Multiparametric MRI-Based Machine Learning Models for the Characterization of Cystic Renal Masses Compared to the Bosniak Classification, Version 2019: A Multicenter Study.

RATIONALE AND OBJECTIVE: Accurate differentiation between benign and malignant cystic renal masses (CRMs) is challenging in clinical practice. This study aimed to develop MRI-based machine learning models for differentiating between benign and malignant CRMs and compare the best-performing model with the Bosniak classification, version 2019 (BC, version 2019). METHODS: Between 2009 and 2021, consecutive surgery-proven CRM patients with renal MRI were enrolled in this multicenter study. Models were constructed to differentiate between benign and malignant CRMs using logistic regression (LR), random forest (RF), and support vector machine (SVM) algorithms, respectively. Meanwhile, two radiologists classified CRMs into I-IV categories according to the BC, version 2019 in consensus in the test set. A subgroup analysis was conducted to investigate the performance of the best-performing model in complicated CRMs (II-IV lesions in the test set). The performances of models and BC, version 2019 were evaluated using the area under the receiver operating characteristic curve (AUC). Performance was statistically compared between the best-performing model and the BC, version 2019. RESULTS: 278 and 48 patients were assigned to the training and test sets, respectively. In the test set, the AUC and accuracy of the LR model, the RF model, the SVM model, and the BC, version 2019 were 0.884 and 75.0%, 0.907 and 83.3%, 0.814 and 72.9%, and 0.893 and 81.2%, respectively. Neither the AUC nor the accuracy of the RF model that performed best were significantly different from the BC, version 2019 (P = 0.780, P = 0.065). The RF model achieved an AUC and accuracy of 0.880 and 81.0% in complicated CRMs. CONCLUSIONS: The MRI-based RF model can accurately differentiate between benign and malignant CRMs with comparable performance to the BC, version 2019, and has good performance in complicated CRMs, which may facilitate treatment decision-making and is less affected by interobserver disagreements.

Assessment of Ki-67 proliferation index in prognosis prediction in patients with nonmetastatic clear cell renal cell carcinoma and tumor thrombus.

PURPOSE: To determine the optimal cut-off value of Ki-67 for predicting the survival of patients with clear cell renal cell carcinoma (ccRCC) and tumor thrombus and to explore the correlation between Ki-67 expression and pathological features. PATIENTS AND METHODS: We retrospectively analyzed Ki-67 immunohistochemical staining of ccRCC and tumor thrombus resected from February 2006 to February 2022. The survival rate was evaluated using the Kaplan-Meier method. The optimal cut-off value of the Ki-67 expression for predicting survival was determined by the minimum P-value method. Clinicopathological data were compared based on Ki-67 status (low versus high expression). Univariate and multivariate Cox regression analysis was used to explore independent predictors. RESULTS: A total of 202 patients (median age, 58 years [IQR, 52-65 years], 147 men) with ccRCC and tumor thrombus were included in the study. The optimal cut-off value of Ki-67 for predicting survival was 30%. 159 (78.7%) and 43 (21.3%) patients were included in the low-expression and high-expression groups. Patients with Ki-67 high expression had significantly worse recurrence-free survival (P < 0.001) and cancer-specific survival (P < 0.001). Ki-67 high expression was associated with adverse pathological features, including tumor necrosis, ISUP nuclear grade, sarcomatoid differentiation, perirenal fat invasion, renal pelvis invasion, and inferior vena cava wall invasion (all P < 0.050). Ki-67 expression ≥ 30% (P = 0.016), tumor side (P = 0.003), diabetes (P = 0.040), blood loss (P = 0.016), inferior vena cava wall invasion (P = 0.016), and sarcomatoid differentiation (P = 0.014) were independent predictors of cancer-specific survival. CONCLUSION: The optimal cut-off level of Ki-67 in predicting the prognosis of ccRCC and tumor thrombus was 30%. The high expression of Ki-67 was associated with the aggressive pathological phenotype and poor prognosis.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging and Venous Tumor Thrombus Consistency in Renal Cell Carcinoma.

