Mechanical strain

Understanding the reaction mechanism and origin of regioselectivity in transition metal-catalyzed C-H activation/annulation reactions with 1,3-diynes has remained an intriguing challenge. In this article, to establish the mechanism and decipher the origin of regioselectivity, we report a detailed computational density functional theory-based mechanistic investigation on the recently developed Ru(II)-catalyzed [4 + 2] annulation of N -chlorobenzamides with 1,3-diynes for the synthesis of 3-alkynylated isoquinolone derivatives...

This study aimed to investigate azole resistance mechanisms in Aspergillus flavus, which involve cyp 51A and cyp 51B genes. Real-time Reverse Transcriptase qPCR method was applied to determine the overexpression of cyp 51A and cyp 51B genes for 34 A. flavus isolates. PCR sequencing of these two genes was used to detect the presence of gene mutations. Susceptibility test found sensitivity to voriconazole (VOR) in all strains. 14.7% and 8.8% of isolates were resistant to itraconazole (IT) and posaconazole (POS), respectively, with a cross-resistance in 5...

The complex relationship between probiotics and human health goes beyond their traditional function in gut health, generating considerable interest for their broad potential in disease treatment. This review explores the various functions of probiotics, highlighting their impact on the immune system, their benefits for gut and oral health, their effects on metabolic and neurological disorders, and their emerging potential in cancer therapy. We give significant importance to studying the effects of probiotics on the gut-brain axis, revealing new and non-invasive therapeutic approaches for complex neurological disorders...

UNLABELLED: Plasmids play important roles in microbial ecosystems, serving as carriers of antibiotic resistance and virulence. In the laboratory, they are essential tools for genetic manipulation and recombinant protein expression. We uncovered an intriguing survival phenotype in a fraction of the bacterial population while using plasmid-mediated arabinose-inducible gene expression to monitor the production of toxic ParE proteins. This phenotype was not correlated with changes to the plasmid sequence and could not be rescued by increasing arabinose uptake...

Adherent and invasive Escherichia coli (AIEC) is a pathobiont that is involved in the onset and exacerbation of Crohn's disease. Although the inducible expression of virulence traits is a critical step for AIEC colonization in the host, the mechanism underlying AIEC colonization remains largely unclear. We here showed that the two-component signal transduction system CpxRA contributes to AIEC gut competitive colonization by activating type 1 fimbriae expression. CpxRA from AIEC strain LF82 functioned as a transcriptional regulator, as evidenced by our finding that an isogenic cpxRA mutant exhibits reduced expression of cpxP , a known regulon gene...

UNLABELLED: Multi-resistant bacteria are a rapidly emerging threat to modern medicine. It is thus essential to identify and validate novel antibacterial targets that promise high robustness against resistance-mediating mutations. This can be achieved by simultaneously targeting several conserved function-determining protein-protein interactions in enzyme complexes from prokaryotic primary metabolism. Here, we selected two evolutionary related glutamine amidotransferase complexes, aminodeoxychorismate synthase and anthranilate synthase, that are required for the biosynthesis of folate and tryptophan in most prokaryotic organisms...

Four species of non-tuberculous mycobacteria (NTM) rated as biosafety level 1 or 2 (BSL-1/BSL-2) organisms and showing higher genomic similarity with Mycobacterium tuberculosis ( Mtb ) than previous comparator species Mycobacterium kansasii and Mycobacterium marinum were subjected to genomic and phenotypic characterization. These species named Mycobacterium decipiens , Mycobacterium lacus , Mycobacterium riyadhense, and Mycobacterium shinjukuense might represent "missing links" between low-virulent mycobacterial opportunists and the highly virulent obligate pathogen Mtb ...

UNLABELLED: Novel antimicrobial agents are needed to combat antimicrobial resistance. This study tested novel pentafluorosulfanyl-containing triclocarban analogs for their potential antibacterial efficacy. Standard procedures were used to produce pentafluorosulfanyl-containing triclocarban analogs. Twenty new compounds were tested against seven Gram-positive and Gram-negative indicator strains as well as 10 clinical isolates for their antibacterial and antibiofilm activity. Mechanistic investigations focused on damage to cell membrane, oxidizing reduced thiols, iron-sulfur clusters, and oxidative stress to explain the compounds' activity...

Aeromonas hydrophila, a prevalent pathogen in the aquaculture industry, poses significant challenges due to its drug-resistant strains. Moreover, residues of antibiotics like streptomycin, extensively employed in aquaculture settings, drive selective bacterial evolution, leading to the progressive development of resistance to this agent. However, the underlying mechanism of its intrinsic adaptation to antibiotics remains elusive. Here, we employed a quantitative proteomics approach to investigate the differences in protein expression between A...

