SHP2 mediates the ROS/JNK/NFAT4 signaling pathway in gastric cancer cells prompting lncRNA SNHG18 to drive gastric cancer growth and metastasis via CAR-T cells.

OBJECTIVE: In gastric cancer cells, the influence of CAR T cells can be produced in the process of inhibiting the progression of gastric cancer, and the role of tyrosine phosphatase SHP2 can be explored in this study, along with its molecular mechanisms. METHODS: The research utilized subcutaneous tumor models in nude mice to assess gastric cancer progression. Protein expression was detected using Western blotting, while Q-PCR examined the expression levels of lncRNA SNHG18 and miR-211-5p in MGC-803 cells. The relationship between miR-211-5p and lncRNA SNHG18 can be analyzed by dual luciferase reporter genes. The migratory ability of MGC-803 cells was determined through wound healing and transwell experiments, and cell proliferation was evaluated using a CCK-8 assay. RESULTS: SHP2 was found to inhibit the cytotoxic effects of CAR-T cells on MGC-803 cells, and it suppressed the expression of proteins related to the ROS/JNK/NFAT4 signaling pathway in MGC-803 cells and the miR-211-5p/BRD4 axis in CAR-T cells. In addition, the proliferation, invasion and migration of MGC-803 cells were promoted, and the expression of miR-211-5p could be inhibited specifically by ncRNA SNHG18, as shown below:SHP2 in gastric cancer cells mediates the ROS/JNK/NFAT4 signaling pathway and induces lncRNA SNHG18, which, through the miR-211-5p/BRD4 axis in CAR-T cells, promotes gastric cancer growth and metastasis.

Integration of miRNA expression analysis of purified leukocytes and whole blood reveals blood-borne candidate biomarkers for lung cancer.

Changes in leukocyte populations may confound the disease-associated miRNA signals in the blood of cancer patients. We aimed to develop a method to detect differentially expressed miRNAs from lung cancer whole blood samples that are not influenced by variations in leukocyte proportions. The Ref-miREO method identifies differential miRNAs unaffected by changes in leukocyte populations by comparing the within-sample relative expression orderings (REOs) of miRNAs from healthy leukocyte subtypes and those from lung cancer blood samples. Over 77% of the differential miRNAs observed between lung cancer and healthy blood samples overlapped with those between myeloid-derived and lymphoid-derived leukocytes, suggesting the potential impact of changes in leukocyte populations on miRNA profile. Ref-miREO identified 16 differential miRNAs that target 19 lung adenocarcinoma-related genes previously linked to leukocytes. These miRNAs showed enrichment in cancer-related pathways and demonstrated high potential as diagnostic biomarkers, with the LASSO regression models effectively distinguishing between healthy and lung cancer blood or serum samples (all AUC > 0.85). Additionally, 12 of these miRNAs exhibited significant prognostic correlations. The Ref-miREO method offers valuable candidates for circulating biomarker detection in cancer that are not affected by changes in leukocyte populations.

Optimization of Ti-PA efficiently catalytic the alcoholysis of waste PET using response surface methodology.

A new type of titanium phthalate (Ti-PA) catalyst was prepared by exchange method of phthalic acid and isopropyl titanate, which is never been reported before. The Ti-PA catalyst was characterized by FT-IR, TG, Uv-vis, BET, SEM, and EDS. The Ti-PA catalyst shows good catalytic activity in the alcoholysis reaction of polyethylene terephthalate (PET) and optimal experimental conditions for the alcoholysis process were optimized by response surface methodology; the Ti-PA catalyst provided a BHET yield of 81.98% for reaction lasting 3.98 h at 191 °C of 0.86% catalyst and 13.7 ml ethylene glycol; the model has good reliability. The kinetics and reaction mechanism of the process were explored and apparent activation energy is 75.52 kJ/mol. Finally, the good catalytic activity of Ti-PA was illustrated by comparing it with currently reported catalysts.

Efficacy and safety of bimekizumab in the treatment of psoriatic arthritis: a systematic review and meta-analysis.

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.