BACKGROUND: Venous tumor thrombus (VTT) consistency of renal cell carcinoma (RCC) is an important consideration in nephrectomy plus thrombectomy. However, evaluation of VTT consistency through preoperative MR imaging is lacking. PURPOSE: To evaluate VTT consistency of RCC through intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters (Dt , Dp , f, and ADC) and the apparent diffusion coefficient (ADC) value. STUDY TYPE: Retrospective. POPULATION: One hundred and nineteen patients (aged 55.8 ± 11.5 years, 85 male) with histologically-proven RCC and VTT who underwent radical resection. FIELD STRENGTH/SEQUENCES: 3.0-T; two-dimensional single-shot diffusion-weighted echo planar imaging sequence at 9 b-values (0-800 s/mm2 ). ASSESSMENT: IVIM parameters and ADC values of the primary tumor and the VTT were calculated. The VTT consistency (friable vs. solid) was determined through intraoperative findings of two urologists. The accuracy of VTT consistency classification based on the individual IVIM parameters of primary tumors and of VTT, and based on models combining parameters, was assessed. Type of operation, intra-operative blood loss, and operation length were recorded. STATISTICAL TESTS: Shapiro-Wilk test; Mann-Whitney U test; Student's t-test; Chi-square test; Receiver operating characteristic (ROC) analysis. Statistical significance level was P < 0.05. RESULTS: Of the enrolled 119 patients, 33 patients (27.7%) had friable VTT. Patients with friable VTT were significantly more likely to experience open surgery, have significantly more intraoperative blood loss, and significantly longer operative duration. The area under the ROC curve (AUC) values of Dt of the primary tumor and VTT in classifying VTT consistency were 0.758 (95% CI 0.671-0.832) and 0.712 (95% CI 0.622-0.792), respectively. The AUC value of the model combining Dp and Dt of VTT was 0.800 (95% CI 0.717-0.868). Furthermore, the AUC of the model combining Dp and Dt of VTT and Dt of the primary tumor was 0.886 (95% CI 0.814-0.937). CONCLUSION: IVIM-derived parameters had the potential to predict VTT consistency of RCC. EVIDENCE LEVEL: 3 Technical Efficacy: Stage 2.

Differentiation between renal epithelioid angiomyolipoma and clear cell renal cell carcinoma using clear cell likelihood score.

PURPOSE: Clear cell likelihood score (ccLS) may be a reliable diagnostic method for distinguishing renal epithelioid angiomyolipoma (EAML) and clear cell renal cell carcinoma (ccRCC). In this study, we aim to explore the value of ccLS in differentiating EAML from ccRCC. METHODS: We performed a retrospective analysis in which 27 EAML patients and 60 ccRCC patients underwent preoperative magnetic resonance imaging (MRI) at our institution. Two radiologists trained in the ccLS algorithm scored independently and the consistency of their interpretation was evaluated. The difference of the ccLS score was compared between EAML and ccRCC in the whole study cohort and two subgroups [small renal masses (SRM; ≤ 4 cm) and large renal masses (LRM; > 4 cm)]. RESULTS: In total, 87 patients (59 men, 28 women; mean age, 55±11 years) with 90 renal masses (EAML: ccRCC = 1: 2) were identified. The interobserver agreement of two radiologists for the ccLS system to differentiate EAML from ccRCC was good (k = 0.71). The ccLS score in the EAML group and the ccRCC group ranged from 1 to 5 (73.3% in scores 1-2) and 2 to 5 (76.7% in scores 4-5), respectively, with statistically significant differences (P < 0.001). With the threshold value of 2, ccLS can distinguish EAML from ccRCC with the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 87.8%, 95.0%, 73.3%, 87.7%, and 88.0%, respectively. The AUC (area under the curve) was 0.913. And the distribution of the ccLS score between the two diseases was not affected by tumor size (P = 0.780). CONCLUSION: The ccLS can distinguish EAML from ccRCC with high accuracy and efficiency.

