Integrated Circuit of a Chua's System Based on the Integral-Differential Nonlinear Resistance with Multi-Path Voltage-Controlled Oscillator.

In this paper, we present a fully integrated circuit without inductance implementing Chua's chaotic system. The circuit described in this study utilizes the SMIC 180 nm CMOS process and incorporates a multi-path voltage-controlled oscillator (VCO). The integral-differential nonlinear resistance is utilized as a variable impedance component in the circuit, constructed using discrete devices from a microelectronics standpoint. Meanwhile, the utilization of a multi-path voltage-controlled oscillator ensures the provision of an adequate oscillation frequency and a stable waveform for the chaotic circuit. The analysis focuses on the intricate and dynamic behaviors exhibited by the chaotic microelectronic circuit. The experimental findings indicate that the oscillation frequency of the VCO can be adjusted within a range of 198 MHz to 320 MHz by manipulating the applied voltage from 0 V to 1.8 V. The circuit operates within a 1.8 V environment, and exhibits power consumption, gain-bandwidth product (GBW), area, and Lyapunov exponent values of 1.0782 mW, 4.43 GHz, 0.0165 mm2, and 0.6435∼1.0012, respectively. The aforementioned circuit design demonstrates the ability to generate chaotic behavior while also possessing the benefits of low power consumption, high frequency, and a compact size.

Eco-friendly triboelectric nanogenerator based on degradable rape straw powder for monitoring human movement.

Green energy from the surrounding environment has great potential for reducing environmental pollution and sustainable development. Triboelectric nanogenerators (TENGs) are of great interest as they can easily harvest mechanical energy from the environment. Here, we present a triboelectric nanogenerator (RS-TENG) based on rape straw (RS), which was developed from a film composed of waste RS and polyvinyl alcohol (PVA). Due to the high content of carbonyl, hydroxyl and amino acid functional groups in RS, the ability of RS/PVA to lose electrons is increased. The proposed RS-TENG device with a size of 6.25 cm2exhibits open circuit voltage (78 V), short circuit current (5.3µA) performance under uniform external stress at a frequency of 3.5 Hz and 10 N in the cylinder motor. 104.5µW was obtained with a load resistance of 25 MΩ. Results obtained from degradability tests revealed that the RS/PVA film was able to degrade over a period of 30 d (In PBS solution). The RS-TENG produces a significantly high current signal under conditions of finger bending, elbow movements, and foot tapping. Practical tests of the RS-TENG have shown that it is a promising sensing device that will be widely used in the future.

Selection of allosteric dnazymes that can sense phenylalanine by expression-SELEX.

Aptamers are ligand-binding RNA or DNA molecules and have been widely examined as biosensors, diagnostic tools, and therapeutic agents. The application of aptamers as biosensors commonly requires an expression platform to produce a signal to report the aptamer-ligand binding event. Traditionally, aptamer selection and expression platform integration are two independent steps and the aptamer selection requires the immobilization of either the aptamer or the ligand. These drawbacks can be easily overcome through the selection of allosteric DNAzymes (aptazymes). Herein, we used the technique of Expression-SELEX developed in our laboratory to select for aptazymes that can be specifically activated by low concentrations of l-phenylalanine. We chose a previous DNA-cleaving DNAzyme known as II-R1 as the expression platform for its low cleavage rate and used stringent selection conditions to drive the selection of high-performance aptazyme candidates. Three aptazymes were chosen for detailed characterization and these DNAzymes were found to exhibit a dissociation constant for l-phenylalanine as low as 4.8 µM, a catalytic rate constant improvement as high as 20 000-fold in the presence of l-phenylalanine, and the ability to discriminate against closely related l-phenylalanine analogs including d-phenylalanine. This work has established the Expression-SELEX as an effective SELEX method to enrich high-quality ligand-responsive aptazymes.

Salvianolic acid B exerts an anti-hepatocellular carcinoma effect by regulating the Hippo/YAP pathway and promoting pSmad3L to pSmad3C simultaneously.

