YABBY proteins are important transcription factors that regulate morphogenesis and organ development in plants. In order to study the YABBY of strawberry, bioinformatic technique were used to identify the YABBY gene families in Fragaria vesca (diploid) and Fragaria×ananassa (octoploid), and then analyze the sequence characters, phylogeny and collinearity of the family members. The RNA-seq data and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) technique were used to assay the expression patterns of the family members. A green fluorescent protein (GFP) was fused with FvYABBYs and transiently expressed in tobacco leaf cells for the subcellular localization. As the results, six FvYABBY genes and 26 FxaYABBY genes were identified from F. vesca and F.×ananassa, respectively. The FvYABBY genes were grouped into five clades, and five family members were orthologous with AtYABBY genes of Arabidopsis. In F. vesca, all of the FvYABBYs were basically not expressed not expressed in root and receptacle, while FvYABBY1, FvYABBY2, FvYABBY5 and FvYABBY6 were highly expressed in leaf, shoot, flower and achene. In F.×ananassa, FxaYABBY1, FxaYABBY2, FxaYABBY5 and FxaYABBY6 were expressed in achene, and all FxaYABBY were poorly or not expressed in receptacle. Additionally, under the abiotic stresses of low temperature, high salt and drought, the expression of FvYABBY1, FvYABBY3, FvYABBY4 and FvYABBY6 were down-regulated, FvYABBY5 was up-regulated, and FvYABBY2 was up-regulated and then down-regulated. In tobacco leaf cells, the subcellular localization of FvYABBY proteins were in the nucleus. These results provides a foundation for the functional researches of YABBY gene in strawberry.
Fragaria/genetics* ; Arabidopsis ; Biological Assay ; Cold Temperature ; Computational Biology

Objective To identify small molecule inhibitors of APC-mutant colon cancer and provide lead compounds for targeted therapy of colon cancer.Methods APC-mutant colon cancer cell lines that stably express 7*Tcf-GFP/SV40-Cherry(7TGC)dual fluorescence reporter system was constructed for small-molecule inhibitor screening.Cell viability,colony formation,EdU incorporation,and xenograft tumor assay were used to evaluate the inhibitory effect of these inhibitors on APC-mutant colon cancer in vitro and in vivo.Western blot and co-immunoprecipitation assays were used to explore the molecular mechanism.Results Four small molecules that inhibited Wnt activity in APC-mutant colon cancer cells were discovered.Shikonin exhibited significant inhibition of cell viability and proliferation while inducing apoptosis of APC-mutant colon cancer cells.Xenograft tumor assay demonstrated that shikonin significantly reduced tumor growth in vivo.Furthermore,Western blot and co-immunoprecipitation assays revealed that shikonin markedly decreased β-catenin levels.Conclusion Shikonin effectively inhibits Wnt activity and suppresses tumor growth in APC-mutant colon cancer.

Objective To study the effect and mechanism of Anchusa italica Retz on cerebral ischemia-reperfusion inju-ry in rats based on the target network of active compounds in Anchusa italica Retz.Methods The rat model of cerebral ische-mia-reperfusion injury was established by the thread occlusion method.After performing ischemia for 1.5 h and then reperfusion for 24 h,the neurological function of rats was scored and the volume of cerebral infarction was measured by the 2,3,5-triphenyltet-razolium chloride staining method.The molecular network analysis technique of network pharmacology,protein-protein interaction network,gene ontology(GO)enrichment analysis,KEGG signal pathway analysis,and molecular docking was used to study the mechanism of Anchusa italica Retz in the treatment of cerebral ischemia-reperfusion injury.Results The administration of An-chusa italica Retz could significantly improve the neurobehavioral dysfunction caused by cerebral ischemia-reperfusion injury and reduce the pathological injury of brain tissue.Anchusa italica Retz could regulate inflammation,apoptosis,protein phosphorylation,and other biological processes through 143 ischemic stroke-related targets,and interfere with the TNF signal pathway,VEGF signal pathway,HIF-1 signal pathway,and other pathways.Conclusion Network pharmacology and experimental verification had shown that Anchusa italica Retz could effectively reduce brain injury and protect neurological function through multi-target,multi-mechanism,and holistic treatment of cerebral ischemia-reperfusion injury.

Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.