Assessment of the Added Value of Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging in Identifying Non-Diabetic Renal Disease in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear. PURPOSE: To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. STUDY TYPE: Prospective. POPULATION: Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). FIELD STRENGTH/SEQUENCE: 3 T/ T2 weighted imaging (T2 WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: The parameters derived from IVIM-DWI (true diffusion coefficient [D], pseudo-diffusion coefficient [D*], and pseudo-diffusion fraction [f]) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy [DR], fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant. RESULTS: The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively). DATA CONCLUSION: The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Haspin balances the ratio of asymmetric cell division through Wnt5a and regulates cell fate decisions in mouse embryonic stem cells.

Many different types of stem cells utilize asymmetric cell division (ACD) to produce two daughter cells with distinct fates. Haspin-catalyzed phosphorylation of histone H3 at Thr3 (H3T3ph) plays important roles during mitosis, including ACD in stem cells. However, whether and how Haspin functions in ACD regulation remains unclear. Here, we report that Haspin knockout (Haspin-KO) mouse embryonic stem cells (mESCs) had increased ratio of ACD, which cumulatively regulates cell fate decisions. Furthermore, Wnt5a is significantly downregulated due to decreased Pax2 in Haspin-KO mESCs. Wnt5a knockdown mESCs phenocopied Haspin-KO cells while overexpression of Wnt5a in Haspin-KO cells rescued disproportionated ACD. Collectively, Haspin is indispensable for mESCs to maintain a balanced ratio of ACD, which is essential for normal development and homeostasis.

Nutrient-Sensing Ghrelin Receptor in Macrophages Modulates Bisphenol A-Induced Intestinal Inflammation in Mice.

Bisphenols are environmental toxins with endocrine disruptor activity, yet bisphenol A (BPA) and its analogs are still widely used in manufacturing plastic products. There is evidence showing that BPA elicits inflammation in humans and animals, but the target cell types of BPA are not well understood. In this study, we sought to determine BPA's direct effect on macrophages and BPA immunotoxicity in mouse intestine. Ghrelin is an important nutrient-sensing hormone, acting through its receptor growth hormone secretagogue receptor (GHSR) to regulate metabolism and inflammation. We found that BPA promotes intestinal inflammation, showing increased infiltrating immune cells in colons and enhanced expression of Ghsr and pro-inflammatory cytokines and chemokines, such as Il6 and Ccl2, in colonic mucosa. Moreover, we found that both long- and short-term BPA exposure elevated pro-inflammatory monocytes and macrophages in mouse peripheral blood mononuclear cells (PBMC) and peritoneal macrophages (PM), respectively. To determine the role of GHSR in BPA-mediated inflammation, we generated Ghsr deletion mutation in murine macrophage RAW264.7 using CRISPR gene editing. In wild-type RAW264.7 cells, the BPA exposure promotes macrophage pro-inflammatory polarization and increases Ghsr and cytokine/chemokine Il6 and Ccl2 expression. Interestingly, Ghsr deletion mutants showed a marked reduction in pro-inflammatory cytokine/chemokine expression in response to BPA, suggesting that GHSR is required for the BPA-induced pro-inflammatory response. Further understanding how nutrient-sensing GHSR signaling regulates BPA intestinal immunotoxicity will help design new strategies to mitigate BPA immunotoxicity and provide policy guidance for BPA biosafety.

UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling.

