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1.
Int J Biol Sci ; 20(9): 3675-3690, 2024.
Article in English | MEDLINE | ID: mdl-38993567

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly tumors; however, its pathogenic mechanism remains largely elusive. In-depth researches are needed to reveal the expression regulatory mechanisms and functions of the RNA-binding protein RALY in HCC. Here, we identify RALY as a highly expressed oncogenic factor that affects HCC cells proliferation both in vitro and in vivo. O-GlcNAcylation of RALY at Ser176 enhances its stability by protecting RALY from TRIM27-mediated ubiquitination, thus maintaining hyper-expression of the RALY protein. Mechanistically, RALY interacts with USP22 messenger RNA, as revealed by RNA immunoprecipitation, to increase their cytoplasmic localization and protein expression, thereby promoting the proliferation of HCC cells. Furthermore, we develop a novel RALY protein degrader based on peptide proteolysis-targeting chimeras, named RALY-PROTAC, which we chemically synthesize by linking a RALY-targeting peptide with the E3 ubiquitin ligase recruitment ligand pomalidomide. In conclusion, our findings demonstrate a novel mechanism by which O-GlcNAcylation/RALY/USP22 mRNA axis aggravates HCC cells proliferation. RALY-PROTACs as degraders of the RALY protein exhibit potential as therapeutic drugs for RALY-overexpressing HCC.


Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , Liver Neoplasms , Ubiquitin Thiolesterase , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , Cell Line, Tumor , Animals , RNA, Messenger/metabolism , RNA, Messenger/genetics , Mice , Mice, Nude , Ubiquitination , Active Transport, Cell Nucleus
2.
Sci Rep ; 14(1): 10850, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740861

ABSTRACT

In Fenwei Basin, most of the tectonic ground fissures show characteristics of growth faults on the section. They continue to destroy the engineering properties of soil at different depths. This has introduced significant security risks to the construction processes of deep underground spaces. However, there are few studies have been conducted on syn-depositional ground fissures. Therefore, in this study, a physical simulation test was used to study the fracture propagation of syn-depositional ground fissures. The characteristics of sections and surface fractures were analyzed. The engineering properties of model soil were divided into bad and poor areas. The syn-depositional ground fissure fracture propagation process was divided into five phases. The results show that soil profile exhibited a composite Y-shaped fracture morphology. Syn-deposition affects the fracture angle and healing state of fractures. The soil strain and surface displacement were positively correlated with the number of deposition layers. The conclusions of this study provide a theoretical geological basis and practical engineering significance for design of deep underground space structures.

3.
Materials (Basel) ; 17(7)2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38612112

ABSTRACT

In the process of the ultrasonic-assisted arc welding of metal materials, traditional ultrasonic application methods, such as the low-frequency impact of ultrasonic horns on a base material, can easily cause the non-fusion defect. In order to solve this problem, a rotating sonotrode with a groove and double thin ends was designed in this study. The ultrasonic vibration is transmitted into the weld pool by the rolling of the sonotrode on both sides of the weld. The resonant frequency was set at 50 kHz. Firstly, based on the Mindlin theory, a rotating sonotrode without a groove was designed by solving the frequency equation and by conducting a finite element simulation. Secondly, the effects of the groove, perforation, and transition mode on the resonant frequency, stress distribution, and amplification factor were investigated by finite element simulation. Finally, the optimum rotating sonotrode with a groove was obtained. The results show that the size of a rotating sonotrode that has a small frequency error can be obtained by using the discrete interval solver method combined with finite element simulation. The groove can significantly reduce the resonant frequency. The stress concentration can be effectively reduced by using the elliptical transition mode. The resonant frequency and amplification factor of a rotating sonotrode with a groove could be effectively adjusted by a method of double-position joint perforation. The final resonant frequency was 49.721 kHz and the amplification factor was 3.02. This study provides an effective design method for a sonotrode with double thin ends and a groove structure.

