A high rain-erosion resistant bio-based nanogel with continuous immunity induction for plant virus inhibition.

Tobacco mosaic virus (TMV) is the most widely spread and harmful virus in the world, causing serious economic losses annually. However, the low anti-erosion ability of the pesticides for TMV management make it easy to be washed by the rain, which makes the effective duration of the pesticides shorter. In this paper, a new bio-based nanogel with superior antiviral activity was reported, and its slow-release behavior, rain erosion resistance and the antiviral mechanism was systematically studied. The results determined that the nanogels (Zn2+@ALGNP and Zn2+@ALGNP@PL) exhibited sustained releasing of Zn2+ with a 7 days duration, and the ε-PL coating could enhance the releasing rate of Zn2+. Moreover, Zn2+@ALGNP@PL displayed a lower contact angle, indicating greater adhesion to the leaf surface, and in consequence imposed better resistance to simulate rain erosion than pure Zn2+. Strikingly, Zn2+@ALGNP@PL could inhibit plant virus infection by aggregating the virions and reducing its coat protein stability, as well as inducing the efficient expression of reactive oxygen species, antioxidant enzymes and resistance genes to enhance plant resistance and promote plant growth. Overall, this study had successfully developed a high rain-erosion resistant bio-based nanogel capable of continue to induce resistant plants and promote plant growth.

A chitosan-coated lentinan-loaded calcium alginate hydrogel induces broad-spectrum resistance to plant viruses by activating Nicotiana benthamiana calmodulin-like (CML) protein 3.

Control of plant virus diseases largely depends on the induced plant defence achieved by the external application of synthetic chemical inducers with the ability to modify defence-signalling pathways. However, most of the molecular mechanisms underlying these chemical inducers remain unknown. Here, we developed a chitosan-coated lentinan-loaded hydrogel and discovered how it protects plants from different virus infections. The hydrogel was synthesized by coating chitosan on the surface of the calcium alginate-lentinan (LNT) hydrogel (SL-gel) to form a CSL-gel. CSL-gels exhibit the capacity to prolong the stable release of lentinan and promote Ca2+ release. Application of CSL-gels on the root of plants induces broad-spectrum resistance against plant viruses (TMV, TRV, PVX and TuMV). RNA-seq analysis identified that Nicotiana benthamiana calmodulin-like protein gene 3 (NbCML3) is upregulated by the sustained release of Ca2+ from the CSL-gel, and silencing and overexpression of NbCML alter the susceptibility and resistance of tobacco to TMV. Our findings provide evidence that this novel and synthetic CSL-gel strongly inhibits the infection of plant viruses by the sustainable release of LNT and Ca2+ . This study uncovers a novel mode of action by which CSL-gels trigger NbCML3 expression through the stable and sustained release of Ca2+ .

Synthesis of chitin nanocrystals supported Zn2+ with high activity against tobacco mosaic virus.

Chitin is a kind of natural nitrogenous organic polysaccharide. It contains antibacterial and antiviral properties, and it can induce plant disease resistance and promote plant growth. However, its application is constrained due to its insolubility and intricate molecular structure. Tobacco mosaic disease is caused by tobacco mosaic virus (TMV) infection, which seriously harms tobacco production. Zinc-containing chemical agents are commonly used to control tobacco mosaic disease, but overuse of chemical agents will cause serious environmental pollution. In this study, a novel nanomaterial (ChNC@Zn) was prepared by using chitin nanocrystals loaded with Zn2+, which has the function of inducing disease resistance to plants and reducing virus activity. When the Zn2+ concentration of ChNC@Zn is 105.6 µg/mL, it shows higher resistance to TMV than Lentinan (LNT). ChNC@Zn can improve the enzymes activities of peroxidase (POD) and catalase (CAT) in tobacco, and reduce the damage of reactive oxygen species (ROS) caused by TMV infection, thereby inducing resistance to TMV in tobacco. Besides, it can promote the growth of tobacco. As a result, ChNC@Zn can exhibit strong antiviral activity at low Zn2+ concentration and minimize the pollution of Zn2+ to the environment, which has high potential application value in the control of virus disease.

