circSNTB2 and CUL4A Induces Dysfunction of Nucleus Pulposus Cells by Competitively Binding miR-665.

Circular RNA (circRNA) plays important roles in lumbar degenerative diseases. This study aimed to investigate the role of circSNTB2 in regulating the development of lumbar disc herniation (LDH) in vitro and in vivo. The abnormally expressed circSNTB2 in intervertebral disc degeneration (IDD) through bioinformatics analysis was identified, and verified in nucleus pulposus (NP) tissues of patients with LDH. NP cells were treated with TNF-α to mimic the LDH microenvironment. RT-qPCR was applied to determine levels of mRNA and microRNA (miRNA) in clinical samples and cells. We performed CCK-8, EdU, TUNEL and flow cytometric apoptosis assays to evaluate the proliferation and apoptosis of NP cells. The predicted the miRNAs and downstream target genes were verified with the help of luciferase reporter gene and RNA pull-down experiments. Finally, we established an LDH rat model to further verify the role of circSNTB2 in vivo. circSNTB2 was significantly up-regulated in the NP tissues of LDH group and TNF-α -treated NP cells. miR-665 binds to circSNTB2 and cullin 4A (CUL4A) is the downstream target gene of miR-665. Knockdown of circSNTB2 promoted NP cells proliferation and inhibited apoptosis, which was reversed by down-regulation of miR-665. In addition, up-regulated CUL4A reversed the effects of over-expressed miR-665 on proliferation and apoptosis of NP cells. Meanwhile, results of in vivo experiments demonstrated that knocking down circSNTB2 alleviated LDH-induced thermo-mechanical pain and NP injury. In summary, circSNTB2 regulates the proliferation and apoptosis of NP by mediating miR-665 regulation of CUL4A, which provides a reliable idea for targeted therapy of LDH.

Nitrogen and Sulfur Codoped Porous Carbon Directly Derived from Potassium Citrate and Thiourea for High-Performance Supercapacitors.

By introducing a heteroatom into carbon material, an effective improvement in capacitance can be realized owing to surface oxidation and reduction reactions of pseudocapacitors. Herein, a simple one-pot carbonization activation method was proposed to convert potassium citrate into three-dimensional interconnected porous carbon (PC). Then, an effective double heteroatom doping method by thiourea was used to prepare nitrogen-sulfur-doped PC (N,S-PC). This porous structure facilitates the storage of a large number of ions and reduces their diffusion path. The synthesized N,S-PC nanomaterial has a capacitance of 674 F/g at 1 A/g in a 1 M H2SO4 electrolyte, can retain 94.41% of the initial capacitance after 10 000 cycles at 5 A/g, and has a long cycle life. More importantly, a symmetric supercapacitor assembled with this material can exhibit an energy density of up to 32.6 (W·h)/kg at a high-power density of 750 W/kg. This is due to the high performance of N,S-PC in supercapacitor electrode materials.

HMGB1 promotes Ox-LDL-induced endothelial cell damage by inhibiting PI3K/Akt signaling pathway.

BACKGROUND: Atherosclerosis is the pathological basis of cardio-cerebrovascular diseases. Oxidized low-density lipoprotein (ox-LDL) is an important risk factor for atherosclerosis. Ox-LDL leads to endothelial cell (EC) damage and dysfunction through various processes and promotes the occurrence and deterioration of atherosclerosis. High mobility group box-1 (HMGB1) is a protein associated with cellular damage. In the present study, the effect of HMGB1 on ox-LDL-induced EC damage was determined and the underlying mechanism explored. MATERIALS AND METHODS: Human umbilical vein ECs (HUVECs) were exposed to ox-LDL to induce endothelial damage and changes in HMGB1 expression level were detected using western blotting analysis and reverse transcription-quantitative PCR. To observe the effect of HMGB1 on ox-LDL-induced damage, the HMGB1 expression was downregulated with siRNA, and cell viability, cytotoxicity, and apoptosis rate were assessed. HUVECs were pretreated with LY294002, an inhibitor of the PI3K/Akt pathway, to determine whether the effect of HMGB1 on damage is via the PI3K-Akt pathway. RESULTS: The results showed that ox-LDL can upregulate HMGB1 expression in HUVECs and downregulation of HMGB1 expression can prevent ox-LDL-induced damage in HUVECs. Furthermore, the effect of HMGB1 on ox-LDL-induced damage could be promoted by inhibiting the PI3K/Akt signaling pathway. CONCLUSION: The results indicate HMGB1 may be a promising research target to alleviate ox-LDL-induced EC damage.

