Both Xp11 translocation renal cell carcinomas and the corresponding mesenchymal neoplasms are characterized by a variety of gene fusions involving TFE3. It has been known that tumors with different ...gene fusions may have different clinicopathologic features; however, further in-depth investigations of subtyping Xp11 translocation-associated cancers are needed in order to explore more meaningful clinicopathologic correlations. A total of 22 unusual cases of Xp11 translocation-associated cancers were selected for the current study; 20 cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners. RNA sequencing identified 17 of 20 cases (85%) with TFE3-associated gene fusions, including 4 ASPSCR1/ASPL-TFE3, 3 PRCC-TFE3, 3 SFPQ/PSF-TFE3, 1 NONO-TFE3, 4 MED15-TFE3, 1 MATR3-TFE3, and 1 FUBP1-TFE3. The results have been verified by fusion fluorescence in situ hybridization (FISH) assays or reverse transcriptase polymerase chain reaction (RT-PCR). The remaining 2 cases with specific pathologic features highly suggestive of MED15-TFE3 renal cell carcinoma were identified by fusion FISH assay. We provide the detailed morphologic and immunophenotypic description of the MED15-TFE3 renal cell carcinomas, which frequently demonstrate extensively cystic architecture, similar to multilocular cystic renal neoplasm of low malignant potential, and expressed cathepsin K and melanotic biomarker Melan A. This is the first time to correlate the MED15-TFE3 renal cell carcinoma with specific clinicopathologic features. We also report the first case of the corresponding mesenchymal neoplasm with MED15-TFE3 gene fusion. Additional novel TFE3 gene fusion partners, MATR3 and FUBP1, were identified. Cases with ASPSCR1-TFE3, SFPQ-TFE3, PRCC-TFE3, and NONO-TFE3 gene fusion showed a wide variability in morphologic features, including invasive tubulopapillary pattern simulating collecting duct carcinoma, extensive calcification and ossification, and overlapping and high columnar cells with nuclear grooves mimicking tall cell variant of papillary thyroid carcinoma. Furthermore, we respectively evaluated the ability of TFE3 immunohistochemistry, TFE3 FISH, RT-PCR, and RNA sequencing to subclassify Xp11 translocation-associated cancers. In summary, our study expands the list of TFE3 gene fusion partners and the clinicopathologic features of Xp11 translocation-associated cancers, and highlights the importance of subtyping Xp11 translocation-associated cancers combining morphology, immunohistochemistry, and multiple molecular techniques.
Matrix factorization as a popular technique for collaborative filtering in recommendation systems computes the latent factors for users and items by decomposing a user-item rating matrix. Most matrix ...factorization methods including probabilistic matrix factorization that projects (parameterized) users and items probabilistic matrices to maximize their inner product suffer from data sparsity and result in poor latent representations of users and items. To alleviate these problems, we propose a novel deep generative model, namely Neural Variational Matrix Factorization, that incorporates side information (features) of both users and items to capture better latent representations of them for more effective collaborative-filtering recommendation. Our model consists of two end-to-end variational autoencoder neural networks, namely user neural network and item neural network respectively, that are capable of learning complex nonlinear distributed representations of users and items through our proposed variational inference. We present a Stochastic Gradient Variational Bayes estimator to estimate the intractable posterior distributions of latent factors of users and items and parameters of our model, and derive the variational evidence lower bounds of the model. Experiments conducted on three publicly available datasets show that our model significantly outperforms the state-of-the-art methods on recommendation accuracy measured by Hit Ratio and Normalized Discounted Cumulative Gain respectively.
