scATAC-Ref: a reference of scATAC-seq with known cell labels in multiple species.

Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.

SpatialRef: a reference of spatial omics with known spot annotation.

Spatial omics technologies have enabled the creation of intricate spatial maps that capture molecular features and tissue morphology, providing valuable insights into the spatial associations and functional organization of tissues. Accurate annotation of spot or domain types is essential for downstream spatial omics analyses, but this remains challenging. Therefore, this study aimed to develop a manually curated spatial omics database (SpatialRef, https://bio.liclab.net/spatialref/), to provide comprehensive and high-quality spatial omics data with known spot labels across multiple species. The current version of SpatialRef aggregates >9 million manually annotated spots across 17 Human, Mouse and Drosophila tissue types through extensive review and strict quality control, covering multiple spatial sequencing technologies and >400 spot/domain types from original studies. Furthermore, SpatialRef supports various spatial omics analyses about known spot types, including differentially expressed genes, spatially variable genes, Gene Ontology (GO)/KEGG annotation, spatial communication and spatial trajectories. With a user-friendly interface, SpatialRef facilitates querying, browsing and visualizing, thereby aiding in elucidating the functional relevance of spatial domains within the tissue and uncovering potential biological effects.

scImmOmics: a manually curated resource of single-cell multi-omics immune data.

Single-cell sequencing technology has enabled the discovery and characterization of subpopulations of immune cells with unique functions, which is critical for revealing immune responses under healthy or disease conditions. Efforts have been made to collect and curate single-cell RNA sequencing (scRNA-seq) data, yet an immune-specific single-cell multi-omics atlas with harmonized metadata is still lacking. Here, we present scImmOmics (https://bio.liclab.net/scImmOmics/home), a manually curated single-cell multi-omics immune database constructed based on high-quality immune cells with known immune cell labels. Currently, scImmOmics documents >2.9 million cell-type labeled immune cells derived from seven single-cell sequencing technologies, involving 131 immune cell types, 47 tissues and 4 species. To ensure data consistency, we standardized the nomenclature of immune cell types and presented them in a hierarchical tree structure to clearly describe the lineage relationships within the immune system. scImmOmics also provides comprehensive immune regulatory information, including T-cell/B-cell receptor sequencing clonotype information, cell-specific regulatory information (e.g. gene/chromatin accessibility/protein/transcription factor states within known cell types, cell-to-cell communication and co-expression networks) and immune cell responses to cytokines. Collectively, scImmOmics is a comprehensive and valuable platform for unraveling the heterogeneity and diversity of immune cells and elucidating the specific regulatory mechanisms at the single-cell level.

SEanalysis 2.0: a comprehensive super-enhancer regulatory network analysis tool for human and mouse.

Super-enhancers (SEs) play an essential regulatory role in various biological processes and diseases through their specific interaction with transcription factors (TFs). Here, we present the release of SEanalysis 2.0 (http://licpathway.net/SEanalysis), an updated version of the SEanalysis web server for the comprehensive analyses of transcriptional regulatory networks formed by SEs, pathways, TFs, and genes. The current version added mouse SEs and further expanded the scale of human SEs, documenting 1 167 518 human SEs from 1739 samples and 550 226 mouse SEs from 931 samples. The SE-related samples in SEanalysis 2.0 were more than five times that in version 1.0, which significantly improved the ability of original SE-related network analyses ('pathway downstream analysis', 'upstream regulatory analysis' and 'genomic region annotation') for understanding context-specific gene regulation. Furthermore, we designed two novel analysis models, 'TF regulatory analysis' and 'Sample comparative analysis' for supporting more comprehensive analyses of SE regulatory networks driven by TFs. Further, the risk SNPs were annotated to the SE regions to provide potential SE-related disease/trait information. Hence, we believe that SEanalysis 2.0 has significantly expanded the data and analytical capabilities of SEs, which helps researchers in an in-depth understanding of the regulatory mechanisms of SEs.

