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As a member of the Ephrin protein family that elicits short distance cell-cell signaling, EphrinA3 has been shown to promote or inhibit tumorigenesis depending on tumor types, but its roles and the underlying mechanisms in lung adenocarcinoma (LUAD) have not been reported.The TCGA database and Kaplan-Meier Plotter database were used to analyze the differential expression of EphrinA3 between LUAD and para-carcinoma tissues, and its effect on overall survival of LUAD patients. CCK-8 assay, Edu assay, and flow cytometry were used to probe the effect of EphrinA3 on the proliferation of LUAD cells, and transwell assay was employed to examine its effect on migration and invasion. In addition, the effect of EphrinA3 on the growth of LUAD was further evaluated using a xenograft tumor model.EphrinA3 was expressed highly in LUAD, and its expression level was negatively correlated with the prognosis of LUAD patients. In addition, EphrinA3 promoted proliferation, migration, and invasion of LUAD cells, and accelerated tumor growth in a xenograft LUAD model. The reported EphrinA3 receptors, EphA1 and EphA10, were expressed in clinical LUAD tissues and co-localized with EphrinA3 in LUAD cells. Mechanistically, EphrinA3/Eph signaling activated AKT, ERK, and p38MAPK, induced epithelial-mesenchymal transition (EMT), and upregulated matrix metalloproteases-2 and -9 (MMP-2/-9).EphrinA3 expression was negatively correlated with prognosis of patients with LUAD. EphrinA3 promoted proliferation, migration, and invasion of LUAD cells. EphrinA3 enhanced the phosphorylation of ERK and AKT, and potentiates EMT and MMP expression in LUAD cells.

The efficacy of rapid on-site evaluation (ROSE) combined with computed tomography-guided transthoracic core needle biopsy (CT-guided TCNB) is rarely investigated. This study aimed to evaluate the diagnostic efficiency and safety of ROSE combined with CT-guided TCNB for suspected lung cancer patients.Clinical data from 285 patients who received CT-guided TCNB for suspected lung cancer in Huashan Hospital from 2015 to 2018 were retrospectively analysed. Of these 163 patients underwent CT-guided TCNB combined with ROSE (ROSE group), while the remaining 122 patients underwent without ROSE (non-ROSE group). The smears from TCNB were quickly processed with Diff-Quick staining and analysed by a skilled cytologist on-site. The consistency of ROSE with the final clinicopathological diagnosis and the diagnostic efficiency and safety of ROSE combined with CT-guided TCNB in suspected lung cancer patients were evaluated.ROSE was highly concordant with pathological diagnosis (κ = 0.791; P 0.001), with an accuracy of 95.7%. Diagnostic accuracy was significantly higher in the ROSE compared with the non-ROSE group (96.3% vs 86.1%; P = 0.002), with overall incidences of complications of 36.8% and 23.8%, respectively. Minor pneumothorax without drainage was slightly greater in the ROSE compared with the non-ROSE group (14.1% vs 6.6%; P = 0.046). However, there was no significant difference in serious complications between the two groups.ROSE was highly consistent with the final clinicopathological diagnosis for suspected lung cancer. ROSE further improved the diagnostic efficiency of CT-guided TCNB with no increased incidence of serious complications.

This is the replication package for the paper titled "An Empirical Study on Effort of Propagating Code Changes in Code Clones"

Objective. To investigate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) samples or lung biopsy specimens from which suspected pulmonary tuberculosis (PTB) patients have no sputum or negative smear. Materials and Methods. Sputum-scarce or smear-negative cases with suspected PTB ( n = 107 ) were analyzed from January 2018 to June 2020. We collected BALF or lung tissue biopsy samples with these cases of suspected TB during hospitalization. The diagnostic accuracy of mNGS for these samples was compared with those of conventional tests or the T-SPOT.TB assay. Results. 46 cases of PTB patients and 61 cases of non-PTB patients were finally enrolled and analyzed. mNGS exhibited a sensitivity of 89.13%, which was higher than conventional tests (67.39%) but equivalent to those of the T-SPOT.TB assay alone (76.09%) or T-SPOT.TB assay in combination with conventional tests (91.30%). The specificity of mNGS was 98.36%, similar to conventional tests (95.08%) but significantly higher than those of the T-SPOT.TB assay alone (65.57%) or the T-SPOT.TB assay in combination with conventional tests (63.93%). There was no significant difference in the diagnostic accuracy of mNGS in BALF samples and lung biopsy tissue specimens. Conclusion. Our findings demonstrate that mNGS could offer improved detection of Mycobacterium tuberculosis in BALF or lung tissue biopsy samples in sputum-scarce or smear-negative cases with suspected PTB.