Emerging evidence has demonstrated that ubiquitin conjugating enzyme E2 J1 (UBE2J1) exerts pivotal function in many cancers. UBE2J1 was reported to be dysregulated in endometrial cancer (EC). This study was designed to further investigate the regulatory character and mechanism of UBE2J1 in EC. Bioinformatic tools and databases were used to analyze gene expression pattern and gene expression correlation in EC tissues, and the prognosis of EC patients. Gene expression was evaluated by reverse-transcription quantitative polymerase chain reaction. Western blot was used for protein level detection. In vitro cell apoptosis was detected by flow cytometry analyses and TUNEL assays. In vivo cell apoptosis was evaluated by detecting Bax and Bcl-2 expression in tumor tissues via immunohistochemical and western blot analyses. In this study, UBE2J1 knockdown promoted cell apoptosis in EC cells and in mouse models of EC. PI3K and AKT expression is positively correlated with UBE2J1 level and is related to poor prognosis of EC patients. UBE2J1 knockdown repressed the PI3K/AKT pathway both in vitro and in vivo. UBE2J1 downregulation decreased MDM2 expression, but increased p53 expression. MDM2 overexpression reverses the promotion of UBE2J1 knockdown on cell apoptosis in EC. Overall, UBE2J1 knockdown induces cell apoptosis in EC by inactivating the PI3K/AKT signaling and suppressing the MDM2/p53 signaling.

Dataset for transcriptomic, H3K9ac and H3K9me3 profiles during cardiac regeneration.

Acetylation and tri-methylation of histone H3 lysine 9 (H3K9ac and H3K9me3) play an interactive regulatory role in the epigenetic regulation of gene expression during heart development and cardiovascular disease, but little is known about their possible role in heart regeneration. Here we utilized genome-wide high-throughput RNA sequencing (RNA-seq) and chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) for H3K9ac and H3K9me3, carried out on regenerative cardiac tissues at different days post amputation in zebrafish (Danio rerio) to investigate dynamic changes in gene expression and the epigenetic landscape of H3K9ac and H3K9me3. The STAR, Bowtie2, MACS2, and deepTools2 were mainly used for RNA-Seq or ChIP-seq data analysis. In this article, we present detailed information on experiment design, data generation, quality assessment and processing pipeline. Raw reads of the RNA-seq and ChIP-seq data have been deposited at the NCBI GEO repository with the accession number GSE158104. Our data will be a valuable resource for the elucidation of H3K9ac and H3K9me3 involvement in the regulation of gene transcription during cardiac regeneration.

Global changes in chromatin accessibility and transcription in growth hormone-secreting pituitary adenoma.

PURPOSE: Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, causing increased morbidity and mortality. Previous studies have investigated the transcription of GHPA. However, the gene regulatory landscape has not been fully characterized. The objective of our study was to unravel the changes in chromatin accessibility and transcription in GHPA. METHODS: Six patients diagnosed with GHPA in the Department of Neurosurgery at Huashan Hospital were enrolled in our study. Primary pituitary adenoma tissues and adjacent normal pituitary specimens with no morphologic abnormalities from these six patients were obtained at surgery. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were applied to investigate the underlying relationship between gene expression and chromatin accessibility changes in GHPA. RESULTS: Totally, 1528 differential expression genes (DEGs) were identified by transcriptomics analyses, including 725 up-regulated and 803 down-regulated. Further, we obtained 64 significantly DEGs including 10 DEGs were elevated and 54 DEGs were negligibly expressed in tumors tissues. The up-regulated DEGs were mainly involved in terms related to synapse formation, nervous system development and secretory pathway. In parallel, 3916 increased and 2895 decreased chromatin-accessible regions were mapped by ATAC-seq. Additionally, the chromatin accessible changes were frequently located adjacent to transcription factor CTCF and Rfx2 binding site. CONCLUSIONS: Our results are the first to demonstrate the landscape of chromatin accessibility in GHPA, which may contribute to illustrate the underlying transcriptional regulation mechanism of this disease.

Keratin5-cytoskeleton-BMP4 network regulates cell phenotype conversions during cardiac regeneration.