Efficacy and Safety of Risankizumab in Patients with Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. METHODS: We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. RESULTS: Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24 weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR 1.760, 95% CI 1.568-1.977, P < 0.001). Additionally, the risankizumab group showed a significantly higher Minimal Disease Activity (MDA) response rate compared to the placebo group (RR 1.827, 95% CI 1.048-3.184, P < 0.05). The risankizumab group also exhibited improvement in Short Form 36 Questionnaire (SF-36) score (SMD 0.51, 95% CI 0.33-0.69, P < 0.001), with significantly lower Health Assessment Questionnaire Disability Index (HAQ-DI) score (SMD - 0.27, 95% CI - 0.37 to - 0.17, P < 0.001) and higher Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (SMD 0.27, 95% CI 0.20-0.35, P < 0.001) compared to the placebo group. Moreover, the risankizumab group had a significantly lower Psoriasis Area and Severity Index (PASI) score (SMD - 6.12, 95% CI - 10.02 to 2.23, P < 0.001). A study by Mease et al. indicated that patients receiving risankizumab generally demonstrated numerical improvements in the Leeds Enthesitis Index (LEI), although the small sample size limits the evidence. Further research is necessary to provide evidence-based guidelines. There were no significant differences in the incidence of serious adverse events (SAE) and serious treatment-emergent adverse events (STEAE) between the risankizumab and placebo groups (RR 0.76, 95% CI 0.45-1.28, P = 0.31; RR 0.99, 95% CI 0.49-1.99, P = 0.97, respectively), and the overall incidence of adverse events (AE) was not comparable (RR 1.10, 95% CI 0.63-1.94, P = 0.73). CONCLUSION: Risankizumab showed superior efficacy across multiple outcome measures compared to placebo, with no significant increase in adverse events. Our findings endorse risankizumab as an excellent treatment option for PsA, offering valuable insights for clinicians and patients when choosing appropriate therapeutic interventions. TRIAL REGISTRATION: Retrospectively registered (CRD42023451894, 16 August 2023).

Integrated analysis of diverse cancer types reveals a breast cancer-specific serum miRNA biomarker through relative expression orderings analysis.

PURPOSE: Serum microRNA (miRNA) holds great potential as a non-invasive biomarker for diagnosing breast cancer (BrC). However, most diagnostic models rely on the absolute expression levels of miRNAs, which are susceptible to batch effects and challenging for clinical transformation. Furthermore, current studies on liquid biopsy diagnostic biomarkers for BrC mainly focus on distinguishing BrC patients from healthy controls, needing more specificity assessment. METHODS: We collected a large number of miRNA expression data involving 8465 samples from GEO, including 13 different cancer types and non-cancer controls. Based on the relative expression orderings (REOs) of miRNAs within each sample, we applied the greedy, LASSO multiple linear regression, and random forest algorithms to identify a qualitative biomarker specific to BrC by comparing BrC samples to samples of other cancers as controls. RESULTS: We developed a BrC-specific biomarker called 7-miRPairs, consisting of seven miRNA pairs. It demonstrated comparable classification performance in our analyzed machine learning algorithms while requiring fewer miRNA pairs, accurately distinguishing BrC from 12 other cancer types. The diagnostic performance of 7-miRPairs was favorable in the training set (accuracy = 98.47%, specificity = 98.14%, sensitivity = 99.25%), and similar results were obtained in the test set (accuracy = 97.22%, specificity = 96.87%, sensitivity = 98.02%). KEGG pathway enrichment analysis of the 11 miRNAs within the 7-miRPairs revealed significant enrichment of target mRNAs in pathways associated with BrC. CONCLUSION: Our study provides evidence that utilizing serum miRNA pairs can offer significant advantages for BrC-specific diagnosis in clinical practice by directly comparing serum samples with BrC to other cancer types.

REDH: A database of RNA editome in hematopoietic differentiation and malignancy.

BACKGROUND: The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking. METHODS: We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases. RESULTS: We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control. CONCLUSIONS: REDH is accessible at http://www.redhdatabase.com/ . This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

Deciphering the Functional Long Non-Coding RNAs Derived from MicroRNA Loci.

Albeit the majority of eukaryotic genomes can be pervasively transcribed to a diverse population of lncRNAs and various subtypes of lncRNA are discovered. However, the genome-wide study of miRNA-derived lncRNAs is still lacking. Here, it is reported that over 800 miRNA gene-originated lncRNAs (molncRNAs) are generated from miRNA loci. One of them, molnc-301b from miR-301b and miR-130b, functions as an "RNA decoy" to facilitate dissociation of the chromatin remodeling protein SMARCA5 from chromatin and thereby sequester transcription and mRNA translation. Specifically, molnc-301b attenuates erythropoiesis by mitigating the transcription of erythropoietic and translation-associated genes, such as GATA1 and FOS. In addition, a useful and powerful CRISPR screen platform to characterize the biological functions of molncRNAs at large-scale and single-cell levels is established and 29 functional molncRNAs in hematopoietic cells are identified. Collectively, the focus is on miRNA-derived lncRNAs, deciphering their landscape during normal hematopoiesis, and comprehensively evaluating their potential roles.

