The design, synthesis and bioactivity evaluation of novel androgen receptor degraders based on hydrophobic tagging.

Prostate Cancer (PCa) easily progress to metastatic Castration-Resistant Prostate Cancer (mCRPC) that remains a significant cause of cancer-related death. Androgen receptor (AR)-dependent transcription is a major driver of prostate tumor cell proliferation. Proteolysis-targeting chimaera (PROTAC) technology based on Hydrophobic Tagging (HyT) represents an intriguing strategy to regulate the function of therapeutically androgen receptor proteins. In the present study, we have designed, synthesized, and evaluated a series of PROTAC-HyT AR degraders using AR antagonists, RU59063, which were connected with adamantane-based hydrophobic moieties by different alkyl chains. Compound D-4-6 exhibited significant AR protein degradation activity, with a degradation rate of 57 % at 5 µM and nearly 90 % at 20 µM in 24 h, and inhibited the proliferation of LNCaP cells significantly with an IC50 value of 4.77 ± 0.26 µM in a time-concentration-dependent manner. In conclusion, the present study lays the foundation for the development of a completely new class of therapeutic agents for the treatment of mCRPC, and further design and synthesis of AR-targeting degraders are currently in progress for better degradation rate.

lncRNA ANRIL accelerates wound healing in diabetic foot ulcers via modulating HIF1A/VEGFA signaling through interacting with FUS.

BACKGROUND: Diabetic foot ulcer (DFU) is a frequently diagnosed complication of diabetes, and remains a heathcare burden worldwide. However, the pathogenesis of DFU is still largely unclear. The objective of this study is to delineate the function and underlying mechanism of lncRNA antisense non coding RNA in the INK4 locus (ANRIL) in endothelial progenitor cells (EPCs) and DFU mice. METHODS: The DFU mouse model was established, and EPCs were subjected to high glucose (HG) treatment to mimic diabetes. qRT-PCR or western blot was employed to detected the expression of ANRIL, HIF1A, FUS and VEGFA. CCK-8 and Annexin V/PI staining were used to monitor cell proliferation and apoptosis. Wound healing, Transwell invasion and tube formation assays were conducted to assess cell migration, invasion and angiogenesis, respectively. The association between ANRIL and FUS was verified by RNA pull-down and RIP assays. Luciferase and ChIP assays were employed to investigate HIF1A-mediated transcriptional regulation of VEGFA and ANRIL. The histological alterations of DFU wound healing were observed by H&E and Masson staining. RESULTS: ANRIL was downregulated in peripheral blood samples of DFU patients, DFU mice and HG-treated EPCs. Mechanistically, ANRIL regulated HIFA mRNA stability via recruiting FUS. VEGFA and ANRIL were transcriptionally regulated by HIF1A. Functional experiments revealed that HG suppressed EPC proliferation, migration, invasion and tube formation, but promoted apoptosis via ANRIL/HIF1A axis. ANRIL accelerated DFU wound healing via modulating HIF1A expression in vivo. CONCLUSION: ANRIL accelerated wound healing in DFU via modulating HIF1A/VEGFA signaling in a FUS-dependent manner.

6-Heterocyclic carboxylic ester derivatives of gliotoxin lead to LSD1 inhibitors in gastric cancer cells.

Gliotoxin is a representative compound of the epipolythiodioxopiperazine (ETP) class of fungal metabolites. Histone Lysine Specific Demethylase 1 (LSD1) is highly expressed in a variety of cancers. Herein, a series of 6-heterocyclic carboxylic ester derivatives of gliotoxin was designed and synthesized as new LSD1 inhibitors and their biological evaluations in human gastric MGC-803 and HGC-27 cells were carried out. All of the derivatives effectively suppressed the enzymatic activities of LSD1. In particular, compound 4e exhibited excellent LSD1 inhibition with IC50 = 62.40 nM, as well as anti-proliferation against MGC-803 and HGC-27 cells with IC50 values of 0.31 µM and 0.29 µM, respectively. 4e also had a remarkable capacity to inhibit the colony formation, suppress migration and induce the apoptosis of these two cancer cell lines. In sum, our findings identified and characterized the 6-heterocyclic carboxylic ester derivatives of gliotoxin as potent and cellular active LSD1 inhibitors, which may provide a novel chemotype of LSD1 inhibitors for gastric cancer treatment.

