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.

Objective To analyze the research status and predict the development trend of clinical comprehensive evaluation of drugs in China, and to provide reference for clinical comprehensive evaluation. Methods CNKI, Wanfang and VIP database were used to search the published articles of clinical comprehensive evaluation. Literature searching was set from the building time of the database to 2022, the basic information about the published articles was obtained for the evaluation of the literature quality. Bibliometrics and CiteSpace 6.1.R3 software were used to visualize the research authors, research institutions, and key words. Results After data screening, a total of 126 Chinese published articles were selected. The analysis showed that the numbers of published articles were rising continuously, and China Academy of Chinese Medical Sciences and Xie Yanming were the institute and the author with the maximum number of literatures, respectively. Conclusion The clinical comprehensive evaluation of drugs was conducted based on the clinical value of drugs, guided by the policy requirements. It is suggested that researchers should conduct the comprehensive evaluation according to the focus and requirements of government agencies, the pharmaceutical industry and the clinical applications.

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

Objective:To quantitatively evaluate the retinal ischemia in different retinal regions of diabetic retinopathy (DR) patients in ultra-widefield fluorescein fundus angiography (UWFA) images with ischemic index (ISI), and to explore its correlation with diabetic macular edema (DME).Methods:A cross-sectional study was conducted.Seventy-nine eyes of 79 patients with DR were enrolled in Renmin Hospital of Wuhan University from September 2017 to October 2020, including 44 males (44 eyes) and 35 females (35 eyes) aged 31 to 73 years old, with an average age of (55.95±8.80) years.UWFA and spectral-domain optical coherence tomography (SD-OCT) were performed in all patients.Patients were divided into DME group (37 eyes) and non-DME group (42 eyes) according to the presence or absence of DME in OCT images.The retina in middle phase UWFA images were divided into posterior, middle peripheral and far peripheral regions by ImageJ software, and ISI in each region was calculated.Central macular thickness (CMT) was automatically calculated using the built-in software of the OCT equipment.The correlation between ISI and CMT was analyzed by Spearman rank correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2019-K037). Written informed consent was obtained from each patient prior to any medical examination.Results:The ISI of the total, posterior, middle peripheral and far peripheral retina was 2.460 (0.603, 5.640)%, 2.670 (1.062, 9.574)%, 1.382 (0.245, 4.378)% and 0.000 (0.000, 1.262)%, respectively, with a statistically significant difference among different regions ( χ2=65.307, P<0.001). There were statistically significant differences in ISI between the total and far peripheral, the posterior and middle peripheral, the posterior and far peripheral, the middle and far peripheral (all at P<0.01). ISI of the total, posterior and middle peripheral retina in DME group were significantly higher than those in non-DME group ( U=424.000, P=0.001; U=403.000, P<0.001, U=493.000, P=0.005), but there was no significant difference in the ISI of the far peripheral region between the two groups ( U=609.000, P=0.061). There was no statistically significant correlation between ISI and CMT in the total, posterior, middle peripheral and far peripheral retina in DME group ( rs=-0.134, -0.018, -0.152, -0.163; all at P>0.05). Conclusions:The retinal non-perfusion area in DR eyes is mainly located in the posterior and middle peripheral retina.The ISI of the posterior and middle peripheral retina in DME eyes is significantly higher than that in eyes without DME.ISI of each retinal region may not be related to the severity of DME.

The separation of outer retinal photoreceptors in patients with toxoplasmosis chorioretinitis was first named bacillary layer detachment (BALAD), which was manifested as a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity in optical coherence tomography.Subsequently BALAD has been reported by many researchers in different diseases.In the outer retina, the myoid is a relatively weak structure in photoreceptor inner segment.When the outward force that promotes the attachment of the photoreceptor outer segment to the retinal pigment epithelium exceeds the tensile strength of the photoreceptor inner segment myoid, the myoid zone splits and BALAD occurs.BALAD has its unique multimodal imaging characteristics, and the identification of it can provide a new idea for the diagnosis, detection and treatment of ocular diseases.This paper reviewed the development of BALAD nomenclature, its anatomical structure, pathophysiological mechanism and multimodal image features.

Objective:To observe the choroidal vascular changes of chronic central serous chorioretinopathy (cCSC), and analyze their correlations with central macular thickness (CMT).Methods:A cross-sectional study was adopted.Seventy-six eyes of 38 patients with monocular cCSC who were treated in Renmin Hospital of Wuhan University from March 2018 to December 2019 were enrolled, and 30 eyes of 30 normal control matched with age, gender, and spherical equivalent (SE) were included.Choroidal images of all subjects, and the CMT, subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), total choroidal area (TCA), choroidal stromal area (SA), and choroidal luminal area (LA) were measured by Heidelberg enhanced depth imaging optical coherence tomography.The differences in SFCT, LA, SA, TCA, CMT and CVI between the cCSC eye, fellow eye and normal eye, as well as the correlation between SFCT and CVI, SFCT and CMT, and CVI and CMT were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2020-K234).Results:The CVI and the SFCT of the cCSC eyes, fellow eyes and normal eyes were (71.67±5.60)% and 483.82(409.01, 550.87)μm, (68.33±3.85)% and 444.66(351.25, 505.15)μm, (64.70±1.88)% and 373.46(327.98, 405.48)μm, respectively.The CMT, SFCT, TCA, LA, CVI in cCSC eyes were significantly higher than those in the contralateral eyes and normal control eyes, while SFCT, TCA, LA, CVI in the contralateral eyes were higher than those in normal control eyes (all at P<0.05). Pairwise comparison among the three groups showed no significant difference in SA (all at P>0.05). Correlation analysis showed that in cCSC eyes, SFCT was strongly positively correlated with CVI ( rs=0.703, P<0.001), and there was no correlation between CMT and SFCT ( rs=0.181, P=0.278), or CMT and CVI ( r=0.231, P=0.164). Conclusions:The SFCT and CVI are higher in cCSC and the fellow eyes compared with normal eyes, and the choroidal vessels are significantly dilated in cCSC patients.The SFCT and CVI of the cCSC eye are slightly higher in comparison with the fellow eye.CMT is not correlated with SFCT or CVI in cCSC eyes.