lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2.

Lung cancer (LC) is a prevailing primary tumor in the lung. lncRNA non-coding RNA activated by DNA damage (NORAD) is a popular target in human cancers. This experiment is designed to probe the mechanism of lncRNA in LC progression. NORAD expression in normal lung epithelial cells and LC cells was examined and then silenced to assess its effect on LC cell proliferation, invasion, and migration. Subcellular localization of NORAD was analyzed through online databases and then corroborated by fractionation of nuclear and cytoplasmic RNA assay. The target binding relations between NORAD and miR-28-3p and between miR-28-3p and E2F2 were verified. Eventually, LC cells with NORAD silencing were transfected with miR-28-3p inhibitor or pcDNA3.1-E2F2 to measure LC cell proliferation, invasion, and migration. NORAD was overexpressed in LC cells and NORAD knockout led to suppressed LC cell proliferation, invasion, and migration. Besides, NORAD targeted miR-28-3p and miR-28-3p targeted E2F2 transcription. Inhibiting miR-28-3p or overexpressing E2F2 could both annul the inhibitory role of si-NORAD in LC cell proliferation, invasion, and migration. Generally, our findings demonstrated that NORAD competitively bound to miR-28-3p with E2F2, to promote LC cell progression.

Novel Au-Se Nanoprobes for Specific Thrombin Detection in Diagnosis of Lung Cancer.

Thrombin is associated with malignant tumors and promotes tumor development, metastasis, and angiogenesis, therefore its identification especially in lung cancer cells is crucial. Because the interference of in vivo biothiols caused false positive findings with prior gold fluorescent nanoprobes, in this manuscript, an Au-selenol(Se) nanoprobe (5-FAM-peptide-Se-AuNPs) that could specifically detect thrombin was designed and compared to traditional Au-S nanoprobes. For reaching this goal, fluorophore-bearing thrombin-specific peptide containing selenol at the end was synthesized. The nanoprobe may be broken by thrombin to regain its fluorescence in lung cancer cells, allowing for high-sensitivity thrombin detection. Since the Au-Se bond is more stable than the Au-S bond, the accuracy of the detection results can be guaranteed. The probe synthesis method is simple and cost-effective, as well as having high biocompatibility. Low concentrations of thrombin can be detected and imaged in lung cancer cells. The synthetic method of this probe opens up new avenues for the application of Au-Se bonds.

circCCT3 Enhances Invasion and Epithelial-Mesenchymal Transition (EMT) of Non-Small-Cell Lung Cancer (NSCLC) via the miR-107/Wnt/FGF7 Axis.

Background: CircRNAs play a role in a variety of biological processes, including tumorigenesis. circCCT3 has been shown to regulate cancer initiation and progression. Unfortunately, whether circCCT3 is involved in non-small-cell lung cancer (NSCLC) metastasis remains unclear. Methods: Our study utilized RT-qPCR to examine gene expression levels. A transwell assay was used to measure invasion ability of cells. Starbase software and TargetScan software were used to predict target genes. Results: circCCT3 knockdown attenuated invasion and epithelial-mesenchymal transition (EMT) of A549 and Calu-1 cells. miR-107 mimics could rescue circCCT3-induced invasion and EMT. Next, miR-107 mimics and circCCT3 knockdown suppressed Wnt3a and FGF7 expression. An miR-107 inhibitor promoted Wnt3a and FGF7 expressions. Finally, FGF7 greatly restored miR-107-inhibited invasion and EMT of A549 cells. Conclusion: Here, we reveal a molecular mechanism circCCT3/miR-107/Wnt/FGF7 responsible for NSCLC metastasis.

Recurrent lung adenocarcinoma benefits from microwave ablation following multidisciplinary treatments: A case with long-term survival.