Dihydroartemisinin inhibits melanoma migration and metastasis by affecting angiogenesis.

Tumor angiogenesis is critical for tumor metastasis by providing oxygen, nutrients, and metastatic pathways. As a potential anti-angiogenic agent, Dihydroartemisinin (DHA) can effectively inhibit tumor metastasis. However, the mechanism how it regulates angiogenesis to affect tumor metastasis has not been fully clarified. To investigate the mechanisms of how DHA regulates melanoma progression. In this study, bioinformatics methods were used to analyze the correlation between angiogenesis and melanoma metastasis. Then, B16F10, A375, HUVECs and mouse metastasis models were adapted to clarify the inhibition of DHA in melanoma. GESA analysis revealed melanoma metastasis significantly positive correlated with angiogenesis. Meanwhile, DHA significantly decreased melanoma nodules and lung wet weight in metastatic tumor mice, and inhibited the expression of the angiogenic marker CD31 in vitro and in vivo. Similarly, DHA inhibited the expression of the angiogenic signal molecule VEGFR2 in A375 and B16F10 cells, and significantly suppressed the formation of their tubular structures. DHA-treated supernatants significantly inhibited the tubule-forming ability as well as lateral and longitudinal migration ability of HUVECs compared with untreated melanoma cell supernatants. Screening yielded the angiogenic pathways HIF-1α/VEGF, PI3K/ATK/mTOR associated with melanoma metastasis, and DHA may inhibit tumor metastasis by inhibiting these angiogenic pathways in melanoma cells to inhibit tumor metastasis. Further non-targeted metabolomics analysis revealed that DHA-treated model mice produced differential metabolites that were also associated with angiogenic pathways. DHA inhibits melanoma invasion and metastasis by mediating angiogenesis. These results have important implications for the potential use of DHA in treatment of melanoma.

Diagnostic performance of perfusion-weighted imaging combined with serum MMP-2 and -9 levels in tumor recurrence after postoperative concomitant chemoradiotherapy of glioblastoma.

OBJECTIVE: To evaluate diagnostic accuracy of dynamic susceptibility contrast- perfusion weighted imaging (DSC-PWI) combined with serum MMP-2 and -9 levels in differentiating recurrent glioblastoma (GBM). METHODS: We enrolled a total of 220 GBM patients, including recurrent cases (n = 150) and non-recurrent cases (n = 70) after postoperative concomitant chemoradiotherapy. All patients performed preoperative and follow-up DSC-PWI, and two parameters [normalized cerebral blood volume (nCBV) and cerebral blood flow (nCBF)] were obtained. Preoperative serum levels of MMP-2 and MMP-9 were detected using ELISA. The diagnostic performance was evaluated by analyzing receiver operating characteristic (ROC) and area under the curve (AUC). RESULTS: At baseline, the recurrence patients had higher nCBF and nCBV than the non-recurrence patients, accompanying by the increased MMP-2 and MMP-9 levels in serum. Serum MMP-2 level were positively associated with MMP-9 in recurrent patients. In patients classified as recurrence, both MMP-9 and MMP-2 in serum had a significant correlation with nCBV and nCBF. A sensitivity and specificity of nCBF for recurrence vs. non-recurrence were 94.29% and 63.33%, respectively. nCBV also could provide high discrimination between recurrence and non-recurrence patients (sensitivity: 84.29%, specificity: 62.67%, AUC: 0.821). In ROC analyses, both MMP-2 and MMP-9 distinguished recurrence from non-recurrence with AUC values of 0.883 and 0.900, respectively. Finally, the combination of DSC-PWI parameters (nCBF and nCBV) and serum MMP-2 and -9 levels showed much better discrimination capacity between recurrence and non-recurrence patients with a sensitivity of 92.86%, specificity of 79.33% and AUC of 0.899. CONCLUSION: The combination of DSC-PWI parameters together with serum MMP-2 and -9 levels offered an attractive approach to noninvasively distinguish recurrence after postoperative radiotherapy of GBM.

Development of a Macrophage-Related Risk Model for Metastatic Melanoma.