4.
Int J Gen Med ; 17: 1193-1211, 2024.
Article in English | MEDLINE | ID: mdl-38559590

ABSTRACT

Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive and fatal malignancy that leads to epithelial cancer. The association between epithelial cell heterogeneity, prognosis, and immune response in this cancer remains uncertain. This study aimed to investigate epithelial cell heterogeneity in ESCC and develop a predictive risk model using the identified cell types. Methods: Single-cell RNA sequencing (scRNA-seq) and differential ESCC gene data were accessed from the Gene Expression Omnibus. Functional enrichment analysis, inferCNV, cell development trajectories, and intercellular communication were analyzed following epithelial cell characterization. Differentially expressed ESCC (n = 773) and epithelial cell marker genes (n = 3407) were intersected to obtain core genes, and epithelial cell-related prognostic genes were identified. LASSO regression analysis was used to construct a prognostic model. The external dataset GSE53624 was used to further validate the stability of the model. Drug sensitivity predictions, and immune cell infiltration were analyzed. Molecular docking clarified the possible therapeutic role of ß-sitosterol in ESCC. Finally, wound healing assay, cell colony, and transwell assay were constructed to detect the effects of the core gene PDLIM2 on ESCC cell proliferation, invasion, and migration. Results: Eight cell clusters were identified, and epithelial cells were categorized into tumor and paratumor groups. The tumor group possessed more chromosomal variants than the paratumor group. Epithelial cells were associated with multiple cell types and significantly correlated with the Wnt, transforming growth factor, and epidermal growth factor signaling pathways. From 231 intersected genes, five core genes were screened for use in the risk model: CTSL, LAPTM4B, MYO10, NCF2, and PDLIM2. These genes may contribute to the cancerous transformation of normal esophageal epithelial cells and thereby act as biomarkers and potential therapeutic targets in patients with ESCC. ß-Sitosterol furthermore displayed excellent docking potential with these genes. Meanwhile, further experiments demonstrated that the gene PDLIM2 plays a major role in the progression of oesophageal squamous carcinoma. Conclusion: We successfully developed a risk model for the prognosis of ESCC based on epithelial cells that addresses the response of ESCC to immunotherapy and offers novel cancer treatment options.

5.
Analyst ; 149(7): 2103-2113, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38421308

ABSTRACT

The surface modification technique is applied in microfluidic devices to modify wettability and achieve different flow velocities. Currently available methods for poly(dimethylsiloxane) (PDMS) surfaces may reliably induce wettability changes, but only one area can be altered at a time. This work introduces the controlled gradient oxygen plasma modification (CGPM) technique, which layers several resin masks with varying porosities on top of the PDMS surface. Selective wettability of the PDMS surface can be achieved by varying the oxygen plasma density above the modified material's surface by manipulation of the porosity value. Through the implementation of the COMSOL plasma module, the impact of the mask's porosity, through-hole size, distribution, and distance from the PDMS surface on wettability was studied. The suggested CGPM approach was characterized by contact angle measurements. During the 25-second CGPM procedure, the PDMS surface's contact angle continually changed from 8.77° to 76.98°. An integrated microfluidic device was created and manufactured to identify D-dimers to illustrate this method. In comparison with standard oxygen plasma treatment, the D-dimer assay was finished in 10 minutes and had a dynamic range of 1-1000 ng mL-1, with a peak fluorescence signal augmentation of 78.3% and an average fluorescence intensity enhancement of 31.1%.

6.
Cardiovasc Intervent Radiol ; 47(2): 225-233, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38273130

ABSTRACT

PURPOSE: To elucidate incidence rates of vascular lake phenomenon (VLP) in hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatic metastasis (HMT) on transarterial angiography before chemoembolization, and to identity CT features predictive for it. MATERIALS AND METHODS: A comprehensive evaluation involved 665 subjects for incidence analysis, comprising 527 of HCC, 33 of ICC and 105 of HMT. VLP was characterized as intratumoral contrast material pool persisting late into venous phase. Incidences were cataloged on both super-selective and common hepatic artery angiography. For CT features analysis, a subset of 182 cases were analyzed. Enhancement ratio served as an index for comparative analysis of nodule enhancement degrees. RESULTS: In HCC, incidence of VLP ascertained via super-selective angiography was 13.5%, whereas it as 7.8% on common hepatic artery angiography. Remarkably, no incidences of VLP were recorded in either ICC or HMT cases. On pre-interventional CT, the prevalence of pseudocapsule was statistically greater in VLP group than Non-VLP group (66.6% vs. 37.6%, P = 0.015). The Houndsfield units (HU) of tumors in plain scan (P = 0.007), arterial phase (P = 0.001), venous phase (P = 0.041), arterial phase enhancement ratio (P < 0.001) were statistically higher in VLP group compared to Non-VLP group. Arterial phase enhancement ratio (P = 0.025), presence of pseudocapsule (P = 0.001), HU of tumor in plain scan (P = 0.035) serve as independent risk factors for VLP manifestation. CONCLUSION: VLP is a distinct angiography phenomenon uniquely associated with HCC. High arterial phase enhancement ratio, presence of pseudocapsule, high HU of tumor in plain scan are independent risk factors for VLP.


