Fault Reconstruction Algorithm for Fractional-Order Nonlinear Switching Systems Based on Optimal Fault-Tolerant Control.

In this article, a novel fault reconstruction algorithms for fractional-order nonlinear switching systems (FONSSs) with actuator and sensor faults are investigated. First, fractional-order nonlinear system (FONS) with faults, is transformed into two fast and slow subsystems using global differential homogeneous transformation, one of which is unaffected by the fault and the state is partially observable; the other subsystem is affected by the fault but the state is fully observable. After that, it is introduced for the first time that persistent dwell-time (PDT) switching is taken into consideration in the design process of the observer for FONSS, which overcomes the transient problem of the switching moment and ensures the stability of the error dynamics equations of the two fast and slow subsystems. In addition, to eliminate the impact of faults, an optimal adaptive fault-tolerant control strategy based on actor-critic architecture NN are designed to effectively compensate. Finally, the effectiveness of the proposed control strategy is verified by simulation results.

Photovoltaic-enhanced water splitting properties of low-temperature-synthesized BiVO4 photoanode films.

The fabrication of photoelectrodes on indium tin oxide (ITO) glass at low temperatures poses a significant challenge due to the inherent instability of ITO at reduced temperatures, while the inexpensive production of high-functionality photoanode technology is a critical determinant facilitating large-scale photovoltaic conversion in water splitting. In this work, highly efficient BiVO4 (BVO) photoanodes with different thicknesses were grown on ITO glass at a low temperature by the sol-gel spin coating method. Pure BVO photoanode, enriched with nanostructures, exhibits a current density of 2.25 mA cm-2 (@1.23 V vs. RHE) under AM-1.5G illumination. The photovoltaic effect induces a continual oxygen evolution reaction at zero bias voltage on the photoanode, resulting in a photocurrent density of 0.04 mA cm-2 at zero bias. This study not only evaluates the feasibility of the large-scale fabrication of a photoanode from economic considerations but also presents potential for water splitting properties of the BVO photoanode.

New link between RNH1 and E2F1: regulates the development of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a non-small cell carcinoma. Ribonuclease/angiogenin inhibitor 1 (RNH1) exerts multiple roles in virous cancers. E2F1 is a critical transcription factor involved in the LUAD development. Here, we analyze the expression of RNH1 in LUAD patients, investigate the biological function of RNH1 in LUAD, and demonstrate its potential mechanisms through E2F1 in LUAD. METHODS: In the present study, we presented the expression of RNH1 in LUAD based on the database and confirmed it by western blot detection of RNH1 in human LUAD tissues. Lentiviral infection was constructed to silence or overexpress RNH1 in NCI-H1395 and NCI-H1437 cells. We assess the role of RNH1 on proliferation in LUAD cells by MTT assay, colony formation assays, and cell cycle detection. Hoechst staining and flow cytometry were used to evaluate the effects of RNH1 on apoptosis of LUAD cells. The function of RNH1 in invasion and migration was investigated by Transwell assay. Dual luciferase assay, ChIP detection, and pull-down assay were conducted to explore the association of E2F1 in the maintenance of RNH1 expression and function. The regulation of E2F1 on the functions of RNH1 in LUAD cells was explored. Mouse experiments were performed to confirm the in-vivo role of RNH1 in LUAD. mRNA sequencing indicated that RNH1 overexpression altered the expression profile of LUAD cells. RESULTS: RNH1 expression in LUAD tissues of patients was presented in this work. Importantly, RNH1 knockdown improved the proliferation, migration and invasion abilities of cells and RNH1 overexpression produced the opposite effects. Dual luciferase assay proved that E2F1 bound to the RNH1 promoter (-1064 ∼ -1054, -1514 ∼ -1504) to reduce the transcriptional activity of RNH1. ChIP assay indicated that E2F1 DNA was enriched at the RNH1 promoter (-1148 ∼ -943, -1628 ∼ -1423). Pull-down assays also showed the association between E2F1 and RNH1 promoter (-1148 ∼ -943). E2F1 overexpression contributed to the malignant behavior of LUAD cells, while RNH1 overexpression reversed it. High-throughput sequencing showed that RNH1 overexpression induced multiple genes expression changes, thereby modulating LUAD-related processes. CONCLUSION: Our study demonstrates that binding of E2F1 to the RNH1 promoter may lead to inhibition of RNH1 expression and thus promoting the development of LUAD.

