Silicomolybdic Acid Cluster as Biocompatible Catalyst for One-Pot Tandem Synthesis of Orthogonally Protected Glycosides.

The present paper describes a new and practical approach for the one-pot preparation of O-isopropylidene derivatives and also orthogonally protected S- and O-glycosides from the corresponding unprotected saccharides by employing 2 mol % of a silicomolybdic acid (SMA) cluster as a versatile and biocompatible catalyst. The present protocol is applicable to two-step one-pot tandem transformations, which include the O-isopropylidation, spiroketal functionalization, 4,6-O-arylidene acetalations, and arylidene acetylation processes under relatively mild reaction conditions. One-pot sequential transformations, low catalyst loading, rapid transformation, high to excellent reaction yields, mild reaction conditions, and a nontoxic biocompatible workup procedure are the notable advantages of devised protocol.

The novel chaperonin 10 like protein (SbCPN10L) from Salicornia brachiata (Roxb.) augment the heat stress tolerance in transgenic tobacco.

The heat stress is a significant environmental challenge and impede the plant growth, development and productivity. The characterization and utilization of novel genes for improving stress tolerance represents a paramount approach in crop breeding. In the present study, we report on cloning of a novel heat-induced chaperonin 10-like gene (SbCPN10L) from Salicornia brachiata and elucidation of its in-planta role in conferring the heat stress endurance. The transgenic tobacco over-expressing SbCPN10L gene exhibited enhanced growth attributes such as higher rate of seed germination, germination and vigor index at elevated (35 ± 1 °C) temperature (eT). The SbCPN10L tobacco exhibited greenish and healthy seedling growth under stress. Compared with control tobacco at eT, the transgenic tobacco had higher water contents, membrane stability index, stress tolerance index and photosynthetic pigments. Lower electrolyte leakage and less accumulation of malondialdehyde, hydrogen peroxide and reactive oxygen species indicated better heat stress tolerance in transgenic tobacco over-expressing SbCPN10L gene. Transgenic tobacco accumulated higher contents of sugars, starch, amino acids and polyphenols at eT. The negative solute potential observed in transgenic tobacco contributed to maintain water content and support improved growth under stress. The up-regulation of NtAPX, NtPOX and NtSOD in transgenic tobacco under stress indicated higher ROS scavenging ability and better physiological conditioning. The results recommend the SbCPN10L gene as a potential candidate gene with an ability to confer heat stress tolerance for climate resilient crops.

S-adenosyl-l-methionine interaction signatures in methyltransferases.

The switching on or off of methylation, a change from a normal methylation to hyper or hypo methylation is implicated in many diseases that include cancers, infectious, neurodegenerative diseases and others. Methyltransferases are one of the most sought targets that have diversified for the methylation of a variety of substrates. However, without S-adenosyl-l-methionine (SAM), the universal methyl donor, the majority of the methyltransferases remain functionally inactive. In this article, we did a comprehensive analysis of all available SAM-receptor crystal structures at atom, moiety and structure levels to gain deeper insights into the structure and function of SAM. SAM demonstrated flexibility in binding to a variety of receptors irrespective of the size of the binding pockets. Further analysis of the binding pockets resulted in all SAM conformations clustering into four natural shapes. The conserved interaction analysis provides an unambiguous orientation of SAM binding to receptors which has been elusive till now. SAM peptide moiety (SPM) and SAM nucleobase moiety (SNM) show up to 89% interactions with receptors whereas only 11% interactions with SAM ribose moiety (SRM). It is found that SPM and SNM terminal atoms anchor to the highly conserved receptor subsites creating a workbench for catalysis. It is seen that every interacting atom and its position is crucial in the methyl transfer phenomenon. A very unique observation is that the methyl group of SAM does not have even one interaction with the receptor. The deep insights gained help in the design and development of novel drugs against the methyltransferases.Communicated by Ramaswamy H. Sarma.

Triazole-Appended Glycohybrid/CuI-Catalyzed C-C Cross-Coupling of Aryl/Heteroaryl Halides with Alkynyl Sugars.