As a metastasis-prone malignancy, the metastatic form and location of melanoma seriously affect its prognosis. Although effective surgical methods and targeted drugs are available to enable the treatment of carcinoma in situ, for metastatic tumors, the diagnosis, prognosis assessment and development of immunotherapy are still pending. This study aims to integrate multiple bioinformatics approaches to identify immune-related molecular targets viable for the treatment and prognostic assessment of metastatic melanoma, thus providing new strategies for its use as an immunotherapy. Immunoinfiltration analysis revealed that M1-type macrophages have significant infiltration differences in melanoma development and metastasis. In total, 349 genes differentially expressed in M1-type macrophages and M2-type macrophages were extracted from the MSigDB database. Then we derived an intersection of these genes and 1111 melanoma metastasis-related genes from the GEO database, and 31 intersected genes identified as melanoma macrophage immunomarkers (MMIMs) were obtained. Based on MMIMs, a risk model was constructed using the Lasso algorithm and regression analysis, which contained 10 genes (NMI, SNTB2, SLC1A4, PDE4B, CLEC2B, IFI27, COL1A2, MAF, LAMP3 and CCDC69). Patients with high+ risk scores calculated via the model have low levels of infiltration by CD8+ T cells and macrophages, which implies a poor prognosis for patients with metastatic cancer. DCA decision and nomogram curves verify the high sensitivity and specificity of this model for metastatic cancer patients. In addition, 28 miRNAs, 90 transcription factors and 29 potential drugs were predicted by targeting the 10 MMIMs derived from this model. Overall, we developed and validated immune-related prognostic models, which accurately reflected the prognostic and immune infiltration characteristics of patients with melanoma metastasis. The 10 MMIMs may also be prospective targets for immunotherapy.

Supramolecular Combination Chemotherapy: Cucurbit[8]uril Complex Enhanced Platinum Drug Infiltration and Modified Nanomechanical Property of Colorectal Cancer Cells.

Combination chemotherapy is recognized as a vital medical treatment for cancer, but it has not achieved clinical ideal effects of combination therapy. Herein, we designed a supramolecular combination chemotherapy strategy based on cucurbit[8]uril (CB[8]), which can be facilely assembled into dual platinum drugs. Interestingly, employing the CB[8] carrier led to a greater than 10-fold intracellular Pt content compared to that of dual drugs at 4 h, and the CB[8] complex (CLE) can enhance the infiltration of platinum drugs in colorectal tumor cells tremendously. The platinum drugs can be released from CLE through consuming more tumor biomarker spermidine. Through analyzing the nanomechanical property of the colorectal tumor cellular surface by bioscope AFM, it was revealed that CLE modified the property by decreasing the adhesion and increasing the stiffness. This study provided a facile and sensitive strategy for improving combination chemotherapy by supramolecular materials.

Identification of Novel Hub Genes Associated with Psoriasis Using Integrated Bioinformatics Analysis.

Psoriasis is a chronic, prolonged, and recurrent inflammatory skin disease and the current therapeutics can only alleviate the symptoms rather than cure it completely. Therefore, we aimed to identify the molecular signatures and specific biomarkers of psoriasis to provide novel clues for psoriasis and targeted therapy. In the present study, the Gene Expression Omnibus (GEO) database was used to retrieve three microarray datasets (GSE166388, GSE50790 and GSE42632) and to explore the differentially expressed genes (DEGs) in psoriasis using the Affy package in R software. The gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment were utilized to determine the common DEGs and their capabilities. The STRING database was used to develop DEG-encoded proteins and a protein-protein interaction network (PPI) and the Cytohubba plugin to classify hub genes. Using the NetworkAnalyst platform, we detected transcription factors (TFs), microRNAs and drug candidates interacting with hub genes. In addition, the expression levels of hub genes in HaCaT cells were detected by western blot. We screened the up- and downregulated DEGs from the transcriptome microarrays of corresponding psoriasis patients. Functional enrichment of DEGs in psoriasis was mainly associated with positive regulation of leukocyte cell-cell adhesion and T cell activation, cytokine binding, cytokine activity and the Wnt signaling pathway. Through further data processing, we obtained 57 intersecting genes in the three datasets and probed them in STRING to determine the interaction of their expressed proteins and we obtained the critical 10 hub genes in the Cytohubba plugin, including TOP2A, CDKN3, MCM10, PBK, HMMR, CEP55, ASPM, KIAA0101, ESC02, and IL-1ß. Using these hub genes as targets, we obtained 35 TFs and 213 miRNAs that may regulate these genes and 33 potential therapeutic agents for psoriasis. Furthermore, the expression levels of TOP2A, MCM10, PBK, ASPM, KIAA0101 and IL-1ß were observably increased in HaCaT cells. In conclusion, we identified potential biomarkers, risk factors and drugs for psoriasis.

