Endoribonuclease YbeY Is Essential for RNA Processing and Virulence in Pseudomonas aeruginosa

Posttranscriptional regulation plays an essential role in the quick adaptation of pathogenic bacteria to host environments, and RNases play key roles in this process by modifying small RNAs and mRNAs. We find that the Pseudomonas aeruginosa endonuclease YbeY is required for rRNA processing and the bacterial virulence in a murine acute pneumonia model. Transcriptomic analyses reveal that knocking out the ybeY gene results in downregulation of oxidative stress response genes, including the catalase genes katA and katB Consistently, the ybeY mutant is more susceptible to H2O2 and neutrophil-mediated killing. Overexpression of katA restores the bacterial tolerance to H2O2 and neutrophil killing as well as virulence. We further find that the downregulation of the oxidative stress response genes is due to defective expression of the stationary-phase sigma factor RpoS. We demonstrate an autoregulatory mechanism of RpoS and find that ybeY mutation increases the level of a small RNA, ReaL, which directly represses the translation of rpoS through the 5' UTR of its mRNA and subsequently reduces the expression of the oxidative stress response genes. In vitro assays demonstrate direct degradation of ReaL by YbeY. Deletion of reaL or overexpression of rpoS in the ybeY mutant restores the bacterial tolerance to oxidative stress and the virulence. We also demonstrate that YbeZ binds to YbeY and is involved in the 16S rRNA processing and regulation of reaL and rpoS as well as the bacterial virulence. Overall, our results reveal pleiotropic roles of YbeY and the YbeY-mediated regulation of rpoS through ReaL.IMPORTANCE The increasing bacterial antibiotic resistance imposes a severe threat to human health. For the development of effective treatment and prevention strategies, it is critical to understand the mechanisms employed by bacteria to grow in the human body. Posttranscriptional regulation plays an important role in bacterial adaptation to environmental changes. RNases and small RNAs are key players in this regulation. In this study, we demonstrate critical roles of the RNase YbeY in the virulence of the pathogenic bacterium Pseudomonas aeruginosa We further identify the small RNA ReaL as the direct target of YbeY and elucidate the YbeY-regulated pathway on the expression of bacterial virulence factors. Our results shed light on the complex regulatory network of P. aeruginosa and indicate that inference with the YbeY-mediated regulatory pathway might be a valid strategy for the development of a novel treatment strategy.</p

TELEX HEBDOMADAIRE NR 95 DU 17.09.82 DESTINE A L'ENSEMBLE DES DELEGATIONS EXTERIEURES ET BUREAUX DE PRESS ET D'INFORMATION INDEPENDANTS DANS LES PAYS TIERS = WEEKLY MEMO NO. 95 FOR 17.09.82 TO FOREIGN DELEGATIONS AND PRESS BUREAUS OF THIRD COUNTRIES

<p>High-performance liquid chromatography (HPLC) results of (A) commercial surfactin sample, and (B) our extract surfactin of <i>B</i>. <i>subtilis</i> HH2 in LB medium. There were three main peaks (Peak A-C) of the extract and the surfactin standard in the same location.</p

Navigating the Evolution of Digital Twins Research through Keyword Co-Occurence Network Analysis

Digital twin technology has become increasingly popular and has revolutionized data integration and system modeling across various industries, such as manufacturing, energy, and healthcare. This study aims to explore the evolving research landscape of digital twins using Keyword Co-occurrence Network (KCN) analysis. We analyze metadata from 9639 peer-reviewed articles published between 2000 and 2023. The results unfold in two parts. The first part examines trends and keyword interconnection over time, and the second part maps sensing technology keywords to six application areas. This study reveals that research on digital twins is rapidly diversifying, with focused themes such as predictive and decision-making functions. Additionally, there is an emphasis on real-time data and point cloud technologies. The advent of federated learning and edge computing also highlights a shift toward distributed computation, prioritizing data privacy. This study confirms that digital twins have evolved into complex systems that can conduct predictive operations through advanced sensing technologies. The discussion also identifies challenges in sensor selection and empirical knowledge integration

LINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis

Background: Studies have shown that long non-coding RNAs (lncRNAs) play essential roles in tumor progression and can affect the response to radiotherapy, including in clear cell renal cell carcinoma (ccRCC). LINC02532 has been found to be upregulated in ccRCC. However, not much is known about this lncRNA. Hence, this study aimed to investigate the role of LINC02532 in ccRCC, especially in terms of radioresistance. Methods: Quantitative real-time PCR was used to detect the expression of LINC02532, miR-654-5p, and YY1 in ccRCC cells. Protein levels of YY1, cleaved PARP, and cleaved-Caspase-3 were detected by Western blotting. Cell survival fractions, viability, and apoptosis were determined by clonogenic survival assays, CCK-8 assays, and flow cytometry, respectively. The interplay among LINC02532, miR-654-5p, and YY1 was detected by chromatin immunoprecipitation and dual-luciferase reporter assays. In addition, in vivo xenograft models were established to investigate the effect of LINC02532 on ccRCC radioresistance in 10 nude mice. Results: LINC02532 was highly expressed in ccRCC cells and was upregulated in the cells after irradiation. Moreover, LINC02532 knockdown enhanced cell radiosensitivity both in vitro and in vivo. Furthermore, YY1 activated LINC02532 in ccRCC cells, and LINC02532 acted as a competing endogenous RNA that sponged miR-654-5p to regulate YY1 expression. Rescue experiments indicated that miR-654-5p overexpression or YY1 inhibition recovered ccRCC cell functions that had been previously impaired by LINC02532 overexpression. Conclusions: Our results revealed a positive feedback loop of LINC02532/miR-654-5p/YY1 in regulating the radiosensitivity of ccRCC, suggesting that LINC02532 might be a potential target for ccRCC radiotherapy. This study could serve as a foundation for further research on the role of LINC02532 in ccRCC and other cancers

Highly Flexible and Stretchable Nanowire Superlattice Fibers Achieved by Spring‐Like Structure of Sub‐1 nm Nanowires

Conventional inorganic nanowire (NW) fibers are usually not stretchable and elastic, which may limit their practical applications. Inspired by the similarity between inorganic sub-1 nm NWs and polymer chains in dimension, and helical spring-like structure of cellulose in cherry bark, highly flexible and stretchable NW superlattice fibers composed of sub-1 nm GdOOH NWs are fabricated. The NW fibers could be twined, bent, twisted, and tied without any damage. When the strain is less than 10%, the fibers present elastic deformation. The elongation at break of the fibers usually reaches ≈40–50% and the highest elongation could reach ≈86%. Excellent flexibility and stretchability of the NW fibers are attributed to the well-aligned spring-like NWs assembled superlattice, which are demonstrated by scanning electron microscopy tests, synchrotron small-angle X-ray scattering, and obvious birefringence. Moreover, NW-nanoparticle (NP) fibers are fabricated, inspired by inorganic nanoparticle–reinforced polymers. The strength is improved compared with the NW fibers. Based on this work, it is possible to fabricate multifunctional, flexible, and stretchable inorganic NW materials composed of different inorganic sub-1 nm NWs, which may be useful in practical applications

Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in Pseudomonas aeruginosa

Bacterial persisters are slow-growing or dormant cells that are highly tolerant to bactericidal antibiotics and contribute to recalcitrant and chronic infections. Toxin/antitoxin (TA) systems play important roles in controlling persister formation. Here, we examined the roles of seven predicted type II TA systems in the persister formation of a Pseudomonas aeruginosa wild-type strain PA14. Overexpression of a toxin gene PA14_51010 or deletion of the cognate antitoxin gene PA14_51020 increased the bacterial tolerance to antibiotics. Co-overexpression of PA14_51010 and PA14_51020 or simultaneous deletion of the two genes resulted in a wild-type level survival rate following antibiotic treatment. The two genes were located in the same operon that was repressed by PA14_51020. We further demonstrated the interaction between PA14_51010 and PA14_51020. Sequence analysis revealed that PA14_51010 contained a conserved RES domain. Overexpression of PA14_51010 reduced the intracellular level of nicotinamide adenine dinucleotide (NAD+). Mutation of the RES domain abolished the abilities of PA14_51010 in reducing NAD+ level and promoting persister formation. In addition, overproduction of NAD+ by mutation in an nrtR gene counteracted the effect of PA14_51010 overexpression in promoting persister formation. In combination, our results reveal a novel TA system that contributes to persister formation through reducing the intracellular NAD+ level in P. aeruginosa

Nickel Diselenide Ultrathin Nanowires Decorated with Amorphous Nickel Oxide Nanoparticles for Enhanced Water Splitting Electrocatalysis.

Well-designed hybrid materials based on noble metal-free elements have great potential to generate hydrogen (H2 ) and oxygen (O2 ) sustainably via overall water splitting for developing practical energy-related technologies. Herein, an accessible method is presented to synthesize nickel diselenide (NiSe2 ) ultrathin nanowires decorated with amorphous nickel oxide nanoparticles (NiOx NPs) as multifunctional electrocatalysts (NSWANs) for hydrogen and oxygen evolution reaction (HER and OER). The NSWANs exhibit quite low HER and OER overpotentials of 174 and 295 mV, respectively, holding the current density of 20 mA cm-2 for 24 h continuous operations in alkaline media. Meanwhile, a cell voltage of 1.547 V at the current density of 10 mA cm-2 for overall water splitting has been achieved by the NSWANs for the practical application, which could maintain fascinating activity of 20 mA cm-2 for 72 h without degradation. The decorated NiOx NPs not only prevent the NiSe2 from further oxidation but also expose requisite active sites for electrocatalytic process. It is believed that this study may provide a valuable strategy to design high-efficiency electrocatalysts and expand the applications of selenide-based materials