The reconstruction of a blood supply system and myocardial recovery from inflamamtory reactions in the infract zone remains a challenge in cardiac regeneration after myocardial infarction. Here, we observed that the local myocardial cells and the clotted blood cells undergo cellular remodeling via cytoplasmic exocytosis and nuclear reorganization in zebrafish hearts after resection of the ventricular apex. The subsequent tissue regeneration processes were visualized by detection of the spatiotemporal expression of three tissue specific genes (α-SMA which marks for vasculature/fibrogenesis, Flk1for angiogenesis/hematopoiesis, and Pax3a for remusculogensis), and two histone modification markers (H3K9Ac and H3K9Me3 for chromatin remodeling). By analyzing the composition of the blastema tissue fractions we found that Krt5 peptide could promote F-actin assembly, BMP4-pSmad2/5/8 signaling activity, and H3K9Me3-mediated chromatin accessibility at the blastema representative genes in the cultured zebrafish embryonic fibroblasts. Further in vivo tests demonstrated that Krt5 interacted with beta actin, and promoted Gata3 expression and Flk1-GFP marked blastema angiogenesis. These results proposed a new Krt5-cytoskeleton-BMP4 mechanotransduction mechanism in the epithelial-dependent and cell phenotype conversion-based tissue regeneration.

Analysis of Related Factors of Coping Styles in Infertile Patients in Central China.

Objective: To investigate the psychosocial factors, including personality characteristics, coping style, social support and alexithymia of infertile patients, and explore the relevant factors regarding the medical coping style choice of infertile patients in central China. Methods: Sixty infertile patients in the reproductive medicine centre in our hospital were investigated using a self-made general situation questionnaire; internal control, powerful others and opportunities scale; social support rating scale; and medical coping questionnaire, and the data was analysed. Results: Of the 60 infertile patients, 57 (95%) were female, with an average age of 27.85 ± 14.52 years old, and 42 (70%) had secondary infertility. The score of the face dimension was lower than the norm (19.17 ± 2.18 vs 19.43 ± 3.82, P = 0.012), and those of the avoidance (15.98 ± 2.43 vs 14.41 ± 2. 94, P = 0.030) and yield (9.48 ± 3.19 vs 8.83 ± 3.19, P = 0.012) dimensions were higher than the norm. The multiple linear regression analysis showed that internal control and the utilisation of support were influencing factors for the coping style (R2 = 0.271, adjusted R2 = 0.144, F = 9.827, P < 0.001), and internal control was the influencing factor for the avoidance coping style (R2 = 0.024, adjusted R2 = 0.021, F = 3.363, P = 0.014). The education level, opportunity and utilisation of support factors influenced the yield dimension (R2 = 0.087, adjusted R2 = 0.076, F = 7.749, P < 0.001). Conclusion: Considering the association between the coping styles and psychosocial factors, it was recommended to formulate targeted intervention strategies based on these influencing factors to guide patients to adopt positive coping styles and achieve good outcomes.

Mucinous tubular and spindle cell carcinomas of the kidney (MTSCC-Ks): CT and MR imaging characteristics.

