Corrigendum: High expression of PARP1 in tumor and stroma cells predicts prognosis and platinum resistance in patients with advanced epithelial ovarian cancer.

[This corrects the article DOI: 10.3389/fonc.2022.931445.].

Brain region-specific synaptic function of FUS underlies the FTLD-linked behavioural disinhibition.

Synaptic dysfunction is one of the earliest pathological processes that contribute to the development of many neurological disorders, including Alzheimer's disease and frontotemporal lobar degeneration. However, the synaptic function of many disease-causative genes and their contribution to the pathogenesis of the related diseases remain unclear. In this study, we investigated the synaptic role of fused in sarcoma, an RNA-binding protein linked to frontotemporal lobar degeneration and amyotrophic lateral sclerosis, and its potential pathological role in frontotemporal lobar degeneration using pyramidal neuron-specific conditional knockout mice (FuscKO). We found that FUS regulates the expression of many genes associated with synaptic function in a hippocampal subregion-specific manner, concomitant with the frontotemporal lobar degeneration-linked behavioural disinhibition. Electrophysiological study and molecular pathway analyses further reveal that fused in sarcoma differentially regulates synaptic and neuronal properties in the ventral hippocampus and medial prefrontal cortex, respectively. Moreover, fused in sarcoma selectively modulates the ventral hippocampus-prefrontal cortex projection, which is known to mediate the anxiety-like behaviour. Our findings unveil the brain region- and synapse-specific role of fused in sarcoma, whose impairment might lead to the emotional symptoms associated with frontotemporal lobar degeneration.

The function of FUS in neurodevelopment revealed by the brain and spinal cord organoids.

The precise control of proliferation and differentiation of neural progenitors is crucial for the development of the central nervous system. Fused in sarcoma (FUS) is an RNA-binding protein pathogenetically linked to Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) disease, yet the function of FUS on neurodevelopment is remained to be defined. Here we report a pivotal role of FUS in regulating the human cortical brain and spinal cord development via the human iPSCs-derived organoids. We found that depletion of FUS via CRISPR/CAS9 leads to an enhancement of neural proliferation and differentiation in cortical brain-organoids, but intriguingly an impairment of these phenotypes in spinal cord-organoids. In addition, FUS binds to the mRNA of a Trk tyrosine kinase receptor of neurotrophin-3 (Ntrk3) and regulates the expression of the different isoforms of Ntrk3 in a tissue-specific manner. Finally, alleviated Ntrk3 level via shRNA rescued the effects of FUS-knockout on the development of the brain- and spinal cord-organoids, suggesting that Ntrk3 is involved in FUS-regulated organoids developmental changes. Our findings uncovered the role of FUS in the neurodevelopment of the human CNS.

High Expression of PARP1 in Tumor and Stroma Cells Predicts Different Prognosis and Platinum Resistance in Patients With Advanced Epithelial Ovarian Cancer.

Objective: This study aimed to explore the roles of PARP1 mRNA and protein expression in platinum resistance and prognosis of EOC patients, and reveal the different roles of PARP1 protein in epithelial tumor and stroma cells. Methods: The PARP1 mRNA expression of the EOC tissues was examined by RT-qPCR. The impacts of PARP1 expression on prognosis were measured by Kaplan-Meier and Cox regression. Receiver operating characteristic (ROC) curve analysis was employed for calculating the diagnostic value of PARP1 on platinum resistance. The microarray of formalin-fixed, paraffin-embedded (FFPE) tissues was processed for multiplex immunofluorescence to detect the protein levels of PARP1 and cytokeratin (CK). Results: The PARP1mRNA expression of EOC patients was higher in the platinum-resistant group compared with the sensitive group (P<0.01). Kaplan-Meier analysis demonstrated that high PARP1 mRNA expression was associated with poor survival of EOC patients. In Cox regression analyses, high PARP1 mRNA expression independently predicted poor prognosis (P=0.001, HR=2.076, 95%CI=1.373-3.140). The area under the ROC curve of PARP1 mRNA for predicting the platinum resistance in EOC patients was 0.649, with a sensitivity of 0.607 and specificity of 0.668. Furthermore, the protein expression of PARP1 was higher in the platinum-resistant group than in the sensitive group (P<0.01) and associated with a worse prognosis. Additionally, according to CK labeling, we observed that enhanced expression of PARP1 in the CK+ region was associated with platinum resistance and lower survival, but in CK- region, it predicted a good prognosis and platinum sensitivity. Conclusion: PARP1 may be a potential biomarker to predict platinum resistance and prognosis for EOC patients, exerting different roles on epithelial tumor and stromal cells.