Lung cancer has become the leading cause of cancer death all over the world. Nowadays, there is a consensus that the treatment of non-small cell lung cancer (NSCLC) prefers a combination of multidisciplinary comprehensive treatment and individualized treatment, which can significantly improve the prognosis of patients. Here, we report a female patient with recurrence-prone NSCLC. She had a decade-long disease course, during which the lesion recurred twice and finally cured with Multi-Disciplinary Treatment (MDT). An elderly female patient was admitted to the hospital after diagnosis of lung cancer, and treated with surgery and postoperative adjuvant chemotherapy. Five years later, suspicious lesions were found by computed tomography (CT) reexamination, and then confirmed tumor recurrence by puncture biopsy. Based on the genetic test results, gefitinib was used for subsequent targeted therapy, and the lesion gradually shrunk to disappear. However, the lesion appeared again two years later, after consultation the microwave ablation was adopted and the curative effect was excellent. At last, regular reexamination showed no abnormality, the patient has survived so far. The case proves the great benefit of multidisciplinary comprehensive treatment, especially microwave ablation for patient with recurrence-prone NSCLC. And the effect of systemic anti-tumor immune response induced by microwave ablation on lung cancer also needs to be further explored.

Erratum to "lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2".

[This corrects the article DOI: 10.1515/med-2022-0538.].

Optical polarization division multiplexing fiber-wireless integration system at Ka-band based on a low-cost dual-drive MZM.

In this paper, a low-cost dual-drive Mach-Zehnder modulator (DDMZM) based 40 Gbit/s polarization division multiplexing (PDM) fiber-wireless-integration system at Ka-band is experimentally demonstrated. Since the DDMZM is biased at the quadrature point for electro-to-optical (E/O) conversion, a high-power direct current (DC)/radio frequency (RF) component will appear within the received signal bandwidth. This high-power component becomes a narrowband interference due to the phase noise of lasers, which will lead to the incorrect convergence of the constant-modulus algorithm (CMA) during equalization at the receiver side. In order to deal with the broadened DC component, twin-single-sideband (twin-SSB) signal with bandwidth interleave and RF-pilot based phase noise compensation scheme are adopted. Enabled by the combination of optical PDM technique and heterodyne coherent detection, a 40 Gbit/s PDM twin-SSB Nyquist-shaped quadrature-phase-shift-keying (QPSK) signal transmitting over 20-km single mode fiber (SMF) and 1-m 2×2 multiple-input multiple-output (MIMO) wireless distance is achieved with the bit error rate (BER) below the hard-decision forward-error-correction (HD-FEC) threshold of 3.8×10-3.

Circular RNA 0006349 Augments Glycolysis and Malignance of Non-small Cell Lung Cancer Cells Through the microRNA-98/MKP1 Axis.

Background: The involvement of dysregulated circular RNAs (circRNAs) in human diseases has been increasingly recognized. In this study, we focused on the function of a newly screened circRNA, circ_0006349, in the progression of non-small-cell lung cancer (NSCLC) and the molecules of action. Methods: The NSCLC circRNA dataset GSE101684, microRNA (miRNA) dataset GSE29250, and mRNA dataset GSE51852 obtained from the GEO database were used to identify the differentially expressed genes in NSCLC samples. Tumor and normal tissues were collected from 59 patients with NSCLC. The expression of circ_0006349, miR-98, and MAP kinase phosphatase 1 (MKP1) in collected tissue samples and in acquired cells was determined. The binding relationships between miR-98 and circ_0006349/MKP1 were predicted and validated. Altered expression of circ_0006349, miR-98, and MKP1 was introduced in NSCLC cells to examine their roles in cell growth, apoptosis, and glycolysis. Results: Circ_0006349 and MKP1 were upregulated, and miR-98 was poorly expressed in the collected tumor tissues and the acquired NSCLC cell lines. Circ_0006349 was identified as a sponge for miR-98 to elevate MKP1 expression. Silencing of circ_0006349 suppressed proliferation and increased apoptosis of Calu-3 and H1299 cells, and it reduced glycolysis, glucose uptake, and the production of lactate in cells. Upon circ_0006349 knockdown, further downregulation of miR-98 or upregulation of MKP1 restored the malignant behaviors of cells. Conclusion: This research demonstrated that circ_0006349 derepressed MKP1 expression by absorbing miR-98, which augmented the proliferation and glycolysis of NSCLC cells and promoted cancer development.

