Enhanced fatty acid biosynthesis by Sigma28 in stringent responses contributes to multidrug resistance and biofilm formation in Helicobacter pylori.

The metabolic state of bacteria significantly contributes to their resistance to antibiotics; however, the specific metabolic mechanisms conferring antimicrobial resistance in Helicobacter pylori remain largely understudied. Employing transcriptomic and non-targeted metabolomics, we characterized the metabolic reprogramming of H. pylori when challenged with antibiotic agents. We observed a notable increase in both genetic and key proteomic components involved in fatty acid biosynthesis. Inhibition of this pathway significantly enhanced the antibiotic susceptibility of the sensitive and multidrug-resistant H. pylori strains while also disrupting their biofilm-forming capacities. Further analysis revealed that antibiotic treatment induced a stringent response, triggering the expression of the hp0560-hp0557 operon regulated by Sigma28 (σ28). This activation in turn stimulated the fatty acid biosynthetic pathway, thereby enhancing the antibiotic tolerance of H. pylori. Our findings reveal a novel adaptive strategy employed by H. pylori to withstand antibiotic stress.

miRNAs in patients with alcoholic liver disease: a systematic review and meta-analysis.

INTRODUCTION: Alcoholic liver disease (ALD) encompasses a spectrum of liver conditions, including liver steatosis, alcoholic hepatitis (AH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). microRNAs (miRNAs) have garnered significant interest as potential biomarkers for ALD. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) systemically from inception to June 2024. All extracted data was stratified according to the stages of ALD. The vote-counting strategy performed a meta-analysis on miRNA expression profiles. RESULTS: We included 40 studies. In serum of individuals with alcohol-use vs. no alcohol-use, miRNA-122 and miRNA-155 were upregulated, and miRNA-146a was downregulated. In patients with ALD vs. healthy controls, miRNA-122 and miRNA-155 were also upregulated, and miRNA-146a was downregulated. However, in patients with AH vs. healthy individuals, only the serum miRNA-122 level was upregulated. Due to insufficient data on diagnostic accuracy, we failed to conclude the ability of miRNAs to distinguish between different stages of ALD-related liver fibrosis. The results for ALD-related HCC were also insufficient and controversial. CONCLUSIONS: Circulating miRNA-122 was the most promising biomarker to manage individuals with ALD. More studies were needed for the diagnostic accuracy of miRNAs in ALD. REGISTRATION: This protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (www.crd.york.ac.uk/prospero/) with registration number CRD42023391931.

Antibiotic-induced ROS-mediated Fur allosterism contributes to Helicobacter pylori resistance by inhibiting arsR activation of mutS and mutY.

The increasing antibiotic resistance of Helicobacter pylori primarily driven by genetic mutations poses a significant clinical challenge. Although previous research has suggested that antibiotics could induce genetic mutations in H. pylori, the molecular mechanisms regulating the antibiotic induction remain unclear. In this study, we applied various techniques (e.g., fluorescence microscopy, flow cytometry, and multifunctional microplate reader) to discover that three different types of antibiotics could induce the intracellular generation of reactive oxygen species (ROS) in H. pylori. It is well known that ROS, a critical factor contributing to bacterial drug resistance, not only induces damage to bacterial genomic DNA but also inhibits the expression of genes associated with DNA damage repair, thereby increasing the mutation rate of bacterial genes and leading to drug resistance. However, further research is needed to explore the molecular mechanisms underlying the ROS inhibition of the expression of DNA damage repair-related genes in H. pylori. In this work, we validated that ROS could trigger an allosteric change in the iron uptake regulatory protein Fur, causing its transition from apo-Fur to holo-Fur, repressing the expression of the regulatory protein ArsR, ultimately causing the down-regulation of key DNA damage repair genes (e.g., mutS and mutY); this cascade increased the genomic DNA mutation rate in H. pylori. This study unveils a novel mechanism of antibiotic-induced resistance in H. pylori, providing crucial insights for the prevention and control of antibiotic resistance in H. pylori.

Investigation on Recrystallization Channel for Vertical C-Shaped-Channel Nanosheet FETs by Laser Annealing.

Transistor scaling has become increasingly difficult in the dynamic random access memory (DRAM). However, vertical devices will be good candidates for 4F2 DRAM cell transistors (F = pitch/2). Most vertical devices are facing some technical challenges. For example, the gate length cannot be precisely controlled, and the gate and the source/drain of the device cannot be aligned. Recrystallization-based vertical C-shaped-channel nanosheet field-effect transistors (RC-VCNFETs) were fabricated. The critical process modules of the RC-VCNFETs were developed as well. The RC-VCNFET with a self-aligned gate structure has excellent device performance, and its subthreshold swing (SS) is 62.91 mV/dec. Drain-induced barrier lowering (DIBL) is 6.16 mV/V.

High-Quality Recrystallization of Amorphous Silicon on Si (100) Induced via Laser Annealing at the Nanoscale.

