Non-line-of-sight optical wireless communication system enabled by wavefront shaping for multi-user indoor access.

In this Letter, we experimentally investigate a non-line-of-sight (NLOS) optical wireless communication (OWC) system that utilizes wavefront shaping techniques to realize simultaneous data transmission for multiple users. Wavefront shaping techniques are employed to address the issue of low intensity of diffusely reflected light at the receiver in NLOS scenarios for indoor high-speed access. To achieve communication path planning and tracing for two different users in free-space optical communication, the pixels of the spatial light modulator (SLM) are divided into two halves to separately manipulate the wavefront of two independent data carriers centered at different wavelengths. The maximum received optical power can be effectively improved by more than 15 dB with the wavefront shaping technique. To avoid power enhancement of non-target wavelength, the wavelength difference of two different users is experimentally studied. The difference in power enhancement ratio (DPER) is increased with the wavelength difference, and 14.95 dB DPER is obtained with a 10 nm wavelength difference. Under the aforementioned wavelength planning strategy, successful transmission and reception of 2 × 160 Gbit/s 16-QAM signals for two users with coherent detection is achieved using wavelengths of 1550 and 1560 nm in an indoor access scenario.

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.

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.

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∘.

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.

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.

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.

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.

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.

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.

Extinction-ratio-independent electrical method for measuring chirp parameters of Mach-Zehnder modulators using frequency-shifted heterodyne.

An extinction-ratio-independent electrical method is proposed for measuring chirp parameters of Mach-Zehnder electric-optic intensity modulators based on frequency-shifted optical heterodyne. The method utilizes the electrical spectrum analysis of the heterodyne products between the intensity modulated optical signal and the frequency-shifted optical carrier, and achieves the intrinsic chirp parameters measurement at microwave region with high-frequency resolution and wide-frequency range for the Mach-Zehnder modulator with a finite extinction ratio. Moreover, the proposed method avoids calibrating the responsivity fluctuation of the photodiode in spite of the involved photodetection. Chirp parameters as a function of modulation frequency are experimentally measured and compared to those with the conventional optical spectrum analysis method. Our method enables an extinction-ratio-independent and calibration-free electrical measurement of Mach-Zehnder intensity modulators by using the high-resolution frequency-shifted heterodyne technique.

Electro-absorption optical modulator using dual-graphene-on-graphene configuration.

An electro-absorption optical modulator based on dual-graphene-on-graphene configuration is presented and investigated. Four graphene layers are embedded in a silicon-on-insulator (SOI) waveguide, the total metal-graphene contact resistance of this structure is reduced 50% by the graphene layers co-electrode design. By optimizing the position of each graphene-on-graphene (GOG) layer in the waveguide, a strong interaction between graphene layers and light is obtained, which leads to a significant change of the effective mode index (EMI) in the waveguide. Calculations show that an electro-absorption optical modulator can achieve 34 dB extinction ratio (ER) and 100 GHz modulation bandwidth with 5 µm-long active region and 17.6 fJ/bit consumption.

Self-calibrating measurement of high-speed electro-optic phase modulators based on two-tone modulation.

We propose a self-calibrating method for high-frequency response measurement of electro-optic phase modulators based on two-tone modulation. The method utilizes the electrical domain measurement of heterodyning spectrum between the two-tone modulation optical signal and the frequency-shifted optical carrier, and eliminates the need to correct the responsivity fluctuation in the photodetection. High-frequency modulation depth and half-wave voltages are measured and compared to those with the traditional optical spectrum analysis method in the experimental demonstration. The proposed method enables calibration-free and accurate frequency response measurement of electro-optic phase modulators by using high-resolution electrical spectrum analysis.

DNA methylation analysis in plasma for early diagnosis in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) represents the most prevalent type of lung cancer. SHOX2 and RASSF1A methylation have been identified as important biomarkers for diagnosis and prognosis of lung cancer. Bronchoalveolar lavage fluid (BALF) exhibits good specificity and sensitivity in diagnosing pulmonary diseases, but its acquisition is challenging and may cause discomfort to patients. In clinical, plasma samples are more convenient to obtain than BALF; however, there is little research on the concurrent detection of SHOX2 and RASSF1A methylation in plasma. This study aims to assess the diagnostic value of a combined promoter methylation assay for SHOX2 and RASSF1A in early-stage LUAD using plasma samples. METHODS: BALF and blood samples were obtained from 36 early-stage LUAD patients, with a control group of nineteen non-tumor individuals. The promoter methylation levels of SHOX2 and RASSF1A in all subjects were assessed using the human SHOX2 and RASSF1A gene methylation kit. RESULTS: The methylation detection rate of SHOX2 and RASSF1A in plasma was 61.11%, slightly lower than that in BALF (66.7%). The Chi-square test revealed no significant difference in the methylation rate between BALF and plasma (P > 0.05). The area under the receiver operating characteristic (ROC) curve analysis for blood was 0.806 (95% CI, 0.677 to 0.900), while for BALF it was 0.781 (95% CI, 0.649 to 0.881). Additionally, we conducted an analysis on the correlation between SHOX2 and RASSF1A methylation levels in plasma with gender, age, tumor differentiation, pathologic classification, and other clinicopathological variables; however, no significant correlations were observed. CONCLUSIONS: Measurement of SHOX2 and RASSF1A methylation for early diagnosis of LUAD can be achieved with high sensitivity and specificity by using plasma as a substitute for BALF samples.

The diagnostic potential role of thioredoxin reductase and TXNRD1 in early lung adenocarcinoma: A cohort study.

Background: Lung adenocarcinoma (LUAD) is the primary form of lung cancer, yet the reliable biomarkers for early diagnosis remain insufficient. Thioredoxin reductase (TrxR) is strongly linked to the occurrence, development, and drug resistance of lung cancer, making it a potential biomarker. However, further research is required to assess its diagnostic value in LUAD. Methods: A retrospective analysis was performed on patients who underwent pulmonary nodule resection at our center from 2018 to 2022. Clinical data, including preoperative TrxR levels, imaging, and laboratory characteristics, were identified as study variables. Two prediction models were constructed using multiple logistic regression, and their prediction performance was evaluated comprehensively. Besides, bioinformatics analyses of TrxR coding genes including differential expression, functional enrichment, immune infiltration, drug sensitivity, and single-cell landscape were performed based on TCGA database, which were subsequently validated by Human Protein Atlas. Results: A total of 506 eligible patients (72 benign lesions, 77 AISs, 185 MIAs and 172 IACs) were identified in the clinical cohort. Two TrxR-based models were developed, which were able to distinguish between benign and malignant pulmonary nodules, as well as pathological subtypes of LUAD, respectively. The models exhibited good predictive ability with all AUC values ranging from 0.7 to 0.9. Based on calibration curves and clinical decision analysis, the nomogram models showed high reliability. Functional analysis indicated that TXNRD1 primarily participated in cell cycle and lipid metabolism. Immune infiltration analysis showed that TXNRD1 has a strong association with immune cells and could impact immunotherapy. Then, we identified small molecular compounds that inhibit TXNRD1 and confirmed TXNRD1 expression by single-cell landscape and immunohistochemistry. Conclusion: This study validated the diagnostic value of TrxR and TXNRD1 in clinical cohorts and transcriptional data, respectively. TrxR and TXNRD1 could be used in the risk diagnosis of early LUAD and facilitate personalized treatment strategies.

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.

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.

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.

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.].

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.