Extended Risley scanning system with 30 × 360 coverage.

We propose a beam scanning system based on an extended Risley prism structure. This system uses a rotating mirror structure and expands the original construction of the balanced and stable Risley prism. There is much research on extended Risley prism structures, but the scanned angle of their extended systems is less than 180°. The proposed system in this paper can expand scanned angle to 360°, showing practical significance and application value in the field of beam scanning. This is achieved by using reflectors and multiple transmitter and receiver structures with optimized positions and transmission directions. Simulation results show that the scanning range is 360° and ±14∘ in the horizontal and vertical directions, respectively, at 110 m while the angular resolution is 0.2∘×2∘.

Germline mutation analyses of malignant ground glass opacity nodules in non-smoking lung adenocarcinoma patients.

BACKGROUND: Germline mutations play an important role in the pathogenesis of lung cancer. Nonetheless, research on malignant ground glass opacity (GGO) nodules is limited. METHODS: A total of 13 participants with malignant GGO nodules were recruited in this study. Peripheral blood was used for exome sequencing, and germline mutations were analyzed using InterVar. The whole exome sequencing dataset was analyzed using a filtering strategy. KOBAS 3.0 was used to analyze KEGG pathway to further identify possible deleterious mutations. RESULTS: There were seven potentially deleterious germline mutations. NM_001184790:exon8: c.C1070T in PARD3, NM_001170721:exon4:c.C392T in BCAR1 and NM_001127221:exon46: c.G6587A in CACNA1A were present in three cases each; rs756875895 frameshift in MAX, NM_005732: exon13:c.2165_2166insT in RAD50 and NM_001142316:exon2:c.G203C in LMO2, were present in two cases each; one variant was present in NOTCH3. CONCLUSIONS: Our results expand the germline mutation spectrum in malignant GGO nodules. Importantly, these findings will potentially help screen the high-risk population, guide their health management, and contribute to their clinical treatment and determination of prognosis.

Graphene-Based Polarization-Independent Mid-Infrared Electro-Absorption Modulator Integrated in a Chalcogenide Glass Waveguide.

A polarization-insensitive graphene-based mid-infrared optical modulator is presented that comprised SiO2/ Ge23Sb7S70, in which two graphene layers are embedded with a semiellipse layout to support transverse magnetic (TM) and transverse electric (TE) polarizing modes with identical absorption. The key performance index for the polarization independent modulator is polarization-sensitivity loss (PSL). The waveguide of our device just supports basic TE and TM modes, and the PSL between two modes is of < 0.24 dB. The model can offer extinction ratio (ER) more than 16 dB and insertion loss less than 1 dB. The operation spectrum ranges from 2 to 2.4 µm with optical bandwidth of 400 nm. The 3 dB modulation bandwidth is as high as 136 GHz based on theoretical calculation.

Highly linear wavelength-tunable microring-assisted Mach-Zehnder modulator.

This paper proposes a wavelength-tunable microring-assisted Mach-Zehnder modulator (MRAMZM) based on the graphene structure. The integrated graphene on the racetrack microring achieves the tunability of the working wavelength and introduces the one-cycle loss of the microring corresponding to the working wavelength. Through the analysis of the modulation characteristic curve with loss, it is determined to eliminate the second- and third-order nonlinearities. The graphene-embedded asymmetric coupling structure is used to control the coupling efficiency, and finally, the linearity of the device in the range of 2 nm (1.5543 to 1.5562 µm) is improved. The simulation result shows that when the working wavelength is in this range, the spurious-free dynamic range third-order intermodulation distortion of this modulator is about 114dB⋅Hz2/3.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis.