Subject(s)
Bile Duct Neoplasms , Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Cholangiocarcinoma , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/blood supply , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Incidence , Angiography , Contrast Media , Cholangiocarcinoma/pathology , Hepatic Artery/pathology , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/pathology , Tomography, X-Ray Computed
7.
Vet Microbiol ; 288: 109923, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38061277

ABSTRACT

Escherichia coli and Salmonella Typhimurium are the main pathogens of diarrhea in weaned piglets. The prevention of bacterial diarrhea in weaned piglets by phage is rarely reported. We conducted this study to evaluate the preventive effect of phages on mixed Escherichia coli and Salmonella Typhimurium infections in weaned piglets. A novel phage named NJ12 was isolated by using Salmonella Typhimurium SM022 as host bacteria and characterized by electron microscopy, genomic analysis and in vitro bacteriostatic activity. Phage NJ12 and a previously reported phage EP01 were microencapsulated with sodium alginate to make phage cocktail. Microencapsulated phage cocktail and PBS (Phosphate buffer solution) were used to piglets the phage and phage-free group through oral administration before bacterial infection 2 h, respectively. Piglets of the phage and phage-free group were consumed with feed contaminated with 6 mL (108CFU/mL) Escherichia coli O157:H7 GN07 (GXEC-N07) and 6 mL (108CFU/mL) SM022 every day for seven consecutive days. The results showed that piglets in the phage-free group had more severe diarrhea, larger decreased average weight gain and higher levels of neutrophils compared with piglets in phage group. Meanwhile, piglets in the phage-free group had higher load of SM022 and GN07 in jejunal tissue and more severe intestinal damage compared with piglets in group phage in vivo. In addition, oral administration phage can significant decreased the relative abundance of Enterobacteriaceae but hardly repaired the changes of diversity and composition of gut microbiota caused by the mixed infection of SM022 and GN07. This implies that phage used as a feed additive have a marvelous preventive effect on bacterial diarrhea during weaning of piglets.


Subject(s)
Bacteriophages , Dysentery , Escherichia coli Infections , Escherichia coli O157 , Salmonella Infections , Swine Diseases , Animals , Swine , Salmonella typhimurium , Escherichia coli O157/genetics , Weaning , Diarrhea/prevention & control , Diarrhea/veterinary , Diarrhea/microbiology , Escherichia coli Infections/prevention & control , Escherichia coli Infections/veterinary , Escherichia coli Infections/microbiology , Dysentery/veterinary , Swine Diseases/prevention & control , Swine Diseases/microbiology
8.
ACS Appl Mater Interfaces ; 15(43): 50069-50082, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37871135

ABSTRACT

Multimodal treatment is an important tool to overcome tumor drug resistance. The reactive oxygen species (ROS) generated by photodynamic therapy (PDT) can directly play a killing role on tumor cells, which has the advantages of repeatable treatment and no drug resistance. However, its therapeutic oxygen consumption and destruction of tumor microvessels lead to hypoxia in tumor tissues, and hypoxia leads to overexpression of the receptor tyrosine kinase (c-MET) and vascular endothelial growth factor receptor (VEGFR). Overexpression of these two receptors leads to increased tumor invasiveness and metastasis. The molecularly targeted drug cabozantinib (CAB) has multiple targets, including anti-c-MET and VEGFR, to inhibit the development of hepatocellular carcinoma (HCC). In this study, our team designed a pH-sensitive nanoparticle CAB/Ce6@ZIF-8@PEG-FA (CCZP) loaded with CAB and Ce6, which exerted a multimodal therapeutic effect of PDT and molecularly targeted therapy by laser irradiation, and the PDT-induced overexpression of MET and VEGFR could also be inhibited by the target of CAB, thus reducing the invasive tumor cells metastasis. In summary, CCZP gives full play to the advantages of both drugs, exerting multimodal treatment while reducing HCC invasion and metastasis, providing a safe, potential approach to clinical treatment.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Metal-Organic Frameworks , Nanoparticles , Photochemotherapy , Humans , Carcinoma, Hepatocellular/drug therapy , Metal-Organic Frameworks/pharmacology , Vascular Endothelial Growth Factor A , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Combined Modality Therapy , Nanoparticles/chemistry , Hydrogen-Ion Concentration , Hypoxia/drug therapy , Cell Line, Tumor , Photosensitizing Agents/chemistry
9.
Open Med (Wars) ; 18(1): 20230809, 2023.
Article in English | MEDLINE | ID: mdl-37829841