Schwannomas are homogeneous tumors of schwann cells and occur at peripheral and cranial nerves on the upper limbs, the head and neck area. Rarely, a bronchial schwannoma may appear in the lung and be misdiagnosed as lung neoplasms. Here, we report a 56‐year old woman with a 5.8 × 7.0 × 2.8 cm lesion in her right upper lobe bronchus. The lesion had a maximum standardized uptake value (SUVmax) of 8.5 by 18‐fluorodeoxyglucose positron emission tomography (FDG‐PET). Bronchoscopy showed a mass obstructing the bronchus that bled easily. Despite repeated biopsies, a lung malignancy could not be excluded, and surgical resection was subsequently performed. Pathological examination demonstrated a primary bronchial schwannoma that was positive for molecular markers S‐100 and SOX‐10, negative for immune checkpoint marker PD‐1/PD‐L1 but also demonstrated certain uncommon pathological features. This case highlights the heterogeneity of bronchial masses and the diagnostic challenge for differentiating benign and malignant tumors in the thorax. Key points Rare bronchial schwannoma mimics lung malignancy and poses a diagnostic challenge. This case of bronchial schwannoma, unlike peripheral schwannoma, lacks PD‐L1. Pathological features indicate autonomic nerve origin for pulmonary schwannomas.

Background: The mechanism underlying vascular remodeling of hypoxia-induced pulmonary hypertension (HPH) is not fully elucidated. We hypothesized that hypoxia promotes expression of N-myc downstream regulated gene-1 (NDRG1) in human pulmonary arterial endothelial cells (HPAECs), which in turn leads to endothelial dysfunction and contributing to HPH. Methods: Lung samples were obtained from qualified patients and HPH rat models. Quantitative polymerase chain reactions, western blotting and immunohistochemistry were used to measure the expression of NDRG1. EdU incorporation assays, cell counting kit-8 (CCK-8) assays, transwell migration assays, and matrigel assays were conducted to detect the role of NDRG1 in HPACE function in vitro. HPH models were established in SD rats and were treated with plasmids expressing short hairpin RNAs (shRNAs) to silence NDRG1. The candidate binding partner(s) of NDRG1 was screened and validated via co-immunoprecipitation and immunofluorescence staining. Results: NDRG1 is up-regulated by hypoxia in a time-dependent manner in HPAECs. Expression of NDRG1 was increased in lung tissues of HPH patient and rat model. In vitro, silencing NDRG1 attenuated proliferation, migration and tube formation of HPAECs under hypoxia, while NDRG1 over-expression promoted these behaviors of HPAECs in normoxia. NDRG1 knock-down alleviated vascular remodeling and right ventricular hypertrophy in rat models of HPH. NDRG1 can directly interact with TATA-box binding protein associated factor 15 (TAF15) and promote its nuclear localization. Bioinformatics study found that Notch1 signaling was downstream of TAF15 in endothelial cells. TAF15 can promote HPAECs dysfunction via binding to Notch1 promoter region and subsequently increasing Notch1 expression. Conclusions: Taken together, hypoxia-induced up-regulation of NDRG1 contributes to endothelial dysfunction and HPH development through TAF15 upregulation of Notch1, suggesting the applicability of targeting NDRG1 in clinical treatment of HPH.

A wavelength-tunable chaotic optical signal generation and on-chip O/E conversion scheme based on an integrated laser-photodiode chip subject to filtered optical feedback is proposed and experimentally demonstrated. The integrated chip consists of a Fabry–Perot (FP) gain section and a photodiode, which was fabricated on an n-InP substrate with the same active material. By applying a filtered feedback signal to the FP gain section, wavelength-tunable chaotic carrier ranging from 1576 to 1587 nm was achieved. On-chip microwave chaotic signal generation with a standard bandwidth over 5.5 GHz was obtained using the integrated photonic chip.

The effects of doping profile and well thickness on the light extinction properties of electroabsorption modulators (EAM) are studied experimentally. It is found that both light p type doping in the InP cladding layer and a large well thickness help to get higher extinction ratios at a given reverse bias voltage. A 3D EAM model has been built for optimizing the performance of EAMs. The simulation results are in a good agreement with the experimental results. With the optimized EAM designs, a modulator with an over 20 dB extinction ratio at a low bias voltage is demonstrated.