The pursuit of fabricating high-performance graphene films has aroused considerable attention due to their potential for practical applications. However, developing both stretchable and tough graphene films remains a formidable challenge. To address this issue, we herein introduce mechanical bond to comprehensively improve the mechanical properties of graphene films, utilizing [2]rotaxane as the bridging unit. Under external force, the [2]rotaxane cross-link undergoes intramolecular motion, releasing hidden chain and increasing the interlayer slip distance between graphene nanosheets...

l-Phenylalanine (l-Phe) is widely used in the food and pharmaceutical industries. However, the biosynthesis of l-Phe using Escherichia coli remains challenging due to its lower tolerance to high concentration of l-Phe. In this study, to efficiently synthesize l-Phe, the l-Phe biosynthetic pathway was reconstructed by expressing the heterologous genes aroK1 , aroL1 , and pheA1 , along with the native genes aroA , aroC , and tyrB in the shikimate-producing strain E. coli SA09, resulting in the engineered strain E...

BACKGROUND AND OBJECTIVE: Osteoporosis is associated with bone microarchitecture alterations, and the depletion of estrogen during menopause is a major contributing factor to its development. The literature highlights the noteworthy role of gut microbiota in bone metabolism, particularly in the progression of osteoporosis. Periodontal disease leads to alveolar bone loss, which may be influenced by estrogen deficiency, and this mechanism is intricately associated with an imbalance in systemic microbiota...

Cyanobacteria, which have a photoautotrophic lifestyle, are threatened by ultraviolet solar rays and the reactive oxygen species generated during photosynthesis. They can adapt to environmental conditions primarily because of their DNA damage response and repair mechanisms, notably an efficient homologous recombination repair system. However, research on double-strand break (DSB) repair pathways, including the Holliday junction (HJ) resolution process, in Synechocystis sp. PCC6803 is limited. Here, we report that SynRuvC from cyanobacteria Synechocystis sp...

In heart disease patients, myocyte loss or malfunction invariably leads to fibrosis, involving the activation and accumulation of cardiac fibroblasts that deposit large amounts of extracellular matrix. Apart from the vital replacement fibrosis that follows myocardial infarction, ensuring structural integrity of the heart, cardiac fibrosis is largely considered to be maladaptive. Much work has focused on signaling pathways driving the fibrotic response, including TGF-β signaling and biomechanical strain...

In the search for new antibiotics, it is a common occurrence that already known molecules are "rediscovered" while new promising ones remain unnoticed. A possible solution to this problem may be the so-called "target-oriented" search, using special reporter microorganisms that combine increased antibiotic sensitivity with the ability to identify a molecule's damaging effect. The use of such test organisms makes it possible to discover new promising properties even in known metabolites. In this study, we used a high-throughput screening method based on the pDualrep2 dual reporter system, which combines high sensitivity through the use of modified strains of test organisms and makes it possible to easily and accurately identify the interaction mechanisms of a substance and a bacterial cell at the initial stages of screening...

The complement system is an innate immune mechanism against microbial infections. It involves a cascade of effector molecules that is activated via classical, lectin and alternative pathways. Consequently, many pathogens bind to or incorporate in their structures host negative regulators of the complement pathways as an evasion mechanism. Factor H (FH) is a negative regulator of the complement alternative pathway that protects "self" cells of the host from non-specific complement attack. FH has been shown to bind viruses including human influenza A viruses (IAVs)...

BACKGROUND AND AIMS: The "hypervirulent" variant of Klebsiella pneumoniae (hvKp) is an emerging pathogen that cause life-threatening infection. The present study was conducted to identify the prevalence of hvKp and to investigate the presence class 1, 2, and 3 integrons in these isolates. METHODS: A cross-sectional study was conducted at three teaching hospitals, Ahvaz, South-west of Iran, from January 1, 2019 to December 31, 2020. Samples were collected from inpatients and included only the first samples collected from each patient...

Background: Dormant ribosomes are typically associated with preservation factors to protect themselves from degradation under stress conditions. Stm1/SERBP1 is one such protein that anchors the 40S and 60S subunits together. Several proteins and tRNAs bind to this complex as well, yet the molecular mechanisms remain unclear. Methods: Here, we reported the cryo-EM structures of five newly identified Stm1/SERBP1-bound ribosomes. Results: These structures highlighted that eIF5A, eEF2, and tRNA might bind to dormant ribosomes under stress to avoid their own degradation, thus facilitating protein synthesis upon the restoration of growth conditions...

Highly flexible and superelastic aerogels at large deformation have become urgent mechanical demands in practical uses, but both properties are usually exclusive. Here a trans-scale porosity design is proposed in graphene nanofibrous aerogels (GNFAs) to break the trade-off between high flexibility and superelasticity. The resulting GNFAs can completely recover after 1000 fatigue cycles at 60% folding strain, and notably maintain excellent structural integrity after 10000 cycles at 90% compressive strain, outperforming most of the reported aerogels...

The shoulder joint has a high degree of freedom and an extremely complex and unstable kinematic mechanism. Coordinated contraction of the rotator cuff muscles that stop around the humeral head and the deltoid muscles and the extensibility of soft tissues, such as the joint capsule, labrum, and ligaments, contribute to shoulder-joint stability. Understanding the mechanics of shoulder-joint movement, including soft-tissue characteristics, is important for disease prevention and the development of a device for disease treatment...