Design and Analysis of a Fluid-Filled RF MEMS Switch.

In the present study, a fluid-filled RF MEMS (Radio Frequency Micro-Electro-Mechanical Systems) switch is proposed and designed. In the analysis of the operating principle of the proposed switch, air, water, glycerol and silicone oil were adopted as filling dielectric to simulate and research the influence of the insulating liquid on the drive voltage, impact velocity, response time, and switching capacity of the RF MEMS switch. The results show that by filling the switch with insulating liquid, the driving voltage can be effectively reduced, while the impact velocity of the upper plate to the lower plate is also reduced. The high dielectric constant of the filling medium leads to a lower switching capacitance ratio, which affects the performance of the switch to some extent. By comparing the threshold voltage, impact velocity, capacitance ratio, and insertion loss of the switch filled with different media with the filling media of air, water, glycerol, and silicone oil, silicone oil was finally selected as the liquid filling medium for the switch. The results show that the threshold voltage is 26.55 V after filling with silicone oil, which is 43% lower under the same air-encapsulated switching conditions. When the trigger voltage is 30.02 V, the response time is 10.12 µs and the impact speed is only 0.35 m/s. The frequency 0-20 GHz switch works well, and the insertion loss is 0.84 dB. To a certain extent, it provides a reference value for the fabrication of RF MEMS switches.

Design and synthesis of novel GluN2A NMDAR positive allosteric modulators via scaffold hopping strategy as anti-stroke therapeutic agents.

NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo . Activation of NR2A-containing NMDA receptors promotes neuronal survival and exerts a neuroprotective action, whereas over activating GluN2B-containing receptor results in excitotoxicity, increasing neuronal apoptosis. Our previous study has identified Npam 43 as a NMDAR positive allosteric modulators. However, the cis-trans isomerization impedes the development of Npam 43 as potential neuroprotective agents. To discover more potent and selective GluN2A NMDAR positive allosteric modulators, 38 derivatives were synthesized and evaluated their neuroprotective effect on glutamate-exposed PC-12 cells. The allosteric activities of compounds were evaluated using calcium imaging approaches. Among them, compound 5c exhibit GluN1/2A selectivity over GluN1/2B and show neuroprotective activity in vitro and in vivo. This study reported a series of GluN1/2A positive allosteric modulators as neuroprotective agents, and provided a potential opportunity to discover new drugs for stroke treatment.

Synthesis of a crystalline zeolitic imidazole framework-8 nano-coating on single environment-sensitive viral particles for enhanced immune responses.

Encapsulating antigens with zeolitic imidazole framework-8 (ZIF-8) exhibits many advantages in vaccine development. However, most viral antigens with complex particulate structures are sensitive to pH or ionic strength, which cannot tolerate harsh synthesis conditions of ZIF-8. Balancing the viral integrity and the growth of ZIF-8 crystals is crucial for the successful encapsulation of these environment-sensitive antigens in ZIF-8. Here, we explored the synthesis of ZIF-8 on inactivated foot and mouth disease virus (known as 146S), which is easily disassociated into no immunogenic subunits under the existing ZIF-8 synthesis conditions. Our results showed that intact 146S could be encapsulated into ZIF-8 with high embedding efficiency by lowering the pH of the 2-MIM solution to 9.0. The size and morphology of 146S@ZIF-8 could be further optimized by increasing the amount of Zn2+ or adding cetyltrimethylammonium bromide (CTAB). 146S@ZIF-8 with a uniform diameter of about 49 nm could be synthesized by adding 0.01% CTAB, which was speculated to be composed of single 146S armored with nanometer-scale ZIF-8 crystal networks. Plenty of histidine on the 146S surface forms a unique His-Zn-MIM coordination in the near vicinity of 146S particles, which greatly increases the thermostability of 146S by about 5 °C, and the nano-scale ZIF-8 crystal coating exhibited extraordinary stability to resist EDTE-treatment. More importantly, the well-controlled size and morphology enabled 146S@ZIF-8(0.01% CTAB) to facilitate antigen uptake. The immunization of 146S@ZIF-8(4×Zn2+) or 146S@ZIF-8(0.01% CTAB) significantly enhanced the specific antibody titers and promoted the differentiation of memory T cells without adding another immunopotentiator. This study reported for the first time the strategy of the synthesis of crystalline ZIF-8 on an environment-sensitive antigen and demonstrated that the nano-size and appropriate morphology of ZIF-8 are crucial to exert adjuvant effects, thus expanding the application of MOFs in vaccine delivery.