Effect of MicroRNA-126a-3p on Bone Marrow Mesenchymal Stem Cells Repairing Blood-brain Barrier and Nerve Injury after Intracerebral Hemorrhage.

OBJECTIVE: Intracerebral hemorrhage (ICH) is a disease that threatens human health due to its high morbidity and mortality. On behalf of finding the better methods in the treatment of ICH, researchers pay more attention to a new technology which is finding effective genes to modify stem cells. METHODS: In this study, we isolated, cultured and identified bone marrow mesenchymal stem cells (MSCs) in vitro. Further, the MSCs (transfected with lentivirus expressing microRNA-126a-3p (miR-126)) were injected into the type Ⅶ collagenase-induced ICH rats to investigate the recovery effects of blood-brain barrier (BBB) and nerve damage in vivo. RESULTS: The MSCs surface marker molecules (CD29: 98.5%; CD90: 96.5%) were highly expressed, and the blood cell surface molecule was negatively expressed (CD45: 2%). Meanwhile, it was verified that miR-126 facilitated the differentiation of MSCs into vascular endothelial cells, owing to the rise of markers (CD31 and VE-cadherin). The modified neurological severity score, modified limb placing test score, brain water content and evans blue content were reduced after transplanted miR-126-modified MSCs. It was found that miR-126 accelerated the differentiation of MSCs into vascular endothelial cells via immunohistochemical staining in vivo. HE staining indicated the area of edema was obviously decreased compared with that in ICH + vector-MSCs group. MiR-126-modified MSCs alleviated the cell apoptosis in brain tissues by TUNEL assay. In addition, the mRNA and protein expression of protease activated receptor-1 and matrix metalloproteinase-9 were diminished, whilst the expression of zonula occludens-1 (ZO-1) and claudin-5 were enhanced in ICH+miR-126-MSCs group. Immunofluorescence assay revealed that miR-126-modified MSCs decreased the disruption of tight junction (ZO-1 and claudin-5). CONCLUSIONS: All data illustrate that miR-126-modified MSCs repair BBB and nerve injury after ICH.

STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells via mTOR signal-mediated inhibition of autophagy.

BACKGROUND: Long noncoding RNAs (lncRNAs) are an important class of functional regulators involved in human cancers development, including gastric cancer (GC). Studying aberrantly expressed lncRNAs may provide us with new insights into the occurrence and development of gastric cancer by acting as oncogenes or tumor suppressors. In this study, we aim to examine the expression pattern of lncRNA HAGLROS in GC and its clinical significance as well as its biological role in tumor progression. METHODS: Bioinformatics analysis and qRT-PCR were performed to detect the relative expression of HAGLROS in GC tissues and cell lines. Gain or loss of function approaches were used to investigate the biological functions of HAGLROS. The effect of HAGLROS on proliferation was evaluated by MTT, colony formation assay and nude mouse xenograft model. Wound healing and Transwell assays were used to study the invasion and migration of GC cells. FISH, RIP, RNA-seq, Luciferase report assays, RNA pulldown and Western blot were fulfilled to measure molecular mechanisms. Results are shown as means ± S.D. and differences were tested for significance using Student's t-test (two-tailed). RESULTS: We screened out HAGLROS, whose expression was significantly increased and correlated with outcomes of GC patients by publicly available lncRNAs expression profiling and integrating analyses. Exogenous down-regulation of HAGLROS expression significantly suppressed the cell proliferation, invasion and migration. Mechanistic investigations showed that HAGLROS was a direct target of transcriptional factor STAT3. Moreover, HAGLROS knockdown decreased mTOR expression and increased autophagy-related genes ATG9A and ATG9B expression. Further investigation showed that HAGLROS regulated mTOR signals in two manners. In the one hand, HAGLROS competitively sponged miR-100-5p to increase mTOR expression by antagonizing miR-100-5p-mediated mTOR mRNA inhibition. On the other hand, HAGLROS interacted with mTORC1 components to activate mTORC1 signaling pathway which was known to be an important negative signal of autophagy. Here activation of mTORC1 signaling pathway by HAGLROS inhibited autophagy, thereby promoted excessive proliferation and maintained the malignant phenotype of GC cells. CONCLUSION: The present study demonstrates that HAGLROS overexpression contributes to GC development and poor prognosis and will be a target for GC therapy and further develop as a potential prognostic biomarker.

