Positive GLI1/INHBA feedback loop drives tumor progression in gastric cancer.

GLI1, a key transcription factor of the Hedgehog (Hh) signaling pathway, plays an important role in the development of cancer. However, the function and mechanisms by which GLI1 regulates gene transcription are not fully understood in gastric cancer (GC). Here, we found that GLI1 induced the proliferation and metastasis of GC cells, accompanied by transcriptional upregulation of INHBA. This increased INHBA expression exerted a promoting activity on Smads signaling and then transcriptionally activated GLI1 expression. Notably, our results demonstrate that disrupting the interaction between GLI1 and INHBA could inhibit GC tumorigenesis in vivo. More intriguingly, we confirmed the N6-methyladenosine (m6A) activation mechanism of the Helicobacter pylori/FTO/YTHDF2/GLI1 pathway in GC cells. In conclusion, our study confirmed that the GLI1/INHBA positive feedback loop influences GC progression and revealed the mechanism by which H. pylori upregulates GLI1 expression through m6A modification. This positive GLI1/INHBA feedback loop suggests a novel noncanonical mechanism of GLI1 activity in GC and provides potential therapeutic targets for GC treatment.

Screening, identification, and mechanism analysis of starch-degrading bacteria during curing process in tobacco leaf.

Tobacco, a vital economic crop, had its quality post-curing significantly influenced by starch content. Nonetheless, the existing process parameters during curing were inadequate to satisfy the starch degradation requirements. Microorganisms exhibit inherent advantages in starch degradation, offering significant potential in the tobacco curing process. Our study concentrated on the microbial populations on the surface of tobacco leaves and in the rhizosphere soil. A strain capable of starch degradation, designated as BS3, was successfully isolated and identified as Bacillus subtilis by phylogenetic tree analysis based on 16SrDNA sequence. The application of BS3 on tobacco significantly enhanced enzyme activity and accelerated starch degradation during the curing process. Furthermore, analyses of the metagenome, transcriptome, and metabolome indicated that the BS3 strain facilitated starch degradation by regulating surface microbiota composition and affecting genes related to starch hydrolyzed protein and key metabolites in tobacco leaves. This study offered new strategies for efficiently improving the quality of tobacco leaves.

Myricetin Induces Ferroptosis and Inhibits Gastric Cancer Progression by Targeting NOX4.

Ferroptosis holds great potential as a therapeutic approach for gastric cancer (GC), a prevalent and deadly malignant tumor associated with high rates of incidence and mortality. Myricetin, well-known for its multifaceted biomedical attributes, particularly its anticancer properties, has yet to be thoroughly investigated regarding its involvement in ferroptosis. The aim of this research was to elucidate the impact of myricetin on ferroptosis in GC progression. The present study observed that myricetin could trigger ferroptosis in GC cells by enhancing malondialdehyde production and Fe2+ accumulation while suppressing glutathione levels. Mechanistically, myricetin directly interacted with NADPH oxidase 4 (NOX4), influencing its stability by inhibiting its ubiquitin degradation. Moreover, myricetin regulated the inhibition of ferroptosis induced by Helicobacter pylori cytotoxin-associated gene A (CagA) through the NOX4/NRF2/GPX4 pathway. In vivo experiments demonstrated that myricetin treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice. It was accompanied by increased NOX4 expression in tumor tissue and suppression of the NRF2/GPX4 antioxidant pathway. Therefore, this research underscores myricetin as a novel inducer of ferroptosis in GC cells through its interaction with NOX4. It is a promising candidate for GC treatment.

The role of phosphorus speciation of biochar in reducing available Cd and phytoavailability in mining area soil: Effect and mechanism.

The effect of phosphorus (P) speciation in biochar on soil available Cd and its mechanism to alleviate plant Cd stress remain largely unknown. Here, ammonium polyphosphate (PABC)-, phosphoric acid (PHBC)-, potassium dihydrogen phosphate (PKBC)-, and ammonium dihydrogen phosphate (PNBC)-modified biochar were used to investigate P speciation. The Cd immobilization mechanism of biochar was analyzed by XPS and 31P NMR, and the soil quality and the mechanism for the biochar to alleviate Cd stress were also determined. The results demonstrated that PBC (pristine biochar), PABC, PHBC, PKBC, and PNBC reduced the content of soil DTPA-Cd by 14.96 % - 32.19 %, 40.44 % - 47.26 %, 17.52 % - 41.78 %, and 21.90 % - 36.64 %, respectively. The XPS and 31P NMR results demonstrated that the orthophosphate on the surface of PABC, PHBC, PKBC, and PNBC accounted for 82.06 %, 62.77 %, 33.1 %, and 54.46 %, respectively, indicating that PABC has the highest passivation efficiency on soil Cd, which was ascribed to the highest orthophosphate content on the biochar surface. Pot experiments revealed that PABC could reduce the Cd content by 4.18, 4.41, 4.43, 2.94, and 2.57 folds in roots, stems, leaves, pods, and grains, respectively, and at the same time increase the dry and fresh weight of soybean and decrease Cd toxicity to soybean by improving the antioxidant system. In addition, application of the P-modified biochars improved the enzyme activity and physicochemical properties of the soil. This study provides a new perspective for studying the effect of P-modified biochars on soil Cd immobilization.

PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori related gastric cancer.