Small extracellular vesicles from irradiated lung epithelial cells promote the activation of fibroblasts in pulmonary fibrosis.

BACKGROUND: Alveolar epithelial injury and dysfunction are the risk factors for radiation-induced pulmonary fibrosis (RIPF). However, it is not clear about the relationship between RIPF and the small extracellular vesicles (sEV) secreted by irradiated alveolar epithelial cells. Based on the activation of fibroblasts, this study explored the role of sEV derived from alveolar epithelial cells in RIPF and the potential mechanisms. METHODS: Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were used to characterize sEV. Western blotting was used to detect fibrosis-associated proteins. Cell counts and transwell assays were used to evaluate the proliferation and migration ability of fibroblasts. RT-PCR was used to observe the extracellular matrix (ECM) synthesized by fibroblasts, miRNA changes in the sEV were determined by second-generation sequencing. RESULTS: TEM, NTA, and western blotting showed the extracellular vesicles with a double-layer membrane structure of approximately 100 nm in diameter. The sEV derived from irradiated A549, HBEC3-KT, and MLE12 cells upregulated FN1 and alpha-SMA proteins expression in fibroblasts and drove the fibroblast to myofibroblast transition, and the sEV from irradiated mouse bronchoalveolar lavage fluid (BALF) affirmed the same results. In addition, the sEV derived from irradiated alveolar epithelial cells significantly increased the migration ability of fibroblasts and the expression of extracellular matrix proteins such as FN1. The results of miRNA sequencing of sEV in BALF of rats with RIPF showed that the metabolic pathway may be important for miRNA to regulate the activation of fibroblasts. CONCLUSION: The sEV derived from radiated pulmonary epithelial cells promote the activation, migration and extracellular matrix proteins expression of lung fibroblasts; miRNA in sEV may be an important molecular that affects the activation of lung fibroblasts.

Estimating rainfall interception loss of three dominant shrub species in an oasis-desert ecotone using in situ measurements and the revised Gash analytical model.

Canopy interception loss affects the local water budget by removing a non-negligible proportion of rainfall from the terrestrial surface. Thus, quantifying interception loss is essential for thoroughly understanding the role of vegetation in the local hydrological cycle, especially in dryland ecosystems. However, sparse shrubs in dryland ecosystems have not been sufficiently studied, owing to time- and labor-intensive field experiments and challenging model parameterization. In this work, 4-year growing season field experiments on rainfall partitioning were conducted for three dominant shrub species (Haloxylon ammodendron, Nitraria sphaerocarpa, and Calligonum mongolicum) in an oasis-desert ecotone in northwestern China. The revised Gash analytical model was well parameterized, which reliably simulated the cumulative interception loss for sparse shrubs, and the validated model performed better for H. ammodendron, followed by C. mongolicum and N. sphaerocarpa, with relative errors of 8.4%, 15.4%, and 23.9%, respectively. The mean individual interception loss percentage for H. ammodendron (28.4%) was significantly higher than that for C. mongolicum (11.0%) and N. sphaerocarpa (10.9%) (p < 0.05), which could be ascribed to the higher canopy storage capacity and wet-canopy evaporation rate of H. ammodendron. For all shrub species, the majority proportion of interception loss occurred during canopy saturation and drying-out periods, accounting for approximately 79-85% of the cumulative interception loss. Overall, the mean local interception loss of three dominant shrub species in the ecotone removed nearly 17% of the corresponding cumulative rainfall during the growing season. These results not only provide methodological references for estimating the interception loss of sparse vegetation in dryland ecosystems, but also provide scientific insights for water resource management and ecosystem restoration in water-limited regions similar to the experimental site.

