Elucidation of critical chemical moieties of metallo-ß-lactamase inhibitors and prioritisation of target metallo-ß-lactamases.

The urgent demand for effective countermeasures against metallo-ß-lactamases (MBLs) necessitates development of novel metallo-ß-lactamase inhibitors (MBLIs). This study is dedicated to identifying critical chemical moieties within previously developed MBLIs, and critical MBLs should serve as the target in MBLI evaluations. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic literature analysis was conducted, and the NCBI RefSeq genome database was exploited to access the abundance profile and taxonomic distribution of MBLs and their variant types. Through the implementation of two distinct systematic approaches, we elucidated critical chemical moieties of MBLIs, providing pivotal information for rational drug design. We also prioritised MBLs and their variant types, highlighting the imperative need for comprehensive testing to ensure the potency and efficacy of the newly developed MBLIs. This approach contributes valuable information to advance the field of antimicrobial drug discovery.

Efficacy of Allogeneic and Xenogeneic Exosomes for the Treatment of Canine Atopic Dermatitis: A Pilot Study.

Canine atopic dermatitis (CAD) is a genetically predisposed inflammatory pruritic skin disease. The available treatments for CAD have several adverse effects and vary in efficacy, indicating the need for the development of improved treatments. In this study, we aimed to elucidate the therapeutic effects of allogeneic and xenogeneic exosomes on CAD. Six laboratory beagle dogs with CAD were randomly assigned to three treatment groups: control, canine exosome (cExos), or human exosome (hExos) groups. Dogs in the cExos and hExos groups were intravenously administered 1.5 mL of cExos (5 × 1010) and hExos (7.5 × 1011) solutions, respectively, while those in the control group were administered 1.5 mL of normal saline three times per week for 4 weeks. Skin lesion score and transepidermal water loss decreased in cExos and hExos groups compared with those in the control group. The exosome treatments decreased the serum levels of inflammatory cytokines (interferon-γ, interleukin-2, interleukin-4, interleukin-12, interleukin-13, and interleukin-31) but increased those of anti-inflammatory cytokines (interleukin-10 and transforming growth factor-ß), indicating the immunomodulatory effect of exosomes. Skin microbiome analysis revealed that the exosome treatments alleviated skin bacterial dysbiosis. These results suggest that allogeneic and xenogeneic exosome therapy may alleviate CAD in dogs.

Prioritization of Critical Factors for Surveillance of the Dissemination of Antibiotic Resistance in Pseudomonas aeruginosa: A Systematic Review.

Pseudomonas aeruginosa is the primary opportunistic human pathogen responsible for a range of acute and chronic infections; it poses a significant threat to immunocompromised patients and is the leading cause of morbidity and mortality for nosocomial infections. Its high resistance to a diverse array of antimicrobial agents presents an urgent health concern. Among the mechanisms contributing to resistance in P. aeruginosa, the horizontal acquisition of antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) has gained recognition as a substantial concern in clinical settings, thus indicating that a comprehensive understanding of ARG dissemination within the species is strongly required for surveillance. Here, two approaches, including a systematic literature analysis and a genome database survey, were employed to gain insights into ARG dissemination. The genome database enabled scrutinizing of all the available sequence information and various attributes of P. aeruginosa isolates, thus providing an extensive understanding of ARG dissemination within the species. By integrating both approaches, with a primary focus on the genome database survey, mobile ARGs that were linked or correlated with MGEs, important sequence types (STs) carrying diverse ARGs, and MGEs responsible for ARG dissemination were identified as critical factors requiring strict surveillance. Although human isolates play a primary role in dissemination, the importance of animal and environmental isolates has also been suggested. In this study, 25 critical mobile ARGs, 45 critical STs, and associated MGEs involved in ARG dissemination within the species, are suggested as critical factors. Surveillance and management of these prioritized factors across the One Health sectors are essential to mitigate the emergence of multidrug-resistant (MDR) and extensively resistant (XDR) P. aeruginosa in clinical settings.

Structural Insights for ß-Lactam Antibiotics.