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS: LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Epidermal Growth Factor Receptor Mutations in Resectable Non-Small Cell Lung Cancer Patients and their Potential Role in the Immune Landscape.

BACKGROUND The epidermal growth factor receptor (EGFR) is a therapeutic target for non-small cell lung cancer (NSCLC), but knowledge on gene mutations that contribute to NSCLC development and persistence is lacking. In this study, we investigated genetic variations in EGFR and their association with the clinical and pathological factors of NSCLC. MATERIAL AND METHODS Clinical cases (331 patients) and The Cancer Genome Atlas (TCGA) cases (1040 patients) were selected and analyzed using the refractory mutation systems cBioPortal and the Tumor Immune Estimation Resource (TIMER). RESULTS EGFR mutation frequencies were 54.4% (180 of 331 patients) and 8.0% (83 of 1040 patients) in the clinical and TCGA cohorts, respectively. EGFR mutations were strongly associated with smoking and pathology (P≤0.05) in the clinical cohort, and with gender, smoking, and pathology (P=0.001, P<0.001, and P<0.001, respectively) in TCGA cohort. In cases of lung squamous carcinoma (LUSC), EGFR was overexpressed as a result of DNA amplification, but this amplified expression showed no association with the overall survival (OS) or progression-free survival of LUSC patients. EGFR gene alterations were, however, associated with worse OS in lung adenocarcinoma (LUAD) patients. Immune cell infiltrates from LUAD and LUSC tumors differed according to EGFR expression. EGFR mutations resulted in a decline of immune infiltration or a lack of infiltrating immune cells in the NSCLC microenvironment. CONCLUSIONS Mutational profiles of the EGFR in NSCLC patients provide useful information for the use of tyrosine kinase inhibitors for adjuvant or neoadjuvant therapy and immunotherapy.

Isolation and Retrieval of Extracellular Vesicles for Liquid Biopsy of Malignant Ground-Glass Opacity.

Extracellular vesicles (EVs) are cell-released vesicles of submicrometer size. EVs contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Recent studies validate that EVs can be used for cancer diagnostics, staging, and treatment monitoring. EV-related clinical translation requires effective EV isolation as a prerequisite. However, lengthy procedures, low yield, low throughput, and high levels of contaminants disqualify the existing isolation approaches for large-scale clinical use. Hence, new approaches for rapid, efficient, and low-cost isolation of EVs in high purity for flexible analyses of the diverse contents in real-world clinical settings are highly desired yet are currently unavailable. Here, we report the effective use of heparin/polymer-coated microspheres (HPM) for EV isolation and retrieval. Approximately 81% of EVs can be isolated from plasma in 1 h with depletion of ∼99.5% plasma protein and nucleic acid contaminants, and 72% of isolated EVs can be retrieved with saline in 5 min for various cargo analyses. This approach was further validated with clinical samples derived from patients with malignant ground-glass opacity (GGO). In eight patients, the mutation concordance between EV DNA and tissue DNA is 39.8%. The prevalence and mutation count of EGFR, TP53, and NF1 are higher than those of other oncogenes and antioncogenes that are intensely associated with lung adenocarcinoma. Moreover, different mutation prevalence and patterns between smokers and nonsmokers can be observed. Our findings suggest that the combination of HPM assay and targeted sequencing of EV DNA could be translated in the differential diagnosis of malignant GGO with short turnaround time.

40 Gb/s all-optical unicast and multicast wavelength converter array on an InP monolithically integrated chip fabricated by MPW technology.

