Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

Peripapillary pachychoroid syndrome (PPS), a new entity in pachychoroid disease spectrum, is characterized by the thickening of the choroid in the peripapillary area.PPS is more likely to occur in middle-aged and older males, and some of the affected eyes are hyperopic and have short axial lengths.The diagnosis and differentiation of PPS depends mainly on the imaging characteristics.Optical coherence tomography shows that dilated Haller layer vessels are located in the nasal macula and associated with intraretinal fluid in the corresponding locations.Indocyanine green angiography shows dilated large choroidal vessels and choroidal hyperpermeability in the nasal maculal and peripapillary region.PPS should be differentiated from uveal effusion syndrome, central serous chorioretinopathy, and pachychoroid neovascularization.Photodynamic therapy may improve retinal effusion in patients with PPS.At present, the research on PPS is insufficient.It is still controversial whether PPS can be considered as a separate entity.The effectiveness of treatment needs more prospective studies.Further research is needed to provide new insights into the definition, diagnosis, treatment and pathogenesis of PPS.

Subretinal hyperreflective material (SHRM) is a morphologic feature seen on optical coherence tomography as hyperreflective material outside the retina and within the retinal pigment epithelium.SHRM is common in untreated neovascular age-related macular degeneration (nAMD) and often persists after anti-vascular endothelial growth factor therapy.It is also seen in central serous chorioretinopathy, uveitis, myopic choroidal neovascularization, myopic macular degeneration, Best disease, retinal malnutrition, Erdheim-Chester disease and so on.SHRM is closely associated with loss of the ellipsoid zone, scarring, disruption of outer limiting membrane, macular atrophy and outer retinal tubulations, and is significantly associated with visual impairment.Some SHRM was regression after anti-vascular endothelial growth factor therapy.The prognosis and responses to treatment of SHRM may vary depending on its components and characteristics.Identifying the morphologic characteristics and functional consequences of SHRM in nAMD may deepen the clinical understanding of SHRM.

Papilledema is due to the increase of intracranial pressure, which leads to the disorder of axoplasmic flow of nerve fibers, optic disc edema and elevation.Pseudopapilledema is mostly due to congenital morphological abnormality of the optic disc, such as optic disc drusen, optic disc tilt and so on.Fundus photography shows unclear optic disc boundaries.It is difficult to distinguish papilledema from pseudopapilledema.Spectral-domain optical coherence tomography (SD-OCT) provides a noninvasive and easy imaging method to obtain high-resolution images that can improve diagnostic accuracy through quantitative indexes such as peripheral nerve fiber layer thickness, optic disc volume and total retinal thickness, or qualitative index such as shape and displacement around the optic disc, retinal fold, and so on.This paper mainly discusses the application value of SD-OCT in differentiating papilledema from pseudopapilledema.

Humans ; Asthma/drug therapy* ; Biological Therapy

OBJECTIVE: AP2/ERF (APETALA2/ethylene-responsive factor) superfamily is one of the largest gene families in plants and has been reported to participate in various biological processes, such as the regulation of biosynthesis of active lignan. However, few studies have investigated the genome-wide role of the AP2/ERF superfamily in Isatis indigotica. This study establishes a complete picture of the AP2/ERF superfamily in I. indigotica and contributes valuable information for further functional characterization of IiAP2/ERF genes and supports further metabolic engineering. METHODS: To identify the IiAP2/ERF superfamily genes, the AP2/ERF sequences from Arabidopsis thaliana and Brassica rapa were used as query sequences in the basic local alignment search tool. Bioinformatic analyses were conducted to investigate the protein structure, motif composition, chromosome location, phylogenetic relationship, and interaction network of the IiAP2/ERF superfamily genes. The accuracy of omics data was verified by quantitative polymerase chain reaction and heatmap analyses. RESULTS: One hundred and twenty-six putative IiAP2/ERF genes in total were identified from the I. indigotica genome database in this study. By sequence alignment and phylogenetic analysis, the IiAP2/ERF genes were classified into 5 groups including AP2, ERF, DREB (dehydration-responsive element-binding factor), Soloist and RAV (related to abscisic acid insensitive 3/viviparous 1) subfamilies. Among which, 122 members were unevenly distributed across seven chromosomes. Sequence alignment showed that I. indigotica and A. thaliana had 30 pairs of orthologous genes, and we constructed their interaction network. The comprehensive analysis of gene expression pattern in different tissues suggested that these genes may play a significant role in organ growth and development of I. indigotica. Members that may regulate lignan biosynthesis in roots were also preliminarily identified. Ribonucleic acid sequencing analysis revealed that the expression of 76 IiAP2/ERF genes were up- or down-regulated under salt or drought treatment, among which, 33 IiAP2/ERF genes were regulated by both stresses. CONCLUSION This study undertook a genome-wide characterization of the AP2/ERF superfamily in I. indigotica, providing valuable information for further functional characterization of IiAP2/ERF genes and discovery of genetic targets for metabolic engineering.
Abscisic Acid ; Isatis/genetics* ; Multigene Family ; Phylogeny ; Homeodomain Proteins/genetics* ; Genome, Plant

Humans ; COVID-19 ; SARS-CoV-2

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

Perifoveal exudative vascular anomalous complex (PEVAC) is a very rare macular vascular disease characterized by an isolated large aneurysmal lesion in the fovea, with accompanied by small retinal hemorrhage and exudation. The main clinical symptoms of the patients are various degree of impaired vision. Clinically, it is often confused with type 1 macular telangiectasia and type 3 macular neovascularization. A thorough understanding of the clinical features of PEVAC is particularly important for its differential diagnosis. Due to the unclear pathogenesis of PEVAC, there is no specific treatment for the cause of disease. Most scholars use intravitreal injection against vascular endothelial growth factor drugs for treatment, but can not improve patients' visual acuity. At present, many attempts have been made to eliminate abnormal exudation of the lesion, maintain visual function and achieve a good prognosis by simple or combined laser photocoagulation. At present, it is still necessary to explore the pathogenesis of PEVAC, improve the understanding of the disease, and find a better treatment plan.