Remote Sensing Image Scene Classification in Hybrid Classical-Quantum Transferring CNN with Small Samples.

The scope of this research lies in the combination of pre-trained Convolutional Neural Networks (CNNs) and Quantum Convolutional Neural Networks (QCNN) in application to Remote Sensing Image Scene Classification(RSISC). Deep learning (RL) is improving by leaps and bounds pretrained CNNs in Remote Sensing Image (RSI) analysis, and pre-trained CNNs have shown remarkable performance in remote sensing image scene classification (RSISC). Nonetheless, CNNs training require massive, annotated data as samples. When labeled samples are not sufficient, the most common solution is using pre-trained CNNs with a great deal of natural image datasets (e.g., ImageNet). However, these pre-trained CNNs require a large quantity of labelled data for training, which is often not feasible in RSISC, especially when the target RSIs have different imaging mechanisms from RGB natural images. In this paper, we proposed an improved hybrid classical-quantum transfer learning CNNs composed of classical and quantum elements to classify open-source RSI dataset. The classical part of the model is made up of a ResNet network which extracts useful features from RSI datasets. To further refine the network performance, a tensor quantum circuit is subsequently employed by tuning parameters on near-term quantum processors. We tested our models on the open-source RSI dataset. In our comparative study, we have concluded that the hybrid classical-quantum transferring CNN has achieved better performance than other pre-trained CNNs based RSISC methods with small training samples. Moreover, it has been proven that the proposed algorithm improves the classification accuracy while greatly decreasing the amount of model parameters and the sum of training data.

Pan-ERBB kinase inhibition augments CDK4/6 inhibitor efficacy in oesophageal squamous cell carcinoma.

OBJECTIVE: Oesophageal squamous cell carcinoma (OSCC), like other squamous carcinomas, harbour highly recurrent cell cycle pathway alterations, especially hyperactivation of the CCND1/CDK4/6 axis, raising the potential for use of existing CDK4/6 inhibitors in these cancers. Although CDK4/6 inhibition has shown striking success when combined with endocrine therapy in oestrogen receptor positive breast cancer, CDK4/6 inhibitor palbociclib monotherapy has not revealed evidence of efficacy to date in OSCC clinical studies. Herein, we sought to elucidate the identification of key dependencies in OSCC as a foundation for the selection of targets whose blockade could be combined with CDK4/6 inhibition. DESIGN: We combined large-scale genomic dependency and pharmaceutical screening datasets with preclinical cell line models, to identified potential combination therapies in squamous cell cancer. RESULTS: We identified sensitivity to inhibitors to the ERBB family of receptor kinases, results clearly extending beyond the previously described minority of tumours with EGFR amplification/dependence, specifically finding a subset of OSCCs with dual dependence on ERBB3 and ERBB2. Subsequently. we demonstrated marked efficacy of combined pan-ERBB and CDK4/6 inhibition in vitro and in vivo. Furthermore, we demonstrated that squamous lineage transcription factor KLF5 facilitated activation of ERBBs in OSCC. CONCLUSION: These results provide clear rationale for development of combined ERBB and CDK4/6 inhibition in these cancers and raises the potential for KLF5 expression as a candidate biomarker to guide the use of these agents. These data suggested that by combining existing Food and Drug Administration (FDA)-approved agents, we have the capacity to improve therapy for OSCC and other squamous cancer.

Patterns of chromosome 18 loss of heterozygosity in multifocal ileal neuroendocrine tumors.

Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.

Design, Fabrication and Characterization of a MEMS-Based Three-Dimensional Electric Field Sensor with Low Cross-Axis Coupling Interference.

