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Banana Fusarium wilt (BFW), caused by Fusarium oxysporum f. sp. cubense (Foc), poses a major challenge to the worldwide banana industry. Fungal microRNA-like small RNAs (milRNAs) play crucial roles in regulating fungal growth, conidiation, development, and pathogenicity. However, the milRNAs and their functions in the pathogenesis of Foc remain poorly understood. In this study, we employed high-throughput sequencing and bioinformatics to profile Foc sRNAs during both pure culture and early infection stages. Our analysis identified six milRNAs exhibiting significantly upregulated expression at the initial Foc infection. Of these, milR106’s biogenesis was found to be Dicer-dependent, whereas milR87, milR133, milR138, and milR148 were associated with Dicer and Argonaute proteins. Genetic manipulation and phenotype analysis confirmed that milR106 is crucial for Foc virulence by regulating conidiation, hydrogen peroxide sensitivity, and infective growth. Gene Ontology analysis of milRNA targets in the banana genome revealed enrichment in defence response to fungus and cellular response to hypoxia, implying the importance of these target genes in response to pathogen infection. In conclusion, our sRNA profiling of Foc identified several infection-induced milRNAs. The corresponding results provide valuable molecular targets for the development of an efficient strategy to control BFW. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding gene expression primarily found in plants and animals. Fungi produce microRNA-like RNAs (milRNAs) that are structurally similar to miRNAs and functionally important in various biological processes. The fungus Fusarium oxysporum f. sp. cubense (Foc) is the causal agent of Banana Fusarium vascular wilt that threatens global banana production. It remains uncharacterized about the biosynthesis and functions of milRNAs in Foc. In this study, we investigated the biological function of milRNAs contributing to Foc pathogenesis. Within 24 hours post infecting the host, the Argonaute coding gene FoQDE2, and two Dicer coding genes FoDCL1 and FoDCL2, all of which are involved in milRNA biosynthesis, were significantly induced. FoQDE2 deletion mutant exhibited decreased virulence, suggesting the involvement of milRNA biosynthesis in the Foc pathogenesis. By small RNA sequencing, we identified 364 small RNA-producing loci in the Foc genome, 25 of which were significantly down-regulated in the FoQDE2 deletion mutant, from which milR-87 was verified as a FoQDE2-depedent milRNA based on qRT-PCR and Northern blot analysis. Compared to the wild-type, the deletion mutant of milR-87 was significantly reduced in virulence, while overexpression of milR-87 enhanced disease severity, confirming that milR-87 is crucial for Foc virulence in the infection process. We furthermore identified FOIG_15013 (a glycosyl hydrolase-coding gene) as the direct target of milR-87 based on the expression of FOIG_15013-GFP fusion protein. The FOIG_15013 deletion mutant displayed similar phenotypes as the overexpression of milR-87, with a dramatic increase in the growth, conidiation and virulence. Transient expression of FOIG_15013 in Nicotiana benthamiana leaves activates the host defense responses. Collectively, this study documents the involvement of milRNAs in the manifestation of the devastating fungal disease in banana, and demonstrates the importance of milRNAs in the pathogenesis and other biological processes. Further analyses of the biosynthesis and expression regulation of fungal milRNAs may offer a novel strategy to combat devastating fungal diseases. Author summary: The fungus Fusarium oxysporum f. sp. cubense (Foc) is the causal agent of Banana Fusarium vascular wilt that threatens global banana production. However, knowledge about pathogenesis of Foc is limited. In particular, pathogenic regulatory mechanism of the microRNA like small RNAs (milRNAs) found in Foc is unknown. Here, we found that FoQDE2, an Argonaute coding gene, and two Dicer coding genes FoDCL1 and FoDCL2, which are involved in milRNA biosynthesis, are significantly induced during the early infection stage of Foc. The results suggested that the milRNAs biosynthesis mediated by these genes may play an active role in the infection process of Foc. Based on this assumption, we subsequently found a FoQDE2-dependent milRNA (milR-87) and identified its target gene. Functional analysis showed that FoQDE2, milR-87 and its target gene were involved in the pathogenicity of Foc in different degree. The studies help us gain insight into the pathogenesis with FoQDE2, milR-87, and its target gene as central axis in Foc. The identified pathogenicity-involved milRNA provides an active target for developing novel and efficient biocontrol agents against Banana Fusarium wilt. [ABSTRACT FROM AUTHOR]