MoS2/graphene van der Waals heterojunctions combined with two-layered Au NP for SERS and catalysis analyse.

MoS2-plasmonic hybrid platforms have attracted significant interest in surface-enhanced Raman scattering (SERS) and plasmon-driven photocatalysis. However, direct contact between the metal and MoS2 creates strain that deteriorates the electron transport across the metal/ MoS2 interfaces, which would affect the SERS effect and the catalytic performance. Here, the MoS2/graphene van der Waals heterojunctions (vdWHs) were fabricated and combined with two-layered gold nanoparticles (Au NP) for SERS and plasmon-driven photocatalysis analyse. The graphene film is introduced to provide an effective buffer layer between Au NP and MoS2, which not only eliminates the inhomogeneous contact on MoS2 but also benefits the electron transfer. The substrate exhibits excellent SERS capability realizing ultra-sensitive detection for 4-pyridinethiol molecules. Also, the surface catalytic reaction of p-nitrothiophenol (PNTP) to p,p-dimercaptobenzene (DMAB) conversion was in situ monitored, demonstrating that the vdWHs-plasmonic hybrid could effectively accelerate reaction process. The mechanism of the SERS and catalytic behaviors are investigated via experiments combined with theoretical simulations (finite element method and quantum chemical calculations).

MoS2-based multiple surface plasmonic coupling for enhanced surface-enhanced Raman scattering and photoelectrocatalytic performance utilizing the size effect.

MoS2-based heterostructures have received increasing attention for not only surface-enhanced Raman scattering (SERS) but also for enhanced photoelectrocatalytic (PEC) performance. This study presents a hydrothermal method for preparing vertical MoS2 nanosheets composed of in situ grown AuNPs with small size and chemically reduced AgNPs with large size to achieve the synergistic enhancement of SERS and PEC properties owing to the size effect of the plasmonic structure. Compared with pristine MoS2 nanosheets and unitary AuNPs or AgNPs composited with MoS2 nanosheets, the ternary heterostructure exhibited the strongest electromagnetic field and surface plasmon coupling, which was confirmed by finite-difference time-domain (FDTD) simulation and absorption spectra. In addition, the experimental results confirmed the outstanding SERS enhancement with an EF of 1.1×109, and the most efficient hydrogen evolution reaction (HER) activity with a sensitive photocurrent response, attributing to the multiple surface plasmonic coupling effects of the Au-Ag bimetal and efficient charge-transfer process between MoS2 and the bimetal. That is, it provides a robust method for developing multi-size bimetal-semiconductor complex nanocomposites for high-performance SERS sensors and PEC applications.

Preparation and surface-enhanced Raman scattering properties of GO/Ag/Ta2O5 composite substrates.

The composite substrate composed of precious metal, semiconductor and graphene has not only high sensitivity and uniform Raman signal but also stable chemical properties, which is one of the important topics in the field of surface-enhanced Raman scattering (SERS). In this paper, a sandwich SERS substrate based on tantalum oxide (Ta2O5) is designed and fabricated. The substrate has high sensitivity, stable performance and high quantification capability. The composite substrate can achieve a high sensitivity Raman detection of crystal violet (CV) with a detection limit of 10-11 M and an enhancement factor of 1.5 × 109. This is the result of the synergistic effect of electromagnetic enhancement and chemical enhancement, in which the chemical enhancement is the cooperative charge transfer in the system composed of probe molecules, silver nanoparticles (AgNPs) and Ta2O5, and the electromagnetic enhancement comes from the strong local surface plasmon resonance between the adjacent AgNPs. After exposing the composite substrate to the air for one month, the Raman signal did not weaken, indicating that the performance of the composite substrate is stable. In addition, there is an excellent linear relationship between the intensity of Raman characteristic peak and the concentration of probe molecules, which proves that the composite substrate has high quantification capability. In practical application, the composite SERS substrate can be used to detect harmful malachite green quickly and sensitively and has a broad application prospect in the field of food safety and chemical analysis.