We report data transmissions using a packaged two-section distributed Bragg reflector (DBR) laser, which has InGaAlAs multi-quantum wells as the gain material. The tunable DBR laser has a wavelength tuning range of 11.44 nm. The DBR laser has uniform 3-dB direct modulation bandwidth (over 12 GHz) within the over 11-nm wavelength tuning range; 10-Gb/s data transmissions are performed at up to 25-km distance and different wavelength emissions at 25 °C and 50 °C.

With the deployment of the fifth generation of mobile networks (5G), 25 and 100 Gb/s directly modulated lasers and modules will become the mainstream optical transmitters. A directly modulated InGaAlAs/InP distributed Bragg reflector (DBR) laser is fabricated by butt-joint technology. A 25 Gb/s data transmission over a single-mode fiber of up to 10 km is demonstrated, and a wavelength tuning range of 14.28 nm is achieved through injection current tuning of a DBR section and temperature control of a thermoelectric cooler (TEC), which is the best candidate of colorless light sources for wavelength-division-multiplexed passive optical network (WDM-PON) systems.

Granulomatosis with polyangiitis (GPA) is a rheumatic auto-immune disease involved in vasculitis. It is rarely reported that anti-neutrophil cytoplasmic antibodies (ANCAs) associated with GPA would cause main tract stenosis. The current report documents a 54-year-old woman, with a history of severe cough, presented with wheezing and shortness of breath. Although she was treated with cephalosporin antibiotics for half a month, the symptoms were not alleviated. Accordingly, laboratory testing, radiology and pathology was performed at the Department of Respiratory and Critical Care Medicine, Huashan Hospital. Blood samples were tested negative for ANCAs. Chest CT revealed stenosis of the main trachea and uneven thickening of the tracheal wall. Nasal sinuses CT scanning indicated thickening of the nasal mucosa. Pathological analysis demonstrated chronic granulomatous inflammation with focal lesions. According to the classification criteria of ACR/EULAR provisional 2017, the patient was diagnosed with the ANCAs-negative GPA. Following treatment with oral prednisone only for 6 months, obstruction of main tract was significantly improved. This case study is of interest for the promotion a potentially novel therapeutic intervention for GPA associated with the absence ANCA of in clinic.

The latest emergence of a novel coronavirus (COVID-19) had caused an outbreak of respiratory virus infections in Wuhan, China, and other countries so that the world health organization (WHO) declared the COVID-19 epidemic as a Public Health Emergency of International Concern (PHEIC) on January 31, 2020. At present, it is the fact that we have identified the bats as the host, the route of respiratory droplets, contact, and aerosol can accelerate the transmission from person to person. However, it is not well known about the intermediator and other approaches. Identifying and characterizing the origin and host(s) of COVID-19 can help us to evaluate the potential risk of COVID-19 for transmission among humans or cross-species.

Background The signal transducer and activator of transcription (STAT) and transforming growth factor-β (TGF-β) signaling pathways play important roles in epithelial ovarian cancer (EOC). However, the mechanism of crosstalk between two pathways is not completely understood. Methods The expression of STAT1 protein was detected by tissue microarray and immunoblotting (IB). The interaction of STAT1 isoforms with TGF-β receptors was confirmed by immunoprecipitation and IB. The effect of TGF-β signaling on STAT1 activation was examined in EOC and non-tumorous HOSEpiC cells treated with TGF-β1 in the presence or absence of the inhibitor of TGF-β type I receptor. The gain-of-function and loss-of-function approaches were applied for detecting the role of STAT1 on EOC cell behaviours. Results The high level of STAT1 was observed in patients with high-grade serous EOC. STAT1 expression was higher in ovarian cancer cells than noncancerous cells. TGF-β1 activated the STAT1 pathway by inducing the phosphorylation of STAT1α on S727 residue. The full-length STAT1α and the truncated STAT1β directly interacted with TGF-β receptors (ALK1/ALK5 and TβRII), which was mediated by TGF-β1. STAT1α and STAT1β blocked the activation of the TGF-β1 signaling pathway in EOC cells by reducing Smad2 phosphorylation. STAT1 overexpression induced EOC cell proliferation, migration, and invasion; whereas its inhibition enhanced TGF-β1-induced phospho-Smad2 and suppressed EOC cell proliferation, migration, and invasion. Conclusions Our data unveil a novel insight into the molecular mechanism of crosstalk between the STAT1 and TGF-β signaling pathways, which affected the cancer cell behavior. Suppression of STAT1 may be a potential therapeutic strategy for targeting ovarian cancer. Electronic supplementary material The online version of this article (10.1186/s13046-018-0773-8) contains supplementary material, which is available to authorized users.

