Pygopus 2 promotes kidney cancer OS-RC-2 cells proliferation and invasion in vitro and in vivo

AbstractObjectiveHuman Pygopus 2 (Pygo2) was recently discovered to be a component of the Wnt signaling pathway required for β-catenin/Tcf-mediated transcription. But the role of Pygo2 in malignant cell proliferation and invasion has not yet been determined.MethodsLentivirus-mediated small interfering RNA (siRNA) and vector-based overexpression were used to study the function of Pygo2 in OS-RC-2 cells. The resulted cells were subject to Western blotting assay, MTT assay, colony formation and cell invasion assays. Furthermore, renal cell carcinoma (RCC) models were established in BALB/c nude mice inoculated with OS-RC-2 cells. Immunohistochemistry (IHC) staining of matrix metalloproteinase-7 (MMP-7), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) was performed in tumor tissue.ResultsPygo2 gene was successful knocked down and overexpressed in RCC OS-RC-2 cells by using an shRNA and overexpressing vector, respectively. Overexpression of Pygo2 effectively promoted cell proliferation, colony formation and invasion in vitro. Knockdown of Pygo2 obviously inhibited xenograft tumor growth in nude mice. In addition, overexpression of Pygo2 increased the levels of MMP-7, MMP-9 and VEGF in the xenograft tumors.ConclusionPygo2 has a role in promoting cell proliferation, invasion and metastasis, and may regulate angiogenesis via the Wnt/β-catenin signaling pathway

Repeated misdiagnosis of small intestine bronchogenic cyst: a case report

Bronchogenic cysts are uncommon congenital malformations of the respiratory system. These cysts can be categorized as intrapulmonary, mediastinal, or ectopic. Ectopic bronchogenic cysts, which lack distinctive clinical and imaging features, are particularly challenging to diagnose. This study presents a 48-year-old woman having a small intestinal bronchogenic cyst. She was repeatedly misdiagnosed as having an ovarian chocolate cyst or a cystic mass of bladder origin three years ago. However, no cyst was found during the operation. Half a year prior to presenting at our hospital, the patient developed frequent urination, prompting her to seek further treatment. We eventually discovered a cyst in the small intestine. The histological evaluation of the specimen showed a bronchogenic cyst. Small intestine bronchogenic cysts are extremely rare and easily misdiagnosed. It should be considered as one of the differential diagnoses of pelvic cysts. Particularly, when intraoperative exploration of the pelvic cavity fails to detect any cysts, consideration should be given to the possibility of small intestine bronchogenic cysts

The Deviation Analysis and Application of Correlation Tracking Algorithm

Correlation tracking algorithm is the most widely used image tracking algorithm . Its main error sources include processing error and positioning error. In order to improve the accuracy of correlation tracking algorithm, a mathematical model of positioning error based on the theory of random walk and martingale is set up, and the average time of positioning error exceeds the range is presented. The image-interpolation method and surfaces-fitting method are put forward to suppress the positioning error and improve the accuracy. Simulation results show that: compared with the whole pixel tracking, quadratic interpolation tracking can double the accuracy, and quartic interpolation and surfaces-fitting can improve the tracking accuracy of about 4 times

The Deviation Analysis and Application of Correlation Tracking Algorithm

Correlation tracking algorithm is the most widely used image tracking algorithm . Its main error sources include processing error and positioning error. In order to improve the accuracy of correlation tracking algorithm, a mathematical model of positioning error based on the theory of random walk and martingale is set up, and the average time of positioning error exceeds the range is presented. The image-interpolation method and surfaces-fitting method are put forward to suppress the positioning error and improve the accuracy. Simulation results show that: compared with the whole pixel tracking, quadratic interpolation tracking can double the accuracy, and quartic interpolation and surfaces-fitting can improve the tracking accuracy of about 4 times

DNA damage response alterations in clear cell renal cell carcinoma: clinical, molecular, and prognostic implications

Abstract Background DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic responses. Nonetheless, the characteristics and significance of DDR alterations in clear cell renal cell carcinoma (ccRCC) remain undefined. This study aimed to explore the predictive role, molecular mechanism, and tumor immune profile of DDR genes in ccRCC. Methods We prospectively sequenced 757 tumors and matched blood DNA samples from Chinese patients with ccRCC using next-generation sequencing (NGS) and analyzed data from 537 patients from The Cancer Genome Atlas (TCGA). A comprehensive analysis was performed. Results Fifty-two percent of Chinese patients with ccRCC harbored DDR gene mutations and 57% of TCGA patients. The immunotherapy treatment prognosis of patients with DDR gene mutations was superior to that of patients without DDR gene mutations (p = 0.047). DDR gene mutations were associated with more gene mutations and a higher tumor mutation load (TMB, p < 0.001). Moreover, patients with DDR gene mutations have a distinct mutational signature compared with those with wild-type DDR. Furthermore, the DDR-mut group had elevated neoantigen load (including single-nucleotide variants (SNV) and indel neoantigen load, p = 0.037 and p = 0.002, respectively), TCR Shannon (p = 0.025), and neutrophils (p = 0.010). DDR gene mutations exhibited a distinct immune profile with significantly higher expression levels of TNFSF9, CD70, ICAM1, and indoleamine-2,3-dioxygenase (IDO) and lower expression levels of VTCN1 and IL12A. Conclusions Our data suggest that the detection of somatic mutations in DDR genes can predict the efficacy of immunotherapy in patients with ccRCC. Furthermore, we revealed the unique molecular and immune mechanisms underlying ccRCC with DDR gene mutations