The SWGEDWGEIW from Soybean Peptides Reduces Insulin Resistance in 3T3-L1 Adipocytes by Activating p-Akt/GLUT4 Signaling Pathway.

Diabetes mellitus, a group of metabolic disorders characterized by persistent hyperglycemia, affects millions of people worldwide and is on the rise. Dietary proteins, from a wide range of food sources, are rich in bioactive peptides with anti-diabetic properties. Notably, the protective mechanism of the single peptide SWGEDWGEIW (TSP) from soybean peptides (SBPs) on insulin resistance of adipocytes in an inflammatory state was investigated by detecting the lipolysis and glucose absorption and utilization of adipocytes. The results showed that different concentrations of TSP (5, 10, 20 µg/mL) intervention can reduce 3T3-L1 adipocytes' insulin resistance induced by inflammatory factors in a dose-dependent manner and increase glucose utilization by 34.2 ± 4.6%, 74.5 ± 5.2%, and 86.7 ± 6.1%, respectively. Thus, TSP can significantly alleviate the lipolysis of adipocytes caused by inflammatory factors. Further mechanism analysis found that inflammatory factors significantly reduced the phosphorylation (p-Akt) of Akt, two critical proteins of glucose metabolism in adipocytes, and the expression of GLUT4 protein downstream, resulting in impaired glucose utilization, while TSP intervention significantly increased the expression of these two proteins. After pretreatment of adipocytes with PI3K inhibitor (LY294002), TSP failed to reduce the inhibition of p-Akt and GLUT4 expression in adipocytes. Meanwhile, the corresponding significant decrease in glucose absorption and the increase in the fat decomposition of adipocytes indicated that TSP reduced 3T3-L1 adipocytes' insulin resistance by specifically activating the p-Akt/GLUT4 signal pathway. Therefore, TSP has the potential to prevent obesity-induced adipose inflammation and insulin resistance.

m6 A Reader YTHDF1-Targeting Engineered Small Extracellular Vesicles for Gastric Cancer Therapy via Epigenetic and Immune Regulation.

N6 -methyladenosine (m6 A) modulators decide the fate of m6 A-modified transcripts and drive cancer development. RNA interference targeting m6 A modulators promise to be an emerging cancer therapy but is challenging due to its poor tumor targeting and high systematic toxicity. Here engineered small extracellular vesicles (sEVs) with high CD47 expression and cyclic arginine-glycine-aspartic (c(RGDyC)) modification are developed for effective delivery of short interfering RNA against m6 A reader YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) to treat gastric cancer via epigenetic and immune regulation. This nanosystem efficiently depletes YTHDF1 expression and suppresses gastric cancer progression and metastasis through hampering frizzled7 translation and inactivating Wnt/ß-catenin pathway in an m6 A dependent manner. Loss of YTHDF1 mediates overexpression of interferon (IFN)-γ receptor 1 and enhances IFN-γ response, promoting expression of major histocompatibility complex class I on tumor cells to achieve self-presentation of the immunogenic tumor cells to stimulate strong cytotoxic T lymphocytes responses. CD47 expression on the engineered sEVs can competitively bind with signal regulatory protein α to enhance phagocytosis of the tumor cells by tumor-associated macrophages. This versatile nanoplatform provides an efficient and low toxic strategy to inhibit epigenetic regulators and holds great potential in promoting immunotherapy.

KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation.

RNA-binding proteins (RBPs) are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes. The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs (Che-RBPs). One of these proteins, KH-type splicing regulatory protein (KHSRP), is a multifunctional RBP that has been implicated in mRNA decay, alternative splicing, and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129. In this study, we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing. KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation. Of note, KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1. Taken together, our analyses revealed the dual DNA- and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.

METTL3 preferentially enhances non-m6A translation of epigenetic factors and promotes tumourigenesis.