Salvianolic acid B (Sal B) is a component obtained from Salvia miltiorrhiza and is empirically used for liver diseases. The TGF-ß/Smad and Hippo/YAP pathways may interact with each other in hepatocellular carcinoma (HCC). Previously, we found that Sal B mediates the TGF-ß/Smad pathway in mice and delays liver fibrosis-carcinoma progression by promoting the conversion of pSmad3L to pSmad3C, but the effect of Sal B on the Hippo/YAP pathway has not been determined. Therefore, we used a DEN/CCl4/C2H5OH-induced liver cancer model in mice to analyze liver index and tumor incidence, detect AST and ALT serological markers, observe liver pathology and the number of Ki67-positive cells to evaluate the anti-HCC effect of Sal B in vivo. We used a TGF-ß1-induced HepG2 cell model, and applied an MST1/2 inhibitor, XMU-MP-1, to detect the changes in pSmad3C/pSmad3L signaling induced by MST1/2 inhibition. Sal B significantly inhibited tumorigenesis in DEN/CCl4/C2H5OH-induced mice in vivo, and suppressed the growth of HepG2 cells by inhibiting cell proliferation and migration in vitro. Here, our study also validated the role of Sal B in reversing XMU-MP-1-induced proliferation and migration of HepG2 cells in vitro. Most importantly, we elucidated for the first time the potential mechanism of Sal B against HCC via the Hippo/YAP pathway, which may be specifically related to upregulation of MST1 and inhibition of its downstream effector protein YAP. In conclusion, these findings indicate that Sal B possesses anti- HCC effects both in vivo and in vitro by regulating the Hippo/YAP pathway and promoting pSmad3L to pSmad3C synchronously.

Integration of an Expression Platform in the SELEX Cycle to Select DNA Aptamer Binding to a Disease Biomarker.

Aptamers can be developed for biosensors, diagnostic tools, and therapeutic reagents. These applications usually require a fusion of aptamers and expression platforms. However, the fusion process is usually time-consuming and laborious. In this study, we integrated the deoxyribozyme (I-R3) as an expression platform in the SELEX cycle (called Expression-SELEX) to select aptazymes that can sense diverse molecules. We used the Maple syrup urine disease (MSUD) biomarker L-allo-isoleucine to test the selection model. After five rounds of screening, the cleavage products were sufficiently enriched to be visualized on polyacrylamide gel electrophoresis (PAGE) gel. Through high-throughput sequencing analysis, several candidates were identified. One such candidate, IR3-I-DNA, binds L-allo-isoleucine with a dissociation constant (K D) of 0.57 mM. When the ligand was present, the cleavage fraction of IR3-I-DNA increased from 0.3 to 0.5, and its K obs value improved from 1.38 min-1 to 1.97 min-1. Our selection approach can also be applied to produce aptazymes that can bind to variable ligands and be used more directly as biosensors.

The expression and clinical significance of programmed cell death receptor 1 and its ligand in tumor tissues of patients with extranodal nasal NK/T cell lymphoma.

Appropriate biomarkers may help distinguish the biological behavior of different types of lymphoma and their response to traditional chemotherapy. Extranodal natural killer/T-cell lymphoma (ENKTL) and diffuse large B-cell lymphoma (DLBCL) belong to different subtypes of non-Hodgkin's lymphoma, the biological behavior and prognosis of them are very different, programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) have been investigated in these two types of diseases. However, few studies addressed the difference of PD-1/PD-L1 levels between ENKTL and DLBCL, in order to find out the difference and related clinical application value, the clinical data and tumor tissue paraffin sections of 24 newly diagnosed ENKTL patients and 42 newly diagnosed diffuse large B-cell lymphoma (DLBCL) were collected. PD-1/PD-L1 levels in tumor tissues were detected by immunohistochemical staining. The relationship between the PD-1/PD-L1 levels and clinical data of patients with ENKTL patients was analyzed. Both patient groups showed PD-1 level in tumor tissue of ENKTL patients was significantly lower than that of DLBCL patients (P < 0.05), while the PD-L1 level in tumor tissues of ENKTL patients was not different from DLBCL (P < 0.05). In addition, the ENKTL patients with B symptoms, elevated lactate dehydrogenase (LDH) levels and decreased hemoglobin (HGB) concentrations had lower level of PD-1 in tumor tissue. PD-L1 level in tumor tissues, the LDH level, Epstein-Barr genome (EBV-DNA) copy and Ki-67 index may affect the outcomes of ENKTL patients (P < 0.05), but they were not independent factors. PD-L1 levels in tumor tissues has clinical significance in ENKTL patients, which suggested that the PD-1/PD-L1 signal pathway may be involved in the immune escape of ENKTL and play different roles in different lymphoma subtypes.