At sub-3 nm nodes, the scaling of lateral devices represented by a fin field-effect transistor (FinFET) and gate-all-around field effect transistors (GAAFET) faces increasing technical challenges. At the same time, the development of vertical devices in the three-dimensional direction has excellent potential for scaling. However, existing vertical devices face two technical challenges: "self-alignment of gate and channel" and "precise gate length control". A recrystallization-based vertical C-shaped-channel nanosheet field effect transistor (RC-VCNFET) was proposed, and related process modules were developed. The vertical nanosheet with an "exposed top" structure was successfully fabricated. Moreover, through physical characterization methods such as scanning electron microscopy (SEM), atomic force microscopy (AFM), conductive atomic force microscopy (C-AFM) and transmission electron microscopy (TEM), the influencing factors of the crystal structure of the vertical nanosheet were analyzed. This lays the foundation for fabricating high-performance and low-cost RC-VCNFETs devices in the future.

DnFCA Isoforms Cooperatively Regulate Temperature-Related Flowering in Dendrobium nobile.

Timely flowering is a determinative trait for many economically valuable species in the Dendrobium genus of the Orchidaceae family, some of which are used for ornamental and medicinal purposes. D. nobile, a representative species of nobile-type Dendrobium, normally flowers in spring after exposure to sufficient low temperatures in winter. However, flowering can be stopped or disrupted by the untimely application of high temperatures. Little is known about the regulation and the mechanisms behind this switch. In this study, we report two isoforms from the KFK09_017173 locus of the D. nobile genome, named DnFCAγ and DnFCAß, respectively, that cooperatively regulate flowering in D. nobile. These two isoforms are generated by alternative 3' polyadenylation of DnFCA (FLOWERING CONTROL LOCUS C in D. nobile) pre-mRNA and contain a distinct 3'-terminus. Both can partially rescue late flowering in the Arabidopsis fca-1 mutant, while in wild-type Arabidopsis, they tend to delay the flowering time. When introduced into the detached axillary buds or young seedlings of D. nobile, both were able to induce the transcription of DnAGL19 (AGAMOUS LIKE 19 in D. nobile) in seedlings, whereas only DnFCAγ was able to suppress the transcription of DnAPL1 (AP1-LIKE 1 in D. nobile) in axillary buds. Furthermore, the time-course change of DnFCAγ accumulation was opposite to that of DnAPL1 in axillary buds, which was remarkable under low temperatures and within a short time after the application of high temperatures, supporting the suggestion that the expression of DnAPL1 can be inhibited by a high accumulation of DnFCAγ in floral buds. In leaves, the accumulation of DnFCAß was in accordance with that of DnAGL19 and DnFT (FLOWERING LOCUS T in D. nobile) to a large extent, suggesting the activation of the DnAGL19-DnFT pathway by DnFCAß. Taken together, these results suggest that the DnFCAγ-DnAPL1 pathway in axillary buds and the DnFCAß-DnAGL19 pathway in the leaves cooperatively promote flowering under low temperatures. The long-term and constant, or untimely, application of high temperatures leads to the constitutive suppression of DnAPL1 by a high level of DnFCAγ in axillary buds, which consequently delays floral development.

MiR-1193 Inhibits the Malignancy of Cervical Cancer Cells by Targeting Claudin 7 (CLDN7).

OBJECTIVE: MicroRNAs (miRNAs) are highly involved in cancer development, including in cervical cancer (CC). In this study, we aimed to investigate the role and possible mechanism of a poorly studied miRNA, miR-1193, in CC progression. MATERIALS AND METHODS: Expression of miR-1193 was determined in 60 pairs of cervical samples. The impacts of miR-1193 on CC cell proliferation, invasion and migration capacities were verified by CCK-8, transwell and wound healing assays, respectively. Then, bioinformatics prediction, luciferase reporter assay, qRT-PCR and Western blot were successively conducted to study the targeting of claudin 7 (CLDN7) by miR-1193. After CLDN7 was restored in miR-1193-overexpressed cells, the rescue effects were determined. Finally, CLDN7 expression was analyzed in cervical samples, and its expression correlation with miR-1193 was explored. RESULTS: Compared with paired normal tissues, miR-1193 was sharply decreased in abnormal tissues (intraepithelial lesions and cancerous tissues). Especially, miR-1193 expression was gradually decreased in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions and CC. Enforced expression of miR-1193 inhibited CC cell proliferation, invasion and migration. Mechanistically, we confirmed CLDN7 as a target of miR-1193, and restoration of CLDN7 robustly rescued the tumor suppressing effects of miR-1193 in CC cells. CLDN7 was upregulated in abnormal cervical tissues and its expression exhibited inverse correlation with that of miR-1193 in CC. CONCLUSION: Our results suggested that miR-1193 exerted tumor inhibitory roles in CC malignancy by directly targeting CLDN7.