Ferroptosis is a newly discovered form of regulatory cell death induced by iron-dependent lipid peroxidation. Infection with Helicobacter pylori (H. pylori) is regarded as a high-risk factor for the development of gastric cancer (GC) and is associated with an increase in the levels of reactive oxygen species with activation of oncogenic signaling pathways. However, whether GC arising in the context of infection with H. pylori is correlated with ferroptosis is still unknown. In this study, we demonstrate that H. pylori infection increased the sensitivity of GC cells to RSL3 (RAS-selective lethal3)-induced ferroptosis. The molecular subtypes mediated by ferroptosis-related genes are associated with tumor microenvironment (TME) cell infiltration and patient survival. Importantly, we identified that the expression of phosphorylase kinase G2 (PHKG2) was remarkably correlated with H. pylori infection, metabolic biological processes, patient survival and therapy response. We further found the mechanism of H. pylori-induced cell sensitivity to ferroptosis, which involves PHKG2 regulation of the lipoxygenase enzyme Arachidonate 5-Lipoxygenase (ALOX5). In conclusion, PHKG2 facilitates RSL3-induced ferroptosis in H. pylori-positive GC cells by promoting ALOX5 expression. These findings may contribute to a better understanding of the unique pathogenesis of H. pylori-induced GC and allow for maximum efficacy of genetic, cellular, and immune therapies for controlling ferroptosis in diverse contexts.

Mitigation of tobacco bacteria wilt with microbial degradation of phenolic allelochemicals.

Long-term continuous monoculture cropping of tobacco leads to high incidence of tobacco bacterial wilt (TBW) caused by Ralstonia solanacearum, which threatening world tobacco production and causing great economy loss. In this study, a safe and effective way to control TBW by microbial degradation of phenolic allelochemicals (PAs) was explored. Eleven kinds of PAs were identified from continuous tobacco cropping soil. These PAs exhibited various effects on the growth, chemotaxis and biofilm formation of R. solanacearum. Then we isolated eight strains of Bacillus, one strain of Brucella, one strain of Enterobacter and one strain of Stenotrophomonas capable of degrading these PAs. The results of degradation assay showed that these isolated strains could degrade PAs both in culture solutions and soil. Besides, the incidence of TBW caused by R. solanacearum and deteriorated by PAs were significantly decreased by treating with these degrading strains. Furthermore, six out of eleven isolated strains were combined to degrade all the identified PAs and ultimately sharply reduced the incidence of TBW by 61.44% in pot experiment. In addition, the combined degrading bacteria could promote the plant growth and defense response. This study will provide a promising strategy for TBW control in tobacco production.

A highly selective fluorescent probe for hydrogen polysulfides in living cells based on a naphthalene derivative.

Hydrogen polysulfides (H2Sn, n > 1) are members of reactive sulfur species (RSS) and signaling molecules derived from hydrogen sulfide (H2S). Recently, the functions of H2Sn in physiological and pathological processes have been increasingly recognized. However, their biological effects and detailed mechanisms of action are still little known. Therefore, there is an urgent need to develop highly selective and sensitive techniques for monitoring hydrogen polysulfides (H2Sn) in living cells. In this study, we designed and synthesized a fluorescent probe based on a naphthalene derivative for the detection of hydrogen polysulfides. A naphthalene derivative was applied as the fluorescent main structure and the 2-fluoro-5-nitrobenzoate group was chosen as the recognition unit. In the absence of hydrogen polysulfides, the fluorescent probe displayed almost no fluorescence. In the presence of hydrogen polysulfides, the fluorescent probe exhibited strong fluorescence. The sensing mechanism was based on H2Sn-mediated aromatic substitution-cyclization reactions. The linear range of the response concentration of the probe to hydrogen polysulfide was acquired in a concentration range of H2Sn from 7.5 × 10-7 to 2.5 × 10-5 mol L-1. The detection limit was evaluated to be 5.0 × 10-7 mol L-1 for H2Sn. The fluorescent probe can applied in a wide pH range including physiological condition pH. The fluorescent probe showed high specificity for H2Sn over other reactive sulfur species (RSS). Moreover, the fluorescent probe has been successfully applied to confocal imaging of hydrogen polysulfides in HepG2 cells without cell cytotoxicity. All of such good qualities indicated that it could be used to detect H2Sn in living cells.

Long non-coding RNAs in ocular diseases: new and potential therapeutic targets.

Long non-coding RNAs (lncRNAs) are non-protein coding transcripts containing more than 200 nucleotides. In the past, lncRNAs were considered as 'transcript noise' or 'pseudogenes' and were thus ignored. However, in recent years, lncRNAs have been proven to regulate gene expression at the epigenetic, transcriptional and translational level, and thereby influence cell proliferation, apoptosis, viability, immune response and oxidative stress. Furthermore, increasing evidence points to their involvement in different diseases, including cancer and heart diseases. Recently, lncRNAs were shown to be differentially expressed in ocular tissues and play a significant role in the pathogenesis of ophthalmological disorders such as glaucoma, corneal diseases, cataract, diabetic retinopathy, proliferative vitreoretinopathy and ocular tumors. In this review, we summarize the classification and mechanisms of known lncRNAs, while detailing their biological functions and roles in ocular diseases. Moreover, we provide a concise review of the clinical relevance of lncRNAs as novel, potential therapeutic targets in the treatment of eye diseases.