ZNF746 promotes M2 macrophage polarisation and favours tumour progression in breast cancer via the Jagged1/Notch pathway.

Breast cancer (BC) is a major threat to women's health. BC is a heterogeneous disease and treatment strategies and outcomes differ between subtypes. Investigating the molecular mechanisms of BC will help to identify potential therapeutic targets and develop new therapies. Here we report that zinc finger protein 746 (ZNF746), a Krüppel-associated box and zinc finger protein, exhibits tumour-promoting properties in BC. Functional experiments (cell growth, colony formation, cell cycle analysis, and transwell analysis) were used to evaluate the proliferation, migration, and invasion capacity of BC cells. Immunohistochemistry was performed to detect the expression of ZNF746, CD163 (M2 macrophage marker), and HES1 (Notch target) in BC tissues. ZNF746 was highly expressed in BC tissues compared to adjacent paired non-tumour tissues. Patients with M1 BC had higher expression of ZNF746 compared to patients with non-metastatic (M0) BC, and higher expression of ZNF746 was associated with poorer overall survival. The immunohistochemical results showed a positive correlation between the expression of ZNF746 and the expression of CD163 or HES1. ZNF746 promoted BC cell proliferation, migration, and invasion and increased the expression of molecules essential for monocyte recruitment and differentiation (CCL2 and CSF1). Furthermore, THP-1 monocytes cultured in the conditioned medium derived from BC cells overexpressing ZNF746 exhibited enhanced M2 polarisation. In contrast, ZNF746 knockdown reduced BC cell proliferation, migration, and invasion and suppressed M2 polarisation. Mechanistically, ZNF746 promoted the activation of the Jagged1/Notch pathway, and the Jagged1 siRNA-mediated blockade of this pathway prevented the tumour-promoting functions of ZNF746. In conclusion, this study uncovers the role of ZNF746 in promoting M2 macrophage polarisation and suggests that ZNF746 may be a promising therapeutic target for limiting BC progression.

(n, m) Distribution of Single-Walled Carbon Nanotubes Grown from a Non-Magnetic Palladium Catalyst.

Non-magnetic metal nanoparticles have been previously applied for the growth of single-walled carbon nanotubes (SWNTs). However, the activation mechanisms of non-magnetic metal catalysts and chirality distribution of synthesized SWNTs remain unclear. In this work, the activation mechanisms of non-magnetic metal palladium (Pd) particles supported by the magnesia carrier and thermodynamic stabilities of nucleated SWNTs with different (n, m) are evaluated by theoretical simulations. The electronic metal-support interaction between Pd and magnesia upshifts the d-band center of Pd, which promotes the chemisorption and dissociation of carbon precursor molecules on the Pd surface, making the activation of magnesia-supported non-magnetic Pd catalysts for SWNT growth possible. To verify the theoretical results, a porous magnesia supported Pd catalyst is developed for the bulk synthesis of SWNTs by chemical vapor deposition. The chirality distribution of Pd-grown SWNTs is understood by operating both Pd-SWNT interfacial formation energy and SWNT growth kinetics. This work not only helps to gain new insights into the activation of catalysts for growing SWNTs, but also extends the use of non-magnetic metal catalysts for bulk synthesis of SWNTs.

Mathematical Model for Oil Recovery Prediction of Polymer Microsphere Conformance Control Based on the Stream Tube Method.