Objective To explore the regulatory mechanism of emodin on pain behavior in a mouse model of osteoarthritis based on mitochondrial key genes.Methods Thirty C57BL/6J mice were randomly divided into the control group,the osteoarthritis(OA)model group and the emodin-treated(OA+emodin)group,10 mice per each group.The mice in the OA group and the OA+emodin group were intra-articular injection of complete Freund's adjuvant(20 μL)in knee to establish the OA model,and mice in the OA+emodin group were treated by intraperitoneal emodin(10 mg/kg)injection.After behavioral testing,knee tissue of mice was collected for hematoxylin-eosin staining.Western blot analysis was used to detect expression levels of proinflammatory factors interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and mitochondria-related proteins NADH dehydrogenase(ubiquinone)flavoprotein 1(NDUFV1),cytochrome C oxidase subunit 5B(COX5B),cytochrome C oxidase assembly protein COX15 homolog(COX15),NADH dehydrogenase(ubiquinone)1 alpha subcomplex subunit 10(NDUFA10)in knee tissue.Results Compared with the control group,mice in the OA group showed decreased mechanical nociceptive threshold(PWT),reduced latency and distance in rotarod test(P＜0.05).Compared with the OA group,mice in the OA+emodin group showed increased PWT,latency,and distance(P＜0.05).In the control group,the structures of cartilage and subchondral bone were intact,while in the OA group,the cartilage was thinner and the subchondral trabeculae was deteriorated.The treatment with emodin alleviated cartilage degeneration.The expression levels of IL-1β,TNF-α,COX15 and NDUFA10 were increased while expression levels of NDUFV1 and COX5B were decreased in the OA group compared with the control group.The emodin treatment restored the above-mentioned protein expression levels(P＜0.05).Conclusion Emodin can alleviate pain behavior in OA mice by regulating the expressions of inflammatory factors and mitochondrial related proteins.

Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.

Purpose To explore the cardioprotective effect of cang-ai volatile oil(CAVO)on rats with cardiac function impairment model under low-pressure and low-oxygen environment in Tibet Plateau based on 7.0T cardiovascular magnetic resonance(CMR)imaging.Materials and Methods Forty SD rats were randomly divided into the normal group,the high altitude model group,the CAVO-treated group and the rhodiola rosea-treated group,with 10 rats in each group.Except for the normal group,the rats in other groups were transferred from the plain(500 m above sea level)to the Tibet Plateau(4 250 m above sea level)for two months,and then administered with the corresponding drugs by gavage for 14 d.The left ventricle function was measured by using a 7.0T high-field strength CMR and myocardial strain was analysed by using tissue tracing technique.HE staining was used to observe the morphology of cardiomyocytes,Masson staining to observe interstitial fibrosis,wheat germ agglutinin staining to observe cardiomyocyte hypertrophy,and transmission electron microscopy to observe the morphological changes of mitochondria in each group.Serum levels of creatine kinase,creatine kinase isoenzyme,lactate dehydrogenase,cardiac troponin T,superoxide dismutase,malondialdehyde and glutathione peroxidase were detected.Intracellular reactive oxygen species levels were detected using flow cytometry.Results The left ventricular ejection fraction of rats in the CAVO-treated group was higher than that of the high altitude model group[(66.61±1.38)％vs.(60.94±3.21)％;t=3.969,P=0.032];meanwhile,the global circumferential strain of the left ventricle in the CAVO-treated group was higher than that of the high altitude model group(-25.68±1.30 vs.-22.84±1.17;t=3.967,P=0.003).HE,Masson and wheat germ agglutinin staining showed hypertrophy and necrosis as well as interstitial fibrosis and ultrastructural disruption of cardiomyocytes in the high altitude model group,which improved after CAVO treatment.The level of cardiac troponin T in the serum of rats with CAVO treatment group was significantly decreased compared with that of the high altitude model group[(314.03±20.05)pg/ml vs.(518.30±18.13)pg/ml;1=13.090,P=0.001].Conclusion CAVO treatment can reduce cardiac injury caused by low-pressure hypoxia in high altitude,and its effect can be detected dynamically and non-invasively by 7.0T high-field strength CMR.

SUN gene is a group of key genes regulating plant growth and development. Here, SUN gene families of strawberry were identified from the genome of the diploid Fragaria vesca, and their physicochemical properties, genes structure, evolution and genes expression were also analyzed. Our results showed that there were thirty-one FvSUN genes in F. vesca and the FvSUNs encoded proteins were classified into seven groups, and the members in the same group showed high similarity in gene structures and conservative motifs. The electronic subcellular localization of FvSUNs was mainly in the nucleus. Collinearity analysis showed that the members of FvSUN gene family were mainly expanded by segmental duplication in F. vesca, and Arabidopsis and F. vesca shared twenty-three pairs of orthologous SUN genes. According to the expression pattern in different tissues shown by the transcriptome data of F. vesca, the FvSUNs gene can be divided into three types: (1) expressed in nearly all tissues, (2) hardly expressed in any tissues, and (3) expressed in special tissues. The gene expression pattern of FvSUNs was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the seedlings of F. vesca were treated by different abiotic stresses, and the expression level of 31 FvSUNs genes were assayed by qRT-PCR. The expression of most of the tested genes was induced by cold, high salt or drought stress. Our studies may facilitate revealing the biological function and molecular mechanism of SUN genes in strawberry.
Fragaria/metabolism* ; Genes, Plant ; Stress, Physiological/genetics* ; Arabidopsis/genetics* ; Plant Development ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism*

