Biogenic synthesis of levofloxacin-loaded copper oxide nanoparticles using Cymbopogon citratus: A green approach for effective antibacterial applications.

Despite the success of antibiotics in medicine, the treatment of bacterial infection is still challenging due to emerging resistance and suitable drug delivery system, therefore, innovative approaches focused on nanoparticles based antimicrobial drug delivery systems are highly desired. This research aimed to synthesize Cymbopogon citratus (C. citratus) aqueous extract-mediated copper oxide (CuO-Nps) conjugated with levofloxacin (LFX). The synthesized CuO NPs-LFX nano conjugate was confirmed by analysis using scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and infrared and ultraviolet/visible spectroscopy. Antibacterial activities were assessed in vitro through the agar well diffusion method against six bacterial strains of clinical relevance. CuO NPs confirmed by UV-Vis analysis absorption peak observed at 380 nm. TGA analysis showed 8.98% weight loss between the 400-800 °C temperature range. The functional group's presence was confirmed by FTIR analysis. Spherical shape nanoparticles with an average particle size of 55 nm were recorded by FESEM. Results from agar well diffusion assay showed that CuO NPs-LFX prohibited the development of both gram-positive and gram-negative bacteria at all established concentrations, and the antibacterial propensity was more pronounced as compared to bare CuO NPs, Levofloxacin and C. citratus aqueous extract alone. The results showed that gram-negative bacteria are more susceptible to CuO NPs-LFX nano conjugate and at 10 µgmL-1 concentration, form a 10.1 mm zone of inhibition (ZOI), whereas gram-positive bacteria on the same concentration form 9.5 mm ZOI. LFX-loaded CuO NPs antibacterial activity was observed higher than plant extract, bare CuO NPs, and standard drug (Levofloxacin). This study provides a novel approach for the fabrication of biogenic CuO NPs with antibacterial drug levofloxacin and their usage as nano antibiotic carriers against pathogenic bacteria, especially antibiotic-resistant microbes.

Correction: Parallel operated hybrid Arithmetic-Salp swarm optimizer for optimal allocation of multiple distributed generation units in distribution networks.

[This corrects the article DOI: 10.1371/journal.pone.0264958.].

A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.

EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 ∗)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1.

Parallel operated hybrid Arithmetic-Salp swarm optimizer for optimal allocation of multiple distributed generation units in distribution networks.

The installation of Distributed Generation (DG) units in the Radial Distribution Networks (RDNs) has significant potential to minimize active power losses in distribution networks. However, inaccurate size(s) and location(s) of DG units increase power losses and associated Annual Financial Losses (AFL). A comprehensive review of the literature reveals that existing analytical, metaheuristic and hybrid algorithms employed on DG allocation problems trap in local or global optima resulting in higher power losses. To address these limitations, this article develops a parallel hybrid Arithmetic Optimization Algorithm and Salp Swarm Algorithm (AOASSA) for the optimal sizing and placement of DGs in the RDNs. The proposed parallel hybrid AOASSA enables the mutual benefit of both algorithms, i.e., the exploration capability of the SSA and the exploitation capability of the AOA. The performance of the proposed algorithm has been analyzed against the hybrid Arithmetic Optimization Algorithm Particle Swarm Optimization (AOAPSO), Salp Swarm Algorithm Particle Swarm Optimization (SSAPSO), standard AOA, SSA, and Particle Swarm Optimization (PSO) algorithms. The results obtained reveals that the proposed algorithm produces quality solutions and minimum power losses in RDNs. The Power Loss Reduction (PLR) obtained with the proposed algorithm has also been validated against recent analytical, metaheuristic and hybrid optimization algorithms with the help of three cases based on the number of DG units allocated. Using the proposed algorithm, the PLR and associated AFL reduction of the 33-bus and 69-bus RDNs improved to 65.51% and 69.14%, respectively. This study will help the local distribution companies to minimize power losses and associated AFL in the long-term planning paradigm.

Ethnobotanical and Biochemical Study of Berberis lycium Royle Collected from Different Areas of Azad Jammu and Kashmir.

Berberis lycium Royle has a long history of medicinal uses to treat different diseases. It naturally grows on the mountains of Indian subcontinent. Its ethnobotanical and biochemical study from the state of Azad Jammu and Kashmir (AJ&K) was not previously explored. So, the objective of the current study was to explore the ethnobotanical and biochemical properties of the B. lycium Royle population of AJ&K. For this purpose, samples of B. lycium Royle were randomly collected from five districts of Azad Jammu and Kashmir, including thirty-five locations. Demographic features of informants such as plant part used, methods of preparation, modes of administration, conservation status, and ethnomedicinal uses were documented. It was used for treating different diseases such as diabetes, arthritis, joint pain, and stomach ulcer. This plant is very famous for providing medicinal roots, leaves, and fruits which are extensively used in many parts of the world. The biochemical analysis was conducted for total phenolic contents (TPC), chlorophyll contents, and antioxidant activity. The highest level of TPC found was 88.66 ± 1.07 µg/g of gallic acid equivalent phenolic (GAE) from leaves collected from Patikka (Chanjhal), Muzaffarabad District, AJ&K. The highest total chlorophyll contents (3.75 ± 0.53 µg/ml) were found in samples collected from Sathrian, Neelum District. The highest antioxidant activity with lowest IC50 value (33.26 µg/ml) was obtained from the root of sample collected from Bakreyali, Muzaffarabad District, as compared with other districts. The concentration of berberine was found to be 4.76 percent in the root bark of B. lycium Royle, estimated by high-performance liquid chromatography (HPLC). In syrup composition, 0.95 mg/5 ml of berberine was used. Hence, it is concluded that amongst the five districts, the plant parts (stem, fruits, and root) collected from Muzaffarabad District, AJ&K, showed the highest medicinal potential due to its unique climatic conditions.

Discovery of a Tin-Piperonal-Entecavir Schiff Base Compound That Overcomes Multidrug Resistance by Inhibiting P-Glycoprotein.

The presence of P-glycoprotein in the human intestine represents a significant barrier to effective drug therapy. These proteins form a multidrug-resistant barrier to most drugs, especially those administered orally. Thus, strategies are needed to prepare molecules to combat these resistant proteins and enable an increase in drug efficacy. We developed a novel tin-Schiff base complex using an ultrasonic bath, a new technique in small molecule synthesis. New bond formation was confirmed using ultraviolet and Fourier transform spectroscopies. A computational study was carried out using Absorption, Distribution, Metabolism, Excretion and Toxicity software. The novel tin-entecavir (ETV)-piperonal Schiff base acts as a potent P-glycoprotein inhibitor, which overcomes the multidrug resistance to all drugs that are substrates for P-glycoprotein. Further study showed that the novel tin complex is less toxic than the parent compound at the same dose. The development of this tin-piperonal-ETV Schiff base complex is a major breakthrough for overcoming multidrug resistance barriers and can be applied to other drug molecules.