Abstract Macrophages are predominant immune cells in the tumor microenvironment where they display an immunosuppressive M2 phenotype to support tumor growth. Reprogramming M2-like tumor-associated macrophages (TAMs) to antitumor M1 phenotype represents as a promising strategy in cancer immunotherapy. In this work we reported that one cationic polysaccharide spermine modified pullulan (PS) could act as an effective immunological stimulator to modulating either naïve (M0) or M2 macrophages towards M1 phenotype. We showed that PS upregulated the expression of TLR1/3/4 and promoted the phosphorylation of Akt, Erk, JNK, following the activation of NF-κB, which led to the polarization towards M1. In a murine breast cancer model of tumor cell 4T1 inoculation, subcutaneous injection of PS induced effective antitumor effect through reprogramming M2 macrophages in the tumor microenvironment to M1, increased CD4+ and CD8+ T cells, and decreased the expression of CD31 in the tumor mass, which together inhibited the tumor progression and the metastasis in lung and liver, leading to the prolong of the mice survival. In conclusion, PS could effectively stimulate the immunological function of macrophages. Therefore, PS may provide a novel immunological stimulator to cancer immune therapies. [ABSTRACT FROM AUTHOR]

In the Funding section, the grant number from the funder The National Science Foundation is listed incorrectly. Reference 1 Li M, Xie L, Wang M, Lin Y, Zhong J, Zhang Y, et al. (2022) FoQDE2-dependent milRNA promotes Fusarium oxysporum f. sp. cubense virulence by silencing a glycosyl hydrolase coding gene expression. [Extracted from the article]

Purpose: Epithelial-mesenchymal transition (EMT) of normal conjunctival tissues is a major reason of pterygium generation; α-smooth muscle actin (α-SMA) is a maker in EMT. In this study, we investigated if human amniotic mesenchymal stem cells (hAMSCs) can inhibit α-SMA expression and migration of human pterygium fibroblasts (hPFs) in vitro. Materials and methods: Coculture of hAMSCs and hPFs was completed by using a Transwell coculture system. The α-SMA expression of hPFs was detected by immunocytochemistry and western blot analysis. The migration ability of hPFs was measured by means of a migration assay. Immunoreactivity for α-SMA was detected in all pterygium fibroblasts examined. Results: The expression of α-SMA in cocultured hPFs was significantly lower than in hPFs. Similar result was demonstrated in western blot analysis. In addition, migration assay showed that hAMSCs reduce the migration of hPFs. Conclusions: These results suggested that hAMSCs have the potential to inhibit the generation and invasiveness of pterygium in vitro. [ABSTRACT FROM AUTHOR]

This work deals with the dynamic-memory event-triggered-based load frequency control issue for interconnected multiarea power systems (IMAPSs) associated with random abrupt variations and deception attacks. To facilitate the transient faults, a semi-Markov process is addressed to model the dynamic behavior of IMAPSs. In order to modulate transmission frequency, a novel area-dependent dynamic-memory event-triggered protocol (DMETP) is scheduled by resorting to a set of the historically released packets (HRPs), which ensures better dynamic performance. From the viewpoint of the defender, the randomly occurring deception attack is taken into account, which is regulated by a Bernoulli-distributed scalar. Benefitting from the DMETP scheduling, a novel framework of the memory-based asynchronous control strategy is formulated, in which the hidden semi-Markov model is adopted to reveal the mode mismatches. Based on the Lyapunov theory, sufficient conditions are established to ensure the stochastic stability of the resulting systems. In the end, the simulation result is presented to reveal the efficiency of the proposed dynamic-memory event-triggered-based approach.

Arsenic sulfide (As 4 S 4 ) is a mineral drug that can be administrated orally and has been applied in the treatment of myeloid leukemia. The aim of this work is to investigate the therapeutic effect of As 4 S 4 in highly metastatic triple-negative breast cancer (TNBC) animal model, as As 4 S 4 has not been applied in the treatment of breast cancer yet. To overcome the poor solubility of original As 4 S 4 , a formulation of hydrophilic As 4 S 4 nanoparticles (e-As 4 S 4 ) developed previously was applied to mouse breast cancer cells as well as the tumor-bearing mice. It was shown that e-As 4 S 4 was much more cytotoxic than r-As 4 S 4 , strongly inhibiting the proliferation of the cells and scavenging intracellular reactive oxygen species (ROS). The oral administration of e-As 4 S 4 significantly increased the accumulation of arsenic in the tumor tissue and eliminated ROS in tumor tissues. Besides, e-As 4 S 4 could also inhibit the activation of hypoxia-inducible factor-1α (HIF-1α) and NLRP3 inflammasomes. Consequently, the angiogenesis was reduced, the metastasis to lung and liver was inhibited and the survival of tumor-bearing mice was prolonged. In conclusion, e-As 4 S 4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment.

We report that the mass ratio of the polycation to serum in the medium determines the (RNA interference) RNAi efficiency in vitro by using spermine-modified pullulan (Ps) and spermine-modified dextran (Ds) as polycation models. The high ratio of Ps to serum protein (Ps/Pr) mediated the formation of larger polyplexes, which led to the promoted cellular uptake, enhanced lysosomal escape, and elevated RNAi efficiency. In addition, the supplementary of free Ps also enhanced small interfering RNA transfection because of the elevation of Ps/Pr. Similar results were obtained with Ds. Compared with the adjustment of the nitrogen to phosphate (N/P) ratio in the polyplex, these findings revealed a more applicable strategy to tune the polycation-mediated RNAi efficiency in the serum-containing culture medium.