Modeling the impact of tissue oxygen profiles and oxygen depletion parameter uncertainties on biological response and therapeutic benefit of FLASH.

BACKGROUND: Ultra-high dose rate (FLASH) radiation has been reported to efficiently suppress tumor growth while sparing normal tissue; however, the mechanism of the differential tissue sparing effect is still not known. Oxygen has long been known to profoundly impact radiobiological responses, and radiolytic oxygen depletion has been considered to be a possible cause or contributor to the FLASH phenomenon. PURPOSE: This work investigates the impact of tissue pO2 profiles, oxygen depletion per unit dose (g), and the oxygen concentration yielding half-maximum radiosensitization (the average of its maximum value and one) (k) in tumor and normal tissue. METHODS: We developed a model that considers the dependent relationship between oxygen depletion and change of radiosensitivity by FLASH irradiation. The model assumed that FLASH irradiation depletes intracellular oxygen more rapidly than it diffuses into the cell from the extracellular environment. Cell survival was calculated based on the linear quadratic-linear model and the radiosensitivity related parameters were adjusted in 1 Gy increments of the administered dose. The model reproduced published experimental data that were obtained with different cell lines and oxygen concentrations, and was used to analyze the impact of parameter uncertainties on the radiobiological responses. This study expands the oxygen depletion analysis of FLASH to normal human tissue and tumor based on clinically determined aggregate and individual patient pO2 profiles. RESULTS: The results show that the pO2 profile is the most essential factor that affects biological response and analyses based on the median pO2 rather than the full pO2 profile can be unreliable and misleading. Additionally, the presence of a small fraction of cells on the threshold of radiobiologic hypoxia substantially alters biological response due to FLASH oxygen depletion. We found that an increment in the k value is generally more protective of tumor than normal tissue due to a higher frequency of lower pO2 values in tumors. Variation in the g value affects the dose at which oxygen depletion impacts response, but does not alter the dose-dependent response trends, if the g value is identical in both tumor and normal tissue. CONCLUSIONS: The therapeutic efficacy of FLASH oxygen depletion is likely patient and tissue-dependent. For breast cancer, FLASH is beneficial in a minority of cases; however, in a subset of well oxygenated tumors, a therapeutic gain may be realized due to induced normal tissue hypoxia.

Daytime variation in non-cardiac surgery impacts the recovery after general anesthesia.

BACKGROUND: Circadian rhythm involved with physiology has been reported to affect pharmacokinetics or pharmacodynamics. We hypothesized that circadian variations in physiology disturb anesthesia and eventually affect recovery after anesthesia. METHODS: A retrospective cohort study initially included 107,406 patients (1 June 2016-6 June 2021). Patients were classified into morning or afternoon surgery groups. The primary outcome was daytime variation in PACU (post-anesthesia care unit) recovery time and Steward score. Inverse probability weighting (IPW) approach based on propensity score and univariable/multivariable linear regression were used to estimate this outcome. RESULTS: Of 28,074 patients, 13,418 (48%) patients underwent morning surgeries, and 14,656 (52%) patients underwent afternoon surgeries. LOWESS curves and IPW illustrated daytime variation in PACU recovery time and Steward score. Before adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (median [interquartile range], 57 [46, 70] vs. 54 [43, 66], p < 0.001) and a higher Steward score (5.62 [5.61, 5.63] vs. 5.66 [5.65, 5.67], p < 0.001). After adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (58 [46, 70] vs. 54 [43, 66], p < 0.001). In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time (coefficient, -3.20; 95% confidence interval, -3.55 to -2.86).Among non-cardiac surgeries, daytime variation might affect recovery after general anesthesia. These findings indicate that the timing of surgery improves recovery after general anesthesia, with afternoon surgery providing protection.KEY MESSAGESIn this retrospective cohort study of 28,074 participants, the afternoon surgery group has a higher Steward score than the morning surgery group.In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time.Among non-cardiac surgeries, daytime variation affects the recovery after general anesthesia, with afternoon surgery providing protection.