The tapetum plays a critical role during the development and maturation of microspores. DYSFUNCTIONAL TAPETUM 1 (DYT1) is essential for early tapetal development. Here, we determined that the ...promoter region (−550 to −463 bp) contains indispensable cis‐elements for DYT1 expression. Although DYT1 transcripts can be detected in both meiocytes and tapetal cells, localization of DYT1–GFP demonstrated that DYT1 is strictly located in tapetal cells during microsporogenesis. Chromatin immunoprecipitation (ChIP) analysis revealed that DYT1 directly binds the promoter region of Defective in Tapetal Development and Function 1 (TDF1), a transcription factor essential for tapetum development. When TDF1 driven by the DYT1 promoter is expressed in a dyt1 mutant, the expression of the transcription factors AMS, MS188/MYB80, TEK and MS1 and the pollen wall‐related genes are restored. Although the pollen wall is not formed and the microspores are ruptured, DIOC₂staining showed that fatty acids, the precursors of the pollen wall, were synthesized in the transgenic lines. These results indicate that DYT1 regulates the expression of AMS, MS188/MYB80, TEK and MS1 for pollen wall formation, primarily via TDF1.
Abstract
The Su–Schrieffer–Heeger (SSH) model perhaps is the easiest and the most basic model for topological excitations. Many variations and extensions of the SSH model have been proposed and ...explored to better understand both fundamental and novel aspects of topological physics. The SSH4 model has been proposed theoretically as an extended SSH model with higher dimension (the internal dimension changes from two to four). It has been proposed that the winding number in this system can be determined through a higher-dimensional extension of the mean chiral displacement measurement, however, this has not yet been verified in experiment. Here, we report the realization of this model with ultracold atoms in a momentum lattice. We verify the winding number through measurement of the mean chiral displacement in a system with higher internal dimension, we map out the topological phase transition in this system, and we confirm the topological edge state by observation of the quench dynamics when atoms are initially prepared at the system boundary.
Jasmonic acid (JA) is well known to promote lateral root formation but the mechanisms by which JA signalling is integrated into the pathways responsible for lateral root formation, and how it ...interacts with auxin in this process remains poorly understood. Here, we report that the highly JA-responsive ethylene response factor 109 (ERF109) mediates cross-talk between JA signalling and auxin biosynthesis to regulate lateral root formation in Arabidopsis. erf109 mutants have fewer lateral roots under MeJA treatments compared with wild type whereas ERF109 overexpression causes a root phenotype that resembles those of auxin overproduction mutants. ERF109 binds directly to GCC-boxes in the promoters of ASA1 and YUC2, which encode two key enzymes in auxin biosynthesis. Thus, our study reveals a molecular mechanism for JA and auxin cross-talk during JA-induced lateral root formation.
Summary
The sexine layer of pollen grain is mainly composed of sporopollenins. The sporophytic secretory tapetum is required for the biosynthesis of sporopollenin. Although several enzymes involved ...in sporopollenin biosynthesis have been reported, the regulatory mechanism of these enzymes in tapetal layer remains elusive. ABORTED MICROSPORES (AMS) and MALE STERILE 188/MYB103/MYB80 (MS188/MYB103/MYB80) are two tapetal cell‐specific transcription factors required for pollen wall formation. AMS functions upstream of MS188. Here we report that AMS and MS188 target the CYP703A2 gene, which is involved in sporopollenin biosynthesis. We found that AMS and MS188 were localized in tapetum while CYP703A2 was localized in both tapetum and locule. Chromatin immunoprecipitation (ChIP) showed that MS188 directly bound to the promoter of CYP703A2 and luciferase‐inducible assay showed that MS188 activated the expression of CYP703A2. Yeast two‐hybrid and electrophoretic mobility shift assays (EMSAs) further demonstrated that MS188 complexed with AMS. The expression of CYP703A2 could be partially restored by the elevated levels of MS188 in the ams mutant. Therefore, our data reveal that MS188 coordinates with AMS to activate CYP703A2 in sporopollenin biosynthesis of plant tapetum.
Significance Statement
Sporopollenin in the pollen wall is produced by the tapetum, but how genes encoding the required biosynthetic enzymes are regulated is unclear. Here we show that two transcription factors, MS188 and AMS, positively regulate the gene encoding CYP703A2, a cytochrome P450 required for sporopollenin biosynthesis.