Sintilimab combined with bevacizumab in relapsed or persistent ovarian clear cell carcinoma (INOVA): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Ovarian clear cell carcinoma rarely responds to second-line chemotherapy, the recommended treatment for relapsed epithelial ovarian cancer. Here, we report the activity and safety of sintilimab in combination with bevacizumab in patients with relapsed or persistent ovarian clear cell carcinoma. METHODS: In the prospective, multicentre, single-arm, phase 2 INOVA trial, patients aged 18-75 years with histologically confirmed relapsed or persistent ovarian clear cell carcinoma were enrolled from eight tertiary hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group performance status score of 0-2 and previous exposure to at least one cycle of platinum-containing chemotherapy. Enrolled patients received sintilimab (200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks until disease progression. The primary endpoint was objective response rate assessed by independent central review based on Response Evaluation Criteria in Solid Tumours version 1.1. Eligible enrolled patients who received at least one cycle of treatment and had at least one tumour response assessment following the baseline assessment per protocol were included in the activity analysis. Patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04735861) and is ongoing. FINDINGS: Between April 8, 2021, and July 3, 2023, 51 patients were screened and 41 patients received at least one dose of sintilimab in combination with bevacizumab. Response evaluation was completed in 37 patients. Objective responses were observed in 15 patients (objective response rate 40·5%; 95% CI 24·8-57·9), of which five (14%) were complete responses and ten (27%) were partial responses. At data cutoff (Jan 29, 2024), the median follow-up was 16·9 months (IQR 7·5-23·4). Three (7%) patients developed grade 3 treatment-related adverse events including one patient with proteinuria, one patient with myocarditis, and one patient with rash. No treatment-related adverse events of worse than grade 3 severity were recorded. Treatment-related serious adverse events occurred in two (5%) patients including one patient with immune-related myocarditis and another with hypertension and renal dysfunction. No treatment-related deaths occurred. INTERPRETATION: Sintilimab in combination with bevacizumab showed promising anti-tumour activity and manageable safety in patients with relapsed or persistent ovarian clear cell carcinoma. Larger, randomised trials are warranted to compare this low-toxicity, chemotherapy-free combinatorial regimen with standard chemotherapy. FUNDING: National Key Technology Research and Development Program of China, National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Tailoring the Hydrophobic Interface of Core-Shell HKUST-1@Cu2O Nanocomposites for Efficiently Selective CO2 Electroreduction.

The electrochemical reduction of carbon dioxide (CO2) to ethylene creates a carbon-neutral approach to converting carbon dioxide into intermittent renewable electricity. Exploring efficient electrocatalysts with potentially high ethylene selectivity is extremely desirable, but still challenging. In this report, a laboratory-designed catalyst HKUST-1@Cu2O/PTFE-1 is prepared, in which the high specific surface area of the composites with improved CO2 adsorption and the abundance of active sites contribute to the increased electrocatalytic activity. Furthermore, the hydrophobic interface constructed by the hydrophobic material polytetrafluoroethylene (PTFE) effectively inhibits the occurrence of hydrogen evolution reactions, providing a significant improvement in the efficiency of CO2 electroreduction. The distinctive structures result in the remarkable hydrocarbon fuels generation with high Faraday efficiency (FE) of 67.41%, particularly for ethylene with FE of 46.08% (-1.0 V vs RHE). The superior performance of the catalyst is verified by DFT calculation with lower Gibbs free energy of the intermediate interactions with improved proton migration and selectivity to emerge the polycarbon（C2+） product. In this work, a promising and effective strategy is presented to configure MOF-based materials with tailored hydrophobic interface, high adsorption selectivity and more exposed active sites for enhancing the efficiency of the electroreduction of CO2 to C2+ products with high added value.

WHO/ISUP grade and pathological T stage of clear cell renal cell carcinoma: value of ZOOMit diffusion kurtosis imaging and chemical exchange saturation transfer imaging.