Promising Mass-Productive 4-Inch Commercial SERS Sensor with Particle in Micro-Nano Porous Ag/Si/Ag Structure Using in Auxiliary Diagnosis of Early Lung Cancer.

The construction of commercial surface enhanced Raman scattering (SERS) sensors suitable for clinical applications is a pending problem, which is heavily limited by the low production of high-performance SERS bases, because they usually require fine or complicated micro/nano structures. To solve this issue, herein, a promising mass-productive 4-inch ultrasensitive SERS substrate available for early lung cancer diagnosis is proposed, which is designed with a special architecture of particle in micro-nano porous structure. Benefitting from the effective cascaded electric field coupling inside the particle-in-cavity structure and efficient Knudsen diffusion of molecules within the nanohole, the substrate exhibits remarkable SERS performance for gaseous malignancy biomarker, with the limit of detection is 0.1 ppb and the average relative standard deviation value at different scales (from cm2 to µm2 ) is ≈16.5%. In practical application, this large-sized sensor can be further divided into small ones (1 × 1 cm2 ), and more than 65 chips will be obtained from just one 4-inch wafer, greatly increasing the output of commercial SERS sensor. Further, a medical breath bag composed of this small chip is designed and studied in detail here, which suggested high-specificity recognition for lung cancer biomarker in mixed mimetic exhalation tests.

QTL Analysis Reveals Conserved and Differential Genetic Regulation of Maize Lateral Angles above the Ear.

Improving the density tolerance and planting density has great importance for increasing maize production. The key to promoting high density planting is breeding maize with a compact canopy architecture, which is mainly influenced by the angles of the leaves and tassel branches above the ear. It is still unclear whether the leaf angles of different stem nodes and tassel branches are controlled by similar genetic regulatory mechanisms, which limits the ability to breed for density-tolerant maize. Here, we developed a population with 571 double haploid lines derived from inbred lines, PHBA6 and Chang7-2, showing significant differences in canopy architecture. Phenotypic and QTL analyses revealed that the genetic regulation mechanism was largely similar for closely adjacent leaves above the ears. In contrast, the regulation mechanisms specifying the angles of distant leaves and the angles of leaves vs. tassel branches are largely different. The liguless1 gene was identified as a candidate gene for QTLs co-regulating the angles of different leaves and the tassel branch, consistent with its known roles in regulating plant architecture. Our findings can be used to develop strategies for the improvement of leaf and tassel architecture through the introduction of trait-specific or pleiotropic genes, thus benefiting the breeding of maize with increased density tolerance in the future.

A Two-Stage Network for Zero-Shot Low-Illumination Image Restoration.

Due to the influence of poor lighting conditions and the limitations of existing imaging equipment, captured low-illumination images produce noise, artifacts, darkening, and other unpleasant visual problems. Such problems will have an adverse impact on the following high-level image understanding tasks. To overcome this, a two-stage network is proposed in this paper for better restoring low-illumination images. Specifically, instead of manipulating the raw input directly, our network first decomposes the low-illumination image into three different maps (i.e., reflectance, illumination, and feature) via a Decom-Net. During the decomposition process, only reflectance and illumination are further denoised to suppress the effect of noise, while the feature is preserved to reduce the loss of image details. Subsequently, the illumination is deeply adjusted via another well-designed subnetwork called Enhance-Net. Finally, the three restored maps are fused together to generate the final enhanced output. The entire proposed network is optimized in a zero-shot fashion using a newly introduced loss function. Experimental results demonstrate that the proposed network achieves better performance in terms of both objective evaluation and visual quality.

Identification of a Novel Coumarins Biosynthetic Pathway in the Endophytic Fungus Fusarium oxysporum GU-7 with Antioxidant Activity.