Antibiotic resistance has emerged as a global threat to modern healthcare systems and has nullified many commonly used antibiotics. ß-Lactam antibiotics are among the most successful and occupy approximately two-thirds of the prescription antibiotic market. They inhibit the synthesis of the peptidoglycan layer in the bacterial cell wall by mimicking the D-Ala-D-Ala in the pentapeptide crosslinking neighboring glycan chains. To date, various ß-lactam antibiotics have been developed to increase the spectrum of activity and evade drug resistance. This review emphasizes the three-dimensional structural characteristics of ß-lactam antibiotics regarding the overall scaffold, working mechanism, chemical diversity, and hydrolysis mechanism by ß-lactamases. The structural insight into various ß-lactams will provide an in-depth understanding of the antibacterial efficacy and susceptibility to drug resistance in multidrug-resistant bacteria and help to develop better ß-lactam antibiotics and inhibitors.

Transmission of antibiotic resistance genes through mobile genetic elements in Acinetobacter baumannii and gene-transfer prevention.

Antibiotic resistance is a major global public health concern. Acinetobacter baumannii is a nosocomial pathogen that has emerged as a global threat because of its high levels of resistance to many antibiotics, particularly those considered as last-resort antibiotics, such as carbapenems. Mobile genetic elements (MGEs) play an important role in the dissemination and expression of antibiotic resistance genes (ARGs), including the mobilization of ARGs within and between species. We conducted an in-depth, systematic investigation of the occurrence and dissemination of ARGs associated with MGEs in A. baumannii. We focused on a cross-sectoral approach that integrates humans, animals, and environments. Four strategies for the prevention of ARG dissemination through MGEs have been discussed: prevention of airborne transmission of ARGs using semi-permeable membrane-covered thermophilic composting; application of nanomaterials for the removal of emerging pollutants (antibiotics) and pathogens; tertiary treatment technologies for controlling ARGs and MGEs in wastewater treatment plants; and the removal of ARGs by advanced oxidation techniques. This review contemplates and evaluates the major drivers involved in the transmission of ARGs from the cross-sectoral perspective and ARG-transfer prevention processes.

Translation-dependent mRNA cleavage by YhaV in Escherichia coli.

Many bacteria have toxin-antitoxin (TA) systems, where toxin gene expression inhibits their own cell growth. mRNA is one of the well-known targets of the toxins in the type II toxin-antitoxin systems. Here, we examined the ribosome dependency of the endoribonuclease activity of YhaV, one of the toxins in type II TA systems, on mRNA in vitro and in vivo. A polysome profiling assay revealed that YhaV is bound to the 70S ribosomes and 50S ribosomal subunits. Moreover, we found that while YhaV cleaves ompF and lpp mRNAs in a translation-dependent manner, they did not cleave the 5' untranslated region in primer extension experiments. From these results, we conclude that YhaV is a ribosome-dependent toxin that cleaves mRNA in a translation-dependent manner.

Responses of human sensory characteristics to 532 nm pulse laser stimuli.

BACKGROUND: Lasers are advantageous in some applications to stimulate a small target area and is used in various fields such as optogenetic, photoimmunological and neurophysiological studies. OBJECTIVE: This study aims to implement a non-contact sense of touch without damaging biological tissues using laser. METHODS: Various laser parameters were utilized in safety range to induce a sense of touch and investigate the human responses. With heat distribution simulation, the amount of changes in the temperature and the tendency in laser parameters of sensory stimulation were analyzed. RESULTS: The results showed the identified tactile responses in safety range with various laser parameters and temperature distribution for the laser stimulus was obtained through the simulation. CONCLUSIONS: This study can be applied to the areas of sensory receptor stimulation, neurophysiology and clinical medicine.

Fabrication of ferromagnetic nanoconstriction using atomic force microscopy nanoscratching.

Nanolithography used in conjunction with atomic force microscopy (AFM) has attracted considerable attention as a technique for fabricating nanoscale structures. To obtain nanostructures and devices, AFM nanoscratching was performed on a photoresist and on NiFe at various values of the applied force, scan speed, and number of scan cycles. The scratching process was carried out using a diamond-coated tip on NiFe and a Si tip on the photoresist. By conducting scratching processes on NiFe and on the photoresist, we investigated the dependence of the size of the scratched part on the scratching parameters. These results show that the width and depth of the scratched part increase as the applied force and number of scan cycles increase, but not as the scan speed increases. This means that it is possible to control the size of the scratched parts by adjusting the applied force and number of scan cycles. AFM nanoscratching was then used to directly fabricate a nanoconstricted area with a width of 139 nm and a cross-sectional area of less than 300 nm2 was fabricated.