OBJECTIVES: To evaluate the value of ZOOMit diffusion kurtosis imaging (DKI) and chemical exchange saturation transfer (CEST) imaging in predicting WHO/ISUP grade and pathological T stage in clear cell renal cell carcinoma (ccRCC). METHODS: Forty-six patients with ccRCC were included in this retrospective study. All participants underwent MRI including ZOOMit DKI and CEST. The non-Gaussian mean kurtosis (MK), mean diffusivity (MD), magnetization transfer ratio asymmetry (MTRasym (3.5 ppm)), and Ssat (3.5 ppm)/S0 were analyzed based on different WHO/ISUP grades and pT stages. Binary logistic regression was used to identify the best combination of the parameters. Pearson's correlation coefficients were calculated between CEST and diffusion-related parameters. RESULTS: The ADC, MD, and Ssat (3.5 ppm)/S0 values were significantly lower for higher WHO/ISUP grade tumors, whereas the MK and MTRasym (3.5 ppm) were higher in higher WHO/ISUP grade and higher pT stage tumors. MTRasym (3.5 ppm) combined with MD (AUC, 0.930; 95% CI, 0.858-1.000) showed the best diagnostic efficacy in evaluating the WHO/ISUP grade. MTRasym (3.5 ppm) and MK were mildly positively correlated (r = 0.324, p = 0.028). Ssat (3.5 ppm)/S0 was moderately positively correlated with ADC (r = 0.580, p < 0.001), mildly positively correlated with MD (r = 0.412, p = 0.005), and moderately negatively correlated with MK (r = -0.575, p < .001). CONCLUSION: The microstructural and biochemical assessment of ZOOMit DKI and CEST allowed for the characterization of different WHO/ISUP grades and pT stages in ccRCC. MTRasym (3.5 ppm) combined with MD showed the best diagnostic performance for WHO/ISUP grading. KEY POINTS: • Both diffusion kurtosis imaging (DKI) and chemical exchange saturation transfer (CEST) can be used to predict the WHO/ISUP grade and pathological T stage. • MTRasym (3.5 ppm) combined with MD showed the highest AUC (0.930; 95% CI, 0.858-1.000) in WHO/ISUP grading. • MTRasym at 3.5 ppm showed a positive correlation with mean kurtosis.

Multi-omics perspective on studying reproductive biology in Daphnia sinensis.

Daphnia sinensis is a widespread freshwater microcrustacean. The assembled D. sinensis genome totaled 131.58 Mb with 92.23% of the assembly anchored onto 10 chromosomes. Based on the whole genome information, we further compared the transcriptomic and epigenomic characterization among parthenogenetic females, sexual females and males in D. sinensis. Transcriptomic analysis showed that the up-regulated genes in males were mainly grouped into the cuticle, sex differentiation and methyl farnesoate synthesis, which might play a pivotal role in steering development and reproduction processes. By comparison, the highly expressed genes in parthenogenetic females were mainly grouped into energy metabolism, mitosis, and DNA replication, which might contribute to maintaining rapid production of parthenogenetic females, and nutrient uptake for the growth of neonates. The whole-genome DNA methylation analysis showed that the methylation rate in parthenogenetic females was higher than that in sexual females and males, which might contribute to its rapid response to environment stress.

Comparison of outcomes between single- and multiple-perforator-based free perforator flaps: A systematic review and meta-analysis.