This report describes a convenient method for the Cu(I)-catalyzed Sonogashira cross-coupling reaction of aryl/heteroaryl halides and alkynyl sugars in the presence of a 1,2,3-triazole-appended glycohybrid as a biocompatible ligand. The Sonogashira cross-coupling products were exclusively formed without the Glaser-Hay homocoupling reaction in the presence of a glycosyl monotriazolyl ligand at 120 °C. However, the Glaser-Hay homocoupling products were obtained at 60-70 °C in the presence of bis-triazolyl-based macrocyclic glycohybrid ligand L8. The glycosyl triazole ligands were synthesized via the CuI/DIPEA-mediated regioselective CuAAC click reaction, and a series of glycohybrids of glucose, mannose, and galactose alkynes including glycosyl rods were developed in good yields. The developed glycohybrids have been well characterized by various spectroscopic techniques, such as nuclear magnetic resonance, high-resolution mass spectrometry, and single-crystal X-ray data of L3. The protocol works well with the heteroaryl and naphthyl halides, and the mechanistic approach leads to CuI/ligand-assisted oxidative coupling. The coupling protocol has notable features, including low catalytic loading, cost-effectiveness, biocompatible nature, and a wide substrate scope.

Organocatalyzed Regioselective Synthesis of 1,5-Disubstituted 1,2,3-Triazolyl Glycoconjugates.

A novel organocatalyzed [3+2] cycloaddition reaction of nitroolefins with glycosyl azides as well as organic azides has been developed for successful construction of 1,5-disubstituted triazolyl glycoconjugates. This metal-free and acid-free, regioselective synthetic protocol proceeds in the presence of only Schreiner thiourea organocatalysts, which enable the required activation of nitroolefins through double hydrogen bonding. The straightforward, operationally simple, and regioselectivity of this methodology, complementing to the classical RuAAC catalyzed synthesis of 1,5-disubstituted 1,2,3-triazoles. In the presence of catalytic amount of Schreiner thiourea organocatalyst, organic azides react with a broad array of nitroolefins producing a series of diverse 1,5-disubstituted 1,2,3- triazoles in good yields with excellent regioselectivity.

Pyridyl Glycosyl Triazole/CuI-Mediated Domino/Tandem Synthesis of Quinazolinones.

The glycosyl 1,2,3-triazoles are expediently accessible from readily available sugar-derived glycosyl azide by utilizing modular CuAAC "Click Chemistry", and the resulting glycohybrid skeleton possesses efficient metal-coordinating centers that support a wide range of metal-mediated efficient catalysis in various imperative organic transformations. Here, we designed and developed pyridyl glycosyl triazoles by employing the CuAAC reaction of d-glucose-derived glycosyl azides and alkynyl pyridines. These pyridyl glycosyl triazoles with Cu(I) salt were explored as an efficient catalyst to successfully assemble 2-amino-3-substituted and 3-substituted quinazolinones by the domino/tandem cross-coupling reaction of various N-substituted o-halobenzamides with cyanamide and formamide, respectively. The devised protocol has some notable features, including biocompatibility, low cost, easily accessible starting materials for the glycosyl ligands, high yield, broad spectrum, low catalytic loading, and mild reaction conditions.

One-pot expeditious synthesis of glycosylated esters through activation of carboxylic acids using trichloroacetonitrile.

Acetimidates, a valuable intermediate has been well explored as versatile synthon in a number of organic transformations particularly as suitable donors in glycosylation reactions. Herein, we explored acetimidates to furnish high-to-excellent yield of diverse glycosylated esters under one-pot mild reaction condition. The commercially available trichloroacetonitrile is implemented for the activation of carboxylic acid via in situ generation of trichloroacetimidate, which was subsequently attacked by sugar alcohols to deliver high-to-excellent yields of desired glycosylated esters. The devised method has some notable features such as metal-free condition, one-pot mild reaction condition, easy-handling, high-to-excellent yields, and broad substrate scope.

Correction to: Callus culture and plantlet regeneration in date palm (Phoenix dactylifera L.): an important horticultural cash crop for arid and semi-arid horticulture.

[This corrects the article DOI: 10.1007/s12298-019-00733-w.].

The red seaweed Kappaphycus alvarezii antiporter gene (KaNa+/H+) confers abiotic stress tolerance in transgenic tobacco.