Noble metal modified ReS2 nanocavity for surface-enhanced Raman spectroscopy (SERS) analysis.

The rhenium disulphide (ReS2) nanocavity-based surface enhanced Raman scattering (SERS) substrates ware fabricated on the gold-modified silicon pyramid (PSi) by thermal evaporation technology and hydrothermal method. In this work, the ReS2 nanocavity was firstly combined with metal nanostructures in order to improve the SERS properties of ReS2 materials, and the SERS response of the composite structure exhibits excellent performance in sensitivity, uniformity and repeatability. Numerical simulation reveals the synergistic effect of the ReS2 nanocavity and the plasmon resonance generated by the metal nanostructures. And the charge transfer between the metal, ReS2 and the analytes was also verified and plays an non-ignorable role. Besides, the plasmon-driven reaction for p-nitrothiophenol (PNTP) to p,p'-dimercaptobenzene (DMAB) conversion was successfully in-situ monitored. Most importantly, it is found for the first time that the SERS properties of ReS2 nanocavity-based substrates are strongly temperature dependent, and the SERS effect achieves the best performance at 45 °C. In addition, the low concentration detection of malachite green (MG) and crystal violet (CV) molecules in lake water shows its development potential in practical application.

Genome Resource of Sphingomonas carotinifaciens L9-754T, an Endophyte Isolated From Leaf Tissues of Jatropha curcas.

Sphingomonas carotinifaciens strain L9-754T (DSM 27347) is a gram-negative, chemoheterotrophic, and rod-shaped endophyte isolated from the stem tissues of Jatropha curcas L. This strain has putative in vitro antagonistic ability against the plant pathogenic fungus Magnaporthe grisea. A draft genome of L9-754T was obtained using the PacBio SMRT cell platform. By analyzing the genome of strain L9-754T, a gene cluster (GQR91_18700 - GQR91_18715) related to an antioxidant enzyme was identified in the obtained draft genome. The information obtained from the draft genome is expected to reveal the putative properties helpful in biocontrol applications.

Aluminum nanoparticle films with an enhanced hot-spot intensity for high-efficiency SERS.

The weak plasmonic coupling intensity in an aluminum (Al) nanostructure has limited potential applications in excellent low-cost surface-enhanced Raman scattering (SERS) substrates and light harvesting. In this report, we aim to elevate the plasmonic coupling intensity by fabricating an Al nanoparticle (NP)-film system. In the system, the Al NP are fabricated directly on different Al film layers, and the nanoscale-thick alumina interlayer obtained between neighboring Al films acts as natural dielectric gaps. Interestingly, as the number of Al film layers increase, the plasmonic couplings generated between the Al NP and Al film increase as well. It is demonstrated that the confined gap plasmon modes stimulated in the nanoscale-thick alumina region between the adjacent Al films contribute significantly to elevating the plasmonic coupling intensity. The finite-difference time-domain (FDTD) method is used to carry out the simulations and verifies this result.

Elevating the density and intensity of hot spots by repeated annealing for high-efficiency SERS.

The simultaneous output of highly sensitive and reproducible signals for surface-enhanced Raman spectroscopy (SERS) technology remains difficult. Here, we propose a two-dimensional (2D) composite structure using the repeated annealing method with MoS2 film as the molecular adsorbent. This method provides enlarged Au nanoparticle (NP) density with much smaller gap spacing, and thus dramatically increases the density and intensity of hot spots. The MoS2 films distribute among the hot spots, which is beneficial for uniform molecular adsorption, and further increases the sensitivity of the SERS substrate. Three kinds of molecules were used to evaluate the SERS substrate. Ultra-sensitive, highly repetitive, and stable SERS signals were obtained, which would promote the application process of SERS technology in quantitative analysis and detection.

Identification of novel hub genes for Alzheimer's disease associated with the hippocampus using WGCNA and differential gene analysis.