Antimicrobial mechanisms of ZnO nanoparticles to phytopathogen Pseudomonas syringae: Damage of cell envelope, suppression of metabolism, biofilm and motility, and stimulation of stomatal immunity on host plant.

Nanoparticles have recently been employed as a new strategy to act as bactericides in agricultural applications. However, the effects and mechanisms of foliar deposition of nanoparticles on bacterial pathogens, plant physiology and particularly plant immunity have not been sufficiently understood. Here, we investigated the effects and mechanisms of ZnO NPs in controlling of tobacco wildfire caused by Pseudomonas syringae pv. tabaci, through the comprehensive analysis of biological changes of both bacteria and plants. The global gene expression changes of Pseudomonas syringae pv. tabaci supported that the functions of "protein secretion", "membrane part", "signal transducer activity", "locomotion", "chemotaxis" and "taxis" in bacteria, as well as the metabolic pathways of "bacterial chemotaxis", "two-component system", "biofilm formation", "ABC transporters" and "valine, leucine and isoleucine degradation" were significantly down-regulated by ZnO NPs. Correspondingly, we reconfirmed that the cell envelope structure, biofilm and motility of Pseudomonas syringae pv. tabaci were directly disrupted or suppressed by ZnO NPs. Different from completely killing Pseudomonas syringae pv. tabaci, ZnO NPs (0.5 mg/mL) potentially improved plant growth and immunity through enzymatic activity and global molecular response analysis. Furthermore, the changes of gene expression in ABA signaling pathway, ABA concentration and stomatal aperture all supported that ZnO NPs can specifically stimulate stomatal immunity, which is important to defend bacterial infection. Taken together, we proposed that both the inhibition or damage of motility, biofilm, metabolisms, virulence and cell envelope on P. syringae pv. tabaci, and the activation of the stomatal immunity formed two-layered antibacterial mechanisms of ZnO NPs on phytopathogenic bacteria.

Fabrication of an alginate-based ZhiNengCong gel showed an enhanced antiviral and plant growth promoting functions.

Tobacco mosaic disease is a worldwide viral disease that can cause huge economic losses. Plant immune inducers have become the main force in the prevention and treatment of viral disease own to their high efficiency and rapid effect. However, since tobacco mosaic disease can occur at any point in the plant growth cycle, a single application period cannot guarantee the completely management. In this study, an extract from Paecilomyces variotii named ZhiNengCong (ZNC), which can fight against tobacco mosaic disease with 65% control effect, and improve the promotion of tobacco stem girth, was selected from five commercial antiviral medicines, and a sustained release sodium alginate (Alg)-based ZNC (ZNC@Alg) was prepared by physical absorption. ZNC@Alg, who contains only 5 mg/mL ZNC, can release ZNC for 7 consecutive days, and displayed an enhanced effect in inducing the PAL-mediated salicylic acid signaling pathway activation to participate in the inhibition of green fluorescent protein (GFP)-tagged tobacco mosaic virus (TMV-GFP) infection, even after 7 days of the application. Notably, field experiments showed that the control effect of ZNC@Alg was up to 88%, which was significantly better than that of ZNC with the same concentration (10 µg per plant). In addition, ZNC@Alg exhibited a stronger growth-promoting effect than ZNC, which significantly increased the wet weight of tobacco. Taken together, we screened out a plant immune inducer ZNC that can effectively inhibit tobacco virus disease, and created ZNC@Alg with higher control effect and growth promotion effect, laying a foundation for effective field management of tobacco mosaic disease.

Chitin nanocrystals supported copper: a new nanomaterial with high activity with P. syringae pv. Tabaci.