PURPOSE: To strengthen the recognition of mucinous tubular and spindle cell carcinomas of the kidney (MTSCC-Ks) by analyzing CT and MR imaging findings of MTSCC-Ks. MATERIALS AND METHODS: This study retrospectively enrolled ten patients with pathologically confirmed MTSCC-Ks from 2007 to 2020. The main observed imaging characteristics included growth pattern, signal characteristics on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), hemorrhage, necrosis, cystic degeneration, lipid component, pseudocapsule and the enhancement pattern. Apparent diffusion coefficient (ADC) value of MTSCC-Ks and normal renal cortex were measured, respectively. All imaging features were evaluated in consensus by two genitourinary radiologists. RESULTS: All patients (53.1 ± 6.5 years, male to female, 3:7) presented with a solitary renal tumor with the mean diameter of 3.5 ± 0.4 cm. All lesions showed iso- or slight hypoattenuation on non-contrast CT with no hemorrhage but cystic degeneration (10%) and necrosis (10%). On T2WI, all lesions showed predominantly slight hypointensity with focal hyperintensity. The ADC value of MTSCC-Ks was 0.845 ± 0.017 × 10-3 mm2/s, and ADCtumor-to-ADCrenal cortex value was 0.376 ± 0.084. Pseudocapsules existed in all MTSCC-Ks on MRI. There were seven lesions showed heterogeneous enhancement, while three lesions showed homogeneous enhancement. Among them, six MTSCC-Ks showed slight multiple patchy enhancement (60%) in the corticomedullary phase, while the remaining MTSCC-Ks showed homogeneously slight enhancement (30%) or slightly stratified enhancement (10%). All MTSCC-Ks exhibited slow and progressive enhancement in the late phases. CONCLUSION: Iso- or slight hypoattenuation on CT, slight hypointensity with focal hyperintensity on T2WI, marked diffusion restriction on DWI and ADC map, slight multiple patchy enhancement in the corticomedullary phase, and slow and progressive enhancement in the late phases are the imaging features of MTSCC-Ks, which may facilitate the diagnosis of MTSCC-Ks.

Preventing autosomal-dominant hearing loss in Bth mice with CRISPR/CasRx-based RNA editing.

CRISPR/RfxCas13d (CasRx) editing system can specifically and precisely cleave single-strand RNAs, which is a promising treatment for various disorders by downregulation of related gene expression. Here, we tested this RNA-editing approach on Beethoven (Bth) mice, an animal model for human DFNA36 due to a point mutation in Tmc1. We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1Bth transcript by 90.8%, and the Tmc1 wild type transcript (Tmc1+) by 44.3%. We then injected a newly developed AAV vector (AAV-PHP.eB) based CasRx into the inner ears of neonatal Bth mice, and we found that Tmc1Bth was reduced by 70.2% in 2 weeks with few off-target effects in the whole transcriptome. Consistently, we found improved hair cell survival, rescued hair bundle degeneration, and reduced mechanoelectrical transduction current. Importantly, the hearing performance, measured in both ABR and DPOAE thresholds, was improved significantly in all ages over 8 weeks. We, therefore, have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss, paving way for its further application in many other hereditary diseases in hearing and beyond.

Pretreatments of Broussonetia papyrifera: in vitro assessment on gas and methane production, fermentation characteristic, and methanogenic archaea profile.

OBJECTIVE: The present study was conducted to examine the gas production, fermentation characteristics, nutrient degradation, and methanogenic community composition of a rumen fluid culture with Broussonetia papyrifera (B. papyrifera) subjected to ensiling or steam explosion (SE) pretreatment. METHODS: Fresh B. papyrifera was collected and pretreated by ensiling or SE, which was then fermented with ruminal fluids as ensiled B. papyrifera group, steam-exploded B. papyrifera group, and untreated B. papyrifera group. The gas and methane production, fermentation characteristics, nutrient degradation, and methanogenic community were determined during the fermentation. RESULTS: Cumulative methane production was significantly improved with SE pretreatment compared with ensiled or untreated biomass accompanied with more volatile fatty acids production. After 72 h incubation, SE and ensiling pretreatments decreased the acid detergent fiber contents by 39.4% and 22.9%, and neutral detergent fiber contents by 10.6% and 47.2%, respectively. Changes of methanogenic diversity and abundance of methanogenic archaea corresponded to the variations in fermentation pattern and methane production. CONCLUSION: Compared with ensiling pretreatment, SE can be a promising technique for the efficient utilization of B. papyrifera, which would contribute to sustainable livestock production systems.

Patients with New-Onset Tumor of Severe Coronary Artery Disease May be at a Higher Risk of Arrhythmia.