METTL3 encodes the predominant catalytic enzyme to promote m6A methylation in nucleus. Recently, accumulating evidence has shown the expression of METTL3 in cytoplasm, but its function is not fully understood. Here we demonstrated an m6A-independent mechanism for METTL3 to promote tumour progression. In gastric cancer, METTL3 could not only facilitate cancer progression via m6A modification, but also bind to numerous non-m6A-modified mRNAs, suggesting an unexpected role of METTL3. Mechanistically, cytoplasm-anchored METTL3 interacted with PABPC1 to stabilize its association with cap-binding complex eIF4F, which preferentially promoted the translation of epigenetic factors without m6A modification. Clinical investigation showed that cytoplasmic distributed METTL3 was highly correlated with gastric cancer progression, and this finding could be expanded to prostate cancer. Therefore, the cytoplasmic METTL3 enhances the translation of epigenetic mRNAs, thus serving as an oncogenic driver in cancer progression, and METTL3 subcellular distribution can assist diagnosis and predict prognosis for patients with cancer.

On Imported and Domestic Human Papillomavirus Vaccines: Cognition, Attitude, and Willingness to Pay in Chinese Medical Students.

This study aimed to analyze the cognition, attitude, and willingness to pay (WTP) for imported and domestic human papillomavirus (HPV) vaccines in Chinese medical students. Methods: Medical students in Eastern, Central and Western China were investigated. We used the HPV cognitive list to measure the cognition of participants and implemented contingent valuation method (CVM) to value WTP. Tobit model was used to analyze the factors associated with WTP. Results: The participants' average score for the 21 cognitive questions was 13.05 (±5.09). Among the participants, 60.82 and 88.01% reported that they would wish to be vaccinated and support the partners to be vaccinated. In addition, 92.54% (670) of the participants were willing to pay for HPV vaccines, at mean values (in RMB) of 1,689.80 (±926.13), 2,216.61 (±1190.62), and 3,252.43 (±2064.71) for imported bivalent, quadrivalent, and 9-valent vaccines, respectively, and at 910.63 (±647.03), 1,861.69 (±1147.80), and 2,866.96 (±1784.41) for their domestic counterparts, respectively. The increase in cognitive score has a positive effect on the WTP for imported vaccines (P < 0.05). Conclusions: Most of the participants were likewise willing to receive the HPV vaccines. Their perceptions of the HPV vaccines valent and origin may affect their willingness to be vaccinated and pay for the vaccines. Increasing awareness of the HPV vaccines and the inclusion of the HPV vaccines in a Medicare reimbursement policy or immunization program could increase the coverage of the HPV vaccine.

Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation.

Single-cell transcriptional profiling has rapidly advanced our understanding of the embryonic hematopoiesis; however, whether and what role RNA alternative splicing (AS) plays remains an enigma. This is important for understanding the mechanisms underlying splicing-associated hematopoietic diseases and for the derivation of therapeutic stem cells. Here, we used single-cell full-length transcriptome data to construct an isoform-based transcriptional atlas of the murine endothelial-to-hematopoietic stem cell (HSC) transition, which enables the identification of hemogenic signature isoforms and stage-specific AS events. We showed that the inclusion of these hemogenic-specific AS events was essential for hemogenic function in vitro. Expression data and knockout mouse studies highlighted the critical role of Srsf2: Early Srsf2 deficiency from endothelial cells affected the splicing pattern of several master hematopoietic regulators and significantly impaired HSC generation. These results redefine our understanding of the dynamic HSC developmental transcriptome and demonstrate that elaborately controlled RNA splicing governs cell fate in HSC formation.

Whitening and inhibiting NF-κB-mediated inflammation properties of the biotransformed green ginseng berry of new cultivar K1, ginsenoside Rg2 enriched, on B16 and LPS-stimulated RAW 264.7 cells.