Low density lipoprotein receptor class A domain containing 4 (LDLRAD4) promotes tumorigenesis of hepatic cancer cells.

LDLRAD4 was previously identified and shown to be connected with psychiatric disorders. The structure of LDLRAD4 protein is similar to that of TMEPAI protein, which is overexpressed in many tumors. However, it is still unknown whether LDLRAD4 is involved in tumorigenesis. In this study, the potential role of LDLRAD4 in tumorigenesis was investigated. LDLRAD4 is elevated in hepatic cancer cells and tumor tissues, and expression of LDLRAD4 promotes hepatic cancer cell HepG2 and SMMC-7721 proliferation and migration. LDLRAD4 interacts Nedd4 to promote cell proliferation and migration and negatively regulates the TGF-ß signaling. Furthermore, immunofluorescence microscopy analysis indicates that LDLRAD4 is localized to the lysosome and association with Nedd4 is necessary for its intracellular transport to the lysosome. In addition, depletion of LDLRAD4 in HepG2 liver cancer cells inhibited tumorigenesis in nude mice. These results reveal an oncogenic role of LDLRAD4 in tumorigenesis through its association with Nedd4.

Design, Synthesis, and Antifungal Activity of Novel Aryl-1,2,3-Triazole-ß-Carboline Hybrids.

The copper catalytic azide and terminal alkyne cycloaddition reaction, namely "click chemistry", gives a new and convenient way to create l,4-disubstitutd-l,2,3-triazoles. In this work, 2-pyrrolecarbaldiminato⁻Cu(II) complexes were established as efficient catalysts for the three-component 1,3-dipolar cycloaddition reaction of arylboronic acid and sodium azide (NaN3) with terminal alkynes in ethanol at room temperature to 50 °C, 1,4-disubstituted 1,2,3-triazoles were synthesized. Following the optimized protocol, two series of new aryl-1,2,3-triazole-ß-carboline hybrids have been designed and synthesized, and the chemical structures were characterized by ¹H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS). All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Fusarium oxysporum, Botrytis cinerea Pers., sunflower sclerotinia rot, and rape sclerotinia rot by mycelia growth inhibition assay at 50 µg/mL. The antifungal evaluation of the novel hybrids showed that, among the tested compounds, 5a, 5b, 5c, and 9b showed good antifungal activity against sunflower sclerotinia rot. Specifically, compound 9b also exhibited high broad-spectrum fungicidal against all the tested fungi with inhibition rates of 58.3%, 18.52%, 63.07%, 84.47%, and 81.23%. However, for F. oxysporum, all the target compounds showed no in vitro antifungal activities with an inhibition rate lower than 20%. These results provide an encouraging framework that could lead to the development of potent novel antifungal agents.

Angular Rate Sensing with GyroWheel Using Genetic Algorithm Optimized Neural Networks.

GyroWheel is an integrated device that can provide three-axis control torques and two-axis angular rate sensing for small spacecrafts. Large tilt angle of its rotor and de-tuned spin rate lead to a complex and non-linear dynamics as well as difficulties in measuring angular rates. In this paper, the problem of angular rate sensing with the GyroWheel is investigated. Firstly, a simplified rate sensing equation is introduced, and the error characteristics of the method are analyzed. According to the analysis results, a rate sensing principle based on torque balance theory is developed, and a practical way to estimate the angular rates within the whole operating range of GyroWheel is provided by using explicit genetic algorithm optimized neural networks. The angular rates can be determined by the measurable values of the GyroWheel (including tilt angles, spin rate and torque coil currents), the weights and the biases of the neural networks. Finally, the simulation results are presented to illustrate the effectiveness of the proposed angular rate sensing method with GyroWheel.