Regulatory T (Treg) cells are essential for maintaining immune homeostasis and tolerance, but the mechanisms regulating the stability and function of Treg cells have not been fully elucidated. Here ...we show SUMO-specific protease 3 (SENP3) is a pivotal regulator of Treg cells that functions by controlling the SUMOylation and nuclear localization of BACH2. Treg cell-specific deletion of Senp3 results in T cell activation, autoimmune symptoms and enhanced antitumor T cell responses. SENP3-mediated BACH2 deSUMOylation prevents the nuclear export of BACH2, thereby repressing the genes associated with CD4
T effector cell differentiation and stabilizing Treg cell-specific gene signatures. Notably, SENP3 accumulation triggered by reactive oxygen species (ROS) is involved in Treg cell-mediated tumor immunosuppression. Our results not only establish the role of SENP3 in the maintenance of Treg cell stability and function via BACH2 deSUMOylation but also clarify the function of SENP3 in the regulation of ROS-induced immune tolerance.
Pulmonary sclerosing pneumocytoma (PSP) is a rare benign tumor. Although lymph node metastasis has been reported, it is still considered benign. No malignant transformation has been reported. This is ...the first case of malignant transformation of both cuboidal surface cells and stromal round cells.
A 64-year-old male had been complaining of intermittent hemoptysis several times per day for eight months. Chest computed tomography scan showed parenchymal infiltration with cystic lesion in the right lower lobe accompanied by enlarged right hilar lymph nodes. Lobectomy and systemic lymph node dissection was performed. On grossly pathological examination, the lesion was 50 mm from the bronchial stump. It was a mixture of both cystic and solid components and 30 mm * 20 mm in size with unclear border. Microscopically, the cuboidal surface cells transformed to adenocarcinoma. The stromal round cells also had a malignant transformation. The Ki-67 proliferation index in malignant cuboidal surface cells and stromal round cells were 70 and 55%, respectively. Furthermore, E-cadherin was negative in primary tumor but positive in metastatic lymph node, which suggested that the mesenchymal to epithelial transition may play an important role in lymph node metastasis.
To our knowledge, we present the first case of malignant transformation of both cuboidal surface cells and stromal round cells in PSP. The process of mesenchymal to epithelial transition may play an important role in lymph node metastasis.
Objective
This study aimed to investigate the value of high‐flow nasal cannula (HNFC) oxygen therapy in treating patients with severe novel coronavirus pneumonia (COVID‐19).
Methods
The clinical data ...of 22 patients with severe COVID‐19 were collected. The heart rate (HR), respiratory rate (RR) and oxygenation index (PO2/FiO2) at 0, 6, 24 and 72 hours after treatment were compared between the HFNC oxygen therapy group and the conventional oxygen therapy (COT) group. In addition, the white blood cell (WBC) count, lymphocyte (L) count, C‐reactive protein (CRP) and procalcitonin (PCT) were compared before and at 72 hours after oxygen therapy treatment.
Results
The differences at 0 hours between the two groups were not statistically significant. Compared with COT group,in the HFNC oxygen therapy group, HR, RR and PaO2/FiO2 were better at 6 hours after treatment, PaO2/FiO2 was better at 24 and 72 hours. After 72 hours, L and CRP had improved in the HFNC oxygen therapy group compared with the COT group, but the differences in WBC and PCT were not statistically significant. The length of stay in the intensive care unit (ICU) and the total length of hospitalization was shorter in the HFNC oxygen therapy group than in the COT group.
Conclusion
Compared with COT, early application of HFNC oxygen therapy in patients with severe COVID‐19 can improve oxygenation and RR, and HFNC oxygen therapy can improve the infection indexes of patients and reduce the length of stay in the ICU of patients. Therefore, it has high clinical application value.
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