Objective:To analyze the current situation and effect of mobile applications for physical activity management in China.Methods:In this systematic review, search terms such as “exercise”, “sports”, “exercise”, “physical activity” and “mobile health” were used to retrieve the applications for physical activity management in the IOS Application Store developed in mainland of China. Then the Mobile Application Rating Scale (MARS) and the Behavior Change Technology (BCT) were used to evaluate the quality of the applications and analyze the behavior change technologies that applications adopted. Moreover, a systematic review of relevant experimental studies was applied to summarize the effectiveness of the applications in promoting physical activity.Results:Total of 141 applications were included in this analysis, and 58 behavior change techniques in 16 categories were applied. The most frequently used 4 categories of BCT were behavior comparison (67.4%), repetition and substitution (67.4%), knowledge construction (67.4%), feedback and monitoring (58.2%). The overall objective quality score of MARS was 3.17±0.42, of which, the score of engagements, functionality, aesthetic design and information quality was 2.67±0.73, 3.75±0.54, 3.44±0.59 and 2.83±0.55, respectively. The number of BCT adopted in each application had a linear relationship with the application′s objective quality score in MARS ( B=0.023, 95% CI: 0.018-0.029) and user rating ( B=0.040, 95% CI: 0.019-0.060) (both P<0.001). A total of 4 articles were included to test the effects of techniques (i.e., physical activity behavior monitoring, physical activity planning and physical activity guidance) in 4 applications. The overall quality of the literatures was good. The main outcomes were physical activity duration (3 articles) and step count (1 article). Compared with those who did not use the application or only used the accelerometer to monitor physical activity, subjects who used the application to monitor physical activity had significant longer physical activity durations and step count (both P<0.05). Conclusions:The number, function and technology of physical activity management applications in China are abundant, but the quality of the applications is moderate. The number of BCT is an important factor in evaluating application′s quality, but its effect on behavior change is still not clear.

Objective:To investigate the predictive value of systemic inflammatory response index (SIRI) for early neurological deterioration (END) and clinical outcome in patients with branch atherosclerotic disease (BAD).Methods:Consecutive patients with BAD admitted to the Department of Neurology, Jiangyin People’s Hospital Affiliated to Southeast University from September 2021 to September 2022 were retrospectively included. The clinical data were collected and SIRI was calculated. The calculation method of SIRI was neutrophil count × monocyte count/lymphocyte count. END was defined as an increase of ≥2 in the total score of the National Institutes of Health Stroke Scale (NIHSS) or an increase of ≥1 in the motor function score within 1 week of onset. The modified Rankin Scale was used for outcome evaluation at 3 months after onset, with a score >2 were defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent correlation between SIRI and END, as well as poor outcome. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SIRI for poor outcome. Results:A total of 125 patients with BAD were included, of which 62 (49.6%) had END and 32 (25.6%) had poor outcome. The multivariate logistic regression analysis showed that intravenous thrombolysis (odds ratio [ OR] 1.083, 95% confidence interval [ CI] 1.082-1.240; P=0.043) and high SIRI ( OR 1.465, 95% CI 1.150-3.676; P=0.028) were independent risk factors for END in patients with BAD; END ( OR 1.130, 95% CI 1.032-1.384; P=0.006), high baseline NIHSS score ( OR 1.571, 95% CI 1.184-2.101; P=0.003) and high SIRI ( OR 2.062, 95% CI 1.152-3.672; P=0.01) were independent risk factors for poor outcome in patients with BAD. ROC curve analysis showed that the area under the curves for SIRI, baseline NIHSS score, and the both combined prediction of poor outcome were 0.66 (95% CI 0.54-0.78), 0.70 (95% CI 0.58-0.81), and 0.83 (95% CI 0.74-0.93), respectively. Conclusions:High SIRI is an independent risk factor for END and poor outcome in patients with BAD. The SIRI and baseline NIHSS scores have certain predictive value for poor outcome in patients with BAD, and their combined diagnostic value is higher.