BACKGROUND: Perforator-based free perforator flaps have become an important tool for the reconstruction of tissue defects. The effect of the number of perforators on the outcomes of perforator flaps has been widely debated. This study aimed to compare the outcomes of single- and multiple-perforator-based free perforator flaps in free-flap reconstruction. METHODS: We searched PubMed, Web of Science, EMBASE, Chinese BioMedical Literature Database (CBM), Cochrane Library, and clinicaltrials.gov between January 2000 and June 2021 to identify studies that reported data on the outcomes of free perforator flaps. Two authors individually extracted data and performed quality assessment. Outcomes, including partial flap loss, total loss, fat necrosis, arterial insufficiency, venous insufficiency, hemorrhage and hematoma, wound dehiscence at recipient sites and donor site complications, were evaluated. RESULTS: Thirty-two studies with 2498 flaps were included in our analysis. No significant difference was found in the rates of partial loss and arterial insufficiency of flaps, hemorrhage and hematoma, wound dehiscence at recipient sites and donor site complications. However, the multiple-perforator group showed significantly lower rates of total loss (relative risk [RR] = 1.08, 95% confidence interval [CI]: 0.78-1.79, p = .754), fat necrosis (RR = 1.79, 95% [CI]: 1.36-2.36, p = .000) and venous insufficiency (RR = 1.72, 95% CI: 1.07-2.79, p = .026) than the single-perforator group. CONCLUSION: The rates of total loss, fat necrosis and venous insufficiency in the multiple-perforator group were lower than those in the single-perforator group. Hence, we recommend that multiple perforators be included in the free perforator flap when appropriate, to yield better clinical outcomes in reconstruction.

Accuracy and Challenges in the Vesical Imaging-Reporting and Data System for Staging Bladder Cancer.

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) scoring system has been widely used to stage bladder cancer (BCa) since 2018. PURPOSE: To describe the characteristics of cases with discordant T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) scores in patients with BCa and further verify the accuracy of the VI-RADS scoring system and the necessity of dynamic contrast-enhanced (DCE) sequence. STUDY TYPE: Retrospective. SUBJECTS: A total of 106 patients (include 16.5% female) with bladder cancer. SEQUENCE: T2WI (fast spin echo), DWI (echo planer imaging), and DCE (gradient echo). ASSESSMENT: Some cases are difficult to score according to the system, mainly when the T2WI (category 4) and DWI (category 2) sequence scores are discordant, termed the discordant group below. The complementary group will be termed concordant group. Each MRI sequence was reviewed respectively according to the 5-point VI-RADS scoring system by three observers. The diagnostic ability of sequences for evaluating muscle invasion by BCa was calculated using histopathology as the reference standards. STATISTICAL TESTS: Receiver operating characteristic (ROC) curve, DeLong test, intraclass correlation coefficient. A P value of 0.05 or less was considered statistically significant. RESULTS: Fourteen cases (13.2%) had discordant VI-RADS scoring system. In the discordant group, the area under the ROC curve (AUC) of DCE was 0.875, while the T2WI and DWI showed limited diagnostic performance (AUCs = 0.50). In the concordant group, there was no significant difference in diagnostic efficacy between the overall VI-RADS (AUC: 0.950) and the combination of T2WI and DWI (AUC: 0.946) (P = 0.56). Among all patients, the AUC of overall VIRADS was 0.939 with a 3 or greater cutoff value. DATA CONCLUSION: The DCE was crucial in the discordant group for evaluating muscle-invasiveness, while DCE may not be necessary for the concordant group. The VI-RADS scoring system performed with overall good diagnostic performance in evaluating muscle-invasiveness in BCa patients. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Evaluation of a fractional-order calculus diffusion model and bi-parametric VI-RADS for staging and grading bladder urothelial carcinoma.

