Electric Fields Are a Key Determinant of Carbapenemase Activity in Class A ß-Lactamases.

Resistance to antibiotics is a public health crisis. Although carbapenems are less susceptible to resistance than other ß-lactam antibiotics, ß-lactamases mediating resistance against these drugs are spreading. Here, we dissect the contributions of electric fields to carbapenemase activity in class A ß-lactamases. We perform QM/MM molecular dynamics simulations of meropenem acyl-enzyme hydrolysis that correctly discriminate carbapenemases. Electric field analysis shows that active-site fields in the deacylation transition state and tetrahedral intermediate are important determinants of activity. The active-site fields identify several residues, some distal, that distinguish efficient carbapenemases. Our field analysis script (www.github.com/bunzela/FieldTools) may help in understanding and combating antibiotic resistance.

Impact of bacterial synthesized nanoparticles on quality attributes and postharvest disease control efficacy of apricot and loquat.

Postharvest fungal attacks on fruits such as apricots and loquats are common. Diseased fruit samples were collected from Murree's local fruit markets. The disease-causing pathogens were identified utilizing molecular, microscopic, and morphological characteristics. Alternaria alternata and Aspergillus niger were identified as the pathogens responsible for brown rot in loquat and black rot in apricot. To combat these fruit diseases, iron oxide (Fe2 O3 ) nanoparticles were synthesized using Bacillus subtilis and were characterized using various techniques. X-ray diffraction examination validated the size of iron oxide nanoparticles. The presence of several capping agents in the synthesized nanoparticles was confirmed by Fourier transform infrared analysis. Scanning electron microscopy revealed the spherical morphology of nanoparticles, whereas energy-dispersive X-ray proved the presence of different elemental compositions. After completing antifungal activities in vitro and in vivo, it was discovered that a nanoparticle concentration of 1.0 mg/mL efficiently suppressed the growth of fungal mycelia. Fungi growth was effectively inhibited in fruit samples treated with 1.0 mg/mL nanoparticles. The results of successful in vitro and in vivo antifungal activities imply that iron oxide (Fe2 O3 ) nanoparticles play an important role in ensuring fruit quality against pathogenic attacks. Bacterial-mediated iron oxide can be widely used because it is less expensive and less harmful to the environment than chemically manufactured fertilizers.

Application of phyto-fabricated zinc oxide nanoparticles to diminish brown spot of pear whilst maintaining its quality.

Pyrus communis is a common fruit of temperate region, its domestication and origin is at two different points, Asia and China. Pear fruits bearing brown spot symptoms were picked, and pathogen was isolated and poured on Potato Dextrose Agar (PDA) media. On basis of molecular and molecular analyses, this isolated pathogen was identified as Alternaria alternata. Zinc oxide nanoparticles (ZnO NPs) were prepared from Theveti peruviana leaf extract and were characterized through various techniques Fourier Transform Infrared Spectroscopy (FTIR) analysis of prepared ZnO NPs depicted the presence of agents responsible for stabilization and reduction such as alkenes, alkynes, nitro compounds, alkyl halides, aromatic compounds and aliphatic amines. X-ray diffraction (XRD) analysis confirmed the size (27 nm) and crystalline nature of ZnO NPs. Scanning electron microscopy (SEM) depicted the irregular shape of the prepared ZnO NPs. Mass percentage of zinc (79.84%) and oxygen (20.16%) was depicted using Energy Dispersive X-Ray (EDX) analysis. The in vitro and in vivo antifungal activity (A.F) of prepared NPs against A. alternata was confirmed by poisoned food technique and wound inoculation method. On the basis of which it was concluded that 1.0 mg/mL concentration of ZnO NPs could effectively inhibit A. alteranata growth and minimize the risk of brown spot of pear. SEM images of A. alternata under 1 mg/mL NPs showed the deformation in morphology of A. alternata. ZnO NPs also aided in the preservation of its various organoleptic and biochemical properties. The high percentage of soluble solids, firmness, ascorbic acid and sugars demonstrated its high quality. It has been concluded that 1 mg/mL ZnO NPs can effectively control brown spot of pear while maintaining its quality. In addition, the method might be applied to control emerging diseases in an ecofriendly way to meet the global food demand. RESEARCH HIGHLIGHTS: Isolation and characterization of pathogen causing brown spot in pear. Pathogenicity of A. alternata was checked on healthy fruits. Thevetia peruviana leaf extract was used for the synthesis, characterization and antifungal assay of ZnO Nanoparticles. Green synthesized nanoparticles can be economically effective alternative fungicide for the large scale in agriculture fields.

Multitargeted Molecular Docking and Dynamic Simulation Studies of Bioactive Compounds from Rosmarinus officinalis against Alzheimer's Disease.

Alzheimer's disease (AD) has been associated with the hallmark features of cholinergic dysfunction, amyloid beta (Aß) aggregation and impaired synaptic transmission, which makes the associated proteins, such as ß-site amyloid precursor protein cleaving enzyme 1 (BACE I), acetylcholine esterase (AChE) and synapsin I, II and III, major targets for therapeutic intervention. The present study investigated the therapeutic potential of three major phytochemicals of Rosmarinus officinalis, ursolic acid (UA), rosmarinic acid (RA) and carnosic acid (CA), based on their binding affinity with AD-associated proteins. Detailed docking studies were conducted using AutoDock vina followed by molecular dynamic (MD) simulations using Amber 20. The docking analysis of the selected molecules showed the binding energies of their interaction with the target proteins, while MD simulations comprising root mean square deviation (RMSD), root mean square fluctuation (RMSF) and molecular mechanics/generalized born surface area (MM/GBSA) binding free energy calculations were carried out to check the stability of bound complexes. The drug likeness and the pharmacokinetic properties of the selected molecules were also checked through the Lipinski filter and ADMETSAR analysis. All these bioactive compounds demonstrated strong binding affinity with AChE, BACE1 and synapsin I, II and III. The results showed UA and RA to be potential inhibitors of AChE and BACE1, exhibiting binding energies comparable to those of donepezil, used as a positive control. The drug likeness and pharmacokinetic properties of these compounds also demonstrated drug-like characteristics, indicating the need for further in vitro and in vivo investigations to ascertain their therapeutic potential for AD.