BACKGROUND: The application of chemical pesticides in control of plant bacterial disease may cause potential environmental pollution. Herein, based on the resistance-inducing ability and the special rod-like structure with high aspect ratio of bio-derived chitin nanocrystals (ChNC), a new Cu composite rod-like nanoparticle was fabricated (ChNC@Cu). The antibacterial activity of the composite nanoparticle was systematically studied, and its safety was evaluated. RESULTS: TEM, FTIR, ICP and other characterization methods proved that ChNC@Cu is a nano rod-like structure, with a Cu2+ loading capacity of 2.63%. In vitro experiments showed that the inhibition rate of ChNC@Cu to P. syringae pv. tabaci was more than 95% when the copper content was 41.6 µg mL-1 . In vivo experiments showed that ChNC@Cu had a good protective effect on P. syringae pv. tabaci of tobacco. In addition, ChNC@Cu exhibited stronger antibacterial activity than Thiodiazole copper (TC) at the same copper content. The study on the antibacterial mechanism of ChNC@Cu proved that ChNC@Cu caused bacterial death by destroying the bacterial cell membrane structure and damaging the DNA bacteria. And ChNC@Cu is highly safe for plants and can promote seed germination and plant growth. CONCLUSION: The special rod-like structure of ChNC can enrich Cu2+ to form ChNC@Cu. ChNC@Cu has a good protective effect on bacterial infection of tobacco, and achieves a great antibacterial activity at low Cu2+ concentration, which indicated that ChNC@Cu has induced resistance and antibacterial effect. As a novel green nanofungicide, ChNC@Cu has high potential application value in control of agricultural bacterial diseases. © 2023 Society of Chemical Industry.

Fabrication of polydopamine reduced CuO nanoparticle-alginate composite nanogels for management of Pseudomonas synringae pv. tabaci in tobacco.

BACKGROUND: The wildfire disease on tobacco can seriously hinder plants. Meanwhile, its pathogen, Pseudomonas syringae, can also infect over 200 plants and threat agriculture production. However, the disease usually occurs after summer rains which washes away most copper (Cu)-based bactericides, allowing the disease to invade. Therefore, we fabricate a new nanogel with high disease control and anti-erosion ability and study the effects of the reductant on the performance of the copper oxide nanoparticle (CuONP) composite nanogel. RESULTS: Polydopamine (PDA) is a polycation for both in situ reduction of CuONP in alginate nanogels and for adjusting the copper ion (Cu2+ ) releasing rate in this work. The composite nanogel fabricated by PDA (PDA-CuONP@ALGNP@CTAC) had a higher Cu2+ releasing rate, damaging the pathogen membrane more efficiently, allowing for better disease control and plant growth promotion when compared to sodium borohydride (SBH)-fabricated nanogel (SBH-CuONP@ALGNP@CTAC) or the commercial bactericide, thiodiazole copper. The PDA-CuONP@ALGNP@CTAC had a high anti-erosion ability and could remain adhered to the leaf surface even after five rain event simulations. CONCLUSION: The addition of polycations (like PDA) into CuONP composite nanogel could increase the Cu2+ releasing rate, resulting in improved disease management when compared to SBH-CuONP@ALGNP@CTAC or thiodiazole copper. The PDA containing gel had an improved anti-erosion ability and water resistance. This new composite nanogel has a high potential for wildfire disease control, improving agricultural production. © 2022 Society of Chemical Industry.

m6A-modified circFOXK2 targets GLUT1 to accelerate oral squamous cell carcinoma aerobic glycolysis.

N6-methyladenosine (m6A) is an abundant nucleotide modification in mRNA, and its emerging roles have been gradually identified. However, the potential function of m6A and m6A-modified circular RNA (circRNA) is still unclear. Here, m6A-circRNA epitranscriptomic microarray analysis revealed a high-expressed m6A-modified circFOXK2 (hsa_circ_0000816, from FOXK2 gene) in oral squamous cell carcinoma (OSCC). For the biofunctions of OSCC, results revealed that circFOXK2 promoted the malignant phenotypes of OSCC cells. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) demonstrated that a remarkable m6A modified site was installed on glucose transporter 1 (GLUT1) mRNA. Mechanistically, circFOXK2 promoted the GLUT1 mRNA stability through cooperating with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in a m6A-dependent manner. In summary, the present study explored the oncogenic role of m6A-modified circFOXK2 in OSCC through the m6A-dependent IGF2BP3/GLUT1 axis, indicating a potential therapeutic target for OSCC.

Tobacco mosaic virus hijacks its coat protein-interacting protein IP-L to inhibit NbCML30, a calmodulin-like protein, to enhance its infection.