Identification of 11 candidate structured noncoding RNA motifs in humans by comparative genomics.

BACKGROUND: Only 1.5% of the human genome encodes proteins, while large part of the remaining encodes noncoding RNAs (ncRNA). Many ncRNAs form structures and perform many important functions. Accurately identifying structured ncRNAs in the human genome and discovering their biological functions remain a major challenge. RESULTS: Here, we have established a pipeline (CM-line) with the following features for analyzing the large genomes of humans and other animals. First, we selected species with larger genetic distances to facilitate the discovery of covariations and compatible mutations. Second, we used CMfinder, which can generate useful alignments even with low sequence conservation. Third, we removed repetitive sequences and known structured ncRNAs to reduce the workload of CMfinder. Fourth, we used Infernal to find more representatives and refine the structure. We reported 11 classes of structured ncRNA candidates with significant covariations in humans. Functional analysis showed that these ncRNAs may have variable functions. Some may regulate circadian clock genes through poly (A) signals (PAS); some may regulate the elongation factor (EEF1A) and the T-cell receptor signaling pathway by cooperating with RNA binding proteins. CONCLUSIONS: By searching for important features of RNA structure from large genomes, the CM-line has revealed the existence of a variety of novel structured ncRNAs. Functional analysis suggests that some newly discovered ncRNA motifs may have biological functions. The pipeline we have established for the discovery of structured ncRNAs and the identification of their functions can also be applied to analyze other large genomes.

Predicting treatment response of patients with extranodal natural killer/T-cell lymphoma based on levels of PD-L1 mRNA and soluble PD-L1.

Appropriate biomarkers may help predict patient response to treatment for extranodal natural killer/T-cell lymphoma (ENKTL), a subtype of non-Hodgkin's lymphoma in China. Programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) have been investigated in various tumors. However, few studies have addressed expression of PD-1/PD-L1 in peripheral blood of ENKTL patients. To identify novel peripheral blood biomarkers for diagnosis and treatment of ENKTL, we retrospectively examined 89 healthy volunteers, 49 patients with ENKTL and 74 patients with diffuse large B-cell lymphoma treated at West China Hospital from September 2017 to September 2018. Both patient groups showed significantly higher expression of PD-1 and PD-L1 on CD4+ T cells, higher levels of PD-L1 mRNA in peripheral blood mononuclear cells (PBMCs) and higher levels of soluble PD-L1 in plasma than healthy volunteers (P < .05). In ENKTL patients, levels of PD-L1 mRNA and soluble PD-L1 were related to disease stage, level of lactate dehydrogenase, lymphocyte count, and copies of Epstein-Barr genome in blood. Levels of PD-L1 mRNA and soluble PD-L1 were similar between healthy volunteers and ENKTL patients who showed complete remission after treatment, and uni- and multivariate analyses identified soluble PD-L1 as a predictor of treatment response in ENKTL patients. Our results suggest that the levels of PD-L1 mRNA in PBMCs and soluble PD-L1 in plasma are useful for ENKTL staging and prediction of treatment response.

Elevated plasma levels of hypermethylated RASSF1A gene sequences in pregnant women with intrahepatic cholestasis.

Intrahepatic cholestasis of pregnancy (ICP) is associated with increased perinatal mortality and morbidity. Circulating cell-free fetal DNA has been a useful parameter for monitoring of pregnancy-associated diseases. The purpose of this study was to determine the concentrations of hypermethylated RAS-association domain family 1, isoform A (RASSF1A) gene sequences in the plasma of pregnant women with intrahepatic cholestasis. This study included 56 women in their third trimester of pregnancy, of whom 26 had ICP (study group) and 30 were healthy (control group). Real time PCR was performed to detect RASSF1A concentrations after methylation-sensitive restriction digestion with HinpII and HhaI to measure cell-free fetal DNA. Beta-actin was detected as an internal control to confirm complete enzyme digestion. The data show a significant increase in the circulating hypermethylated RASSF1A levels regarding the pregnancies complicated with ICP as compared with normal pregnancies. Circulating hypermethylated RASSF1A levels in maternal plasma related to total bile acid. Based on these observations, we suggest that the circulating hypermethylated RASSF1A levels in maternal plasma may be used as a diagnostic marker for ICP.