Acaricidal Activity and Synergistic Effect of Thyme Oil Constituents against Carmine Spider Mite (Tetranychus Cinnabarinus (Boisduval)).

Studies examining the use of essential oils as replacements for synthetic insecticides require an understanding of the contribution of each constituent present, interactions among these components, and how they relate to overall toxicity. In the present study, the chemical composition of commercial thyme oil was identified by gas chromatography-mass spectrometry. Thyme oil and blends of its major constituents were tested for their acaricidal activitities against carmine spider mites (Tetranychus cinnabarinus (Boisduval)) using a slide-dip bioassay. Natural thyme oil showed greater toxicity than any single constituent or blend of constituents. Thymol was the most abundant component (34.4%), and also possessed the strongest acaricidal activity compared with other single constituents. When tested individually, four constituents (linalool, terpinene, p-cymene and carvacrol) also had activity, while α-pinene, benzoic acid and ethyl gallate had almost no activity. The toxicity of blends of selected constituents indicated a synergistic effect among the putatively active and inactive constituents, with the presence of all constituents necessary to reach the highest toxicity. The results indicated that thyme oil and some of its major constituents have the potential to be developed into botanical acaricides.

Aerodynamic Drag Analysis of 3-DOF Flex-Gimbal GyroWheel System in the Sense of Ground Test.

GyroWheel is an innovative device that combines the actuating capabilities of a control moment gyro with the rate sensing capabilities of a tuned rotor gyro by using a spinning flex-gimbal system. However, in the process of the ground test, the existence of aerodynamic disturbance is inevitable, which hinders the improvement of the specification performance and control accuracy. A vacuum tank test is a possible candidate but is sometimes unrealistic due to the substantial increase in costs and complexity involved. In this paper, the aerodynamic drag problem with respect to the 3-DOF flex-gimbal GyroWheel system is investigated by simulation analysis and experimental verification. Concretely, the angular momentum envelope property of the spinning rotor system is studied and its integral dynamical model is deduced based on the physical configuration of the GyroWheel system with an appropriately defined coordinate system. In the sequel, the fluid numerical model is established and the model geometries are checked with FLUENT software. According to the diversity and time-varying properties of the rotor motions in three-dimensions, the airflow field around the GyroWheel rotor is analyzed by simulation with respect to its varying angular velocity and tilt angle. The IPC-based experimental platform is introduced, and the properties of aerodynamic drag in the ground test condition are obtained through comparing the simulation with experimental results.

An Efficient Matching Game Approach to Association Formation in UAV-Enabled Hierarchical Distributed Learning.

Distributed machine learning has emerged as a promising data processing technology for next-generation communication systems. It leverages the computational capabilities of local nodes to efficiently handle large datasets, creating highly accurate data-driven models for analysis and prediction purposes. However, the performance of distributed machine learning can be significantly hampered by communication bottlenecks and node dropouts. In this article, a novel unmanned aerial vehicle (UAV)-enabled hierarchical distributed learning architecture is proposed to support machine learning applications, e.g., regional monitoring. Multiple UAV receivers (URs) are introduced as wireless relays to improve the communication between the UAV transmitters (UTs) and the cloud server. Our objective is to identify the optimal UT-UR association to maximize the social welfare of the network, which is distinctly different from the existing works that focus on the unilateral profit-maximizing problem. We formulate a two-side many-to-one matching game to model the UT-UR association problem, and a two-phase many-to-one matching algorithm is designed to identify the stable matching. The validity of our proposed scheme is verified through in-depth numerical simulations.

A switched extremum seeking control without steady-state oscillation using gradient-based adaptive-amplitude perturbation.