Calcium is an important plant immune signal that is essential for activating host resistance, but how RNA viruses manipulate calcium signals to promote their infections remains largely unknown. Here, we demonstrated that tobacco mosaic virus (TMV) coat protein (CP)-interacting protein L (IP-L) associates with calmodulin-like protein 30 (NbCML30) in the cytoplasm and nucleus, and can suppress its expression at the nucleic acid and protein levels. NbCML30, which lacks the EF-hand conserved domain and cannot bind to Ca2+ , was located in the cytoplasm and nucleus and was downregulated by TMV infection. NbCML30 silencing promoted TMV infection, while its overexpression inhibited TMV infection by activating Ca2+ -dependent oxidative stress in plants. NbCML30-mediated resistance to TMV mainly depends on IP-L regulation as the facilitation of TMV infection by silencing NbCML30 was canceled by co-silencing NbCML30 and IP-L. Overall, these findings indicate that in the absence of any reported silencing suppressor activity, TMV CP manipulates IP-L to inhibit NbCML30, influencing its Ca2+ -dependent role in the oxidative stress response. These results lay a theoretical foundation that will enable us to engineer tobacco (Nicotiana spp.) with improved TMV resistance in the future.

High-throughput microarray reveals the epitranscriptome-wide landscape of m6A-modified circRNA in oral squamous cell carcinoma.

BACKGROUND: Emerging transcriptome-wide high-throughput screenings reveal the landscape and functions of RNAs, such as circular RNAs (circRNAs), in human cancer. In addition, the post-transcriptional RNA internal modifications, especially N6-methyladenosine (m6A), greatly enrich the variety of RNAs metabolism. However, the m6A modification on circRNAs has yet to be addressed. RESULTS: Here, we report an epitranscriptome-wide mapping of m6A-modified circRNAs (m6A-circRNA) in oral squamous cell carcinoma (OSCC). Utilizing the data of m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) and m6A-circRNAs microarray, we found that m6A-circRNAs exhibited particular modification styles in OSCC, which was independent of m6A-mRNA. Besides, m6A modification on circRNAs frequently occurred on the long exons in the front part of the coding sequence (CDS), which was distinct from m6A-mRNA that in 3'-UTR or stop codon. CONCLUSION: In conclusion, our work preliminarily demonstrates the traits of m6A-circRNAs, which may bring enlighten for the roles of m6A-circRNAs in OSCC.

Transcriptome analysis reveals the mechanism of zinc ion-mediated plant resistance to TMV in Nicotiana benthamiana.

Zinc ions (Zn2+) are used to promote plant growth and treat multiple diseases. However, it is still unclear which pathways in plants respond to Zn2+. In this study, we found that supplying (CH3COO)2Zn can effectively delay tobacco mosaic virus (TMV) replication and movement in Nicotiana benthamiana. To further understand the regulatory mechanism of antiviral activity mediated by Zn2+, we examined the transcriptomic changes of leaves treated with Zn2+. Three days after treatment, 7575 differential expression genes (DEGs) were enriched in the Zn2+ treatment group compared with the control group. Through GO and KEGG analysis, the pathway of phosphatidylinositol signaling system and inositol phosphate metabolism were significantly enriched after treated with Zn2+, and a large number of ethylene-responsive transcription factors (ERFs) involved in inositol phosphate metabolism were found to be enriched. We identified ERF5 performed a positive effect on plant immunity. Our findings demonstrated that Zn2+-mediated resistance in N. benthamiana activated signal transduction and regulated the expression of resistance-related genes. The results of the study uncover a global view of mRNA changes in Zn2+-mediated cellular processes involved in the competition between plants and viruses.

Fabrication of copper nanoparticle composite nanogel for high-efficiency management of Pseudomonas syringae pv. tabaci on tobacco.