One of the major concerns in the development of three-dimensional (3D) electric field sensors (EFSs) is their susceptibility to cross-axis coupling interference. The output signal for each sensing axis of a 3D EFS is often coupled by electric field components from the two other orthogonal sensing axes. In this paper, a one-dimensional (1D) electric field sensor chip (EFSC) with low cross-axis coupling interference is presented. It is designed to be symmetrical, forming a pair of in-plane symmetrically-located sensing structures. Using a difference circuit, the 1D EFSC is capable of sensing parallel electric fields along symmetrical structures and eliminating cross-axis coupling interference, which is contrast to previously reported 1D EFSCs designed for perpendicular electric field component measurement. Thus, a 3D EFS with low cross-axis coupling interference can be realized using three proposed 1D EFSCs. This 3D EFS has the advantages of low cross-axis coupling interference, small size, and high integration. The testing and calibration systems of the proposed 3D EFS were developed. Experimental results show that in the range of 0-120 kV/m, cross-axis sensitivities are within 5.48%, and the total measurement errors of this 3D EFS are within 6.16%.

A High Sensitivity Electric Field Microsensor Based on Torsional Resonance.

This paper proposes a high sensitivity electric field microsensor (EFM) based on torsional resonance. The proposed microsensor adopts torsional shutter, which is composed of shielding electrodes and torsional beams. The movable shielding electrodes and the fixed sensing electrodes are fabricated on the same plane and interdigitally arranged. Push-pull electrostatic actuation method is employed to excite the torsional shutter. Simulation results proved that the torsional shutter has higher efficiency of charge induction. The optimization of structure parameters was conducted to improve its efficiency of charge induction further. A micromachining fabrication process was developed to fabricate the EFM. Experiments were conducted to characterize the EFM. A good linearity of 0.15% was achieved within an electrostatic field range of 0-50 kV/m, and the uncertainty was below 0.38% in the three roundtrip measurements. A high sensitivity of 4.82 mV/(kV/m) was achieved with the trans-resistance of 100 MΩ, which is improved by at least one order of magnitude compared with previously reported EFMs. The efficiency of charge induction for this microsensor reached 48.19 pA/(kV/m).

mrskn7, a putative response regulator gene of Monascus ruber M7, is involved in oxidative stress response, development, and mycotoxin production.

Skn7, a response regulator (RR), is associated with oxidative stress adaptation, hypo-osmotic stress response, fungicide sensitivity, cell wall biosynthesis, cell cycle regulation, sexual mating, and sporulation in many filamentous fungi and yeasts. In this study a Skn7-like protein gene mrskn7 (Monascus ruber skn7) was isolated, sequenced, and disrupted to investigate its function in M. ruber Bioinformatics predicted that the deduced protein encoded by mrskn7 contained the conserved DNA-binding and signal-receiver domains similar to the Skn7-like protein structure in other filamentous fungi. The Δmrskn7 strain produced fewer conidia and less mycotoxin, demonstrated increased sensitivity to peroxide but the same level of osmotic resistance to NaCl and glycerol with the wild-type. Additionally, cleistothecia observed at different time point showed a different morphology between the wild-type and the Δmrskn7 strain, suggesting the involvement of mrskn7 in sexual development of M. ruber These results indicated that mrskn7 plays important roles in asexual and sexual development, the production of mycotoxin as well as regulation of oxidative stress signal in M. ruber.

[Effects of aerosol optical thickness on the optical remote sensing imaging quality].

In recent years, due to changes in atmospheric environment, atmospheric aerosol affection on optical sensor imaging quality is increasingly considered by the load developed departments. Space-based remote sensing system imaging process, atmospheric aerosol makes optical sensor imaging quality deterioration. Atmospheric medium causing image degradation is mainly forward light scattering effect caused by the aerosol turbid medium. Based on the turbid medium radiation transfer equation, the point spread function models were derived contained aerosol optical properties of atmosphere in order to analyze and evaluate the atmospheric blurring effect on optical sensor imaging system. It was found that atmospheric aerosol medium have effect on not only energy decay of atmospheric transmittance, but also the degradation of image quality due to the scattering effect. Increase of atmospheric aerosol optical thickness makes aerosol scattering intensity enhanced, variation of aerosol optical thickness is also strongly influences the point spread function of the spatial distribution. it is because the degradation of aerosol in spatial domain, which reduces the quality of remote sensing image, in particularly reduction of the sharpness of image. Meanwhile, it would provide a method to optimize and improve simulation of atmospheric chain.

XRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells.

Emerging data suggest that induction of viral mimicry responses through activation of double-stranded RNA (dsRNA) sensors in cancer cells is a promising therapeutic strategy. One approach to induce viral mimicry is to target molecular regulators of dsRNA sensing pathways. Here, we show that the exoribonuclease XRN1 is a negative regulator of the dsRNA sensor protein kinase R (PKR) in cancer cells with high interferon-stimulated gene expression. XRN1 deletion causes PKR pathway activation and consequent cancer cell lethality. Disruption of interferon signaling with the JAK1/2 inhibitor ruxolitinib can decrease cellular PKR levels and rescue sensitivity to XRN1 deletion. Conversely, interferon-ß stimulation can increase PKR levels and induce sensitivity to XRN1 inactivation. Lastly, XRN1 deletion causes accumulation of endogenous complementary sense/anti-sense RNAs, which may represent candidate PKR ligands. Our data demonstrate how XRN1 regulates PKR and how this interaction creates a vulnerability in cancer cells with an activated interferon cell state.

[Modeling continuous scaling of NDVI based on fractal theory].

Scale effect was one of the very important scientific problems of remote sensing. The scale effect of quantitative remote sensing can be used to study retrievals' relationship between different-resolution images, and its research became an effective way to confront the challenges, such as validation of quantitative remote sensing products et al. Traditional up-scaling methods cannot describe scale changing features of retrievals on entire series of scales; meanwhile, they are faced with serious parameters correction issues because of imaging parameters' variation of different sensors, such as geometrical correction, spectral correction, etc. Utilizing single sensor image, fractal methodology was utilized to solve these problems. Taking NDVI (computed by land surface radiance) as example and based on Enhanced Thematic Mapper Plus (ETM+) image, a scheme was proposed to model continuous scaling of retrievals. Then the experimental results indicated that: (a) For NDVI, scale effect existed, and it could be described by fractal model of continuous scaling; (2) The fractal method was suitable for validation of NDVI. All of these proved that fractal was an effective methodology of studying scaling of quantitative remote sensing.

Shedding light on macrophage immunotherapy in lung cancer.

The search for therapeutic options for lung cancer continues to advance, with rapid advances in the search for therapies to improve patient prognosis. At present, systemic chemotherapy, immune checkpoint inhibitor therapy, antiangiogenic therapy, and targeted therapy for driver gene positivity are available in the clinic. Common clinical treatments fail to achieve desired outcomes due to immunosuppression of the tumor microenvironment (TME). Tumor immune evasion is mediated by cytokines, chemokines, immune cells, and other cells such as vascular endothelial cells within the tumor immune microenvironment. Tumor-associated macrophages (TAMs) are important immune cells in the TME, inducing tumor angiogenesis, encouraging tumor cell proliferation and migration, and suppressing antitumor immune responses. Thus, TAM targeting becomes the key to lung cancer immunotherapy. This review focuses on macrophage phenotype, polarization mechanism, role in lung cancer, and advances in macrophage centric immunotherapies.

A Highly Sensitive and High-Resolution Resonant MEMS Electrostatic Field Microsensor Based on Electrostatic Stiffness Perturbation.

This paper proposes a highly sensitive and high-resolution resonant MEMS electrostatic field sensor based on electrostatic stiffness perturbation, which uses resonant frequency as an output signal to eliminate the feedthrough interference from the driving voltage. The sensor is composed of a resonator, driving electrode, detection electrode, transition electrode, and electrostatic field sensing plate. The working principle is that when there is an electrostatic field, an induction charge will appear at the surface of the electrostatic field sensing plate and induce electrostatic stiffness on the resonator, which will cause a resonant frequency shift. The resonant frequency is used as the output signal of the microsensor. The characteristics of the electrostatic field sensor are analyzed with a theoretical model and verified by finite element simulation. A device prototype is fabricated based on the Silicon on Insulator (SOI) process and tested under vacuum conditions. The results indicate that the sensitivity of the sensor is 0.1384Hz/(kV/m) and the resolution is better than 10 V/m.

XRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells.

Emerging data suggest that induction of viral mimicry responses through activation of double-stranded RNA (dsRNA) sensors in cancer cells is a promising therapeutic strategy. One approach to induce viral mimicry is to target molecular regulators of dsRNA sensing pathways. Here, we show that the exoribonuclease XRN1 is a negative regulator of the dsRNA sensor protein kinase R (PKR) in cancer cells with high interferon-stimulated gene (ISG) expression. XRN1 deletion causes PKR activation and consequent cancer cell lethality. Disruption of interferon signaling with the JAK1/2 inhibitor ruxolitinib can decrease cellular PKR levels and rescue sensitivity to XRN1 deletion. Conversely, interferon-ß stimulation can increase PKR levels and induce sensitivity to XRN1 inactivation. Lastly, XRN1 deletion causes accumulation of endogenous complementary sense/anti-sense RNAs, which may represent candidate PKR ligands. Our data demonstrate how XRN1 regulates PKR and nominate XRN1 as a potential therapeutic target in cancer cells with an activated interferon cell state.

Pharmacogenetic role of ERCC1 genetic variants in treatment response of platinum-based chemotherapy among advanced non-small cell lung cancer patients.

The excision repair cross-complementation group 1 (ERCC1) plays an essential role in DNA repair and has been linked to resistance to platinum-based anticancer drugs among advanced non-small cell lung cancer (NSCLC) patients. We systematically evaluate whether ERCC1 Asn118Asn and C8092A genetic variants are associated with treatment response of platinum chemotherapy. We preformed a meta-analysis using ten eligible cohort studies (including 11 datasets) with a total of 1,252 NSCLC patients to summarize the existing data on the association between the ERCC1 Asn118Asn and C8092A polymorphisms and response to platinum regiments. Odds ratio or hazard ratio with 95% confidence interval were calculated to estimate the correlation. We found that neither ERCC1 C8092A polymorphism nor Asn118Asn variant is associated with different response of platinum-based treatment among advanced NSCLC patients. Additionally, these two genetic variants are not related to treatment response in either Caucasian patients or Asian patients. Our meta-analysis indicates that the ERCC1 Asn118Asn and C8092A polymorphisms may not be good prognostic biomarkers for platinum-based chemotherapy in patients with stage III-IV NSCLC.

Functional Genomic Analysis of CDK4 and CDK6 Gene Dependency across Human Cancer Cell Lines.

Cyclin-dependent kinase 4 (CDK4) and CDK6 are key cell-cycle regulators that are frequently dysregulated in human malignancies. CDK4/6 inhibitors are clinically approved for the treatment of hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer, but improved specificity and reduced toxicity might expand their use to other indications. Through analysis of publicly available genome-wide loss-of-function data combined with single and dual-targeting CRISPR assays, we found differential cell proliferation vulnerability of cell lines to either CDK4 deletion alone, CDK6 deletion alone, combined CDK4/CDK6 deletion, or neither. CDK6 expression was the best single predictor of CDK4 (negatively correlated) and CDK6 (positively correlated) dependencies in the cancer cell lines, with adenocarcinoma cell lines being more sensitive to CDK4 deletion and hematologic and squamous cancer cell lines being more sensitive to CDK6 deletion. RB-E2F signaling was confirmed as a main downstream node of CDK4/6 in these experiments as shown by the survival effects of RB1 deletion. Finally, we show in a subset of cancer cell lines not dependent on CDK4/6 that CDK2-CCNE1 is an important alternative dependency for cell proliferation. Together, our comprehensive data exploration and functional experiments delineate the landscape of pan-cancer CDK4/6 gene dependencies and define unique cancer cell populations that might be sensitive to CDK4-selective or CDK6-selective inhibitors. SIGNIFICANCE: This study provides functional genomic insight toward understanding the scenarios in which cancer cells are differentially sensitive to CDK4 or CDK6 inhibition and their implications in current treatment strategies.