OBJECTIVES: To evaluate the feasibility of high b-value diffusion-weighted imaging (DWI) for distinguishing non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC) and low- from high-grade bladder urothelial carcinoma using a fractional-order calculus (FROC) model as well as a combination of FROC DWI and bi-parametric Vesical Imaging-Reporting and Data System (VI-RADS). METHODS: Fifty-eight participants with bladder urothelial carcinoma were included in this IRB-approved prospective study. Diffusion-weighted images, acquired with 16 b-values (0-3600 s/mm2), were analyzed using the FROC model. Three FROC parameters, D, ß, and µ, were used for delineating NMIBC from MIBC and for tumor grading. A receiver operating characteristic (ROC) analysis was performed based on the individual FROC parameters and their combinations, followed by comparisons with apparent diffusion coefficient (ADC) and bi-parametric VI-RADS based on T2-weighted images and DWI. RESULTS: D and µ were significantly lower in the MIBC group than in the NMIBC group (p = 0.001 for each), and D, ß, and µ all exhibited significantly lower values in the high- than in the low-grade tumors (p ≤ 0.011). The combination of D, ß, and µ produced the highest specificity (85%), accuracy (78%), and the area under the ROC curve (AUC, 0.782) for distinguishing NMIBC and MIBC, and the best sensitivity (89%), specificity (86%), accuracy (88%), and AUC (0.892) for tumor grading, all of which outperformed the ADC. The combination of FROC parameters with bi-parametric VI-RADS improved the AUC from 0.859 to 0.931. CONCLUSIONS: High b-value DWI with a FROC model is useful in distinguishing NMIBC from MIBC and grading bladder tumors. KEY POINTS: • Diffusion parameters derived from a FROC diffusion model may differentiate NMIBC from MIBC and low- from high-grade bladder urothelial carcinomas. • Under the condition of a moderate sample size, higher AUCs were achieved by the FROC parameters D (0.842) and µ (0.857) than ADC (0.804) for bladder tumor grading with p ≤ 0.046. • The combination of the three diffusion parameters from the FROC model can improve the specificity over ADC (85% versus 67%, p = 0.031) for distinguishing NMIBC and MIBC and enhance the performance of bi-parametric VI-RADS.

Self-Sacrificing Template of the POMs-Based Composite for the High-Performance Organic-Inorganic Hybrid Cathode of Lithium-Ion Batteries.

The high theoretical capacity of vanadium oxides makes them promising cathode candidates for the rechargeable lithium-ion batteries (LIBs). Nevertheless, the relatively poor electrical conductivity and capacity retention hinder the practical application and have to be overcome urgently for the increasing demand for storage technologies. Herein, a new BRG system composed of bimetallic oxide/rhodamine B (RB)/reduced graphene oxide (RGO) was prepared through the facile self-sacrificing template of the precursor polyoxometalate (POM) composites POMs/RB/RGO (PRG). RB not only acts as a cationic mediator to facilitate the loading of POMs on graphene for conversion to oxides but also promotes the formation of uniform nanorods on the RGO. The prepared composite FeV3O8-RB/RGO-1 as the cathode exhibits superior cycling stability (specific capacity of 225 mA h g-1 at 100 mA g-1) and elastic rate capabilities for LIBs. What is more, the new PRG precursor provides versatile possibilities for the design of oxide composites from the self-sacrificing template of POMs-based composites with abundant architectural designs and compositions for the energy storage system.

Correction: Arabidopsis WRKY6 Transcription Factor Acts as a Positive Regulator of Abscisic Acid Signaling during Seed Germination and Early Seedling Development.

[This corrects the article DOI: 10.1371/journal.pgen.1005833.].

Therapeutic potential and research progress of diosgenin for lipid metabolism diseases.

Diosgenin, a steroidal saponin, is a natural product found in many plants. Diosgenin has a wide range of pharmacological activities, and has been used to treat cancer, nervous system diseases, inflammation, and infections. Numerous studies have shown that diosgenin has potential therapeutic value for lipid metabolism diseases via various pathways and mechanisms, such as controlling lipid synthesis, absorption, and inhibition of oxidative stress. These mechanisms and pathways have provided ideas for researchers to develop related drugs. In this review, we focus on data from animal and clinical studies, summarizing the toxicity of diosgenin, its pharmacological mechanism, recent research advances, and the related mechanisms of diosgenin as a drug for the treatment of lipid metabolism, especially in obesity, hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and diabetes. This systematic review will briefly describe the advantages of diosgenin as a potential therapeutic drug and seek to enhance our understanding of the pharmacological mechanism, recipe-construction, and the development of novel therapeutics against lipid metabolism diseases.