BACKGROUND: Copper nanoparticles (CuNPs) can release copper ions (Cu2+ ) to control bacterial diseases on crops. However, the high concentration of the CuNPs applied in disease controlling can highly limit their application. In this work, by in situ reducing CuNPs in alginate nanogels and coated with cetyl trimethyl ammonium chloride (CTAC), a CuNP composite nanogel was fabricated as a new nanopesticide with low copper content. RESULTS: Data showed that the CTAC coating would affect the antibacterial activity and leaf surface adhesion of the nanogel, while CuNP content could also influence the membrane damage ability of the gel. The nanogel could depress the growth of bacteria by rupturing its membrane and show a minimum inhibitory concentration (MIC) as low as 500 µg mL-1 , which only contain 58 µg mL-1 CuNP, and achieve a 64% of therapeutic efficiency (with 1000 µg mL-1 nanogel) in in vivo experiments, higher than that of commercial bactericide thiodiazole copper. Furthermore, the application of the nanogel can also perform a growth-promoting effect on the plant, which may be due to the supplement of copper element provided by CuNP. CONCLUSION: The CuNP composite nanogel fabricated in this work performed high leaf disease controllability and safety compared to the commercial bactericide thiodiazole copper. We hope this nanogel can provide a potential high-efficiency nano-bactericide that can be used in the leaf bacterial disease control.

Nicotiana benthamiana asparagine synthetase associates with IP-L and confers resistance against tobacco mosaic virus via the asparagine-induced salicylic acid signalling pathway.

Asparagine synthetase is a key enzyme that catalyses the conversion of amide groups from glutamine or ammonium to aspartate, which leads to the generation of asparagine. However, the role of asparagine synthetase in plant immunity remains largely unknown. Here, we identified a Nicotiana benthamiana asparagine synthetase B (NbAS-B) that associates with tomato mosaic virus coat protein-interacting protein L (IP-L) using the yeast two-hybrid assay and examined its role in tobacco mosaic virus (TMV) resistance. The association of IP-L with NbAS-B was further confirmed by in vivo co-immunoprecipitation, luciferase complementation imaging, and bimolecular fluorescence complementation assays. IP-L and NbAS-B interact in the nucleus and cytosol and IP-L apparently stabilizes NbAS-B, thus enhancing its accumulation. The expressions of IP-L and NbAS-B are continuously induced on TMV-green fluorescent protein (GFP) infection. Co-silencing of IP-L and NbAS-B facilitates TMV-GFP infection. Overexpression of NbAS-B in tobacco reduces TMV-GFP infection by significantly improving the synthesis of asparagine. Furthermore, the external application of asparagine significantly inhibits the infection of TMV-GFP by activating the salicylic acid signalling pathway. These findings hold the potential for the future application of asparagine in the control of TMV.

The Enhancement of Antiviral Activity of Chloroinconazide by Aglinate-based Nanogel and Its Plant Growth Promotion Effect.

Improving the efficiency and prolonging the duration of pesticides are of great significance in agricultural production. In this work, based on the antiviral compound chloroinconazide (CHI) synthesized previously, the improvement of the fabricated CHI-loaded alginate-based nanogel (CHI@ALGNP) was studied. It was found that CHI@ALGNP showed higher foliar adhesion than CHI and exhibited a sustained release for up to 7 days. CHI@ALGNP could also continuously activate the reactive oxygen species and antioxidant levels and induce the increase of salicylic acid content and the expression of its responsive gene PR2 for a long time, thus achieving sustained resistance to tobacco mosaic virus infection in Nicotiana benthamiana. Strikingly, CHI@ALGNP could release Ca2+ and Mg2+ to promote the growth of N. benthamiana. Taken together, for the first time, we have shown the improvement of a nanogel carrier to the antiviral activity and growth promotion of small molecular pesticides. As the alginate-based nanogel can be easily applied to the spray-based pesticide delivery technology, our study provides a new strategy for the development of new pesticide preparations and the application of multifunctional pesticides.

The photocatalytic antibacterial molecular mechanisms towards Pseudomonas syringae pv. tabaci by g-C3 N4 nanosheets: insights from the cytomembrane, biofilm and motility disruption.