Coumarins are generally considered to be produced by natural plants. Fungi have been reported to produce coumarins, but their biosynthetic pathways are still unknown. In this study, Fusarium oxysporum GU-7 and GU-60 were isolated from Glycyrrhiza uralensis, and their antioxidant activities were determined to be significantly different. Abundant dipeptide, phenolic acids, and the plant-derived coumarins fraxetin and scopoletin were identified in GU-7 by untargeted metabolomics, and these compounds may account for its stronger antioxidant activity compared to GU-60. Combined with metabolome and RNA sequencing analysis, we identified 24 potentially key genes involved in coumarin biosynthesis and 6 intermediate metabolites. Interestingly, the best hit of S8H, a key gene involved in hydroxylation at the C-8 position of scopoletin to yield fraxetin, belongs to a plant species. Additionally, nondestructive infection of G. uralensis seeds with GU-7 significantly improved the antioxidant activity of seedlings compared to the control group. This antioxidant activity may depend on the biological characteristics of endophytes themselves, as we observed a positive correlation between the antioxidant activity of endophytic fungi and that of their nondestructively infected seedlings. IMPORTANCE Plant-produced coumarins have been shown to play an important role in assembly of the plant microbiomes and iron acquisition. Coumarins can also be produced by some microorganisms. However, studies on coumarin biosynthesis in microorganisms are still lacking. We report for the first time that fraxetin and scopoletin were simultaneously produced by F. oxysporum GU-7 with strong free radical scavenging abilities. Subsequently, we identified intermediate metabolites and key genes in the biosynthesis of these two coumarins. This is the first report on the coumarin biosynthesis pathway in nonplant species, providing new strategies and perspectives for coumarin production and expanding research on new ways for plants to obtain iron.

Optic nerve lesion length is a biomarker of visual disability in the pre-chronic phase of Leber's hereditary optic neuropathy.

OBJECTIVE: The current research aims to investigate relationships between the optic nerve (ON) lesion length with visual function in the pre-chronic phase ( illness duration < 12 months) of LHON. METHODS: Orbital MRI was retrospectively analyzed for 45 patients with LHON in the pre-chronic phase. ON lesion length was measured by 2 trained independent readers and it was recorded as multiplication of the number of abnormal MRI slices and slice thickness on T2-STIR sequence in the coronal plane. Decimal visual acuity was converted to the logarithm of minimum angle of resolution. Intra-class correlation coefficients (ICCs) were used to assess intra- and inter-observer agreements. Pearson's correlation analysis and multivariate linear regression models were performed to analyze the correlations of the lesion length with best corrected visual acuity (BCVA) and visual field parameters. RESULTS: 81 afflicted eyes were selected. The ICCs for intra-observer and inter-observer analyses were 0.989 and 0.980 respectively. Both Pearson's correlation analysis and multivariate linear regression models indicated a significant positive correlation between the BCVA or mean deviation (MD) and ON lesion length (rBCVA=0.368, PBCVA=0.001; rMD=-0.269, PMD=0.045) with a coefficient of determination (R2) of 0.152 and 0.114 respectively adjusted for patients' sex, age of onset, onset of vision loss to performance of MRI, mitochondrial DNA mutations. CONCLUSION: ON length with T2-STIR hyperintensities was positively associated with both BCVA and MD, and it was suspected to be a biomarker of visual disability in the pre-chronic phase of LHON.

Highly selective NH3 gas sensor based on Co(OH)2/Ti3C2T x nanocomposites operating at room temperature.

Ammonia (NH3) is a common air pollutant and is a biomarker for kidney disease. Therefore, the preparation of ammonia gas sensors with high sensitivity, good selectivity and low operating temperature is of great importance for health protection. Using the in situ electrostatic self-assembly approach, a chemoresistive gas sensor based on Co(OH)2/Ti3C2T x hybrid material was created in this study. The prepared samples were characterized by XRD, XPS, TEM, BET and other testing methods for structure, surface topography and elements. These samples were fabricated into sensors, and the gas sensing properties of the materials were investigated under different test conditions. The results show that the gas response value of the C/M-2 sensor is up to about 14.7%/100 ppm, which is three times the response value of the sensor made of pure MXene to NH3. In addition, the Co(OH)2/Ti3C2T x hybrid sensors exhibit excellent repeatability, high sensitivity under low concentration (less than 5 ppm), fast response/recovery time (29 s/49 s) and long-time stability, which indicates their promising utility in the IoT field.