Oil recovery is an essential parameter for reservoir development performance evaluation, but there is no specific research on the theoretical oil recovery prediction model of polymer microspheres (PMs)' conformance control. This research aims to establish an oil recovery prediction model that depends on the definition of oil recovery based on stream tube theory. PMs' enhanced oil recovery mechanism is to plug the pore throat to expand the swept area. The assumption that the stream tube between injection and production wells is trapezoidal is proposed. Based on this premise, the area sweep efficiency equation suitable for the rhombus inverse nine-spot well pattern is established based on the stream tube theory. The vertical sweep efficiency equation is optimized by introducing the equivalent mobility ratio. Additionally, the model's adaptability and validity are studied. The analysis results show that oil recovery decreases with increasing injection rate, injection concentration, and PMs size but increases with the increasing injection period. The theoretical oil recovery is 1.37%, and the actual oil recovery of the field application is 1.22%, with an error of 0.15%. This model has good consistency with the actual physical process of the field application. The oil recovery prediction model can provide oil recovery and optimize PMs' conformance control injection scheme. This study fills the gap in the mathematical model for oil recovery prediction of PMs' conformance control.

Experimental partitioning of rainfall into throughfall, stemflow and interception loss by Haloxylon ammodendron, a dominant sand-stabilizing shrub in northwestern China.

Rainfall partitioning by the vegetation canopy represents a significant component of the local hydrological cycle by reshaping the amount and spatial distribution of rainfall. Measuring the components of rainfall partitioning, however, has been a challenging task due to laborious- and time-consuming field experiments. In this study, to probe the influences of long-term afforestation on dynamic patterns of rainfall partitioning, the dominant sand-stabilizing shrub Haloxylon ammodendron at three different ages was selected for field measurements during the 2020-2021 growing season. The throughfall percentage for young H. ammodendron (YH, 75.9 %) was significantly higher than that for middle-aged H. ammodendron (MAH, 63.4 %) and mature H. ammodendron (MH, 62.4 %) (p < 0.05 for all cases). However, the interception loss percentage of YH (22.3 %) was significantly lower than that for MAH (35.0 %) and MH (36.5 %) (p < 0.05 for all cases). No significant difference was found for stemflow percentage among YH (1.8 %), MAH (1.5 %) and MH (1.1 %). Smaller rainfall events contributed to a higher interception loss percentage and a lower net rainfall percentage for all ages. Both throughfall and stemflow percentage first showed increasing trends and then tended to be stable with increasing rainfall amount and duration, whereas interception loss percentage showed the opposite patterns. Rainfall partitioning was significantly correlated with the plant area index, stem basal area and canopy height (p < 0.05 for all cases), which may account for significant differences in rainfall partitioning patterns, as all shrubs experienced the same weather conditions. The average funneling ratio was 56.6, 26.7 and 17.9 for YH, MAH and MH, respectively. These results suggested that H. ammodendron afforestation can have a significant impact on rainfall partitioning by reducing net rainfall reaching the soil and may have some implications for local water budget and ecosystem management in oasis-desert ecotones.

Prognostic Biomarkers after Radiotherapy for Nonsmall Cell Lung Cancer Based on Bioinformatics Analysis.

Radiotherapy is one of the main treatment modalities in nonsmall cell lung cancer (NSCLC). However, tumor radiosensitivity is influenced by intrinsic factors like genetic variations and extrinsic factors like tumor microenvironment. Consequently, we hope to develop novel biomarkers, so as to improve the response rate of radiotherapy and overcome resistance to radiotherapy in NSCLC. We investigate the difference genes of primary NSCLC patients before and after radiotherapy in GSE162945 dataset. Gene Ontology (GO), KEGG, Reactome, and GSEA were employed to represent the essential gene and biological function. It was found that most pathway genes clustered in extracellular matrix and ECM-receptor signal pathway. Additionally, TMT-based proteomics was used to survey the differential proteins present in the supernatant of H460 cells before or after irradiation with 2 Gy of γ-rays. And then we take the intersection between the proteomics of H460 cell and ECM-receptor signal pathway proteins of GSE162945 datasets. The data revealed that fibronectin 1 (FN1) and thrombin reactive protein 1 (THBS1) were upregulated after radiation in both datasets. Subsequently, survival analyses using the GEPIA web server demonstrated that FN1 and THBS1 had significant prognostic values (Logrank test P value < 0.05) for LUAD and LUSC. Our observations from this study suggest that FN1 and THBS1 might have potential to serve as novel biomarkers for predicting NSCLC tumor response to radiotherapy.