BACKGROUND: Antibacterial photocatalytic therapy has been employed as a promising strategy to combat antibiotic-resistant bacteria in the water disinfection field, especially some non-metal inorganic nanomaterials. However, their antibacterial activities on plant phytopathogens are poorly understood. Here, the photocatalytic antibacterial mechanism of the urea-synthesized graphitic carbon nitride nanosheets (g-C3 N4 nanosheets) against Pseudomonas syringae pv. tabaci was systematically investigated in vitro and in vivo. RESULTS: The g-C3 N4 nanosheets exhibited remarkable concentration-dependent and irradiation-time-dependent antibacterial properties, and the 0.5 mg mL-1 concentration ameliorated tobacco wildfire disease in host plants. Specifically, under visible irradiation, g-C3 N4 nanosheets produced numerous reactive oxygen species (ROS), supplementing the plentiful extracellular and intracellular ROS in bacteria. After exposing light-induced g-C3 N4 nanosheets for 1 h, 500 genes were differentially expressed, according to transcriptome analyses. Notably, the expression of genes related 'antioxidant activity' and 'membrane transport' was sharply upregulated, and those related to 'bacterial chemotaxis', 'biofilm formation', 'energy metabolism' and 'cell motility' were downregulated. After exposure for over 2 h, the longer-time pressure on the target bacteria cause the decreased biofilm formation and flagellum motility, further injuring the cell membranes leading to cytoplasm leakage and damaged DNA, eventually resulting in the bacterial death. Concomitantly, the attachment of g-C3 N4 nanosheets was a synergistic physical antibacterial pathway. The infection capacity assessment also supported the earlier supposition. CONCLUSION: These results provide novel insights into the photocatalytic antibacterial mechanisms of g-C3 N4 nanosheets at the transcriptome level, which are expected to be useful for dissecting the response pathways in antibacterial activities and for improving g-C3 N4 -based photocatalysts practices in plant disease control. © 2021 Society of Chemical Industry.

Erythropoietin Plays a Protective Role in Submandibular Gland Hypofunction Induced by Irradiation.

PURPOSE: This study aims to explore the radioprotective effects of recombinant human erythropoietin (rhEPO) on rats' submandibular gland hypofunction induced by irradiation (IR). MATERIALS AND METHODS: Thirty rats were divided into 3 groups: 1) control group, 2) IR group, and 3) IR + rhEPO group. The IR group and IR + rhEPO group received a single dose of 15 Grays (Gy) (0.98 Gy/min), plus, the IR + rhEPO group also received subcutaneous administration of rhEPO at a dose of 3,000 IU/kg body weight 3 days before irradiation and then repeated every 24 hours for the first 2 weeks after irradiation. Immunohistochemistry analysis to erythropoietin receptor was performed to detect the levels of erythropoietin receptor in submandibular glands with or without radiation. Ninety days after irradiation, the salivary flow rates were assessed, and the submandibular gland of every rat was subjected to hematoxylin and eosin staining and immunohistochemical staining with antiaquaporin 5 and anti-proliferating cell nuclear antigen antibodies. Apoptosis was examined by the terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling assay. In addition, to examine the protective role of rhEPO on human submandibular gland cells, the apoptotic and proliferation rate of cells under a radiation dose of 8 Gy was detected. One-way analysis of variance was carried out to analyze the results of each group, and the P value was set at 0.05. RESULTS: Erythropoietin receptor was expressed in the submandibular glands at a low level under normal conditions but upregulated after irradiation. rhEPO administration remarkably alleviated gland atrophy, increased salivary flow rates with upregulation of aquaporin-5 compared with the IR group. In addition, fewer apoptotic cells and more proliferative cells were observed in the IR + rhEPO group compared with the IR group, both in vivo and in vitro. CONCLUSIONS: rhEPO administration may be a useful countermeasure to mitigate submandibular gland hypofunction after therapeutic radiation exposure.

Metformin inhibits epithelial-mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF-1α/PKM2/STAT3 pathway.