Willingness of patients with cancer pain to participate in end-of-life decisions: a multi-center cross-sectional study from three coastal provinces in southern China.

BACKGROUND: Little is known about patients' intention for participation in end-of-life decisions (EOLD) in three coastal provinces in southern China. This study aimed to explore the willingness of patients with cancer pain to participate in EOLD and potential influencing factors. METHODS: A multi-center cross-sectional study was performed in three coastal provinces in southern China. Two hundred and thirty patients with cancer pain were recruited and consented to fill out the questionnaires. The patients' willingness to participate in EOLD, demographic and disease-related data was surveyed. RESULTS: In total, 223 patients completed and returned the survey (response rate = 96.95%). One hundred four cases (46.64%) were willing to participate in EOLD. 119 (54.36%) cases not willing to participate in EOLD, respectively. Multivariate logistic regression analysis shows that educational level (OR: 0.683, 95% CI: 0.482-0.966), history of alcoholism (OR: 8.353, 95%CI: 2.535-27.525), Eastern Cooperative Oncology Group (ECOG) score (OR: 0.645, 95% CI: 0.450-0.925) and experience of explosive pain (OR: 6.367, 95% CI: 3.103-13.062) and clinical rescue (OR: 3.844, 95% CI: 1.722-8.577) had significant effects on EOLD intention (P <  0.05). Finally, a predictive model combined above five factors was established, which showed a good discrimination (area under receiver operating characteristic curve: 0.849, 95% CI: 0.796-0.899, P <  0.001) and calibration (Hosmer-Lemeshow Test: Chi-square = 10.103, P = 0.258) for which patients more willing to participate in EOLD. CONCLUSIONS: The willingness of patients with cancer pain to participate in EOLD is at a modest level in three coastal provinces in southern China. Patients with lower educational level, history of alcoholism, better health status and experience of explosive pain and clinical rescue may be more prone to participate in EOLD.

Oncogenic KRAS signaling drives evasion of innate immune surveillance in lung adenocarcinoma by activating CD47.

KRAS is one of the most frequently activated oncogenes in human cancers. While the role of KRAS mutation in tumorigenesis and tumor maintenance has been extensively studied, the relationship between KRAS and the tumor immune microenvironment is not fully understood. Herein, we identified a novel role of KRAS in driving tumor evasion from innate immune surveillance. In lung adenocarcinoma patient samples and Kras-driven genetic mouse models of lung cancer, mutant KRAS activated the expression of cluster of differentiation 47 (CD47), an antiphagocytic signal in cancer cells, leading to decreased phagocytosis of cancer cells by macrophages. Mechanistically, mutant KRAS activated PI3K-STAT3 signaling, which restrained miR-34a expression and relieved the post-transcriptional repression of miR-34a on CD47. In three independent lung cancer patient cohorts, KRAS mutation status positively correlated with CD47 expression. Therapeutically, disruption of the KRAS-CD47 signaling axis with KRAS siRNA, the KRASG12C inhibitor AMG 510 or miR-34a mimic suppressed CD47 expression, enhanced the phagocytic capacity of macrophages and restored innate immune surveillance. Our results revealed a direct mechanistic link between active KRAS and innate immune evasion and identified CD47 as a major effector underlying KRAS-mediated immunosuppressive tumor microenvironment.

Immunological mechanisms and treatable traits of chronic rhinosinusitis in Asia: A narrative review.

OBJECTIVES: To review the current literature on immunological mechanisms and treatable traits of chronic rhinosinusitis (CRS) in Asia. DESIGN: This is a narrative review of published data on the immunological mechanisms and treatable traits of CRS in Asia. Published English literature on CRS in Asian and Western countries was reviewed. Where available, the data extracted included epidemiology, immunology, bacterium, phenotype, endotype and treatment. RESULTS AND CONCLUSION: CRS is a heterogeneous disease characterised by persistent locoregional mucosal inflammation of the paranasal sinuses. The inflammatory signatures of CRS vary across patients with distinct racial and ethnic backgrounds and geographic areas. Compared to CRS patients in Western countries, Asian CRS patients display less eosinophilic and Type 2 inflammation, which is associated with lower asthma and allergic rhinitis comorbidities. In contrast, Asian patients with CRS have more prominent non-eosinophilic inflammation than those in Western countries. In addition, Asian CRS patients may have different bacterial colonisation than patients in Western countries. Our review suggests that the distinct immunological mechanisms between Asian and Western CRS patients may influence the clinical phenotype, responses to treatment and outcomes. The treatable trait is a new strategy and therapeutic target identified by phenotype or endotype and has been proposed as a new paradigm for the management of diseases. Improved understanding of CRS phenotypic and endotypic heterogeneity and incorporation of treatable traits into clinical care pathways may facilitate more effective selections of therapeutic interventions, including surgery and biologics.