To enhance the steady-state and dynamic performance of the extremum seeking control (ESC), a switched ESC scheme is proposed in this paper. Firstly, to solve nonconvex optimization problems, a novel adaptive law for perturbation is established utilizing the hybrid gradient information to accomplish a trade-off between the dynamic and steady-state performance. It is shown that the adaptive-amplitude ESC achieves global optimization despite the existence of local extrema. Then, to overcome the adverse effect of inaccurate gradient estimation on steady-state accuracy, a Lyapunov-based switched strategy is employed to start the bisection-based ESC. The plant output converges to the equilibrium rapidly and accurately without steady-state oscillation. Furthermore, the stability of the proposed scheme is theoretically proved. Numerical simulation examples are carried out to demonstrate the effectiveness of the proposed scheme.

Application Value of PCSK9 Inhibitor in Cardiovascular High Risk Patients: A Meta-Analysis.

Background: Proprotein convertase subtilisin / Kexin type 9 (PCSK9) inhibitors are efficacious lipid-lowering agents. This drug is related to improving the prognosis of patients with cardiovascular disease (CVD). The purpose of this meta-analysis was to systematically analyze the safety and efficacy of PCSK9 inhibitors in all published randomized controlled trials (RCTs). Methods: As of October 25, 2021, we searched PubMed, EMBASE, MEDLINE, Cochrane Library and web of science. Results: From 684 articles, we included 11 trials for meta-analysis, including 52511 participants (26938 in the PCSK9 inhibitor group and 25573 in the control group). In terms of effectiveness, PCSK9 inhibitors reduced the risk of major adverse cardiovascular events(MACE) (OR=0.89, 95% Cl: 0.83-0.95, P=0.0009), but did not significantly reduce the risk of cardiovascular death (OR=0.95, 95% Cl: 0.84-1.07, P=0.38) or all-cause death (OR=0.93, 95% Cl: 0.85-1.03, P=0.18); In terms of safety, PCSK9 did not increase the risk of treatment-emergent adverse events (TEAE)(OR=0.98, 95% Cl: 0.94-1.02, P=0.28). Conclusion: PCSK9 inhibitors can significantly reduce the risk of MACE in patients with high cardiovascular risk, which is well tolerated, but the impact on the risk of death is unclear.

UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage.

The transcription factor nuclear factor erythroid 2 like 1 (NFE2L1 or NRF1) regulates constitutive and inducible expression of proteasome subunits and assembly chaperones. The precursor of NRF1 is integrated into the endoplasmic reticulum (ER) and can be retrotranslocated from the ER to the cytosol where it is processed by ubiquitin-directed endoprotease DDI2. DDI2 cleaves and activates NRF1 only when NRF1 is highly polyubiquitinated. It remains unclear how retrotranslocated NRF1 is primed with large amount of ubiquitin and/or very long polyubiquitin chain for subsequent processing. Here, we report that E3 ligase UBE4A catalyzes ubiquitination of retrotranslocated NRF1 and promotes its cleavage. Depletion of UBE4A reduces the amount of ubiquitin modified on NRF1, shortens the average length of polyubiquitin chain, decreases NRF1 cleavage efficiency and causes accumulation of non-cleaved, inactivated NRF1. Expression of a UBE4A mutant lacking ligase activity impairs the cleavage, likely due to a dominant negative effect. UBE4A interacts with NRF1 and the recombinant UBE4A can promote ubiquitination of retrotranslocated NRF1 in vitro. In addition, knocking out UBE4A reduces transcription of proteasomal subunits in cells. Our results indicate that UBE4A primes NRF1 for DDI2-mediated activation to facilitate expression of proteasomal genes.

Adaptive-Critic Design for Decentralized Event-Triggered Control of Constrained Nonlinear Interconnected Systems Within an Identifier-Critic Framework.

This article studies the decentralized event-triggered control problem for a class of constrained nonlinear interconnected systems. By assigning a specific cost function for each constrained auxiliary subsystem, the original control problem is equivalently transformed into finding a series of optimal control policies updating in an aperiodic manner, and these optimal event-triggered control laws together constitute the desired decentralized controller. It is strictly proven that the system under consideration is stable in the sense of uniformly ultimate boundedness provided by the solutions of event-triggered Hamilton-Jacobi-Bellman equations. Different from the traditional adaptive critic design methods, we present an identifier-critic network architecture to relax the restrictions posed on the system dynamics, and the actor network commonly used to approximate the optimal control law is circumvented. The weights in the critic network are tuned on the basis of the gradient descent approach as well as the historical data, such that the persistence of excitation condition is no longer needed. The validity of our control scheme is demonstrated through a simulation example.