BACKGROUND: Plant establishment, growth, development and productivity are adversely affected by abiotic stresses that are dominant characteristics of environmentally challenged/degraded habitats created in the Anthropocene. Crop breeding for climate resilience properties is need of the hour to sustain the crop productivity. We report on the characterization of Kappaphycus alvarezii (a red seaweed) Na+/H+ antiporter gene (KaNa+/H+) for enhanced salt and osmotic stress tolerance. METHODS: The KaNa+/H+ antiporter gene was cloned and over-expressed in tobacco under the control of CaMV35S promoter. Transgenic analysis was carried out to assess the stress tolerance ability of tobacco over-expressing KaNa+/H+ antiporter gene. RESULTS: Over-expression of KaNa+/H+ gene improved the seed germination and seed vigor index under stress. Transgenic plants grew better and exhibited delayed leaf senescence. Improved K+/Na+, carotenoid/total chlorophyll and relative water content; lower accumulation of reactive oxygen species (ROS), MDA and Na+; lower electrolyte leakage; better membrane stability index and accumulation of K+, photosynthetic pigment, starch, sugar, free amino acid, proline and polyphenol contents indicated better physiological health of the transgenic tobacco under stress. Transgenic tobacco exhibited higher photosynthesis, photosystem II efficiency, electron transfer rate, photochemical quenching and activity of water splitting complex. Compared with control tobacco, transgenic tobacco exhibited higher expression of stress-defence genes under stress and better recovery after long-term osmotic stress. CONCLUSIONS: Lower Na+ cytotoxicity, lower accumulation of ROS and maintenance of the membrane integrity helped transgenic tobacco to maintain the physiological functioning under stress. Present results established K. alvarezii as a potential gene resource and the KaNa+/H+ antiporter gene as a potential candidate gene in molecular breeding of crops for development of the degraded land.

d-Glucosamine as the Green Ligand for Cu(I)-Catalyzed Regio- and Stereoselective Domino Synthesis of (Z)-3-Methyleneisoindoline-1-ones and (E)-N-Aryl-4H-thiochromen-4-imines.

d-Glucosamine, a natural, inexpensive, and conveniently accessible sugar, has been explored as an efficient ligand for the Cu(I)-catalyzed regio- and stereoselective synthesis of an array of (Z)-3-methyleneisoindoline-1-ones and (E)-N-aryl-4H-thiochromen-4-imines in good-to-excellent yield in a tandem fashion via the reaction of 2-halobenzamide and 2-halobenzothioamide with terminal alkynes, respectively. The water solubility and biocompatible nature of the ligand offer easy separation of the catalytic system toward the aqueous phase as well as change in the reaction path in terms of the product also demonstrated the variation of the reaction temperature. The domino reaction proceeds by the Sonogashira and Ullmann type cross-coupling reaction, followed by Cu(I)-promoted additive cyclization of heteroatom to the triple bond. In addition, d-glucosamine causes successful Glaser-Hay coupling of terminal alkynes under Cu catalysis to produce a high yield of respective 1,3-diynes.

CuAAC mediated synthesis of cyclen cored glycodendrimers of high sugar tethers at low generation.

Glycodendrimers are receiving considerable attention to mimic a number of imperative features of cell surface glycoconjugate and acquired excellent relevance to a wide domain of investigations including medicine, pharmaceutics, catalysis, nanotechnology, carbohydrate-protein interaction, and moreover in drug delivery systems. Toward this end, an expeditious, modular, and regioselective triazole-forming CuAAC click approach along with double stage convergent synthetic method was chosen to develop a variety of novel chlorine-containing cyclen cored glycodendrimers of high sugar tethers at low generation of promising therapeutic potential. We developed a novel chlorine-containing hypercore unit with 12 alkynyl functionality originated from cyclen scaffold which was confirmed by its single crystal X-ray data analysis. Further, the modular CuAAC technique was utilized to produce a variety of novel 12-sugar coated (G0) glycodendrimers 12-15 adorn with ß-Glc-, ß-Man-, ß-Gal-, ß-Lac, along with 36-galactose coated (G1) glycodendrimer 18 in good-to-high yield. The structures of the developed glycodendrimer architectures have been well elucidated by extensive spectral analysis including NMR (1H & 13CNMR), HRMS, MALDI-TOF MS, UV-Vis, IR, and SEC (Size Exclusion Chromatogram) data.

