Research progress of the netrins and their receptors in cancer.

Netrins, a family of secreted and membrane-associated proteins, can regulate axonal guidance, morphogenesis, angiogenesis, cell migration, cell survival, and tumorigenesis. Four secreted netrins (netrin 1, 3, 4 and 5) and two glycosylphosphatidylinositols-anchored membrane proteins, netrin-G1 and G2, have been identified in mammals. Netrins and their receptors can serve as a biomarker and molecular therapeutic target for pathological differentiation, diagnosis and prognosis of malignant cancers. We review here the potential roles of the netrins family and their receptors in cancer.

Fusarium-produced vitamin B6 promotes the evasion of soybean resistance by Phytophthora sojae.

Plants can be infected by multiple pathogens concurrently in natural systems. However, pathogen-pathogen interactions have rarely been studied. In addition to the oomycete Phytophthora sojae, fungi such as Fusarium spp. also cause soybean root rot. In a 3-year field investigation, we discovered that P. sojae and Fusarium spp. frequently coexisted in diseased soybean roots. Out of 336 P. sojae-soybean-Fusarium combinations, more than 80% aggravated disease. Different Fusarium species all enhanced P. sojae infection when co-inoculated on soybean. Treatment with Fusarium secreted non-proteinaceous metabolites had an effect equal to the direct pathogen co-inoculation. By screening a Fusarium graminearum mutant library, we identified Fusarium promoting factor of Phytophthora sojae infection 1 (Fpp1), encoding a zinc alcohol dehydrogenase. Fpp1 is functionally conserved in Fusarium and contributes to metabolite-mediated infection promotion, in which vitamin B6 (VB6) produced by Fusarium is key. Transcriptional and functional analyses revealed that Fpp1 regulates two VB6 metabolism genes, and VB6 suppresses expression of soybean disease resistance-related genes. These results reveal that co-infection with Fusarium promotes loss of P. sojae resistance in soybean, information that will inform the sustainable use of disease-resistant crop varieties and provide new strategies to control soybean root rot.

Combination of nucleic acid amplification and CRISPR/Cas technology in pathogen detection.

Major health events caused by pathogenic microorganisms are increasing, seriously jeopardizing human lives. Currently PCR and ITA are widely used for rapid testing in food, medicine, industry and agriculture. However, due to the non-specificity of the amplification process, researchers have proposed the combination of nucleic acid amplification technology with the novel technology CRISPR for detection, which improves the specificity and credibility of results. This paper summarizes the research progress of nucleic acid amplification technology in conjunction with CRISPR/Cas technology for the detection of pathogens, which provides a reference and theoretical basis for the subsequent application of nucleic acid amplification technology in the field of pathogen detection.

Programmable and ultra-efficient Argonaute protein-mediated nucleic acid tests: A review.

With the attributes of high sensitivity, single-base resolution, multiplex detection capability, and programmability upon nucleic acid recognition, Argonaute (Ago)-based biosensing assays are increasingly recognized as one of the most promising tools for precise identification and quantification of target analytes. Employed as highly specific sequence recognition elements of these robust diagnostic methods, Agos are revolutionizing how nucleic acid targets are detected. A systematic and comprehensive summary of this emerging and rapid-advancing technology is necessary to give play to the potential of Ago-based biosensing assays. The structure and function of Agos were briefly overviewed at the beginning of the work, followed by a review of the recent advancements in employing Agos sensing for detecting various targets with a comprehensive analysis such as viruses, tumor biomarkers, pathogens, mycoplasma, and parasite. The significance and benefits of these platforms were then deliberated. In addition, the authors shared subjective viewpoints on the existing challenges and offered relevant guidance for the future progress of Agos assays. Finally, the future research outlook regarding Ago-based sensing in this field was also outlined. As such, this review is expected to offer valuable information and fresh perspectives for a broader group of researchers.

Screening for anti-influenza virus compounds from traditional Mongolian medicine by GFP-based reporter virus.