Multi-Gate Mixture-of-Experts Stacked Autoencoders for Quality Prediction in Blast Furnace Ironmaking.

The blast furnace is an energy-intensive and extremely complex reactor in the ironmaking process. To reduce energy consumption, improve product quality, and ensure the stability of blast furnace operation, it is very important to predict the quality indicators of molten iron accurately and in real time. However, most of the existing product quality prediction models, such as the stacked autoencoder (SAE) model, use a single-channel stack structure. For such models, when the working conditions of the blast furnace ironmaking process change, a large prediction error will occur. To solve this issue, this paper develops a novel deep learning model, called the multi-gate mixture-of-experts stacked autoencoder (MMoE-SAE), for predicting the quality variable in the blast furnace ironmaking processes. The proposed MMoE-SAE model is constructed based on a multi-gate hybrid expert structure, in which a series of SAE networks are selected as experts. The MMoE-SAE model inherits the advantages of MMoE and SAE, which can not only extract the deep features of the data but also have better adaptability to the changes of working conditions in the blast furnace ironmaking process. To verify the effectiveness and practicability of the proposed MMoE-SAE model, it was applied to predict the silicon content of molten iron in the blast furnace ironmaking process. The experimental results demonstrate that the proposed MMoE-SAE model outperforms other prediction models in prediction accuracy.

Immunotherapy for bilateral multiple ground glass opacities: An exploratory study for synchronous multiple primary lung cancer.

Background: Bilateral multiple ground glass opacities (GGOs) are observed in quite a part of patients with early-stage lung adenocarcinoma. For this so-called synchronous multiple primary lung cancer (sMPLC), targeting immune checkpoint is a favorable option in addition to surgical resection. The purpose of this study is to reveal the safety and efficacy of performing immune checkpoint inhibitors (ICIs) on patients with sMPLC and to explore the biomarkers of the efficacy. Methods: A total of 21 patients with sMPLC were enrolled and all included cases were pathologically confirmed adenocarcinoma after conducting surgical treatment for unilateral GGOs. ICIs of Sintilimab were then used to target programmed death 1 (200mg i.v., Q3W) for up to 10 cycles. Seven patients of them received the other surgery for contralateral GGOs, and multiomics assessments, including neoantigens, somatic mutations, and methylated loci, were further performed to investigate potential biomarkers. Results: Grade 1 or 2 treatment-related adverse events (AEs) occurred in most of the patients (12/21, 57.1%), and one subject withdrawn for grade 3 AEs. For the seven patients underwent twice surgeries, twelve and thirteen GGOs were achieved before and after the use of ICIs separately, and a favorable efficacy was observed among six lesions after immunotherapy (> 50% pathologic tumor regression). Tumor infiltration T-cell and B-cell were further shown to be associated with the biological activity of ICIs. According to mechanism-based multiomics analyses, MUC19- and PCDHB5- mutations were indicated to correlate with a favorable prognosis of sMPLC underwent immunotherapy, and our results suggested that immunogenetic mutation and associated promoter methylation could provide a quantitative explanation for the pathologic response of GGOs. Conclusion: Our study provides evidence that the use of ICIs contributed favorable efficacy and safety to patients with sMPLC. Immune infiltration and immunogenic biomarkers are revealed to be implications of performing ICIs on sMPLC. These preliminary findings exhibit the prospects in performing neoadjuvant or adjuvant immunotherapies on patients with sMPLC. Clinical Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=36878, identifier ChiCTR1900022159.

