monodon tested from Vietnam and 39 of 40 P. monodon collected from slow-growth ponds in Thailand. A survey of 81 P. monodon collected in 2007 from Andhra Pradesh, India, indicated 56.8% prevalence of LSNV infection but no clear association with disease or slow growth. Phylogenetic analysis of PCR amplicons obtained from samples from India, Vietnam, Malaysia and Thailand indicated that nucleotide sequence variation was very low (>98% identity) and there was no clustering of viruses according to site of isolation or the health status of the shrimp. The data suggests that LSNV exists as a single genetic lineage and occurs commonly in healthy P. monodon in parts of Asia.

DRF 2655: a unique molecule that reduces body weight and ameliorates metabolic abnormalities.

OBJECTIVE: Preclinical evaluation of DRF 2655, a peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent. RESEARCH METHODS AND PROCEDURES: DRF 2655 was studied in different genetic, normal, and hyperlipidemic animal models. HEK 293 cells were used to conduct the reporter-based transactivation of PPARalpha and PPARgamma. To understand the biochemical mechanism of lipid-, body-weight-, and glucose-lowering effects, activities of key beta-oxidation and lipid catabolism enzymes and gluconeogenic enzymes were studied in db/db mice treated with DRF 2655. 3T3L1 cells were used for adipogenesis study, and HepG2 cells were used to study the effect of DRF 2655 on total cholesterol and triglyceride synthesis using [(14)C]acetate and [(3)H]glycerol. RESULTS: DRF 2655 showed concentration-dependent transactivation of PPARalpha and PPARgamma. In the 3T3L1 cell-differentiation study, DRF 2655 and rosiglitazone showed 369% and 471% increases, respectively, in triglyceride accumulation. DRF 2655 showed body-weight lowering and euglycemic and hypolipidemic effects in various animal models. db/db mice treated with DRF 2655 showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and carnitine acetyltransferase, respectively. HepG2 cells treated with DRF 2655 showed significant reduction in lipid synthesis. DISCUSSION: DRF 2655 showed excellent euglycemic and hypolipidemic activities in different animal models. An exciting finding is its body-weight lowering effect in these models, which might be mediated by the induction of target enzymes involved in hepatic lipid catabolism through PPARalpha activation.