The Isolation of Pyrroloformamide Congeners and Characterization of Its Biosynthetic Gene Cluster from Streptomyces sp. CB02980 Revealed a Unified Mechanism for Dithiolopyrrolone Biosynthesis

Dithiolopyrrolones are microbial natural products containing a disulfide or thiosulfonate bridge embedded in a unique bicyclic structure. In the current study, two new dithiolopyrrolones, pyrroloformamide C (3) and pyrroloformamide D (4), were isolated from Streptomyces sp. CB02980, together with the known pyrroloformamides 1 and 2. The biosynthetic gene cluster for pyrroloformamides was identified from S. sp. CB02980, which shared high sequence similarity with those of dithiolopyrrolones, including holomycin and thiolutin. Gene replacement of pyfE, which encodes a non-ribosomal peptide synthetase, abolished the production of 1－4. Overexpression of pyfN, a type II thioesterase gene, increased the production of 1 and 2. The structure elucidation and biosynthetic characterization of pyrroloformamides 1 - 4 may inspire future efforts to discover new dithiolopyrrolones, which are promising drug leads for the treatment of infectious diseases or cancer

Additional file 1 of DNA damage response alterations in clear cell renal cell carcinoma: clinical, molecular, and prognostic implications

Additional file 1: Figure S1. The relationship between DDR mutation and clinical outcome in the TCGA cohort. (A) Overall survival of patients stratified by DDR-mut/wt status in all patients. (B) Progression-free survival of patients stratified by DDR-mut/wt status in all patients. (C) Progression-free survival of patients stratified by DDR-mut/wt status in the immunotherapy cohort

The Design and Performance Evaluation of a 1550 nm All-Fiber Dual-Polarization Coherent Doppler Lidar for Atmospheric Aerosol Measurements

A 1550 nm all-fiber dual-polarization coherent Doppler lidar (DPCDL) was constructed to measure the depolarization ratio of atmospheric aerosols. In lidar systems, the polarization state of the laser source is typically required to be that of linearly parallel polarization. However, due to the influence of the fiber-optical transmission and the large-mode field output of the telescope, the laser polarization state changes. Hence, a polarizer was mounted to the emitting channel of the telescope to eliminate the depolarization effect. A fiber-optical polarization beam splitter divided the backscattered light into components with parallel and perpendicular polarization. The DPCDL used two coherent channels to receive each of these two polarization components. A calibration procedure was designed for the depolarization ratio to determine the differences in gain and non-responsiveness in the two polarization channels. The calibration factor was found to be 1.13. Additionally, the systematic error and the measured random error of the DPCDL were estimated to evaluate the performance of the system. The DPCDL’s systematic error was found to be about 0.0024, and the standard deviation was lower than 0.0048. The Allan deviations of a 1-min averaging window with a low SNR of 19 dB and a high SNR of 27 dB were 0.0104 and 0.0031, respectively. The random errors at different measured heights were mainly distributed below 0.015. To confirm the authenticity of the atmospheric depolarization ratio measured with the DPCDL, two field observations were conducted with the use of a co-located DPCDL and micro-pulse polarization lidar to perform a comparison. The results showed that the correlation coefficients of the aerosol depolarization ratios were 0.73 and 0.77, respectively. Moreover, the two continuous observations demonstrated the robustness and stability of the DPCDL. The depolarization ratios were detected in different weather conditions

Assessment of the juvenile vulnerability of symbiont-bearing giant clams to ocean acidification

Ocean acidification (OA) severely affects marine bivalves, especially their calcification processes. However, very little is known about the fate of symbiont-bearing giant clams in the acidified oceans, which hinders our ability to develop strategies to protect this ecologically and economically important group in coral reef ecosystems. Here, we explored the integrated juvenile responses of fluted giant clam Tridacna squamosa (Lamarck, 1819) to acidified seawater at different levels of biological organization. Our results revealed that OA did not cause a significant reduction in survival and shell growth performance, indicating that T. squamosa juveniles are tolerated to moderate acidification. Yet, significantly reduced net calcification rate demonstrated the calcifying physiology sensitivity to OA, in line with significant declines in symbiont photosynthetic yield and zooxanthellae density which in turn lowered the amount of energy supply for energetically expensive calcification processes. Subsequent transcriptome sequencing and comparative analysis of differentially expressed genes revealed that the regulation of calcification processes, such as transport of calcification substrates, acid-base regulation, synthesis of organic matrix in the calcifying fluid, as well as metabolic depression were the major response to OA. Taken together, the integration of physiological and molecular responses can provide a comprehensive understanding of how the early life history stages of giant clams respond to OA and make an important leap forward in assessing their fate under future ocean conditions