Development and Optimization of a Prognostic Model Associated with Stemness Genes in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, which is associated with a variety of risk factors. Cancer stem cells are self-renewal cells, which can promote the occurrence and metastasis of tumors and enhance the drug resistance of tumor treatment. This study aimed to develop a stemness score model to assess the prognosis of hepatocellular carcinoma (HCC) patients for the optimization of treatment. The single-cell sequencing data GSE149614 was downloaded from the GEO database. Then, we compared the gene expression of hepatic stem cells and other hepatocytes in tumor samples to screen differentially expressed genes related to stemness. R package "clusterProfiler" was used to explore the potential function of stemness-related genes. We then constructed a prognostic model using LASSO regression analysis based on the TCGA and GSE14520 cohorts. The associations of stemness score with clinical features, drug sensitivity, gene mutation, and tumor immune microenvironment were further explored. R package "rms" was used to construct the nomogram model. A total of 18 stemness-related genes were enrolled to construct the prognosis model. Kaplan-Meier analysis proved the good performance of the stemness score model at predicting overall survival (OS) of HCC patients. The stemness score was closely associated with clinical features, drug sensitivity, and tumor immune microenvironment of HCC. The infiltration level of CD8+ T cells was lower, and tumor-associated macrophages were higher in patients with high-stemness score, indicating an immunosuppressive microenvironment. Our study established an 18 stemness-related gene model that reliably predicts OS in HCC. The findings may help clarify the biological characteristics and progression of HCC and help the future diagnosis and therapy of HCC.

[Temporal and spatial variation of vegetation net primary productivity and its driving factors in Ningxia, China from 2000 to 2019]. / 2000­2019å¹´å®å¤æ¤è¢«å‡€åˆçº§ç”Ÿäº§åŠ›æ—¶ç©ºå˜åŒ–åŠå ¶é©±åŠ¨å› ç´ .

Ningxia is an important agriculture-pastoral area in China. Research on the temporal and spatial variations of net primary productivity (NPP) in this area and its driving factors would help understand the trends and leading factors of NPP variations, and reveal vegetation restoration status and causes. Based on the NPP data of MODIS, we used Theil-Sen Median trend analysis, correlation analysis, overlay analysis and other methods to analyze the spatiotemporal variations and driving factors of NPP in Ningxia. The results showed that NPP of Ningxia vegetation showed a fluctuating upward trend during 2000-2019, with a linear growth rate of 5.46 g C·m-2·a-1. The NPP presented a spatial characteristics of "two high and two low", with the highest in the southern mountain area, followed by the Yellow River irrigation area, and the lowest in the hilly area of the central arid zone and Helan Mountain. 84.2% of the NPP in the study area was under significant restoration, mainly distributed in the central and southern mountainous and hilly areas. The NPP varied significantly with altitude and was significantly affected by the terrain. NPP center of gravity had generally moved to the south, with the increase and growth rate of NPP of vegetation in the south being greater than that in the north. The annual precipitation in Ningxia had shown an increasing trend, while the average annual temperature had slightly decreased. The NPP was significantly affec-ted by precipitation (R2=0.291), whereas the correlation between mean annual temperature and NPP was weak. 96.9% of the study area was at a state of vegetation restoration, which was promoted by both climate change and human activities.

Yu-Ping-Feng Formula Ameliorates Alveolar-Capillary Barrier Injury Induced by Exhausted-Exercise via Regulation of Cytoskeleton.