Epithelial-mesenchymal transition (EMT) serves an important role in the formation and development of various types of cancer, including oral squamous cell carcinoma (OSCC). Metformin, used for treating type 2 diabetes, has been revealed to exert an anticancer effect in various types of cancer, including liver, breast and colorectal cancer. However, its role in the EMT of OSCC has been rarely reported. Therefore, the present study aimed to investigate the effects of metformin on EMT and to identify its underlying mechanism in OSCC. Firstly, EMT was induced in CAL-27 cells using CoCl2. Subsequently, the effects of metformin on cell viability, migration and xenograft growth were evaluated in vitro and in vivo. Reverse transcription-quantitative PCR was performed to detect the expression levels of E-cadherin, vimentin, snail family transcriptional repressor 1, mTOR, hypoxia inducible factor 1α, pyruvate kinase M2 and STAT3. The results demonstrated that metformin abolished CoCl2-induced cell proliferation, migration, invasion and EMT. Moreover, metformin reversed EMT in OSCC by inhibiting the mTOR-associated HIF-1α/PKM2/STAT3 signaling pathway. Overall, the present findings characterized a novel mechanism via which metformin modulated EMT in OSCC.

Circular RNA circMDM2 accelerates the glycolysis of oral squamous cell carcinoma by targeting miR-532-3p/HK2.

Circular RNAs (circRNAs) function as an essential regulator in the progression of oral squamous cell carcinoma (OSCC). However, the potential roles and mechanism of circRNAs in OSCC are still elusive. Here, this research investigates the roles and molecular mechanism of novel circRNA (circMDM2) in OSCC progression. Clinically, circMDM2 was overexpressed in OSCC tissue and cells, and the overexpression served as a poor prognostic factor for OSCC patients. Functionally, cellular experiments confirmed that circMDM2 accelerated OSCC cell proliferation and glycolysis in vitro and circMDM2 knockdown repressed the tumour growth in vivo. Mechanistically, circMDM2 sponged miR-532-3p to promote the hexokinase 2 (HK2), forming the circMDM2/miR-532-3p/HK2 axis. In conclusion, these findings demonstrated that circMDM2/miR-532-3p/HK2 axis promotes the proliferation and glycolysis of OSCC, rendering a potential diagnostic biomarker and prospective therapeutic target for OSCC.

METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m6A Modification.

N6-Methyladenosine (m6A) is the most common internal modification of eukaryotic messenger RNA (mRNA) that occurred on the N6 nitrogen of adenosine. However, the roles of m6A in oral squamous cell carcinoma (OSCC) are still elusive. Here, we investigate the function and mechanism of methyltransferase-like 3 (METTL3) in OSCC tumorigenesis. Clinically, METTL3 was significantly upregulated in tissue samples and correlated with the poor prognosis of OSCC patients. Functionally, loss and gain studies illustrated that METTL3 promoted the proliferation, invasion, and migration of OSCC cells in vitro, and METTL3 knockdown inhibited tumor growth in vivo. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that METTL3 targeted the 3' UTR (near to stop codon) of the c-Myc transcript to install the m6A modification, thereby enhancing its stability. Furthermore, results revealed that YTH N6-methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the m6A-increased stability of c-Myc mRNA catalyzed by METTL3. In conclusion, our findings herein identify that METTL3 accelerates the c-Myc stability via YTHDF1-mediated m6A modification, thereby giving rise to OSCC tumorigenesis.

Fabrication of pH-Sensitive Tetramycin Releasing Gel and Its Antibacterial Bioactivity against Ralstonia solanacearum.

Ralstonia solanacearum (R. solanacearum)-induced bacterial wilt of the nightshade family causes a great loss in agricultural production annually. Although there has been some efficient pesticides against R. solanacearum, inaccurate pesticide releasing according to the onset time of bacterial wilt during the use of pesticides still hinders the disease management efficiency. Herein, on the basis of the soil pH change during R. solanacearum growth, and pH sensitivity of the Schiff base structure, a pH-sensitive oxidized alginate-based double-crosslinked gel was fabricated as a pesticide carrier. The gel was prepared by crosslinking oxidized sodium alginate (OSA) via adipic dihydrazide (ADH) and Ca2+. After loading tetramycin into the gel, it showed a pH-dependent pesticide releasing behavior and anti-bacterial activity against R. solanacearum. Further study also showed that the inhibition rate of the tetramycin-loaded gel was higher than that of industrial pesticide difenoconazole. This work aimed to reduce the difficulty of pesticide administration in the high incidence period of bacterial wilt and we believe it has a great application potential in nightshade production.