Retraction Notice to: MicroRNA-140 Inhibits the Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer.

[This retracts the article DOI: 10.1016/j.omtn.2017.12.022.].

Quantitative prediction of CeO2 and LaAlO3 infrared spectra based on first-principles calculations.

Oxide crystals with specific infrared spectra are widely used in the optical energy industry. Conventional density functional theory calculations reveal various properties of oxide crystals, including their electronic band structure, electronic density of states, vibrational modes, phonon band structure, and phonon density of states, but only provide qualitative analyses of infrared spectra. Herein, we provide a theoretical approach to analyzing how the basic mechanisms of infrared absorption are affected by the above properties and then predicting quantitatively the infrared spectra. The derivation and details of this method are clarified, and the CeO2 and LaAlO3 infrared spectra are finally calculated through an application. The calculated infrared properties are in good agreement with previously reported experiments, demonstrating the accuracy of our method. This study provides a less expensive approach to identifying the infrared spectra of oxide crystals through the use of theoretical calculations and is potentially applicable in the optical energy industry, improving the efficiency by which appropriate materials can be selected.

EphA10 drives tumor progression and immune evasion by regulating the MAPK/ERK cascade in lung adenocarcinoma.

Backgrounds Lung adenocarcinoma is the most frequent histological type among patients with lung cancer. Ephrin receptor A10 (EphA10), a member of the receptor tyrosine kinase family, has been reported to participate in tumor progression, but its role in lung adenocarcinoma (LUAD) remains unknown. Methods Immunohistochemistry staining and real-time PCR were employed to determine the expression of EphA10 in clinical LUAD samples. EphA10 silencing or overexpression in LUAD cells was achieved by transduction of lentivirus. The effects of EphA10 on LUAD cells were evaluated by CCK-8, EdU staining, flow cytometry, Transwell, and Western blot. The in vivo tumor growth was assessed in the xenograft mice model. Results EphA10 was overexpressed in LUAD tissues. Higher EphA10 expression was observed in the tissues at the advanced tumor stage and was positively correlated with the EGFR. Mechanistically, silencing of EphA10 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition of LUAD cells. Additionally, EphA10 knockdown significantly reduced the PD-L1 expression in LUAD cells and enhanced NK cell-mediated anti-tumor effects. Furthermore, EphA10 activated the MAPK/ERK pathway, and U0126, an inhibitor of MEK, markedly reversed the promoting impacts of EphA10 overexpression on LUAD cells. Consistently, results from subcutaneous tumor xenografts in nude mice confirmed that EphA10 knockdown significantly inhibited tumor growth in vivo. Conclusions This work demonstrates that EphA10 drives tumor progression and immune evasion by regulating the MAPK/ERK cascade in LUAD, implying that EphA10 has the potential to be a therapeutic target in treating LUAD.

Integrative Analysis of Biomarkers and Mechanisms in Adamantinomatous Craniopharyngioma.

Craniopharyngioma is a benign tumor, and the predominant treatment methods are surgical resection and radiotherapy. However, both treatments may lead to complex complications, seriously affecting patients' survival rate and quality of life. Adamantinomatous craniopharyngioma (ACP), as one of the histological subtypes of craniopharyngioma, is associated with a high incidence and poor prognosis, and there is a gap in the targeted therapy of immune-related genes for ACP. In this study, two gene expression profiles of ACP, namely GSE68015 and GSE94349, were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by the Limma package, and 271 differentially expressed immune-related genes (DEIRGs) were obtained from the Immport database. The gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed for annotation, visualization, and integrated discovery. Five hub genes, including CXCL6, CXCL10, CXCL11, CXCL13, and SAA1, were screened out through protein-protein interaction (PPI) network interaction construction. Two diagnostic markers, namely S100A2 and SDC1 (both of which have the Area Under Curve value of 1), were screened by the machine learning algorithm. CIBERSORT analysis showed that M2 macrophages, activated NK cells, and gamma delta T cells had higher abundance in ACP infiltration, while CD8+ T cells, regulatory T cells, and Neutrophils had less abundance in ACP infiltration. The expression of gamma delta T cells was positively correlated with CXCL6, S100A2, SDC1, and SAA1, while CD8+ T cells expression was negatively correlated with CXCL6, S100A2, SDC1, and CXCL10. ACP with high CXCL6 showed remarkable drug sensitivity to Pentostatin and Wortmannin via CellMiner database analysis. Our results deepened the understanding of the molecular immune mechanism in ACP and provided potential biomarkers for the precisely targeted therapy for ACP.