Background: Yu-ping-feng powder (YPF) is a compound traditional Chinese medicine extensively used in China for respiratory diseases. However, the role of YPF in alveolar-capillary barrier dysfunction remains unknown. This study aimed to explore the effect and potential mechanism of YPF on alveolar-capillary barrier injury induced by exhausted exercise. Methods: Male Sprague-Dawley rats were used to establish an exhausted-exercise model by using a motorized rodent treadmill. YPF at doses of 2.18 g/kg was administrated by gavage before exercise training for 10 consecutive days. Food intake-weight/body weight, blood gas analysis, lung water percent content, BALF protein concentration, morphological observation, quantitative proteomics, real-time PCR, and Western blot were performed. A rat pulmonary microvascular endothelial cell line (PMVEC) subjected to hypoxia was applied for assessing the related mechanism. Results: YPF attenuated the decrease of food intake weight/body weight, improved lung swelling and hemorrhage, alleviated the increase of lung water percent content and BALF protein concentration, and inhibited the impairment of lung morphology. In addition, YPF increased the expression of claudin 3, claudin 18, occludin, VE-cadherin, and ß-catenin, attenuated the epithelial and endothelial hyperpermeability in vivo and/or in vitro, and the stress fiber formation in PMVECs after hypoxia. Quantitative proteomics discovered that the effect of YPF implicated the Siah2-ubiquitin-proteasomal pathway, Gng12-PAK1-MLCK, and RhoA/ROCK, which was further confirmed by Western blot. Data are available via ProteomeXchange with identifier PXD032737. Conclusion: YPF ameliorated alveolar-capillary barrier injury induced by exhausted exercise, which is accounted for at least partly by the regulation of cytoskeleton.

Diagnostic and prognostic value of genomic instability-derived long non-coding RNA signature of endometrial cancer.

OBJECTIVE: To investigate whether genomic instability (GI)-derived long non-coding RNAs (lncRNAs) have a prognostic impact on the patients with endometrial cancer. MATERIAL AND METHODS: Patients with Uterine Corpus Endometrial Carcinoma (UCEC) were selected from The Cancer Genome Atlas (TCGA) database. Systematic bioinformatics analyses were performed, including Pearson correlations, GO and KEGG enrichment analysis, bivariate and multiple logistic regression analysis, and Kaplan-Meier (KM) method. RESULTS: A total of 552 UCEC samples were included in the study. The differentially expressed lncRNAs (DELs) were identified, including 79 down-regulated lncRNAs and 31 up-regulated lncRNAs. Bivariate logistic regression analysis showed that 19 GI-derived lncRNAs were prognostic factors. By further multivariate logistic regression analysis, AC005256.1 (estimated coefficient = -0.474), AC026336.3 (estimated coefficient = -0.030), AL161618.1 (estimated coefficient = -1.661), and BX322234.1 (estimated coefficient = 1.511) were used to construct a prognostic risk model. In the train set and test set, the risk model was shown to have both a high prognostic and a diagnostic value. CONCLUSION: We developed a novel GI-derived 4-lncRNA signature for the diagnosis and prognosis of patients with endometrial cancer. These findings offered a novel perspective in the clinical management of endometrial cancer.

Dispersive liquid-liquid microextraction coupled with high-performance liquid chromatography-diode array detection for the determination of N-methyl carbamate pesticides in vegetables.

This paper described a simple, rapid and efficient method for the determination of N-methyl carbamate pesticides in tomato, cucumber, carrot and lettuce samples by dispersive liquid-liquid microextraction coupled with HPLC-diode array detection. Some experimental parameters that influenced the extraction efficiency, such as types and volumes of extraction and disperser solvents, extraction time and salt effect were examined and optimized. Under optimum conditions, the LOD of the method were 0.5-3.0 µg/kg depending on the compounds and the kind of vegetables. The linearities of the method were obtained in the range of 10.0-300 µg/kg for aldicarb, MTMC, carbofuran and carbaryl, and 20.0-600 µg/kg for isoprocarb, with the correlation coefficients ranging from 0.9921 to 0.9993. The RSD varied from 2.9 to 7.5% (n=5). The recoveries of the method for the five carbamates from vegetable samples at two different spiking levels were ranged from 77.8 to 98.2%. Results showed that the method we proposed can meet the requirements for the determination of N-methyl carbamate in vegetable samples and was finally applied to the analysis of target pesticides in vegetable samples taken from local markets.