BACKGROUND: Arrhythmia is one of the causes of death in severe coronary artery disease patients who also suffered from cancer. Our research aims to compare the incidence of arrhythmia between severe coronary artery disease patient with and without new-onset tumor. Methodology. We enrolled 79 patients (December 2019-December 2020) with severe coronary artery disease in this study, and 40 of them were complicated with new-onset tumor. The details of all subjects were thoroughly obtained; the laboratory tests were implemented including creatinine before coronary angiography. The appraisal of the severity of coronary artery disease was applied by Gensini score. The cardiac inspection includes UCG, 12-lead ECG, and Holter monitor. RESULTS: Among them, there were 40 patients in the experimental group and 39 patients in the control group. The difference at the baseline between the two sets of figures was not statistically significant (P > 0.05). The incidence of arrhythmia between the two groups was statistically significant (P < 0.05). CONCLUSIONS: The incidence of arrhythmia in severe coronary artery disease patients who were complicated with new-onset tumor was higher than that in patients with severe coronary artery disease alone, and attention should be paid to arrhythmia before tumor treatment.

A liquid scintillation analysis method for low-level radioactive wastewater.

There is currently general concern over low-level radioactive wastewater from the development of nuclear industry. In this paper, a method based on an ultralow-level liquid scintillation spectrometer for measuring uranium radioactivity in low-level radioactive wastewater is proposed. This method can easily and quickly measure the radioactivity level of uranium in samples and can even distinguish the main isotopes of uranium. The liquid scintillation method directly provides results in units of radioactivity activity concentration, which are more convenient for comparison with relevant national standards to determine whether the emission standards are met. The lowest limit of detection of this method is 0.014 Bq l-1within 600 min.

Molecular cloning and functional characterization of Physcomitrella patens UBC13-UEV1 genes required for Lys63-linked polyubiquitination.

Ubc13 and Ubc/E2 variant (Uev) form a stable heterodimer to mediate Lys63-linked polyubiquitination. Unicellular eukaryotic genomes often contain single UBC13 and UEV gene; however, multiple homologs were found in higher plants. As initial land plants, Physcomitrella patens occupies a key evolutionary position between green algae and higher plants. In this study, we report the identification and functional characterization of two UBC13 and three UEV1 genes from P. patens. Both PpUbc13s form heterodimers with PpUev1B or PpUev1C, which catalyze Lys63-linked polyubiquitination in vitro and functionally complement the yeast ubc13 mms2 null mutant from killing by DNA-damaging agents. In contrast, PpUev1A is unable to interact with Ubc13s and cannot complement the yeast mms2 mutant. Two single mutations, PpUev1A-D12N and ΔCT, barely have any effect; however, the corresponding double mutation makes PpUev1A functional in both heterodimer formation and complementation. This study identifies a critical Uev residue located in the Ubc13-Uev interface and reveals that mosses began to evolve multiple UBC13 and UEV orthologs in order to adapt to the terrestrial environment. The evolutionary significance of PpUEV1A is discussed.

Arabidopsis OTU1, a linkage-specific deubiquitinase, is required for endoplasmic reticulum-associated protein degradation.

Endoplasmic reticulum (ER)-associated degradation (ERAD) is part of the ER protein quality-control system (ERQC), which is critical for the conformation fidelity of most secretory and membrane proteins in eukaryotic organisms. ERAD is thought to operate in plants with core machineries highly conserved to those in human and yeast; however, little is known about the plant ERAD system. Here we report the characterization of a close homolog of human OTUB1 in Arabidopsis thaliana, designated as AtOTU1. AtOTU1 selectively hydrolyzes several types of ubiquitin chains and these activities depend on its conserved protease domain and/or the unique N-terminus. The otu1 null mutant is sensitive to high salinity stress, and particularly agents that cause protein misfolding. It turns out that AtOTU1 is required for the processing of known plant ERAD substrates such as barley powdery mildew O (MLO) alleles by virtue of its association with the CDC48 complex through its N-terminal region. These observations collectively define AtOTU1 as an OTU domain-containing deubiquitinase involved in Arabidopsis ERAD.