Clinicopathological significance of CBX3 in colorectal cancer: An intensive expression study based on formalin-fixed and paraffin-embedded tissues.

CBX3 is an isoform of the heterochromatin protein 1 family, which is involved in carcinogenesis and promotes the progression of certain types of cancer. The expression level and clinicopathological significances of CBX3 in colorectal cancer (CRC) are still not well reported. In this study, we examined CBX3 protein expression in formalin-fixed and paraffin-embedded normal mucosae, hyperplastic polyps, low-and high-grade adenomas, and CRC tissue samples using immunohistochemistry. The associations of CBX3 expression levels with clinicopathological parameters, mismatch repair (MMR) protein expression, and kirsten rat sarcoma viral oncogene homolog (KRAS) and B-raf proto-oncogene (BRAF) mutations were analyzed. Our results showed that CBX3 protein was negatively expressed in normal mucosae and hyperplastic polyps, as well as in most low-grade adenomas. Interestingly, CBX3 protein was positively expressed in most high-grade adenomas and CRC tissues. CBX3 expression level was associated with tumor differentiation (p = 0.012), lymph node metastasis (p = 0.024), TNM stage (p = 0.008) and survival (p = 0.029). CBX3 expression was associated with MMR protein expression (p = 0.011) and KRAS mutation (p = 0.013), but not with BRAF mutation (p = 0.097). Our data suggest that CBX3 may be used as a molecular marker in CRC to evaluate tumor differentiation, lymph node metastasis, and pathological stage.

MiR-3682 promotes the progression of hepatocellular carcinoma (HCC) via inactivating AMPK signaling by targeting ADRA1A.

INTRODUCTION AND OBJECTIVES: This study aimed to investigate miR-3682 as a biomarker in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: MiRNA and RNA profiles of 375 HCC tissues and 50 normal liver samples were downloaded from The Cancer Genome Atlas (TCGA) database. Multivariate Cox regression and Kaplan-Meier analyses were applied to examine the prognostic value of factors. Target genes of miR-3682 were analyzed by TargetScan and dual-luciferase reporter assay. Online Database for Annotation, Visualization, and Integrated Discovery (DAVID) to perform KEGG pathway enrichment. Cell counting kit-8, colony formation and migration and invasion assays were performed to analyze biological behaviors of HCC cells. RESULTS: MiR-3682 was identified to be highly expressed in HCC tissues and cell lines. And miR-3682 was negatively and independently associated with the outcome of HCC patients. Inhibition of miR-3682 suppressed HCC cell viability and mobility. ADRA1A, predicted and confirmed as the novel target of miR-3682, was an independent and positive prognostic predictor for HCC. In addition, the knockdown of ADRA1A partially offset the inhibitory effect of miR-3682 inhibitor on the growth and mobility of HCC cells. DAVID enrichment and western blot of key signaling-related proteins analyses revealed that miR-3682 inactivated 5'-AMP-activated protein kinase (AMPK) signaling by negatively regulating ADRA1A. Mechanically, it was partially through suppressing AMPK signaling via targeting ADRA1A that miR-3682 supported the HCC cell malignant phenotype. CONCLUSIONS: This study implicates that miR-3682 plays an oncogenetic role in HCC and can be considered a novel therapeutic target and prognostic indicator of HCC.

