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Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model1. Recently, the clinically vital but also highly renal-toxic small-molecule natural product amphotericin B was instead found to kill fungi primarily by forming extramembraneous sponge-like aggregates that extract ergosterol from lipid bilayers2-6. Here we show that rapid and selective extraction of fungal ergosterol can yield potent and renal-sparing polyene antifungals. Cholesterol extraction was found to drive the toxicity of amphotericin B to human renal cells. Our examination of high-resolution structures of amphotericin B sponges in sterol-free and sterol-bound states guided us to a promising structural derivative that does not bind cholesterol and is thus renal sparing. This derivative was also less potent because it extracts ergosterol more slowly. Selective acceleration of ergosterol extraction with a second structural modification yielded a new polyene, AM-2-19, that is renal sparing in mice and primary human renal cells, potent against hundreds of pathogenic fungal strains, resistance evasive following serial passage in vitro and highly efficacious in animal models of invasive fungal infections. Thus, rational tuning of the dynamics of interactions between small molecules may lead to better treatments for fungal infections that still kill millions of people annually7,8 and potentially other resistance-evasive antimicrobials, including those that have recently been shown to operate through supramolecular structures that target specific lipids9.

The novel coronavirus disease 2019 (COVID‐19) has been a severe health issue affecting the respiratory system and spreads very fast from one human to other overall countries. For controlling such disease, limited diagnostics techniques are utilized to identify COVID‐19 patients, which are not effective. The above complex circumstances need to detect suspected COVID‐19 patients based on routine techniques like chest X‐Rays or CT scan analysis immediately through computerized diagnosis systems such as mass detection, segmentation, and classification. In this paper, regional deep learning approaches are used to detect infected areas by the lungs' coronavirus. For mass segmentation of the infected region, a deep Convolutional Neural Network (CNN) is used to identify the specific infected area and classify it into COVID‐19 or Non‐COVID‐19 patients with a full‐resolution convolutional network (FrCN). The proposed model is experimented with based on detection, segmentation, and classification using a trained and tested COVID‐19 patient dataset. The evaluation results are generated using a fourfold cross‐validation test with several technical terms such as Sensitivity, Specificity, Jaccard (Jac.), Dice (F1‐score), Matthews correlation coefficient (MCC), Overall accuracy, etc. The comparative performance of classification accuracy is evaluated on both with and without mass segmentation validated test dataset. [ABSTRACT FROM AUTHOR]

An efficient protocol for the synthesis of pyrrolo[1,2-a]indole derivatives having sulfide functionality using cascade radical cyclization on propargylindole is described. The nature of the substituents at the propargylic carbon bearing nitrogen of the indole has a profound effect on the rate, yield, and nature of the product obtained by the cascade radical cyclization. An expeditious one-pot route for cascade radical cyclization--desulfurization is also presented. Products obtained were elaborated to the core of the putative structure of the yuremamine and indoline derivative with five contiguous stereocenters. [ABSTRACT FROM AUTHOR]

A transition metal free, acid promoted cascade hydroalkoxylation-formal [4+2] cycloaddition of various alkynols with salicylaldehyde is demonstrated for the synthesis of tetrahydrofurano/pyrano-chromenes and spiroketals. In general, alkynols underwent hydroalkoxylations in an endo- dig manner when internal alkynes were used to furnish the heteroannular ketals, whereas terminal alkynes proceeded in an exo- dig fashion leading to spiroketals. The study revealed that intramolecular hydroalkoxylation of alkynols is a preferred path over a generation of oxonium ions when coupling partner is salicylaldehyde. This metal-free transformation provides a new avenue for the stereoselective synthesis of tetrahydrofurano- and pyrano-chromenes in an expeditious manner. [ABSTRACT FROM AUTHOR]

When users input their passwords in a public place, they may be at risk of attackers stealing their password. An attacker can capture a password by direct observation or by recording the individual's authentication session. This is referred to as shoulder-surfing and is a known risk, of special concern when authenticating in public places. Attacker can also use various keylogger tools which are freely available over internet. This paper reports on the design and evaluation of a game-like graphical method of authentication that is resistant to shoulder-surfing. Since conventional password schemes are vulnerable to shoulder surfing, many shoulder surfing resistant graphical password schemes have been proposed. However, as most users are more familiar with textual passwords than pure graphical passwords, text-based graphical password schemes have been proposed. Unfortunately, none of existing text-based shoulder surfing resistant graphical password schemes is both secure and efficient enough. In this paper, we propose an improved text-based shoulder surfing resistant graphical password scheme by using colors. In the proposed scheme, the user can easily and efficiently login system. Next, we analyze the security and usability of the proposed scheme, and show the resistance of the proposed scheme to shoulder surfing and accidental login. [ABSTRACT FROM AUTHOR]

The synthetic utility of the intramolecular Heck reaction is demonstrated in the racemic formation of monocerolide (VIII). [ABSTRACT FROM AUTHOR]