Long noncoding RNA BS-DRL1 modulates the DNA damage response and genome stability by interacting with HMGB1 in neurons.

Long noncoding RNAs (lncRNAs) are known to regulate DNA damage response (DDR) and genome stability in proliferative cells. However, it remains unknown whether lncRNAs are involved in these vital biological processes in post-mitotic neurons. Here, we report and characterize a lncRNA, termed Brain Specific DNA-damage Related lncRNA1 (BS-DRL1), in the central nervous system. BS-DRL1 is a brain-specific lncRNA and depletion of BS-DRL1 in neurons leads to impaired DDR upon etoposide treatment in vitro. Mechanistically, BS-DRL1 interacts with HMGB1, a chromatin protein that is important for genome stability, and is essential for the assembly of HMGB1 on chromatin. BS-DRL1 mediated DDR exhibits cell-type specificity in the cortex and cerebellum in gamma-irradiated mice and BS-DRL1 knockout mice show impaired motor function and concomitant purkinje cell degeneration. Our study extends the understanding of lncRNAs in DDR and genome stability and implies a protective role of lncRNA against neurodegeneration.

Field Applications of Ultra High Frequency Techniques for Defect Detection in GIS.

The reliable and stable operation of power apparatus is important for the development of GIS. It is important to utilize condition monitoring technologies and anticipate possible failures in advance. Many papers have been published about the partial discharge detection with UHF or X-ray in laboratory, but seldom in field application. Thus, many engineers at project sites are not familiar with the current professional diagnosis techniques. Recently, during the GIS routine data analysis obtained by partial discharge online monitoring system, it was found that the UHF monitoring signals' developing trend of the 220 kV GIS No. 2 high-voltage side of transformer in phase C at an actual station was abnormal and needed further detection. In order to precisely investigate the problem and then guide the operation and maintenance activities, a series of professional diagnoses were conducted. Three new types of partial discharge detection and positioning methods were applied for accuracy, including UHF partial discharge detection based on multi-stage amplified signal demodulation and multiple weighted averages processing; the partial discharge detection based on the signal radiation hole of insulation disk at the ground connection; and the positioning method based on UHF-SHF. After a series of troubleshooting works, the partial discharge defects have been diagnosed, and the case can be referred in the field monitoring of GIS.

A Fiber Bragg Grating-Based Dynamic Tension Detection System for Overhead Transmission Line Galloping.

Galloping of overhead transmission lines (OHTLs) may induce conductor breakage and tower collapse, and there is no effective method for long distance distribution on-line galloping monitoring. To overcome the drawbacks of the conventional galloping monitoring systems, such as sensitivity to electromagnetic interference, the need for onsite power, and short lifetimes, a novel optical remote passive measuring system is proposed in the paper. Firstly, to solve the hysteresis and eccentric load problem in tension sensing, and to extent the dynamic response range, an 'S' type elastic element structure with flanges was proposed. Then, a tension experiment was carried out to demonstrate the dynamic response characteristics. Moreover, the designed tension sensor was stretched continuously for 30 min to observe its long time stability. Last but not the least, the sensor was mounted on a 70 m conductor model, and the conductor was oscillated at different frequencies to investigate the dynamic performance of the sensor. The experimental results demonstrate the sensor is suitable for the OHTL galloping detection. Compared with the conventional sensors for OHTL monitoring, the system has many advantages, such as easy installation, no flashover risk, distribution monitoring, better bandwidth, improved accuracy and higher reliability.

Tracing Acetylene Dissolved in Transformer Oil by Tunable Diode Laser Absorption Spectrum.