Research on a Fractal Dimension Calculation Method for a Nano-Polymer Microspheres Dispersed System.

Polymer microspheres (PMs) are a kind of self-similar volume expansion particle, and their fractal dimension varies with hydration swelling. However, there is no unique fractal dimension calculation method for their characteristics. A new model is established in this paper, which is particular to calculate the fractal dimension of PMs. We carried out swelling hydration experiments and scanning electron microscope (SEM) experiments to verify the new model. The new model and the box-counting model were used to calculate the fractal dimensions of PMs based on the hydration experiment results. Then, a comparison of the calculation results of the two methods was used to verify the validity of the model. Finally, according to the new model calculation results, the fractal dimension characteristics of PMs were analyzed. The research results indicate that the new model successfully correlates the cumulative probability of the PMs dispersed system with the fractal dimension and makes fractal dimension calculation of PMs more accurate and convenient. Based on the experiment results, the new model was used to calculate the fractal dimension of PMs and the box-counting model, and its findings were all 2.638 at initial state hydration and 2.739 and 2.741 at hydration time as of day 1. This result verifies the correctness of the new model. According to the hydration swelling experiments and the new model calculation results, the fractal dimension is linear correlated to the average particle size of PMs and the standard deviation average particle size. This means the fractal dimension of PMs represents the space occupancy ability and space occupancy effectiveness.

High-Throughput NanoBiT-Based Screening for Inhibitors of HIV-1 Vpu and Host BST-2 Protein Interaction.

Bone marrow stromal cell antigen 2 (BST-2), also known as CD317 or tetherin, has been identified as a host restriction factor that suppresses the release of enveloped viruses from host cells by physically tethering viral particles to the cell surface; however, this host defense can be subverted by multiple viruses. For example, human immunodeficiency virus (HIV)-1 encodes a specific accessory protein, viral protein U (Vpu), to counteract BST-2 by binding to it and directing its lysosomal degradation. Thus, blocking the interaction between Vpu and BST-2 will provide a promising strategy for anti-HIV therapy. Here, we report a NanoLuc Binary Technology (NanoBiT)-based high-throughput screening assay to detect inhibitors that disrupt the Vpu-BST-2 interaction. Out of more than 1000 compounds screened, four inhibitors were identified with strong activity at nontoxic concentrations. In subsequent cell-based BST-2 degradation assays, inhibitor Y-39983 HCl restored the cell-surface and total cellular level of BST-2 in the presence of Vpu. Furthermore, the Vpu-mediated enhancement of pesudotyped viral particle production was inhibited by Y-39983 HCl. Our findings indicate that our newly developed assay can be used for the discovery of potential antiviral molecules with novel mechanisms of action.

Research on Optimal Blocking Limits and Injection Parameter Optimization of Polymer Microsphere Conformance Control.

Polymer microsphere (PM) profile control has been attributed to improving sweep efficiency during the oil development process. The critical factors for PM conformance control are the plugging properties controlled by matching the relationship between the throat diameter and particle size and the injection parameters. A new matching relationship between the reservoir and PM based on the function of blocking rate and the ratio of throat diameter to microsphere diameter (C R) is established to choose the most appropriate PM size. The blocking rate indicates that it will get the most excellent plugging effect when C R is 0.5. The displacement experiments under different injection concentrations and other injection volumes show that the blocking rate is increased by injection concentration and finally stabilized. A similar trend is presented between the injection volume and plugging rate. The optimal injection concentration is 0.5%, and the optimal injection volume is 0.3 PV. According to the new size selection method and injection parameter optimal method, PM100 chooses to conduct field application. PM100 presents a good performance with a success rate of 37.5% and a validity period of more than 120 days, and its daily oil production rate increased 1.7 times, on average, and finally, the total oil increase is 556 t. The optimal size microsphere shows a good EOR effect, which indicates that this size selection method is reasonable.