Fast-atom bombardment and tandem mass spectrometry of macrolide antibiotics

Molecular weights of macrolide antibiotics can be determined from either (M + H)⁺ or (M + Met)⁺, the latter desorbed from alkali metal salt-saturated matrices. The ion chemistry of macrolides, as determined by tandem mass spectrometry (MS/MS), is different for ions produced as metallated than those formed as (M + H)⁺ species. An explanation for these differences is the location of the charge. For protonated species, the charge is most likely situated on a functional group with high proton affinity, such as the dimethylamino group of the ammo sugar. The alkali metal ion, however, is bonded to the highly oxygenated aglycone. As a result, the collision-activated dissociation spectra of protonated macrolides are simple with readily identifiable fragment ions in both the high and low mass regions but no fragments in the middle mass range. In contrast, the cationized species give complex spectra with many abundant ions, most of which are located in the high mass range. The complementary nature of the fragmentation of these two species recommends the study of both by MS/MS when determining the structure or confirming the identity of these biomaterials.     

Effect of Cationic Lipid Nanoparticle Loaded siRNA with Stearylamine against Chikungunya Virus

Chikungunya is an infectious disease caused by mosquito-transmitted chikungunya virus (CHIKV). It was reported that NS1 and E2 siRNAs administration demonstrated CHIKV inhibition in in vitro as well as in vivo systems. Cationic lipids are promising for designing safe non-viral vectors and are beneficial in treating chikungunya. In this study, nanodelivery systems (hybrid polymeric/solid lipid nanoparticles) using cationic lipids (stearylamine, C9 lipid, and dioctadecylamine) and polymers (branched PEI-g-PEG -PEG) were prepared, characterized, and complexed with siRNA. The four developed delivery systems (F1, F2, F3, and F4) were assessed for stability and potential toxicities against CHIKV. In comparison to the other nanodelivery systems, F4 containing stearylamine (Octadecylamine; ODA), with an induced optimum cationic charge of 45.7 mV in the range of 152.1 nm, allowed maximum siRNA complexation, better stability, and higher transfection, with strong inhibition against the E2 and NS1 genes of CHIKV. The study concludes that cationic lipid-like ODA with ease of synthesis and characterization showed maximum complexation by structural condensation of siRNA owing to high transfection alone. Synergistic inhibition of CHIKV along with siRNA was demonstrated in both in vitro and in vivo models. Therefore, ODA-based cationic lipid nanoparticles can be explored as safe, potent, and efficient nonviral vectors overcoming siRNA in vivo complexities against chikungunya.     

Quality Related Safety Evaluation of a South African Traditional Formulation (PHELA®) as Novel Anti-Biofilm Candidate

A South African traditional formulation, PHELA^®, is consumed by the traditional people for severe chest problems with coughing, diarrhea, oral ulcers etc. The present study focused on establishing the anti-infective properties of a safe and standardized poly-herbal formulation through a series of criteria and specifications.     

Biofortification—A Frontier Novel Approach to Enrich Micronutrients in Field Crops to Encounter the Nutritional Security

Globally, many developing countries are facing silent epidemics of nutritional deficiencies in human beings and animals. The lack of diversity in diet, i.e., cereal-based crops deficient in mineral nutrients is an additional threat to nutritional quality. The present review accounts for the significance of biofortification as a process to enhance the productivity of crops and also an agricultural solution to address the issues of nutritional security. In this endeavor, different innovative and specific biofortification approaches have been discussed for nutrient enrichment of field crops including cereals, pulses, oilseeds and fodder crops. The agronomic approach increases the micronutrient density in crops with soil and foliar application of fertilizers including amendments. The biofortification through conventional breeding approach includes the selection of efficient genotypes, practicing crossing of plants with desirable nutritional traits without sacrificing agricultural and economic productivity. However, the transgenic/biotechnological approach involves the synthesis of transgenes for micronutrient re-translocation between tissues to enhance their bioavailability. Soil microorganisms enhance nutrient content in the rhizosphere through diverse mechanisms such as synthesis, mobilization, transformations and siderophore production which accumulate more minerals in plants. Different sources of micronutrients viz. mineral solutions, chelates and nanoparticles play a pivotal role in the process of biofortification as it regulates the absorption rates and mechanisms in plants. Apart from the quality parameters, biofortification also improved the crop yield to alleviate hidden hunger thus proving to be a sustainable and cost-effective approach. Thus, this review article conveys a message for researchers about the adequate potential of biofortification to increase crop productivity and nourish the crop with additional nutrient content to provide food security and nutritional quality to humans and livestock.     

Palladium-catalyzed selective C–C bond cleavage and stereoselective alkenylation between cyclopropanol and 1,3-diyne: one-step synthesis of diverse conjugated enynes

The stereoselective synthesis of 1,3-enynes from 1,3-diynes is demonstrated by palladium-catalyzed selective C–C bond cleavage of cyclopropanol. Exclusive formation of mono-alkenylated adducts was achieved by eliminating the possibility of di-functionalization with high stereoselectivity. Indeed, this protocol worked very well with electronically and sterically diverse substrates. Several studies, including deuterium labeling experiments and intermolecular competitive experiments, were carried out to understand the mechanistic details. The atomic-level mechanism followed in the catalytic process was also validated using DFT calculations, and the rate-controlling states in the catalytic cycle were identified. Furthermore, preliminary mechanistic investigations with radical scavengers revealed the non-involvement of the radical pathway in this transformation.

Palladium-catalyzed tandem activation and functionalization of readily accessible cyclopropanols have been demonstrated to access valuable conjugated enynes from 1,3-diynes with high stereo-selectivity.     

Multiple comparisons with a control in direction-mixed families of hypothesis under heteroscedasticity

For general inferential families with a mixture of one- and two-sided inferences two procedures are proposed to compare several treatments with a control under heteroscedasticity. Critical constants required for the proposed procedures are tabulated, and a numerical example is given.     

A multiplicative Gauss-Newton minimization algorithm:Theory and application to exponential functions

Multiplicative calculus(MUC) measures the rate of change of function in terms of ratios, which makes the exponential functions significantly linear in the framework of MUC.Therefore, a generally non-linear optimization problem containing exponential functions becomes a linear problem in MUC. Taking this as motivation, this paper lays mathematical foundation of well-known classical Gauss-Newton minimization(CGNM) algorithm in the framework of MUC. This paper formulates the mathematical derivation of proposed method named as multiplicative Gauss-Newton minimization(MGNM) method along with its convergence properties.The proposed method is generalized for n number of variables, and all its theoretical concepts are authenticated by simulation results. Two case studies have been conducted incorporating multiplicatively-linear and non-linear exponential functions. From simulation results, it has been observed that proposed MGNM method converges for 12972 points, out of 19600 points considered while optimizing multiplicatively-linear exponential function, whereas CGNM and multiplicative Newton minimization methods converge for only 2111 and 9922 points, respectively. Furthermore, for a given set of initial value, the proposed MGNM converges only after 2 iterations as compared to 5 iterations taken by other methods. A similar pattern is observed for multiplicatively-non-linear exponential function. Therefore, it can be said that proposed method converges faster and for large range of initial values as compared to conventional methods.