Ribosomal protein L10 (RPL10) is one of large ribosomal proteins and plays a role in Wilms' tumor and premature ovarian failure. However, the function of RPL10 in human epithelial ovarian cancer (EOC) remains unknown. The purpose of this study was to examine the expression level and function of RPL10 in EOC. RPL10 protein expression was detected by immunohistochemistry and Western blot. The association RPL10 expression with clinical features was analyzed. Loss-of-function and gain-of-function approaches were applied in cellular assays, including cell viability, migration, invasion, and apoptosis. Our study demonstrated for the first time that RPL10 was upregulated in human EOC compared with normal ovarian tissues. Knockdown of RPL10 inhibited cell viability, migration, and invasion, and increased cell apoptosis. On the contrary, upregulation of RPL10 increased cell viability, migration, invasion, and decreased cell apoptosis. Furthermore, miR-143-3p regulated RPL10 expression. Our data indicate that RPL10 is a potential tissue biomarker of patients with EOC and may be a therapeutic target of ovarian cancer.

Primary pulmonary mucinous adenocarcinoma is an unusual histological type of non-small cell lung cancer and has a rare prevalence at a young age. There is no standard first-line therapy for advanced primary pulmonary mucinous adenocarcinoma in children and young adults—this study reports two rare cases of primary pulmonary mucinous adenocarcinoma with wild-type anaplastic lymphoma kinase and epidermal growth factor receptor ( EGFR) genes. One is a 13-year-old boy ( Case#1 ), and another is a 27-year-old male ( Case#2). Both two cases were treated with antibiotics for suspected pulmonary infection. In our hospital, they were diagnosed with advanced primary pulmonary mucinous adenocarcinoma, the Eastern Cooperative Oncology Group (ECGO) performance status was three scores. We chose pembrolizumab and chemotherapy plus angiogenesis inhibitors for Case#1 and Case#2. The two patients' symptoms improved and presented with a partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria，the scores of ECOG performance status were two for Case#1 and one for Case#2. This study illustrates a promising outcome for advanced primary pulmonary mucinous adenocarcinoma with immunotherapy and chemotherapy plus angiogenesis inhibitors at a young age.

We demonstrate a widely tunable InGaAs quantum-wells (QWs) distributed Bragg reflector (DBR) laser, in which the DBR section was realized by using butt-jointed InGaAsP ( λ = 1 . 46 μ m ) material. In the device process, we explored an optimal chemical etchant applied in the butt-jointed active–passive integration technology. A wide tuning range of 10.7 nm with 19 consecutive channels is obtained with a single tuning current at room temperature (RT). With the help of the heat sink temperature, the tuning range is expanded to 16 nm. A side mode suppression ratio (SMSR) of higher than 34 dB is obtained for all channels at 5 °C to 45 °C. A six-wavelength laser array that can cover a wavelength tuning range of 41.6 nm at 20 °C with a side mode suppression ratio higher than 37 dB in all channels is demonstrated by varying the grating periods. It is a promising light source for methane or multispecies gas detection.

Human epithelial ovarian cancer (EOC) is the most lethal gynecological disease. However, the molecular mechanisms by which transforming growth factor-β (TGF-β) regulates ovarian tumor progression markers remain unclear. The present data show cytidine monophosphate kinase (CMPK) as an EOC biomarker and are related to the article entitled “Cytidine monophosphate kinase is inhibited by the TGF-β signalling pathway through the upregulation of miR-130b-3p in human epithelial ovarian cancer” [1]. CMPK, as well as cystatin B [2] and β-2-microglobulin [3], is overexpressed in human epithelial-type ovarian tumors. CMPK is an enzyme required for nucleic acid biosynthesis [4] and is regulated by the TGF-β signaling pathway in EOC cells [1]. Furthermore, the data show the effect of CMPK-shRNA on EOC cell apoptosis and TGF-β-induced Smad2 phosphorylation. CMPK expression in two EOC cell lines OVCAR-3 and SK-OV-3 is regulated by multiple miRNAs and some of these miRNAs may affect EOC chemoresistance [5]. Keywords: TGF-β signaling, UMP/CMP kinase, Tissue microarray, Tumorigenesis, miRNA, Therapeutic target

We report 10 Gb/s data transmission over 30 km using a packaged two-section InGaAsP distributed Bragg reflector (DBR) laser. The tunable DBR laser has a wavelength tuning range over 12 nm.