LncRNA in tumorigenesis of non-small-cell lung cancer: From bench to bedside.

Lung cancer has been one of the leading causes of cancer-related death worldwide, and non-small-cell lung cancer (NSCLC) accounts for the majority of lung cancer morbidity, yet the pathogenesis of NSCLC has not been fully elucidated. Recently, long-chain non-coding RNA (lncRNA) has attracted widespread attention. LncRNA is a type of non-coding RNA whose transcript length exceeds 200 nucleotides. After constant research, academics updated their understanding of lncRNA, especially its role in the biological processes of cancer cells, including epigenetic regulation, cell proliferation, and cell differentiation. Notably, examination of lncRNAs could serve as potential hallmarks for clinicopathological features, long-term prognosis, and drug sensitivity. Therefore, it is necessary to explore the functions of lncRNA in NSCLC and innovate potential strategies against NSCLC based on lncRNA-related research. Herein, we reviewed the functions of lncRNA in the occurrence, diagnosis, treatment, and prognosis of NSCLC, which not only help promote a comprehensive view of lncRNA in NSCLC, but also shed light on the potential of lncRNA-based diagnosis and treatment of NSCLC.

Cuproptosis predicts the risk and clinical outcomes of lung adenocarcinoma.

Copper is an essential microelement for the body and a necessary coregulator for enzymatic reactions, yet an unbalanced copper level promotes reactive oxidation and cytotoxicity, which ultimately induces cell death. Several small molecules targeting copper-induced cell death have been investigated, yet few showed promising therapeutic effects in clinical trials. In March 2022, Science first introduced the concept and mechanisms of cuproptosis, suggesting that copper-induced cell death targets the tricarboxylic acid (TCA) cycle via protein lipoylation. Does this novel form of cell death take part in tumorigenesis or tumor progression? Is cuproptosis related to clinical outcomes of diseases? Is there a cuproptosis-related panel for clinical practice in cancer treatment? Herein, based on 942 samples of lung adenocarcinoma (LUAD), we analyzed on gene set level the existence and predictive value of cuproptosis in disease diagnosis and treatment. We screened out and identified the "cupLA" panel which indicates the risk of LUAD occurrence, clinicopathological features of LUAD patients, and could guide clinicians to refine LUAD subtypes and make treatment choices.

Cutting edges and therapeutic opportunities on tumor-associated macrophages in lung cancer.

Lung cancer is a disease with remarkable heterogeneity. A deep understanding of the tumor microenvironment (TME) offers potential therapeutic strategies against this malignant disease. More and more attention has been paid to the roles of macrophages in the TME. This article briefly summarizes the origin of macrophages, the mutual regulation between anti-tumoral immunity and pro-tumoral statuses derived from macrophage polarization, and the therapeutic opportunities targeting alternately activated macrophages (AAM)-type macrophage polarization. Among them, cellular components including T cells, as well as acellular components represented by IL-4 and IL-13 are key regulators driving the polarization of AAM macrophages. Novel treatments targeting macrophage-associated mechanisms are mainly divided into small molecule inhibitors, monoclonal antibodies, and other therapies to re-acclimate AMM macrophages. Finally, we paid special attention to an immunosuppressive subgroup of macrophages with T cell immunoglobulin and mucin domain-3 (TIM-3) expression. Based on cellular interactions with cancer cells, TIM3+ macrophages facilitate the proliferation and progression of cancer cells, yet this process exposes targets blocking the ligand-receptor recognition. To sum up, this is a systematic review on the mechanism of tumor-associated macrophages (TAM) polarization, therapeutic strategies and the biological functions of Tim-3 positive macrophages that aims to provide new insights into the pathogenesis and treatment of lung cancer.