ABSTRACT

Accumulating evidence shows that Schwann cells' (SCs) death caused by high glucose (HG) is involved in the pathological process of diabetic peripheral neuropathy (DPN). Ferroptosis is a novel form of regulatory cell death driven by iron-dependent lipid peroxidation. However, it is not clear whether ferroptosis is involved in the death process of SCs induced by HG. The expression of ferroptosis-related indicators in the serum of DPN patients was detected by ELISA. Subsequently, using cell counting kit­8, western blot, real-time PCR, and Ki-67 staining, we investigated the effects of HG on the ferroptosis of SCs and initially explored the underlying mechanism. The results showed that the serum levels of glutathione peroxidase 4 (GPX4) and glutathione in patients with DPN decreased, while malondialdehyde levels increased significantly. Then, we observed that erastin and HG induced ferroptosis in SCs, resulting in the decrease in cell activity and the expression level of GPX4 and SLC7A11, which could be effectively reversed by the ferroptosis inhibitor Fer-1. Mechanistically, HG induced ferroptosis in SCs by inhibiting the NRF2 signaling pathway. Our results showed that ferroptosis was involved in the death process of SCs induced by HG. Inhibition of ferroptosis in SCs might create a new avenue for the treatment of DPN.

10.
Aging (Albany NY) ; 15(18): 9614-9632, 2023 Sep 18.
Article in English | MEDLINE | ID: mdl-37724906

ABSTRACT

Despite advancements in therapeutic options, the overall prognosis for non-small cell lung cancer (NSCLC) remains poor. Therefore, it is crucial to further explore the etiology and targets for novel treatments to effectively manage NSCLC. In this study, immunohistochemistry was used to analyze the expression of aldolase, fructose-bisphosphate C (ALDOC) protein in tumor tissues and adjacent non-malignant tissues from 79 NSCLC patients. Our findings revealed that ALDOC was overexpressed in NSCLC tissues. ALDOC expression was associated with lymph node metastasis, lymphatic metastasis and pathological stage. In addition, Kaplan-Meier analysis showed that higher ALDOC levels were indicative of a poorer prognosis. Additionally, we observed elevated ALDOC mRNA levels in NSCLC cell lines relative to normal cells. To investigate the functional roles of ALDOC, we infected cells with small interfering RNA against ALDOC, which led to attenuated proliferation and migration, as well as ameliorated apoptosis. Furthermore, through our investigations, we discovered that ubiquitin-conjugating enzyme E2N (UBE2N) acts as a downstream factor of ALDOC. ALDOC promoted NSCLC through affecting MYC-mediated UBE2N transcription and regulating the Wnt pathway. More importantly, we found that downregulation of UBE2N or the use of Wnt pathway inhibitor could reverse the promoting effects of ALDOC elevation on NSCLC development in vitro and in vivo. Based on these findings, our study highlights the potential of ALDOC as a future therapeutic target for NSCLC.