Genome-Wide Analysis of the RAV Gene Family in Wheat and Functional Identification of TaRAV1 in Salt Stress.

RAV transcription factors (TFs) are unique to higher plants and contain both B3 and APETALA2 (AP2) DNA binding domains. Although sets of RAV genes have been identified from several species, little is known about this family in wheat. In this study, 26 RAV genes were identified in the wheat genome. These wheat RAV TFs were phylogenetically clustered into three classes based on their amino acid sequences. A TaRAV gene located on chromosome 1D was cloned and named TaRAV1. TaRAV1 was expressed in roots, stems, leaves, and inflorescences, and its expression was up-regulated by heat while down-regulated by salt, ABA, and GA. Subcellular localization analysis revealed that the TaRAV1 protein was localized in the nucleus. The TaRAV1 protein showed DNA binding activity in the EMSA assay and transcriptional activation activity in yeast cells. Overexpressing TaRAV1 enhanced the salt tolerance of Arabidopsis and upregulated the expression of SOS genes and other stress response genes. Collectively, our data suggest that TaRAV1 functions as a transcription factor and is involved in the salt stress response by regulating gene expression in the SOS pathway.

MYB77 regulates high-affinity potassium uptake by promoting expression of HAK5.

In Arabidopsis, the high-affinity K+ transporter HAK5 is the major pathway for root K+ uptake when below 100 µM; HAK5 responds to Low-K+ (LK) stress by strongly and rapidly increasing its expression during K+ -deficiency. Therefore, positive regulators of HAK5 expression have the potential to improve K+ uptake under LK. Here, we show that mutants of the transcription factor MYB77 share a LK-induced leaf chlorosis phenotype, lower K+ content, and lower Rb+ uptake of the hak5 mutant, but not the shorter root growth, and that overexpression of MYB77 enhanced K+ uptake and improved tolerance to LK stress. Furthermore, we demonstrated that MYB77 positively regulates the expression of HAK5, by binding to the HAK5 promoter and enhances high-affinity K+ uptake of roots. As such, our results reveal a novel pathway for enhancing HAK5 expression under LK stress, and provides a candidate for increasing the tolerance of plants to LK.

SEanalysis: a web tool for super-enhancer associated regulatory analysis.

Super-enhancers (SEs) have prominent roles in biological and pathological processes through their unique transcriptional regulatory capability. To date, several SE databases have been developed by us and others. However, these existing databases do not provide downstream or upstream regulatory analyses of SEs. Pathways, transcription factors (TFs), SEs, and SE-associated genes form complex regulatory networks. Therefore, we designed a novel web server, SEanalysis, which provides comprehensive SE-associated regulatory network analyses. SEanalysis characterizes SE-associated genes, TFs binding to target SEs, and their upstream pathways. The current version of SEanalysis contains more than 330 000 SEs from more than 540 types of cells/tissues, 5042 TF ChIP-seq data generated from these cells/tissues, DNA-binding sequence motifs for ∼700 human TFs and 2880 pathways from 10 databases. SEanalysis supports searching by either SEs, samples, TFs, pathways or genes. The complex regulatory networks formed by these factors can be interactively visualized. In addition, we developed a customizable genome browser containing >6000 customizable tracks for visualization. The server is freely available at http://licpathway.net/SEanalysis.

Application of R2* and Apparent Diffusion Coefficient in Estimating Tumor Grade and T Category of Bladder Cancer.