Introduction: Screening for effective antiviral compounds from traditional Mongolian medicine not only aids in the research of antiviral mechanisms of traditional medicines, but is also of significant importance for the development of new antiviral drugs targeting influenza A virus. Our study aimed to establish high-throughput, rapid screening methods for antiviral compounds against influenza A virus from abundant resources of Mongolian medicine. Methods: The use of GFP-based reporter viruses plays a pivotal role in antiviral drugs screening by enabling rapid and precise identification of compounds that inhibit viral replication. Herein, a GFP-based reporter influenza A virus was used to identify potent anti-influenza compounds within traditional Mongolian medicine. Results: Our study led to the discovery of three active compounds: Cardamonin, Curcumin, and Kaempferide, all of which exhibited significant antiviral properties in vitro. Subsequent analysis confirmed that their effectiveness was largely due to the stimulation of the antiviral signaling pathways of host cells, rather than direct interference with the viral components, such as the viral polymerase. Discussion: This study showcased the use of GFP-based reporter viruses in high-throughput screening to unearth antiviral agents from traditional Mongolian medicine, which contains rich antiviral compounds and deserves further exploration. Despite certain limitations, fluorescent reporter viruses present substantial potential for antiviral drug screening research due to their high throughput and efficiency.

Comprehensive analysis of the role of Netrin G1 (NTNG1) in hepatocellular carcinoma cells.

Netrin G1 (NTNG1) is a member of the Netrin family and plays a crucial role in various human cancers. However, the molecular functions of NTNG1 in HCC and the underlying mechanisms remain unclear. HCC expression data was obtained from the GEO database and analyzed using various bioinformatics tools. The expression of NTNG1 in HCC tissues and liver cancer cells was evaluated through RT-qPCR and western blotting. Cells with stable NTNG1 overexpression and knockdown were established, and CCK-8, colony formation, and flow cytometry assays were conducted in vitro. The xenograft model was utilized to verify the tumorigenesis capacity of NTNG1 in vivo. IHC was employed to analyze the expression of NTNG1 and CD163 proteins. HCC-specific genes were screened, followed by functional enrichment and immune cell infiltration analysis. Finally, the Co-IP was used to detect the interaction between NTNG1 and N-cadherin. NTNG1 was highly expressed in HCC tissues and liver cancer cells, and associated with significantly poorer OS rates. In addition, NTNG1 overexpression in liver cancer cells significantly increased their proliferation, colony growth, invasion, migration, and EMT, while inhibiting apoptosis. Bioinformatics analyses indicated that NTNG1 was closely related to EMT and tumor infiltration. IHC staining revealed a positive correlation between NTNG1 expression and CD163 in HCC tissues. Additionally, an EMT inhibitor attenuated the expression levels of EMT-related markers and counteracted the effects of NTNG1 overexpression in liver cancer cells. This study is the first to identify NTNG1 as a potential therapeutic target in HCC, promoting tumor development and progression by regulating EMT.

Integrating Single-Cell and Spatial Transcriptomics to Uncover and Elucidate GP73-Mediated Pro-Angiogenic Regulatory Networks in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development. Specifically, we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc, lactate, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, and endoplasmic reticulum stress (ERS) signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo. Mechanistically, we found that GP73, the pivotal hub gene, was activated by histone lactylation and c-Myc, which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. STAT3 potentiates GP73-mediated pro-angiogenic functions. Clinically, serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy. Taken together, the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.

PEGylated dihydromyricetin-loaded nanoliposomes coated with tea saponin inhibit bacterial oxidative respiration and energy metabolism.