11.
BMC Vet Res ; 19(1): 165, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37730566

ABSTRACT

BACKGROUND: Escherichia coli (E. coli) is a common pathogen that often causes diarrhea in piglets. Since bacteria are becoming more and more resistant to antibiotics, phages have become a promising alternative therapy. However, the therapy of oral phage often fails to achieve the desired effect. A novel phage named A221 was isolated by using E. coli GXXW-1103 as host strain, characterized by electron microscopy, genomic sequencing and analyzed by measuring lysis ability in vitro. RESULTS: Phage A221 was identified as a member of Ackermannviridae, Aglimvirinae, Agtrevirus with 153297 bp genome and effectively inhibited bacterial growth in vitro for 16 h. This study was conducted to evaluate the therapeutic effect of oral microencapsulated phage A221 on E. coli GXXW-1103 infections in weaned piglets. The protective effect of phage was evaluated by body weight analysis, bacterial load and histopathological changes. The results showed that with the treatment of phage A221, the body weight of piglets increased, the percentage of Enterobacteriaceae in duodenum decreased to 0.64%, the lesions in cecum and duodenum were alleviated, and the bacterial load in the jejunal lymph nodes, cecum and spleen were also significantly different with infected group (P < 0.001). CONCLUSIONS: The results showed that phage A221 significantly increased the daily weight gain of piglets, reduced the bacterial load of tissues and the intestinal lesions, achieved the same therapeutic effect as antibiotic Florfenicol. Taken together, oral microencapsulated phage A221 has a good therapeutic effect on bacterial diarrhea of weaned piglets, which provides guidance for the clinical application of phage therapy in the future.


Subject(s)
Bacteriophages , Escherichia coli Infections , Phage Therapy , Swine Diseases , Animals , Swine , Escherichia coli , Phage Therapy/veterinary , Escherichia coli Infections/therapy , Escherichia coli Infections/veterinary , Diarrhea/therapy , Diarrhea/veterinary , Anti-Bacterial Agents/therapeutic use , Body Weight , Swine Diseases/therapy
12.
Front Endocrinol (Lausanne) ; 14: 1153802, 2023.
Article in English | MEDLINE | ID: mdl-37469973

ABSTRACT

Background: Increasing evidence elucidated N6-methyladenosine (m6A) dysregulation participated in regulating RNA maturation, stability, and translation. This study aimed to demystify the crosstalk between m6A regulators and the immune microenvironment, providing a potential therapeutic target for patients with hepatocellular carcinoma (HCC). Methods: Totals of 371 HCC and 50 normal patients were included in this study. GSE121248 and GSE40367 datasets were used to validate the expression of HNRNPC. The R package "ConsensusClusterPlus" was performed to screen consensus clustering types based on the expression of m6A regulators in HCC. The R package "pheatmap", "immunedeconv", "survival", "survminer" and "RMS" were applied to investigate the expression, immunity, overall survival, and clinical application in different clusters and expression groups. Comprehensive analysis of HNRNPC in pan-cancer was conducted by TIMER2 database. Besides, HNRNPC mRNA and protein expression were verified by qRT-PCR and immunohistochemistry analysis. Results: Most of m6A regulators were over-expressed excerpt for ZC3H13 in HCC. Three independent clusters were screened based on m6A regulators expression, and the cluster 2 had a favorable prognosis in HCC. Then, the cluster 2 was positively expression in macrophage, hematopoietic stem cell, endothelial cell, and stroma score, while negatively in T cell CD4+ memory and mast cell. We identified HNRNPC was an independent prognostic factor in HCC, and nomogram performed superior application value for clinical decision making. Moreover, PD-L1 was significantly up-regulated in HCC tissues, cluster 1, and cluster 3, and we found PD-L1 expression was positively correlated with HNRNPC. Patients with HCC in high-expression groups was associated with tumor-promoting cells. Besides, HNRNPC was correlated with prognosis, TMB, and immune checkpoints in cancers. Particularly, the experiments confirmed that HNRNPC was positively expression in HCC cells and tissues. Conclusion: The m6A regulators play irreplaceable roles in prognosis and immune infiltration in HCC, and the relationship of HNRNPC and PD-L1 possesses a promising direction for therapeutic targets of immunotherapy response. Exploration of m6A regulators pattern could be build the prognostic stratification of individual patients and move toward to personalized treatment.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/therapy , B7-H1 Antigen , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Liver Neoplasms/therapy , Immunotherapy , Adenosine , Tumor Microenvironment/genetics
13.
Virus Genes ; 59(4): 613-623, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37170002