OBJECTIVE. The objective of our study was to compare the feasibility of R2* and apparent diffusion coefficient (ADC) for differentiating tumor grade and T category of bladder cancer. SUBJECTS AND METHODS. In this prospective study, 58 patients with pathologically confirmed bladder cancers underwent pretreatment T2*-weighted imaging and DWI on a 3-T MRI unit. The apparent transverse relaxation rate R2*, which is derived from T2*-weighted imaging, and ADC, which is derived from DWI, were calculated and compared between low- and high-grade bladder cancers as well as between non-muscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs) using the Mann-Whitney U test. The diagnostic performances of R2*, ADC, and the combination of R2* and ADC were evaluated through an ROC analysis. RESULTS. Significant differences were found in R2* (mean ± SD, 16.55 ± 5.54 vs 20.96 ± 7.75 s-1; p = 0.001) and ADC (1.62 ± 0.31 vs 1.33 ± 0.21 × 10-3 mm2/s; p < 0.001) between lowand high-grade bladder cancers. R2* was significantly higher (22.56 ± 8.41 vs 18.06 ± 6.46 s-1; p = 0.008) and ADC was considerably lower (1.21 ± 0.18 vs 1.53 ± 0.27 × 10-3 mm2/s; p < 0.001) in MIBCs than in NMIBCs. The AUCs for differentiating low-from high-grade groups were 0.714 using R2* and 0.779 using ADC. AUCs for distinguishing between NMIBC and MIBC groups using R2* and ADC were 0.682 and 0.850, respectively. CONCLUSION. In addition to ADC, R2* can be used as a quantitative imaging biomarker to provide additional information for tumor characterization of bladder cancer.

Arabidopsis WRKY6 Transcription Factor Acts as a Positive Regulator of Abscisic Acid Signaling during Seed Germination and Early Seedling Development.

The phytohormone abscisic acid (ABA) plays important roles during seed germination and early seedling development. Here, we characterized the function of the Arabidopsis WRKY6 transcription factor in ABA signaling. The transcript of WRKY6 was repressed during seed germination and early seedling development, and induced by exogenous ABA. The wrky6-1 and wrky6-2 mutants were ABA insensitive, whereas WRKY6-overexpressing lines showed ABA-hypersensitive phenotypes during seed germination and early seedling development. The expression of RAV1 was suppressed in the WRKY6-overexpressing lines and elevated in the wrky6 mutants, and the expression of ABI3, ABI4, and ABI5, which was directly down-regulated by RAV1, was enhanced in the WRKY6-overexpressing lines and repressed in the wrky6 mutants. Electrophoretic mobility shift and chromatin immunoprecipitation assays showed that WRKY6 could bind to the RAV1 promoter in vitro and in vivo. Overexpression of RAV1 in WRKY6-overexpressing lines abolished their ABA-hypersensitive phenotypes, and the rav1 wrky6-2 double mutant showed an ABA-hypersensitive phenotype, similar to rav1 mutant. Together, the results demonstrated that the Arabidopsis WRKY6 transcription factor played important roles in ABA signaling by directly down-regulating RAV1 expression.

A flipped classroom method based on a small private online course in physiology.

A small private online course (SPOC) supports blended learning on a small scale, enabling students to have a more comprehensive and deeper learning experience. It also provides instructors with a flexible and feasible model to better understand the students' learning needs and to supervise students' learning behaviors. In this study, we adopted SPOC flipped classroom blended teaching in the physiology course for clinical undergraduate students of Kunming Medical University. Compared with the control group [lecture-based learning (LBL)], the SPOC flipped classroom method significantly increased the scores of students in the preclass test (65.13 ± 12.45 vs. 53.46 ± 8.09, SPOC vs. LBL) and postclass test (80.43 ± 14.29 vs. 69.01 ± 12.81, SPOC vs. LBL), which is induced by students' increased interest in self-learning. More importantly, the significant difference between the preclass scores of the two groups suggested that the video lecture-based preview is more effective than the textbook-based preview. The study indicated that the SPOC flipped classroom was effective in enhancing the examination scores of students, reflecting an improved learning efficiency and a deeper understanding of the knowledge. In summary, the flipped classroom based on SPOC improves learning outcomes compared with LBL and has a wide application in the learning of basic medical courses.