The novel galactosyl transferase-like (SbGalT) gene from Salicornia brachiata maintains photosynthesis and enhances abiotic stress tolerance in transgenic tobacco.

We hereby report in planta function characterization of a novel galactosyl transferase-like (SbGalT) gene from Salicornia brachiata for enhanced abiotic stress tolerance. The SbGalT gene had an open reading frame of 1563 bp. The ectopic expression of SbGalT gene in tobacco improved the seed germination, seedling growth, biomass accumulation and potassium/sodium ratio under salt and osmotic stress. The SbGalT over-expression delayed stress-induced senescence, pigment break-down and ion induced cytotoxicity in tobacco. Higher contents of organic solutes and potassium under stress maintained the osmotic homeostasis and relative water content in tobacco. Higher activity of antioxidant enzymes under stress in transgenic tobacco curtailed the accumulation of reactive oxygen species (ROS) and maintained the membrane integrity. The chlorophyll a fluorescence transient indicated no effects of the imposed strengths of stress on basal state of photosystem (PS) I in transgenic tobacco over-expressing the SbGalT gene. Due to improved membrane integrity, the transgenic tobacco exhibited improved photosynthesis, stomatal conductance, intercellular CO2, transpiration, maximum quantum yield and operating efficiency of PSII, electron transport, photochemical and non-photochemical quenching. In agreement with photosynthesis, physiological health, tolerance index and growth parameters, transgenic tobacco accumulated higher contents of sugar, starch, amino acid, polyphenol and proline under stress conditions. The multivariate data analysis exhibited significant statistical distinctions among osmotic adjustment, physiological health and growth, and photosynthetic responses in control and SbGalT transgenic tobacco under stress conditions. The results strongly indicated novel SbGalT gene as a potential candidate for developing the smart agriculture.

Getting Vaccinated Helps: Prospective Study Reveals Lower CT Severity Scores amongst COVID Vaccine Recipients.

Context Computerized tomography (CT) is an invaluable imaging investigation for evaluating COVID-19 disease. CT detects early changes of COVID-19 pneumonia and predicts the disease prognosis based on a semiquantitative 25-point CT severity score (CT-SS). India launched its vaccination drive in January 2021 with two different vaccines being approved by the government. These vaccines are believed to prevent the disease itself, in majority of the cases and at least decrease disease severity, in the rest. Aim This study aims to evaluate the CT-SS in vaccinated and non-vaccinated subjects who have been diagnosed with COVID-pneumonia or are COVID suspects. Subjects and Methods A total of 3,235 patients with typical COVID-19 related imaging findings on HRCT thorax were included in the study. These subjects were divided into three age categories, 18-44, 45-59 and ≥60 years. The CT severity scores were allotted by experienced radiologists. Medians of the scores in different age groups were compared amongst vaccinated and non-vaccinated individuals using the Kruskal-Wallis H test. A p- value < 0.05 was considered significant. All results were shown with 95% confidence interval. Results The difference in the medians amongst the vaccinated and non-vaccinated groups was significant, p -values being < 0.001 in all age categories. Conclusion The mean CT-SS was less in vaccinated subjects and the difference in median CT-SS amongst vaccinated and non-vaccinated individuals was statistically significant, thus sending an important message that it is mandatory for the population at large to get vaccinated to reduce infection rate/disease severity.

Ectopic Expression of a Transmembrane Protein KaCyt b6 from a Red Seaweed Kappaphycus alvarezii in Transgenic Tobacco Augmented the Photosynthesis and Growth.