ABSTRACT

As the problem of bacterial resistance becomes serious day by day, bacteriophage as a potential antibiotic substitute attracts more and more researchers' interest. In this study, Escherichia phage Kayfunavirus CY1 was isolated from sewage samples of swine farms and identified by biological characteristics and genomic analysis. One-step growth curve showed that the latent period of phage CY1 was about 10 min, the outbreak period was about 40 min and the burst size was 35 PFU/cell. Analysis of the electron microscopy and whole-genome sequence showed that the phage should be classified as a member of the Autographiviridae family, Studiervirinae subfamily. Genomic analysis of phage CY1 (GenBank accession no. OM937123) revealed a genome size of 39,173 bp with an average GC content of 50.51% and 46 coding domain sequences (CDSs). Eight CDSs encoding proteins involved in the replication and regulation of phage DNA, 2 CDSs encoded lysis proteins, 14 CDSs encoded packing and morphogenesis proteins. Genomic and proteomic analysis identified no sequence that encoded for virulence factor, integration-related proteins or antibiotic resistance genes. In summary, morphological and genomics suggest that phage CY1 is more likely a novel Escherichia phage.


Subject(s)
Bacteriophages , Caudovirales , Swine , Animals , Proteomics , Genome, Viral/genetics , Genomics , Bacteriophages/genetics , Caudovirales/genetics , Escherichia/genetics
14.
Cell Death Dis ; 14(5): 301, 2023 05 03.
Article in English | MEDLINE | ID: mdl-37137887

ABSTRACT

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognoses worldwide. Many studies have reported that long noncoding RNAs (lncRNAs) are related to the progression and prognosis of HCC. However, the functions of downregulated liver-elevated (LE) lncRNAs in HCC remain elusive. Here we report the roles and mechanisms of downregulated LE LINC02428 in HCC. Downregulated LE lncRNAs played significant roles in HCC genesis and development. LINC02428 was upregulated in liver tissues compared with other normal tissues and showed low expression in HCC. The low expression of LINC02428 was attributed to poor HCC prognosis. Overexpressed LINC02428 suppressed the proliferation and metastasis of HCC in vitro and in vivo. LINC02428 was predominantly located in the cytoplasm and bound to insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) to prevent it from binding to lysine demethylase 5B (KDM5B) mRNA, which decreased the stability of KDM5B mRNA. KDM5B was found to preferentially bind to the promoter region of IGF2BP1 to upregulate its transcription. Therefore, LINC02428 interrupts the KDM5B/IGF2BP1 positive feedback loops to inhibit HCC progression. The KDM5B/IGF2BP1 positive feedback loop is involved in tumorigenesis and progression of HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Feedback , Cell Line, Tumor , RNA, Messenger , Gene Expression Regulation, Neoplastic/genetics , Cell Proliferation/genetics , Nuclear Proteins/metabolism , Repressor Proteins/metabolism , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism
15.
Microbiome ; 11(1): 85, 2023 04 21.
Article in English | MEDLINE | ID: mdl-37085934

ABSTRACT

BACKGROUND: Plants sustain intimate relationships with diverse microbes. It is well-recognized that these plant-associated microbiota shape individual performance and fitness of host plants, but much remains to be explored regarding how they exert their function and maintain their homeostasis. RESULTS: Here, using pink lady (Heterotis rotundifolia) as a study plant, we investigated the phenomenon of microbiota-mediated nitrogen fixation and elucidated how this process is steadily maintained in the root mucilage microhabitat. Metabolite and microbiota profiling showed that the aerial root mucilage is enriched in carbohydrates and diazotrophic bacteria. Nitrogen isotope-labeling experiments, 15N natural abundance, and gene expression analysis indicated that the aerial root-mucilage microbiota could fix atmospheric nitrogen to support plant growth. While the aerial root mucilage is a hotspot of nutrients, we did not observe high abundance of other environmental and pathogenic microbes inside. We further identified a fungus isolate in mucilage that has shown broad-spectrum antimicrobial activities, but solely allows the growth of diazotrophic bacteria. This "friendly" fungus may be the key driver to maintain nitrogen fixation function in the mucilage microhabitat. Video Abstract CONCLUSION: The discovery of new biological function and mucilage-habitat friendly fungi provides insights into microbial homeostasis maintenance of microenvironmental function and rhizosphere ecology.