Flexible Threshold-Type Switching Devices with Low Threshold and High Stability Based on Silkworm Hemolymph.

In this paper, a floating-gate flexible nonvolatile memory is reported that is composed of natural biological materials, namely, silkworm hemolymph, graphene quantum dots as the floating-gate layer, and polymethyl methacrylate (PMMA) as the insulating layer. The device has a high ON/OFF current ratio (4.76 × 106), a low setting voltage (<-1.75 V), and good durability and retention ability. The device has two storage characteristics, namely, Flash and WORM, which can be effectively and accurately controlled by adjusting the limiting current during device setting. The resistance switching characteristics are the result of the formation and fracture of conductive filaments. The floating-gate flexible bioresistive random access memory prepared in this paper provides a new idea for the development of multifunctional and biocompatible flexible memory.

Cancer-associated fibroblast-specific lncRNA LINC01614 enhances glutamine uptake in lung adenocarcinoma.

BACKGROUND: Besides featured glucose consumption, recent studies reveal that cancer cells might prefer "addicting" specific energy substrates from the tumor microenvironment (TME); however, the underlying mechanisms remain unclear. METHODS: Fibroblast-specific long noncoding RNAs were screened using RNA-seq data of our NJLCC cohort, TCGA, and CCLE datasets. The expression and package of LINC01614 into exosomes were identified using flow cytometric sorting, fluorescence in situ hybridization (FISH), and quantitative reverse transcription polymerase chain reaction (RT-PCR). The transfer and functional role of LINC01614 in lung adenocarcinoma (LUAD) and CAFs were investigated using 4-thiouracil-labeled RNA transfer and gain- and loss-of-function approaches. RNA pull-down, RNA immunoprecipitation, dual-luciferase assay, gene expression microarray, and bioinformatics analysis were performed to investigate the underlying mechanisms involved. RESULTS: We demonstrate that cancer-associated fibroblasts (CAFs) in LUAD primarily enhance the glutamine metabolism of cancer cells. A CAF-specific long noncoding RNA, LINC01614, packaged by CAF-derived exosomes, mediates the enhancement of glutamine uptake in LUAD cells. Mechanistically, LINC01614 directly interacts with ANXA2 and p65 to facilitate the activation of NF-κB, which leads to the upregulation of the glutamine transporters SLC38A2 and SLC7A5 and eventually enhances the glutamine influx of cancer cells. Reciprocally, tumor-derived proinflammatory cytokines upregulate LINC01614 in CAFs, constituting a feedforward loop between CAFs and cancer cells. Blocking exosome-transmitted LINC01614 inhibits glutamine addiction and LUAD growth in vivo. Clinically, LINC01614 expression in CAFs is associated with the glutamine influx and poor prognosis of patients with LUAD. CONCLUSION: Our study highlights the therapeutic potential of targeting a CAF-specific lncRNA to inhibit glutamine utilization and cancer progression in LUAD.

Prognostic Index for Nonsmall Cell Lung Cancer Based on Immune-Related Genes Expression.

Immune system dysregulation is associated with tumor incidence and growth. Here, we established an RNA-based individualized immune signature associated with prognosis for nonsmall cell lung cancer (NSCLC) to guide adjuvant therapy. We downloaded publicly accessible data on RNA expression and clinical characteristics of NSCLC from the Cancer Genome Atlas (TCGA). From immune-related genes (IRGs) retrieved from the immunology database and analysis portal (ImmPort) database, we then screened differentially expressed immune-related genes (DEIRGs). Using overall survival (OS) as a clinical endpoint, we identified 26 prognostic DEIRGs via univariate and multivariate Cox regression analysis, and then developed a risk model based on these 26 IRGs with an area under the curve (AUC) of 0.701, and its predictive ability independent from other clinical factors. We also downloaded tumor immune infiltrate data and analyzed the correlations between lymphocytic infiltration with our risk scores, but found no significant association. Furthermore, we retrieved 86 differentially expressed transcription factors (TFs) to assess their regulatory relationships with the 26 prognostic DEIRGs. In summary, we developed a robust risk model to predict survival in patients with NSCLC, based on the expression of 26 IRGs. It provides novel predictive and therapeutic molecular targets.