We report the application of two widely tunable directly modulated distributed Bragg reflector (DBR) lasers to cover over 20 nm wavelength. 10 Gb/s data are transmitted up to 30 km distance at different wavelengths with the wavelength range. The results indicate that the DBR lasers are promising light sources for the next generation high capacity wavelength division multiplexed passive optical network (WDM-PON) systems.

We investigate the lateral current spreading effect and its influences on the transmission characteristics of ridge waveguide electroabsorption modulators. An RF equivalent circuit based on a transmission line model explicitly accounting for this effect is proposed. The equivalent circuit parameters in our model extracted from $S_{11}$ curve fitting are used to simulate the $S_{21}$ response (electro-optical response (E/O) response), which matches well with the measured direct $S_{21}$ small-signal modulation response. The physical significance of our model parameters can be well explained based on the secondary ion mass spectroscopy doping profiling and the simulation of the current spreading effect in our device structure.

We report 10 Gb/s data transmissions using a packaged two-section InGaAsP/InP distributed Bragg reflector (DBR) laser. The tunable DBR laser has a wavelength tuning range of 12.12 nm. The DBR laser has greater than 10.84 GHz 3-dB direct modulation bandwidth within the wavelength tuning range. The 10 Gb/s data transmissions are performed at up to a distance of 30-km.

InP-based photonic integrated circuits (PICs) have aroused great interest in recent years to meet the needs of future high-capacity and high-performance optical systems. With the advantages of small size, low power consumption, low cost, high reliability, InP-based PICs are promising solutions to replace the multiple discrete devices used in various systems. In this paper, we will review the design, fabrication, key integration technology and performance of several kinds of InP-based monolithically integrated transmitters developed in our group in recent years. Particular attention will be paid to the electro-absorption modulated laser (EML), multi-wavelength distributed feedback (DFB) laser arrays, widely tunable distributed reflector (DBR) lasers and their arrays, integrated amplified feedback lasers (AFL), and few-mode transmitters.

Figure S1. STAT1 expression in human epithelial-type ovarian tumors. Tissue microarray shows the immunohistochemical (IHC) staining of pSTAT1-Y701, pSTAT1-S727, and total STAT1 in serous, mucinous, endometrioid, transitional cell, and metastatic tumors. Figure S2. STAT1 expression in ovarian surface epithelial cells. a STAT1 mRNA expression detected by quantitative RT-PCR. b STAT1 protein expression detected by immunoblotting. c Densitometric analysis of the gels. Figure S3. Effect of TGF-β1 on the phosphorylation of STAT1. (DOCX 1304 kb)

Table S1. PCR primer and siRNA sequence used in experiments. Table S2. Comparison of pSTAT1-Y701, pSTAT1-S727, and STAT1 immunostaining in the ovarian tissues. Table S3. The expression of pSTAT1-Y701, pSTAT1-S727, and STAT1 in human ovarian tissues. (DOCX 50Â kb)

Pyridoxine 5′-phosphate oxidase (PNPO) is an enzyme that converts pyridoxine 5′-phosphate into pyridoxal 5′-phosphate (PLP), an active form of vitamin B6 implicated in several types of cancer. However, the role of PNPO and its regulatory mechanism in epithelial ovarian cancer (EOC) are unknown. In the present study, PNPO expression in human ovarian tumour tissue and its association with the clinicopathological features of patients with EOC were examined. Further, the biological function of PNPO in EOC cells and in xenograft was evaluated. We demonstrated for the first time that PNPO was overexpressed in human EOC. Knockdown of PNPO induced EOC cell apoptosis, arrested cell cycle at G2/M phase, decreased cell proliferation, migration and invasion. Xenografts of PNPO-shRNA-expressing cells into the nude mouse attenuated tumour growth. PNPO at mRNA and protein levels in EOC cells was decreased after transforming growth factor-β1 (TGF-β1) treatment. The inhibitory effect of TGF-β1 on PNPO expression was abolished in the presence of SB-431542, a TGF-β type I receptor kinase inhibitor. Moreover, we found that TGF-β1-mediated PNPO expression was at least in part through the upregulation of miR-143-3p. These data indicate a mechanism underlying PNPO regulation by the TGF-β signalling pathway. Furthermore, PLP administration reduced PNPO expression and decreased EOC cell proliferation, suggesting a feedback loop between PLP and PNPO. Thus, our findings reveal that PNPO can serve as a novel tissue biomarker of EOC and may be a potential target for therapeutic intervention.