Subject(s)
Microbiota , Nitrogen Fixation , Humans , Polysaccharides/metabolism , Microbiota/genetics , Bacteria/genetics , Bacteria/metabolism , Rhizosphere , Plants/metabolism , Homeostasis , Plant Roots/microbiology , Soil Microbiology
16.
Cancers (Basel) ; 15(4)2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36831430

ABSTRACT

(1) Background: Pancreatic cancer is increasingly becoming the leading cause of cancer deaths worldwide. In eukaryotic cells, m6A is the most abundant mRNA methylation modification. (2) Methods: We performed a bioinformatic multidimensional analysis using files containing the clinical data of patients and m6A-related gene expression differences downloaded from web-based databases, and performed a statistical analysis and image mapping mainly using R-package. Next, we studied the RBM15 expression in cancer and paracancerous tissues. We then validated these findings in two cell lines by western blot, PCR, Transwell, CCK-8, and EDU animal models. (3) Results: We discovered that RBM15 was highly expressed in pancreatic cancer patients and that it is a significant cause of poor prognosis. Its association with lymphatic T cell family aggregation was established through immune infiltration analysis. A retrospective analysis of data from clinical patient specimens revealed that high expression of RBM15 in patients was closely and positively correlated with preoperative glucose values, gender, and lymphocyte counts. Results from cellular experiments and animal experiments indicated that when the RBM15 gene was silenced, cell proliferation, migration, and metastasis were inhibited. (4) Conclusions: We propose that RBM15 plays a key role in the progression of pancreatic cancer by promoting tumor proliferation, migration and metastasis.

17.
Genomics Proteomics Bioinformatics ; 21(1): 127-149, 2023 02.
Article in English | MEDLINE | ID: mdl-36587654

ABSTRACT

Jasminum sambac (jasmine flower), a world-renowned plant appreciated for its exceptional flower fragrance, is of cultural and economic importance. However, the genetic basis of its fragrance is largely unknown. Here, we present the first de novogenome assembly of J. sambac with 550.12 Mb (scaffold N50 = 40.10 Mb) assembled into 13 pseudochromosomes. Terpene synthase (TPS) genes associated with flower fragrance are considerably amplified in the form of gene clusters through tandem duplications in the genome. Gene clusters within the salicylic acid/benzoic acid/theobromine (SABATH) and benzylalcohol O-acetyltransferase/anthocyanin O-hydroxycinnamoyltransferases/anthranilate N-hydroxycinnamoyl/benzoyltransferase/deacetylvindoline 4-O-acetyltransferase (BAHD) superfamilies were identified to be related to the biosynthesis of phenylpropanoid/benzenoid compounds. Several key genes involved in jasmonate biosynthesis were duplicated, causing an increase in copy numbers. In addition, multi-omics analyses identified various aromatic compounds and many genes involved in fragrance biosynthesis pathways. Furthermore, the roles of JsTPS3 in ß-ocimene biosynthesis, as well as JsAOC1 and JsAOS in jasmonic acid biosynthesis, were functionally validated. The genome assembled in this study for J. sambac offers a basic genetic resource for studying floral scent and jasmonate biosynthesis, and provides a foundation for functional genomic research and variety improvements in Jasminum.


Subject(s)
Jasminum , Jasminum/genetics , Jasminum/metabolism , Odorants , Cyclopentanes/metabolism , Flowers/genetics , Flowers/metabolism
18.
Virus Genes ; 59(2): 302-311, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36701048

ABSTRACT

Escherichia coli is a common conditional pathogen, for which antibiotic therapy is considered an effective treatment. The imprudent use of antibiotics has led to the increase of multiple-antibiotic-resistant E. coli species. With the incidence of antibiotic resistance reaching a crisis point, it is imperative to find alternative treatments for multidrug-resistant infections. Using phage for pathogen control is a promising treatment option to combat bacterial resistance. In this study, a novel virulent Podoviridae phage Kayfunavirus TM1 infecting Escherichia coli was isolated from pig farm sewage in Guangxi, China. The one-step growth curve with the optimal multiplicity of infection of 0.01 revealed a latent period of 10 min and a burst size of 50 plaque-forming units per cell. The stability test reveals that it is stable from 4 to 60 °C and pH from 3 to 11. The double-stranded DNA genome of phage Kayfunavirus TM1 is composed of 39,948 base pairs with a GC content of 50.03%.