BACKGROUND: Main bioactive constituents and pharmacological functions of ripened red ginseng berry (Panax ginseng Meyer) have been frequently reported. Yet, the research gap targeting the beneficial activities of transformed green ginseng berries has not reported elsewhere. METHODS: Ginsenosides of new green berry cultivar K-1 (GK-1) were identified by HPLC-QTOF/MS. Ginsenosides bioconversion in GK-1 by bgp1 enzyme was confirmed with HPLC and TLC. Then, mechanisms of GK-1 and ß-glucosidase (bgp1) biotransformed GK-1 (BGK-1) were determined by Quantitative Reverse Transcription-Polymerase Chain Reaction and Western blot. RESULTS: GK-1 possesses highest ginsenosides especially ginsenoside-Re amongst seven ginseng cultivars including (Chunpoong, Huangsuk, Kumpoong, K-1, Honkaejong, Gopoong, and Yunpoong). Ginseng root's biomass is not affected with the harvest of GK-1 at 3 weeks after flowering period. Then, Re is bio-converted into a promising pharmaceutical effect of Rg2 via bgp1. According to the results of cell assays, BGK-1 shows decrease of tyrosinase and melanin content in α-melanocyte-stimulating hormone challenged-murine melanoma B16 cells. BGK-1 which is comparatively more effective than GK-1 extract shows significant suppression of the nuclear factor (NF)-κB activation and inflammatory target genes, in LPS-stimulated RAW 264.7 cells. CONCLUSION: These results reported effective whitening and anti-inflammatory of BGK-1 as compared to GK-1.

A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation.

BACKGROUND: Cellular RNA-binding proteins (RBPs) have multiple roles in post-transcriptional control, and some are shown to bind DNA. However, the global localization and the general chromatin-binding ability of RBPs are not well-characterized and remain undefined in hematopoietic cells. RESULTS: We first provide a full view of RBPs' distribution pattern in the nucleus and screen for chromatin-enriched RBPs (Che-RBPs) in different human cells. Subsequently, by generating ChIP-seq, CLIP-seq, and RNA-seq datasets and conducting combined analysis, the transcriptional regulatory potentials of certain hematopoietic Che-RBPs are predicted. From this analysis, quaking (QKI5) emerges as a potential transcriptional activator during monocytic differentiation. QKI5 is over-represented in gene promoter regions, independent of RNA or transcription factors. Furthermore, DNA-bound QKI5 activates the transcription of several critical monocytic differentiation-associated genes, including CXCL2, IL16, and PTPN6. Finally, we show that the differentiation-promoting activity of QKI5 is largely dependent on CXCL2, irrespective of its RNA-binding capacity. CONCLUSIONS: Our study indicates that Che-RBPs are versatile factors that orchestrate gene expression in different cellular contexts, and identifies QKI5, a classic RBP regulating RNA processing, as a novel transcriptional activator during monocytic differentiation.

Influence of the plant growth promoting Rhizobium panacihumi on aluminum resistance in Panax ginseng.

BACKGROUND: Panax ginseng is an important crop in Asian countries given its pharmaceutical uses. It is usually harvested after 4-6 years of cultivation. However, various abiotic stresses have led to its quality reduction. One of the stress causes is high content of heavy metal in ginseng cultivation area. Plant growth-promoting rhizobacteria (PGPR) can play a role in healthy growth of plants. It has been considered as a new trend for supporting the growth of many crops in heavy metal occupied areas, such as Aluminum (Al). METHODS: In vitro screening of the plant growth promoting activities of five tested strains were detected. Surface-disinfected 2-year-old ginseng seedlings were dipping in Rhizobium panacihumi DCY116T suspensions for 15 min and cultured in pots for investigating Al resistance of P. ginseng. The harvesting was carried out 10 days after Al treatment. We then examined H2O2, proline, total soluble sugar, and total phenolic contents. We also checked the expressions of related genes (PgCAT, PgAPX, and PgP5CS) of reactive oxygen species scavenging response and pyrroline-5-carboxylate synthetase by reverse transcription polymerase chain reaction (RT-PCR) method. RESULTS: Among five tested strains isolated from ginseng-cultivated soil, R. panacihumi DCY116T was chosen as the potential PGPR candidate for further study. Ginseng seedlings treated with R. panacihumi DCY116T produced higher biomass, proline, total phenolic, total soluble sugar contents, and related gene expressions but decreased H2O2 level than nonbacterized Al-stressed seedlings. CONCLUSION: R. panacihumi DCY116T can be used as potential PGPR and "plant strengthener" for future cultivation of ginseng or other crops/plants that are grown in regions with heavy metal exposure.

YTHDF1 Promotes Gastric Carcinogenesis by Controlling Translation of FZD7.