The biofilms produced by the aggregation of bacterial colonies are among the major obstacles of host immune system monitoring and antimicrobial treatment. Herein, we report PEGylated dihydromyricetin-loaded liposomes coated with tea saponin grafted on chitosan (TS/CTS@DMY-lips) as an efficient cationic antibacterial agent against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), which is supported by their deep penetration into bacterial biofilms and broad pH-stable release performance of dihydromyricetin (DMY). The successful construction of the drug delivery system relied on tea saponin grafted on chitosan (TS/CTS) via formatted ester bonds or amido bonds as a polyelectrolyte layer of PEGylated dihydromyricetin-loaded liposomes (DMY lips), which achieved controlled release of DMY in weak acidic and neutral physiological environments. The micromorphology of TS/CTS@DMY-lips was observed to resemble dendritic cells with an average size of 266.49 nm, and they had excellent encapsulation efficiency (41.93%), water-solubility and stability in aqueous solution. Besides, TS/CTS@DMY-lips displayed effective destruction of bacterial energy metabolism and cytoplasmic membranes, resulting in the deformation of the cell wall and leaking of cytoplasmic constituents. Compared to free DMY, DMY lips and chitosan-coated dihydromyricetin liposomes (CTS@DMY-lips), TS/CTS@DMY-lips has more thorough killing activity against E. coli and S. aureus, which is related to its excellent sustained release performance of DMY under the protection of the TS/CTS coating.

Identification and verification immune-related regulatory network in acne.

Acne is a common inflammatory skin disease with the dysregulation of innate and adaptive immunity. However, the underlying mechanism of acne has not been completely elucidated. In this study, we identified gene signatures and the immune-related regulatory network in acne using integrated bioinformatics methods. Here, 303 Differentially expressed genes (DEGs) and 28 Hub genes were identified in acne (GSE53795 and GSE108110), which were associated with the inflammation-related signaling pathway. Subsequently, the CIBERSORT algorithm revealed the increased proinflammatory cells in acne. Moreover, we identified 3 kinases (FGR, HCK and LYN) and 2 transcription factors (TFs) (IRF8 and ZBTB16) from DEGs as the key genes, which regulated immune cell infiltration via targeting immune-related genes in acne. The upregulated 3 kinases (FGR, HCK and LYN) and IRF8, and the downregulated ZBTB16 were also confirmed in GSE6475 and in Acne mice. Based on the expression levels of these key genes, the tissues could be divided into 2 clusters using consensus cluster analysis. GSEA analysis showed that inflammation-related signaling pathways significantly enriched in cluster 2, indicating the important role of kinase and TFs on immune regulation in acne. Finally, we found that isotretinoin and trifarotene (CD5789) treatment repressed the expression of immune genes but not the expression of the kinases and TFs, indicating that kinases and TFs may be novel therapeutic target for acne. In conclusion, 3 kinases and 2 TFs were identified and validated as key regulators in the immune-related regulatory networks in acne, providing a more comprehensive understanding and novel therapeutic targets of acne.

Synthesis and Efficacy of the N-carbamoyl-methionine Copper on the Growth Performance, Tissue Mineralization, Immunity, and Enzymatic Antioxidant Capacity of Nile tilapia (Oreochromis niloticus).

Immunogenic, methionine copper-induced response had proven to be precedent in providing resistance against certain diseases in fish. This study allocates the fitness strategy for Oreochromis niloticus by introducing and incorporating the well-designed, stabilized, and biocompatible N-carbamoyl-methionine copper (NCM-Cu) as a Cu potent source in diet that enhances the bioavailability and fitness. The synchronized NCM-Cu complex was characterized by directing ultraviolet and visible spectrophotometry (UV-vis), Fourier-transform infrared (FTIR), X-ray diffractometry (XRD), thermogravimetric analysis (TGA), and single-crystal X-ray diffraction. Results revealed blue columnar crystalline, NCM-Cu complex with an empirical formula as C12H30CuN4O10S2. Anonymously, the overall growth performance of the fish remained unaltered with NCM-Cu adjunct feed. NCM-Cu significantly raised the Cu accumulation in the fish muscles, liver, gill, and intestine in contrast to the basic Cu-rich feed. The serum antioxidant enzyme activity elevated up to (ceruloplasmin: 19.38 U/L) and the lowest liver malondialdehyde (MDA) content (8.81 nmol/mg prot.) and triglyceride content (0.39 nmol/g prot.) were observed in the NCM-Cu group as compared to the basic Cu and CuSO4 groups, suggesting that NCM-Cu promoted antioxidative responses and alleviated lipid peroxidation of O. niloticus. Overweening, the synthesized complex, NCM-Cu significantly regulated the expression levels of lysozyme, immunoglobulin M, complement 4, and complement 3 up to 10.93 U/mL, 0.72, 0.77, and 1.18 mg/mL in serum, respectively. Thus, such endorsed results reveal the preeminence of NCM-Cu-supplemented diet for the fitness in O. niloticus.