Subject(s)
Bacteriophages , Swine , Animals , Bacteriophages/genetics , Escherichia coli/genetics , Genome, Viral , DNA, Viral/genetics , China , Anti-Bacterial Agents
19.
Bioelectrochemistry ; 150: 108345, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36495704

ABSTRACT

Escherichia coli (E. coli) O157:H7 is one of the most important foodborne pathogens that causing severe foodborne diseases. With the development of foodborne diseases, there is an urgent need to seek new methods for early detection and monitoring of E. coli O157:H7. In this study, an electrochemical biosensor using phage EP01 as the recognition agent for detection of E. coli O157:H7 GXEC-N07 was established due to the specificity and high efficiency of phage EP01 in recognizing GXEC-N07. The biosensor was developed by depositing phages conjugated carboxyl graphene oxide (CFGO) and conductive carbon black (CB) onto the surface of glass carbon electrodes (GCEs). When detecting GXEC-N07 in the concentration range of 102 âˆ¼ 107 CFU/mL, the biosensor showed good linearity with a low detection limit of 11.8 CFU/mL, and the whole progress was in less than 30 min. The biosensor was successfully applied to the quantitative detection of GXEC-N07 in fresh milk and raw pork. The recovery values ranged from 60.8 % to 114.2 %. The biosensor provides a rapid, specific, low cost, and label free tool for E. coli O157:H7 GXEC-N07 detection. It is expected to become a powerful method for the detection of bacteria that threatening food safety and public health security.


Subject(s)
Bacteriophages , Biosensing Techniques , Escherichia coli O157 , Foodborne Diseases , Humans , Food Contamination/analysis , Food Microbiology , Biosensing Techniques/methods , Foodborne Diseases/microbiology
20.
Viruses ; 14(12)2022 11 27.
Article in English | MEDLINE | ID: mdl-36560651

ABSTRACT

Food contamination by Salmonella can lead to serious foodborne diseases that constantly threaten public health. Innovative and effective strategies are needed to control foodborne pathogenic contamination since the incidence of foodborne diseases has increased gradually. In the present study, two broad-spectrum phages named Salmonella phage PSE-D1 and Salmonella phage PST-H1 were isolated from sewage in China. Phages PSE-D1 and PST-H1 were obtained by enrichment with Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) CVCC1806 and Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) CVCC3384, respectively. They were able to lyse Salmonella, E. coli and K. pneumoniae and exhibited broad host range. Further study demonstrated that PSE-D1 and PST-H1 showed high pH and thermal tolerances. Phage PSE-D1 belongs to the Jiaodavirus genus, Tevenvirinae subfamily, while phage PST-H1 belongs to the Jerseyvirus genus, Guernseyvirinae subfamily according to morphology and phylogeny. The results of genome analysis showed that PSE-D1 and PST-H1 lack virulence and drug-resistance genes. The effects of PSE-D1 and PST-H1 on controlling S. Enteritidis CVCC1806 and S. Typhimurium CVCC3384 contamination in three kinds of foods (eggshells, sausages and milk) were further investigated, respectively. Our results showed that, compared to phage-free groups, PSE-D1 and PST-H1 inhibited the growth of their host strain significantly. A significant reduction of host bacteria titers (1.5 and 1.9 log10 CFU/sample, p < 0.001) on eggshells was observed under PSE-D1 and PST-H1 treatments, respectively. Furthermore, administration of PSE-D1 and PST-H1 decreased the counts of bacteria by 1.1 and 1.2 log10 CFU/cm2 (p < 0.001) in sausages as well as 1.5 and 1.8 log10 CFU/mL (p < 0.001) in milk, respectively. Interesting, the bacteriostasis efficacy of both phages exhibited more significantly at 4 °C than that at 28 °C in eggshells and milk and sausages. In sum, the purpose of our research was evaluating the counteracting effect of phage PSE-D1 and PST-H1 on the spread of Salmonella on contaminated foods products. Our results suggested that these two phage-based biocontrol treatments are promising strategies for controlling pathogenic Salmonella contaminated food.


Subject(s)
Foodborne Diseases , Salmonella Phages , Humans , Escherichia coli , Food Microbiology , Salmonella enteritidis , Salmonella typhimurium
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