Evolutionary trends of respiratory syncytial viruses: Insights from large-scale surveillance and molecular dynamics of G glycoprotein.

Human respiratory syncytial virus (RSV) is an underlying cause of lower respiratory illnesses in children, elderly and immunocompromised adults. RSV contains multiple structural and non-structural proteins with two major glycoproteins that control the initial phase of infection, fusion glycoprotein and the attachment (G) glycoprotein. G protein attaches to the ciliated cells of airways initiating the infection. The hypervariable G protein plays a vital role in evolution of RSV strains. We employed multiple bioinformatics tools on systematically accessed large-scale data to evaluate mutations, evolutionary history, and phylodynamics of RSV. Mutational analysis of central conserved region (CCR) on G protein-coding sequences between 163 and 189 positions revealed frequent mutations at site 178 in human RSV (hRSV) A while arginine to glutamine substitutions at site 180 positions in hRSV B, remained prevalent from 2009 to 2014. Phylogenetic analysis indicates multiple signature mutations within G protein responsible for diversification of clades. The USA and China have highest number of surveillance records, followed by Kenya. Markov Chain Monte Carlo Bayesian skyline plot revealed that RSV A evolved steadily from 1990 to 2000, and rapidly between 2003 and 2005. Evolution of RSV B continued from 2003 to 2022, with a high evolution stage from 2016 to 2020. Throughout evolution, cysteine residues maintained their strict conserved states while CCR has an entropy value of 0.0039(±0.0005). This study concludes the notion that RSV G glycoprotein is continuously evolving while the CCR region of G protein maintains its conserved state providing an opportunity for CCR-specific monoclonal antibodys (mAbs) and inhibitors as potential candidates for immunoprophylaxis.

Construction of a Pentacyclic Framework Enabled by Nickel Catalysis.

We present a novel nickel-catalyzed reaction of indole-tethered 2-alkynylphenol esters with various (hetero)aryl boronic acids, resulting in the synthesis of diversely functionalized pentacyclic benzofurocyclohepta[b]indole derivatives. This unprecedented cascade reaction involves the arylative cyclization of alkynes, nucleophilic attack of the indole moiety on the oxonium ion intermediate, 1,2-alkyl group migration, and aromatization. The synthesized molecules exhibit exceptional cytotoxicity against multiple cancer cell lines while maintaining biocompatibility toward healthy cells.

Breaking down the cell wall: Still an attractive antibacterial strategy.

Since the advent of penicillin, humans have known about and explored the phenomenon of bacterial inhibition via antibiotics. However, with changes in the global environment and the abuse of antibiotics, resistance mechanisms have been selected in bacteria, presenting huge threats and challenges to the global medical and health system. Thus, the study and development of new antimicrobials is of unprecedented urgency and difficulty. Bacteria surround themselves with a cell wall to maintain cell rigidity and protect against environmental insults. Humans have taken advantage of antibiotics to target the bacterial cell wall, yielding some of the most widely used antibiotics to date. The cell wall is essential for bacterial growth and virulence but is absent from humans, remaining a high-priority target for antibiotic screening throughout the antibiotic era. Here, we review the extensively studied targets, i.e., MurA, MurB, MurC, MurD, MurE, MurF, Alr, Ddl, MurI, MurG, lipid A, and BamA in the cell wall, starting from the very beginning to the latest developments to elucidate antimicrobial screening. Furthermore, recent advances, including MraY and MsbA in peptidoglycan and lipopolysaccharide, and tagO, LtaS, LspA, Lgt, Lnt, Tol-Pal, MntC, and OspA in teichoic acid and lipoprotein, have also been profoundly discussed. The review further highlights that the application of new methods such as macromolecular labeling, compound libraries construction, and structure-based drug design will inspire researchers to screen ideal antibiotics.

Current challenges of hydrothermal treated wastewater (HTWW) for environmental applications and their perspectives: A review.

Hydrothermal treatment (HT) is an emerged thermochemical approach for the utilization of biomass. In the last decade, intense research has been conducted on bio-oil and hydrochar, during which extensive amount of hydrothermal treated wastewater (HTWW) is produced, containing large amount of organic compounds along with several toxic chemicals. The composition of HTWW is highly dependent on the process conditions and organic composition of biomass, which determines its further utilization. The current study provides a comprehensive overview of recent advancements in HTWW utilization and its properties which can be changed by varying different parameters like temperature, residence time, solid concentration, mass ratio and catalyst including types of biomasses. HTWW characterization, parameters, reaction mechanism and its application were also summarized. By considering the challenges of HTWW, some suggestions and proposed methodology to overcome the bottleneck are provided.

Phosphorus containing layered quadruple hydroxide electrode materials on lab waste recycled flexible current collector.

From environmental waste to energy storage, waste boxes converted into conductive electrodes to further grow active materials has been an interesting way of upcycling. In this study, we transformed waste boxes of KIMTECH Kimwipes® into conductive f-MWCNTs light and flexible substrate (LFS) as current collectors. Then, undoped and P-doped active materials consisting of layered quadruple hydroxides (LQH) was successfully grown on the conductive f-MWCNTs/LFS. Specifically, P-doped f-MWCNTs/LQH demonstrates 1.8 times the capacitance of an undoped f-MWCNTs/LQH. Such conversion of waste boxes not only offers a useful way of reusing waste papers which commonly ends in landfills, but the inexpensive method also offers an extreme way of cutting cost in developing conductive substrates. Also, the effective strategy of synthesizing active materials on the conductive f-MWCNTs/LFS paves its way as potential cheap electrodes of the future generation.

Sustainable radical approaches for cross electrophile coupling to synthesize trifluoromethyl- and allyl-substituted tert-alcohols.

Trifluoromethylated molecules have gained privileged recognition among the medicinal and pharmaceutical chemists. Sustainable photoredox- and electrochemical processes were employed to facilitate the relatively less explored radical cross-electrophile coupling to access trifluoromethyl- and allyl-substituted tert-alcohols. Reactions proceed through trifluoromethyl ketyl radical and allyl radical intermediates, which undergo challenging radical-radical cross-coupling. The developed transformations are mild and chemo-selective to give cross-coupled products and deliver a wide range of valuable trifluoromethyl- and allyl-containing tertiary alcohols. Both processes can also be applied for the synthesis of amine variant containing trifluoromethyl and allyl moiety, which is considered as amide bioisostere.