Wheat Straw Return Influences Nitrogen-Cycling and Pathogen Associated Soil Microbiota in a Wheat-Soybean Rotation System.

Returning straw to soil is an effective way to sustain or improve soil quality and crop yields. However, a robust understanding of the impact of straw return on the composition of the soil microbial communities under field conditions has remained elusive. In this study, we characterized the effects of wheat straw return on soil bacterial and fungal communities in a wheat-soybean rotation system over a 3-year period, using Illumina-based 16S rRNA, and internal transcribed region (ITS) amplicon sequencing. Wheat straw return significantly affected the α-diversity of the soil bacterial, but not fungal, community. It enhanced the relative abundance of the bacterial phylum Proteobacteria and the fungal phylum Zygomycota, but reduced that of the bacterial phylum Acidobacteria, and the fungal phylum Ascomycota. Notably, it enriched the relative abundance of nitrogen-cycling bacterial genera such as Bradyrhizobium and Rhizobium. Preliminary analysis of soil chemical properties indicated that straw return soils had significantly higher total nitrogen (TN) contents than no straw return soils. In addition, the relative abundance of fungal genera containing pathogens was significantly lower in straw return soils relative to control soils, such as Fusarium, Alternaria, and Myrothecium. These results suggested a selection effect from the 3-year continuous straw return treatment and the soil bacterial and fungal communities were moderately changed.

Endophytic fungal communities associated with field-grown soybean roots and seeds in the Huang-Huai region of China.

Plants depend on beneficial interactions between roots and fungal endophytes for growth, disease suppression, and stress tolerance. In this study, we characterized the endophytic fungal communities associated with the roots and corresponding seeds of soybeans grown in the Huang-Huai region of China. For the roots, we identified 105 and 50 genera by culture-independent and culture-dependent (CD) methods, respectively, and isolated 136 fungal strains (20 genera) from the CD samples. Compared with the 52 soybean endophytic fungal genera reported in other countries, 28 of the genera we found were reported, and 90 were newly discovered. Even though Fusarium was the most abundant genus of fungal endophyte in every sample, soybean root samples from three cities exhibited diverse endophytic fungal communities, and the results between samples of roots and seeds were also significantly different. Together, we identified the major endophytic fungal genera in soybean roots and seeds, and revealed that the diversity of soybean endophytic fungal communities was influenced by geographical effects and tissues. The results will facilitate a better understanding of soybean-endophytic fungi interaction systems and will assist in the screening and utilization of beneficial microorganisms to promote healthy of plants such as soybean.

Theoretical study on novel nitrogen-rich energetic compounds of bis(amino)-azobis(azoles) with tetrazene unit.

Six stereoisomers of 5,5'-bis(amino)-1,1'-azobis(tetrazoles) and 30 other structures, including all possible bis(amino)-azobis(azoles) with an N-N=N-N unit, were designed. The molecular geometries were fully optimized at the DFT-B3LYP level with the 6-31++g (d, p) basis set. From the absence of any imaginary frequency in the infrared vibration frequency spectrum, it is predicted that all these studied structures may exist in stable forms. The results of the total energies of the stereoisomers of 5,5'-bis(amino)-1,1'-azobis(tetrazoles) indicate that the two symmetric trans-form structures are more likely to exist than the other four. The pyrolysis process, chemical stability and molecular electrostatic potential were studied via the investigation of their electronic structure. Heats of formation (HOFs) were calculated using the atomization energy method based on the results of the harmonic vibration frequencies, and a linear relationship was found between the HOF and nitrogen chain or nitrogen content. Densities of the title compounds were predicted with the Monte Carlo method. Finally, according to the results of the calculated HOFs and densities, the explosive parameters of these compounds were calculated using the Kamlet-Jacobs formula. 5,5'-Bis(amino)-1,1'-azobis(tetrazoles) and its isomer 5,5'-bis(amino)-2,2'-azobis(tetrazoles) may have potential for use as energetic compounds.