A novel chemical biology and computational approach to expedite the discovery of new-generation polymyxins against life-threatening Acinetobacter baumannii

Multidrug-resistant Gram-negative bacteria represent a major medical challenge worldwide. New antibiotics are desperately required with ‘old’ polymyxins often being the only available therapeutic option. Here, we systematically investigated the structure–activity relationship (SAR) of polymyxins using a quantitative lipidomics-informed outer membrane (OM) model of Acinetobacter baumannii and a series of chemically synthesized polymyxin analogs. By integrating chemical biology and all-atom molecular dynamics simulations, we deciphered how each residue of the polymyxin molecule modulated its conformational folding and specific interactions with the bacterial OM. Importantly, a novel designed polymyxin analog FADDI-287 with predicted stronger OM penetration showed improved in vitro antibacterial activity. Collectively, our study provides a novel chemical biology and computational strategy to expedite the discovery of new-generation polymyxins against life-threatening Gram-negative ‘superbugs’.

Multidrug-resistant Gram-negative bacteria have been an urgent threat to global public health. Novel antibiotics are desperately needed to combat these ''superbugs''.     

Lanthanum sulfide-manganese sulfide/graphene oxide (La2S3-MnS/GO) composite thin film as an electrocatalyst for oxygen evolution reactions

Journal of Solid State Electrochemistry - In this study, the lanthanum sulfide-manganese sulfide (La2S3-MnS) nanosheet composite films with different thicknesses were grown on graphene oxide (GO)...     

Unlocking the Chain-Walking Process in Gold Catalysis**

The successful realization of gold-catalyzed chain-walking reactions, facilitated by ligand-enabled Au(I)/Au(III) redox catalysis, has been reported for the first time. This breakthrough has led to the development of gold-catalyzed annulation reaction of alkenes with iodoarenes by leveraging the interplay of chain-walking and π-activation reactivity mode. The reaction mechanism has been elucidated through comprehensive experimental and computational studies.     

Some classes of Kenmotsu manifolds with respect to semi-symmetric metric connection

In this paper, we study conharmonic curvature tensor in Kenmotsu manifolds with respect to semi-symmetric metric connection and also characterize conharmonically flat, conharmonically semi-symmetric and φ-conharmonically flat Kenmotsu manifolds with respect to semi-symmetric metric connection.     

On the length equalities for one-dimensional rings

In this article we characterize noetherian local one-dimensional analytically irreducible and residually rational domains (R,m_R) which are non-Gorenstein, the non-negative integer is equal to τ_R-1 and ?(R/(C+xR))=2, where τ_R is the Cohen-Macaulay type of R, C is the conductor of R in the integral closure of R in its quotient field Q(R) and xR is a minimal reduction of m by giving some conditions on the numerical semi-group v(R) of R.     

PRESSURE-VELOCITY EQUILIBRIUM HYDRODYNAMIC MODELS

This article describes mathematical models for phase separated mixtures of materials that are in pressure and velocity equilibrium but not necessarily temperature equilibrium. General conditions for constitutive models for such mixtures that exhibit a single mixture sound speed are discussed and specific examples are described.     

Triple diffusive mixed convection flow in a duct using convective boundary conditions

The motivation of the current article is to explore a numerical investigation on steady triply diffusive convection in a vertical channel. Heat is exchanged from the external fluid with the plates. The reference temperature is taken as equal and also as different for the external fluid. Solutions in the absence of viscous dissipation and buoyancy forces are also obtained as special cases. General solutions including the effects of viscous dissipation and buoyancy forces are obtained analytically using the method of perturbation. The analytical solutions can be used only if the Brinkman number is small. Hence to know the flow properties for all values of Brinkman number, we resort to numerical solutions. The effects of thermal Grashof number, solutal Grashof number, and the chemical reaction parameter on the flow field are evaluated numerically. The obtained results are validated against previously published results for special case of the problems.     

Thick Domain Walls Coupled with Viscous Fluid and Electromagnetic Field in Lyra Geometry

In this paper, we have obtained plane symmetric cosmological models of thick domain walls with viscous field coupled with electromagnetic field in the framework of Lyra geometry, by using equation of state. Physical and geometrical implications of the models are also discussed in the presence of magnetic field.     

A simple model potential description of the alkaline earth isoelectronic sequences

We have developed a simple model potential with a hard core and the correct large-r Coulombic behaviour, to describe the interaction of an electron with a closed shell. One has an exact, analytic ground state wave function for this potential. This potential is used to develop two-electron perturbed and unperturbed wave functions, with the correct asymptotic behaviour and cusp conditions. These wave functions allow us to obtain accurate values for the two-electron energies, polarisabilities, hyperpolarisabilities, and dispersion coefficients of alkaline earth sequences. Many of these results are the only ones available in the literature. Received 29 July 1999 and Received in final form 16 November 1999     

Palladium nanoparticles/wool keratin-assisted carbon composite-modified flexible and disposable electrochemical solid-state pH sensor

Several p H-dependent processes and reactions take place in the human body;hence,the p H of body fluids is the best indicator of disturbed health conditions.However,accurate and real-time diagnosis of the p H of body fluids is complicated because of limited commercially available p H sensors.Hence,we aimed to prepare a flexible,transparent,disposable,userfriendly,and economic strip-based solid-state p H sensor using palladium nanoparticles(Pd NPs)/N-doped carbon(NC)composite material.The Pd NPs/NC composite material was synthesized using wool keratin(WK)as a precursor.The insitu prepared Pd NPs played a key role in the controlled switching of protein structure to the N-doped carbon skeleton withπ–πarrangement at the mesoscale level,which mimics the A–B type polymeric structure,and hence,is highly susceptible to H+ions.The optimized carbonization condition in the presence of Pd NPs showed that the material obtained using a modified Ag/Ag Cl reference electrode had the highest p H sensitivity with excellent stability and durability.The optimized p H sensor showed high specificity and selectivity with a sensitivity of 55 m V/p H unit and a relative standard deviation of 0.79%.This study is the first to synthesize Pd NPs using WK as a stabilizing and reducing agent.The applicability of the sensor was investigated for biological samples,namely,saliva and gastric juices.The proposed protocol and material have implications in solid-state chemistry,where biological material will be the best choice for the synthesis of materials with anticipated performance.