Wafer-Level Vacuum-Packaged Electric Field Microsensor: Structure Design, Theoretical Model, Microfabrication, and Characterization.

This paper proposes a novel wafer-level vacuum packaged electric field microsensor (EFM) featuring a high quality factor, low driving voltage, low noise, and low power consumption. The silicon-on-insulator (SOI) conductive handle layer was innovatively used as the sensing channel to transmit the external electric field to the surface of the sensitive structure, and the vacuum packaging was realized through anodic bonding between the SOI and glass-on-silicon (GOS). The fabrication process was designed and successfully realized, featured with a simplified process and highly efficient batch manufacturing, and the final chip size was only 5 × 5 mm. A theoretical model for the packaged device was set up. The influence of key parameters in the packaging structure on the output characteristics of the microsensor was analyzed on the basis of the proposed model. Experiments were conducted on the wafer-level vacuum-packaged EFM to characterize its performance. Experimental results show that, under the condition of applying 5 V DC driving voltage, the required AC driving voltage of the sensor was only 0.05 VP, and the feedthrough was only 4.2 mV. The quality factor was higher than 5000 and was maintained with no drop in the 50-day test. The vacuum in the chamber of the sensor was about 10 Pa. A sensitivity of 0.16 mV/(kV/m) was achieved within the electrostatic field range of 0-50 kV/m. The linearity of the microsensor was 1.62%, and the uncertainty was 4.42%.

Whole genome sequencing reveals the independent clonal origin of multifocal ileal neuroendocrine tumors.

BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are the most common neoplasms of the small bowel. The majority of tumors are located in the distal ileum with a high incidence of multiple synchronous primary tumors. Even though up to 50% of SI-NET patients are diagnosed with multifocal disease, the mechanisms underlying multiple synchronous lesions remain elusive. METHODS: We performed whole genome sequencing of 75 de-identified synchronous primary tumors, 15 metastases, and corresponding normal samples from 13 patients with multifocal ileal NETs to identify recurrent somatic genomic alterations, frequently affected signaling pathways, and shared mutation signatures among multifocal SI-NETs. Additionally, we carried out chromosome mapping of the most recurrent copy-number alterations identified to determine which parental allele had been affected in each tumor and assessed the clonal relationships of the tumors within each patient. RESULTS: Absence of shared somatic variation between the synchronous primary tumors within each patient was observed, indicating that these tumors develop independently. Although recurrent copy-number alterations were identified, additional chromosome mapping revealed that tumors from the same patient can gain or lose different parental alleles. In addition to the previously reported CDKN1B loss-of-function mutations, we observed potential loss-of-function gene alterations in TNRC6B, a candidate tumor suppressor gene in a small subset of ileal NETs. Furthermore, we show that multiple metastases in the same patient can originate from either one or several primary tumors. CONCLUSIONS: Our study demonstrates major genomic diversity among multifocal ileal NETs, highlighting the need to identify and remove all primary tumors, which have the potential to metastasize, and the need for optimized targeted treatments.

An Electric Field Microsensor with Mutual Shielding Electrodes.

This paper proposes an electric field microsensor (EFM) with mutual shielding electrodes. Based on the charge-induction principle, the EFM consists of fixed electrodes and piezoelectric-driving vertically-movable electrodes. All the fixed electrodes and movable electrodes work as both sensing electrodes and shielding electrodes. In other words, all the fixed and movable electrodes are sensing electrodes, and they are mutually shielding electrodes simultaneously. The movable electrodes are driven to periodically modulate the electric field distribution at themselves and the fixed electrodes, and the induced currents from both movable and fixed electrodes are generated simultaneously. The electrode structure adopts an interdigital structure, and the EFM has been simulated by finite element methods. Simulation results show that, since the sensing area of this EFM is doubled, the variation of induced charge is twice, and therefore the output signal of the sensor is increased. The piezoelectric material, lead zirconate titanate (PZT), is prepared by the sol-gel method, and the microsensor chip is fabricated.