N6-methyladenosine (m6A) is the most prevalent internal RNA modification in mammals that regulates homeostasis and function of modified RNA transcripts. Here, we aimed to investigate the role of YTH m6A RNA-binding protein 1 (YTHDF1), a key regulator of m6A methylation in gastric cancer tumorigenesis. Multiple bioinformatic analyses of different human cancer databases identified key m6A-associated genetic mutations that regulated gastric tumorigenesis. YTHDF1 was mutated in about 7% of patients with gastric cancer, and high expression of YTHDF1 was associated with more aggressive tumor progression and poor overall survival. Inhibition of YTHDF1 attenuated gastric cancer cell proliferation and tumorigenesis in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of a key Wnt receptor frizzled7 (FZD7) in an m6A-dependent manner, and mutated YTHDF1 enhanced expression of FZD7, leading to hyperactivation of the Wnt/ß-catenin pathway and promotion of gastric carcinogenesis. Our results demonstrate the oncogenic role of YTHDF1 and its m6A-mediated regulation of Wnt/ß-catenin signaling in gastric cancer, providing a novel approach of targeting such epigenetic regulators in this disease. SIGNIFICANCE: This study provides a rationale for controlling translation of key oncogenic drivers in cancer by manipulating epigenetic regulators, representing a novel and efficient strategy for anticancer treatment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/10/2651/F1.large.jpg.

Comprehensive Genome Analysis on the Novel Species Sphingomonas panacis DCY99T Reveals Insights into Iron Tolerance of Ginseng.

Plant growth-promoting rhizobacteria play vital roles not only in plant growth, but also in reducing biotic/abiotic stress. Sphingomonas panacis DCY99T is isolated from soil and root of Panax ginseng with rusty root disease, characterized by raised reddish-brown root and this is seriously affects ginseng cultivation. To investigate the relationship between 159 sequenced Sphingomonas strains, pan-genome analysis was carried out, which suggested genomic diversity of the Sphingomonas genus. Comparative analysis of S. panacis DCY99T with Sphingomonas sp. LK11 revealed plant growth-promoting potential of S. panacis DCY99T through indole acetic acid production, phosphate solubilizing, and antifungal abilities. Detailed genomic analysis has shown that S. panacis DCY99T contain various heavy metals resistance genes in its genome and the plasmid. Functional analysis with Sphingomonas paucimobilis EPA505 predicted that S. panacis DCY99T possess genes for degradation of polyaromatic hydrocarbon and phenolic compounds in rusty-ginseng root. Interestingly, when primed ginseng with S. panacis DCY99T during high concentration of iron exposure, iron stress of ginseng was suppressed. In order to detect S. panacis DCY99T in soil, biomarker was designed using spt gene. This study brings new insights into the role of S. panacis DCY99T as a microbial inoculant to protect ginseng plants against rusty root disease.

Paraburkholderia panacisoli sp. nov., a potentially antagonistic bacterium against the root rot fungal pathogen Cylindrocarpon destructans, isolated from ginseng cultivation soil.

A new bacterium, designated DCY113T, was isolated from ginseng cultivation soil in Gochang-gun, South Korea, and its taxonomic position identified by the polyphasic approach. 16S rRNA gene sequence analysis determined that this isolate belongs to the genus Paraburkholderia, and was closest to P. dipogonis DL7T (98.6%), P. phytofirmans PsJNT (98.5%), P. kirstenboschensis Kb15T (98.4%) and P. aromaticivorans BNT (98.1%). Strain DCY113T is Gram-reaction negative, strictly aerobic, rod-shaped, non-motile, and catalase and oxidase positive. The predominant isoprenoid quinone of DCY113T was ubiquinone Q-8. The major cellular fatty acids were C16:0, cyclo-C17:0 and the Summed feature 8 (C18:1ω7c and/or C18:1ω6c). The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and an unknown amino lipid (AL1). The G+C content of the genomic DNA was 62.2 mol%. Average nucleotide identity (ANI) between strain DCY113T and the related Paraburkholderia type strains were below the threshold value for species delineation. This low DNA relatedness in combination with phylogenetic and phenotypic tests indicates that strain DCY113T cannot be assigned to any recognized species. Strain DCY113T was also found to have antifungal activity against the pathogenic fungi Cylindrocarpon destructans. In conclusion, this study found DCY113T to be a novel species within the genus Paraburkholderia, for which the name P. panacisoli is proposed. The type strain is DCY113T (= KCTC 52951T = JCM 32098T).