Cytochrome b6f complex is a thylakoid membrane-localized protein and catalyses the transfer of electrons from plastoquinol to plastocyanin in photosynthetic electron transport chain. In the present study, Cytochrome b6 (KaCyt b6) gene from Kappaphycus alvarezii (a red seaweed) was overexpressed in tobacco. A 935 base pair (bp) long KaCyt b6 cDNA contained an open reading frame of 648 bp encoding a protein of 215 amino acids with an expected isoelectric point of 8.67 and a molecular mass of 24.37 kDa. The KaCyt b6 gene was overexpressed in tobacco under control of CaMV35S promoter. The transgenic tobacco had higher electron transfer rate and photosynthetic yield over wild-type and vector control tobacco. The KaCyt b6 tobacco also exhibited significantly higher photosynthetic gas exchange (PN) and improved water use efficiency. The transgenic plants had higher ratio of PN and intercellular CO2. The KaCyt b6 transgenic tobacco showed higher estimates of photosystem II quantum yield, higher activity of the water-splitting complex, PSII photochemistry, and photochemical quenching. The basal quantum yield of nonphotochemical processes in PSII was recorded lower in KaCyt b6 tobacco. Transgenic tobacco contained higher contents of carotenoids and total chlorophyll and also had better ratios of chlorophyll a and b, and carotenoids and total chlorophyll contents hence improved photosynthetic efficiency and production of sugar and starch. The KaCyt b6 transgenic plants performed superior under control and greenhouse conditions. To the best of our knowledge through literature survey, this is the first report on characterization of KaCyt b6 gene from K. alvarezii for enhanced photosynthetic efficiency and growth in tobacco.

Liposomes: Advancements and innovation in the manufacturing process.

Liposomes are well recognised as effective drug delivery systems, with a range of products approved, including follow on generic products. Current manufacturing processes used to produce liposomes are generally complex multi-batch processes. Furthermore, liposome preparation processes adopted in the laboratory setting do not offer easy translation to large scale production, which may delay the development and adoption of new liposomal systems. To promote advancement and innovation in liposome manufacturing processes, this review considers the range of manufacturing processes available for liposomes, from laboratory scale and scale up, through to large-scale manufacture and evaluates their advantages and limitations. The regulatory considerations associated with the manufacture of liposomes is also discussed. New innovations that support leaner scalable technologies for liposome fabrication are outlined including self-assembling liposome systems and microfluidic production. The critical process attributes that impact on the liposome product attributes are outlined to support potential wider adoption of these innovations.

Na+/K+-ATPase a Primary Membrane Transporter: An Overview and Recent Advances with Special Reference to Algae.

The maintenance of ionic homeostasis in the cytoplasm is an essential and crucial physiological process for all living beings. At cellular level, Na+ concentrations are maintained by specialized Na+ transporting molecular machines, which operate in the cell or plasma membrane. In eukaryotes Na+ transporting P-type ATPase play an important role in Na+ homeostasis that is known as Na+/K+-ATPase in animal cells in which K+ acts as a counter ion for the exchange of sodium. Na+/K+-ATPase is not found in plants. In plants and fungi, proton gradients are maintained by plasma membrane H+-ATPase while in animal cells Na+ and K+ gradient is maintained by Na+/K+-ATPase. However, in case of algae, a few reports of Na+/K+-ATPase are available, that maintains optimum concentration gradients in the cytoplasm and is used by Na+/H+ antiporter to exchange of Na+ and H+ ions. The membrane potential derived as a result of ion gradients across the membrane is base for a variety of cellular processes. An active Na+ dependent cycle (P-type ATPase) is scarcely reported in algae as compared to marine bacteria/cyanobacteria and animals. The characterization of these transporter gene-encoding membrane transports in seaweed would contribute to the understanding of abiotic stress tolerance in these organisms. This review highlights the detailed account of algal along with animal type Na+-ATPase i.e. occurrence, properties, significance and their recent progress.

Callus culture and plantlet regeneration in date palm (Phoneix dactylifera L.): an important horticultural cash crop for arid and semi-arid horticulture.