Dissolved gas analysis (DGA) is widely used in monitoring and diagnosing of power transformer, since the insulation material in the power transformer decomposes gases under abnormal operation condition. Among the gases, acetylene, as a symbol of low energy spark discharge and high energy electrical faults (arc discharge) of power transformer, is an important monitoring parameter. The current gas detection method used by the online DGA equipment suffers from problems such as cross sensitivity, electromagnetic compatibility and reliability. In this paper, an optical gas detection system based on TDLAS technology is proposed to detect acetylene dissolved in transformer oil. We selected a 1530.370 nm laser in the near infrared wavelength range to correspond to the absorption peak of acetylene, while using the wavelength modulation strategy and Herriott cell to improve the detection precision. Results show that the limit of detection reaches 0.49 ppm. The detection system responds quickly to changes of gas concentration and is easily to maintenance while has no electromagnetic interference, cross-sensitivity, or carrier gas. In addition, a complete detection process of the system takes only 8 minutes, implying a practical prospect of online monitoring technology.

Research on High Sensitive D-Shaped FBG Hydrogen Sensors in Power Transformer Oil.

Dissolved hydrogen is a symbol gas decomposed by power transformer oil for electrical faults such as overheat or partial discharges. A novel D-shaped fiber Bragg grating (D-FBG) sensor is herein proposed and was fabricated with magnetron sputtering to measure the dissolved hydrogen concentration in power transformer oil in this paper. Different from the RI (refractive index)-based effect, D-FBG in this case is sensitive to curvature caused by stress from sensing coating, leading to Bragg wavelength shifts accordingly. The relationship between the D-FBG wavelength shift and dissolved hydrogen concentration in oil was measured experimentally in the laboratory. The detected sensitivity could be as high as 1.96 µL/L at every 1-pm wavelength shift. The results proved that a simple, polished FBG-based hydrogen sensor provides a linear measuring characteristic in the range of low hydrogen concentrations in transformer oil. Moreover, the stable hydrogen sensing performance was investigated by X-ray diffraction analysis.

Note: Dissolved hydrogen detection in power transformer oil based on chemically etched fiber Bragg grating.

A fiber Bragg grating (FBG) sensor based on chemically etched cladding to detect dissolved hydrogen is proposed and studied in this paper. Low hydrogen concentration tests have been carried out in mixed gases and transformer oil to investigate the repeatability and sensitivity. Moreover, to estimate the influence of etched cladding thickness, a physical model of FBG-based hydrogen sensor is analyzed. Experimental results prove that thin cladding chemically etched by HF acid solution improves the response to hydrogen detection in oil effectively. At last, the sensitivity of FBG sensor chemically etched 16 µm could be as high as 0.060 pm/(µl/l), increased by more than 30% in comparison to un-etched FBG.

[Clinicopathologic features and prognosis of triple negative breast cancer].

OBJECTIVE: To analyze the clinicopathologic features and prognosis of triple negative breast cancer. METHODS: The clinical datas of 477 patients of primary breast cancer which were diagnosed by pathology in the 4th Hospital of Hebei Medical University from Jan. 2004 to Dec. 2004 were analyzed. All of the patients were divided into two groups according to the results of immunohistochemistry: one was triple negative breast cancer (TNBC) which included estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor (HER2) negative and other was non-triple negative breast cancer. We compared TNBC with the group of non-triple negative breast cancer in the clinicopathologic features. The disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier method. RESULTS: Of the 477 patients, 12.6% (60/477) was TNBC patients in which 76.7% of age was younger than fifty years(46/60), 28.3% of T > 5 cm (17/60), 68.3% of lymph nodes metastasis (41/60), 31.7% of grade III (19/60) and 13.3% of family history of breast cancer (8/60), (P < 0. 05). Till June 2008, the median time of follow-up was 48 months (42-54 months). Local recurrence or distant metastasis were 26.7% (16/60) of TNBC which was higher than 15.3% (64/417) of non-triple negative cases; DFS was 68.3% in TNBC group and 79.6% in the non-triple negative breast cancer group. The OS was 81.7% in TNBC group and 90.9% in the non-triple negative breast cancer group (Log-Rank = 3.917, P = 0.048; Log-Rank = 4.838, P = 0.028). CONCLUSION: These patients of triple negative breast carcinoma were usually young (age < 50), with tumor growth fast, much more invasion and poorly prognosis.