We present an InP monolithically integrated all-optical wavelength converter array chip and experimentally validate its performance for unicast (single output wavelength) and multicast (multiple output wavelengths) wavelength conversion. The monolithically integrated chip includes four semiconductor optical amplifiers with an arrayed-waveguide grating and two delayed interferometers. The chip is fabricated on a multi-project wafer (MPW) platform, which allows multiple designers to share space on the same wafer exploiting a generic integration platform. We demonstrate error-free non-return-to-zero (NRZ) unicast wavelength conversions using 231-1 pseudorandom bit sequence data at 10 Gb/s, 20 Gb/s and 40 Gb/s with a 25-nm conversion range. Power penalties as low as 2.3 dB and 2.7 dB for NRZ and return-to-zero (RZ) unicast wavelength conversion at 40 Gb/s are obtained, respectively. Additionally, power penalties of 2.5 dB for NRZ and 3.2 dB for RZ signals at 40 Gb/s 1 × 2 multicast wavelength conversions are also achieved.

Multiport InP monolithically integrated all-optical wavelength router.

An indium phosphide-based monolithically integrated wavelength router is demonstrated in this Letter. The wavelength router has four input ports and four output ports, which integrate four wavelength converters and a 4×4 arrayed-waveguide grating router. Each wavelength converter is achieved based on cross-gain modulation and cross-phase modulation effects in a semiconductor optical amplifier. Error-free wavelength switching for a non-return-to-zero 231-1 ps eudorandom binary sequence at 40 Gb/s data rate is performed. Both 1×4 and 3×1 all-optical routing functions of this chip are demonstrated for the first time with power penalties as low as 3.2 dB.

Tunable and switchable dual-wavelength mode-locked Tm3+-doped fiber laser based on a fiber taper.

We demonstrate a self-starting dual-wavelength mode-locked fiber laser at a 2 µm spectral region by using a fiber taper in a Tm3+-doped ring fiber cavity. The fiber taper fabricated with a flame brushing technique was used as a periodic filter with a modulation depth of ~3.61 dB and a modulation period of ~7.3 nm, respectively. Diverse dual-wavelength regimes including continuous wave (CW)/multi-soliton, soliton/multi-soliton, and soliton/soliton regimes were obtained by adjusting pump power. Wavelength tuning for the dual-wavelength was also precisely controllable through stretching the fiber taper carefully. The tuning range was ~7 nm which was limited by the modulation period of the taper. By inserting a 10.0 m dispersion compensation fiber (DCF) into the fiber cavity, a stable dual-wavelength dissipative-soliton operation was obtained at 2 µm spectral region for the first time.

Black phosphorus: a two-dimension saturable absorption material for mid-infrared Q-switched and mode-locked fiber lasers.

Black phosphorus (BP) as a novel class of two-dimension (2D) materials has recently attracted enormous attention as a result of its unique physical and chemical features. The remarkably strong light-matter interaction and tunable direct band-gap at a wide range make it an ideal candidate especially in the mid-infrared wavelength region as the saturable absorber (SA). In this paper, the simple and effective liquid phase exfoliation (LPE) method was used to fabricate BP. By introducing the same BP SA into two specifically designed rare earth ions doped fluoride fiber lasers at mid-infrared wavebands, Q-switching with the pulse energy of 4.93 µJ and mode-locking with the pulse duration of 8.6 ps were obtained, respectively. The operation wavelength of ~2970 nm for generated pulse is the reported longest wavelength for BP SA based fiber lasers.

Calibration-free absolute frequency response measurement of directly modulated lasers based on additional modulation.

A calibration-free electrical method is proposed for measuring the absolute frequency response of directly modulated semiconductor lasers based on additional modulation. The method achieves the electrical domain measurement of the modulation index of directly modulated lasers without the need for correcting the responsivity fluctuation in the photodetection. Moreover, it doubles measuring frequency range by setting a specific frequency relationship between the direct and additional modulation. Both the absolute and relative frequency response of semiconductor lasers are experimentally measured from the electrical spectrum of the twice-modulated optical signal, and the measured results are compared to those obtained with conventional methods to check the consistency. The proposed method provides calibration-free and accurate measurement for high-speed semiconductor lasers with high-resolution electrical spectrum analysis.