Phoneix dactylifera L. commonly called date palm is a highly valuable horticultural cash crop for arid and semi-arid regions. The availability of offshoots and their survival during plantation are major concern. Being dioecious tree, seed propagation in date palm do not produce true-to-type offspring and tissue culture propagation is the only viable option to supply quality-planting propagules. Hereby, we report callus culture and plantlet regeneration in female date palm using in vitro-derived adventitious shoot bud tissues as explants. Explants (89.33 ± 2.67%) produced callus culture on 0.8% agar-gelled Murashige and Skoog's basal medium containing 100.0 mg l-1 each polyvinylpyrrolidone, ascorbic acid and glutamine, 50.0 mg l-1 each citric acid, adenine sulphate and l-arginine as additives, 0.1% activated charcoal (AC), 100 mg l-1 2,4-dichlorophenoxyacetic acid (2,4-D) and 3.0 mg l-1 2-isopentenyladenine (2-iP). Callus culture were amplified on medium containing 3.0 mg l-1 2-iP along with 50 mg l-1 2,4-D for 2 passages and 10 mg l-1 2,4-D for 2 passages. Cultures grew moderately, organized and subsequently regenerated into shoot bud like structures during gradual transfer from medium containing higher concentration of 2,4-D to lower concentration. Plantlets were developed by sub-culturing of differentiated buds on (1) hormone free medium supplied with 10.0% sucrose and (2) medium containing 100.0 mg l-1 each ascorbic acid and glutamine, 50.0 mg l-1 each citric acid, adenine sulphate and l-arginine as additives, 1.0 mg l-1 each 6-benzylaminopurine, kinetin, 2-iP and α-naphthaleneacetic acid. Plantlets were developed on medium containing 0.1% AC, 1.0 mg l-1 each indole-3-acetic acid and indole-3-butyric acid. Rooted plantlets were soil-transplanted and acclimatized through gradual exposure from in vitro to in vivo conditions. Simple adoption, higher culture regeneration and simultaneous production of rooted plantlets in a cyclic manner render the protocol useful for mass scale propagation of elite genotype of female date palm.

Silicon Industry Waste Polymethylhydrosiloxane-Mediated Benzotriazole Ring Cleavage: A Practical and Green Synthesis of Diverse Benzothiazoles.

A green modification has been introduced to the synthesis of benzothiazoles by using polymethylhydrosiloxane (PMHS) for successive steps of benzotriazole ring cleavage and cyclization, an approach which was previously developed in our lab by the use of n-Bu3SnH. The use of the silicone industry byproduct PMHS makes this protocol a cost-effective and nontoxic one and thus may be considered for the industrial importance.

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Ondansetron.

Literature data pertaining to the physicochemical, pharmaceutical, and pharmacokinetic properties of ondansetron hydrochloride dihydrate are reviewed to arrive at a decision on whether a marketing authorization of an immediate release (IR) solid oral dosage form can be approved based on a Biopharmaceutics Classification System (BCS)-based biowaiver. Ondansetron, a 5HT3 receptor antagonist, is used at doses ranging from 4 mg to 24 mg in the management of nausea and vomiting associated with chemotherapy, radiotherapy, and postoperative treatment. It is a weak base and thus exhibits pH-dependent solubility. However, it is able to meet the criteria of "high solubility" as well as "high permeability" and can therefore be classified as a BCS class I drug. Furthermore, ondansetron hydrochloride 8 mg IR tablets (Zofran® 8 mg) and multiples thereof (16 mg = Zofran® 8 mg × 2 tablets and 24 mg = Zofran® 8 mg × 3 tablets) meet the criteria of "rapidly dissolving" in dissolution testing. Ondansetron hydrochloride has a wide therapeutic window and is well-tolerated after oral administration. Based on its favorable physicochemical properties, pharmacokinetic data and the minimal risks associated with an incorrect bioequivalence decision, the BCS-based biowaiver procedure can be recommended for ondansetron hydrochloride dihydrate IR tablets.

Gracilaria dura extract confers drought tolerance in wheat by modulating abscisic acid homeostasis.

Water stress severely reduces the production of wheat. Application of seaweed extracts have started to show promise in protecting plants from environmental stresses as they contain several biostimulants. However, the modes of action of these biostimulants are not clear. Here, we investigated the role of Gracilaria dura (GD), a red alga, in conferring stress tolerance to wheat during drought under glasshouse and agro-ecological conditions by integrating molecular studies with physiological and field investigations. GD-sap application conferred drought tolerance (as the biomass increased by up to 57% and crop yield by 70%), via facilitating physiological changes associated to maintaining higher water content. GD-sap application significantly increased ABA accumulation (2.34 and 1.46 fold at 4 and 6 days of drought, respectively) due to enhanced expression of biosynthesis genes. This followed an activation of ABA response genes and physiological processes including reduced stomatal opening, thus reducing water loss. Moreover, GD-sap application enhanced the expression of stress-protective genes specifically under water stress. Treatment with fluridone, an ABA inhibitor, further support the role of ABA in GD-sap mediated drought tolerance in wheat. The findings of this study provide insights into the functional role of GD-sap in improving drought tolerance and show the potential to commercialize GD-sap as a potent biostimulant for sustainable agriculture in regions prone to drought.