Background: Alzheimer's disease (AD) is a common, refractory, progressive neurodegenerative disorder in which cognitive and memory deficits are highly correlated with abnormalities in hippocampal brain regions. There is still a lack of hippocampus-related markers for AD diagnosis and prevention. Methods: Differently expressed genes were identified in the gene expression profile GSE293789 in the hippocampal brain region. Enrichment analyses GO, KEGG, and GSEA were used to identify biological pathways involved in the DEGs and AD-related group. WGCNA was used to identify the gene modules that are highly associated with AD in the samples. The intersecting genes of the genes in DEGs and modules were extracted and the top ten ranked hub genes were identified. Finally GES48350 was used as a validation cohort to predict the diagnostic efficacy of hub genes. Results: From GSE293789, 225 DEGs were identified, which were mainly associated with calcium response, glutamatergic synapses, and calcium-dependent phospholipid-binding response. WGCNA analysis yielded dark green and bright yellow modular genes as the most relevant to AD. From these two modules, 176 genes were extracted, which were taken to be intersected with DEGs, yielding 51 intersecting genes. Then 10 hub genes were identified in them: HSPA1B, HSPB1, HSPA1A, DNAJB1, HSPB8, ANXA2, ANXA1, SOX9, YAP1, and AHNAK. Validation of these genes was found to have excellent diagnostic performance. Conclusion: Ten AD-related hub genes in the hippocampus were identified, contributing to further understanding of AD development in the hippocampus and development of targets for therapeutic prevention.

Astragaloside IV Protects against Shear Stress-Induced Glycocalyx Damage and Alleviates Abdominal Aortic Aneurysm by Regulating miR-17-3p/Syndecan-1.

Background: The present study aimed to analyze the impact of astragaloside IV (AS-IV) on abdominal aortic aneurysm (AAA) and the glycocalyx, elucidating the potential mechanism of AS-IV. Methods: Rat models of AAA were established using porcine pancreatic elastase. The effects of intraperitoneal AS-IV injection on the morphology, diameter, and glycocalyx of the aorta and the expression of miR-17-3p and Syndecan-1 (SDC1) protein were examined. Differentially expressed miRNAs from peripheral blood samples of healthy individuals, untreated patients with AAA, and treated patients with AAA were identified through sequencing. The relationship between miR-17-3p and SDC1 was validated using a dual-luciferase reporter assay. In vitro, shear stress was induced in human aortic endothelial cells (HAECs) to simulate AAA. Overexpression of miR-17-3p was performed to assess the effects of AS-IV on miR-17-3p and SDC1 expressions, apoptosis, and glycocalyx in HAECs. Results: AS-IV mitigated aortic damage in AAA rats, reducing the aortic diameter and alleviating glycocalyx damage. In addition, it suppressed the increase in miR-17-3p expression and promoted SDC1 expression in AAA rats. Peripheral blood miR-17-3p levels were significantly higher in patients with AAA than in healthy individuals. miR-17-3p inhibited the SDC1 protein expression in HAECs. In the in vitro AAA environment, miR-17-3p was upregulated and SDC1 was downregulated in HAECs. AS-IV inhibited miR-17-3p expression, promoted SDC1 expression, and mitigated shear stress-induced apoptosis and glycocalyx damage in HAECs. Overexpression of miR-17-3p blocked AS-IV-induced SDC1 expression promotion, glycocalyx protection, and apoptosis suppression in HAECs. Conclusion: miR-17-3p may damage the glycocalyx of aortic endothelial cells by targeting SDC1. AS-IV may promote SDC1 expression by inhibiting miR-17-3p, thereby protecting the glycocalyx and alleviating AAA.

MiR-125b and SATB1-AS1 might be shear stress-mediated therapeutic targets.

The aim of the study was to explore the potential molecular mechanism associated with shear stress on abdominal aortic aneurysm (AAA) progression. This study performed RNA sequencing on AAA patients (SQ), AAA patients after endovascular aneurysm repair (EVAR, SH), and normal controls (NC). Furthermore, we identified the differentially expressed microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNA (cirRNAs) and constructed competing endogenous RNA (ceRNA) networks. Finally, 164 differentially expressed miRNAs, 179 co-differentially expressed lncRNAs, and 440 co-differentially expressed circRNAs among the three groups were obtained. The differentially expressed miRNAs mainly enriched in 325 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Target genes associated with co-differentially expressed genes among the group of SH, SQ, and NC mainly enriched in 66 KEGG pathways. LncRNA-miRNA-mRNA interactions, including 15 lncRNAs, 63 miRNAs and 57 mRNAs, was constructed. CircRNA-miRNA-mRNA ceRNA network included 79 circRNAs, 21 miRNAs, and 49 mRNAs. Among them, KLRC2 and CSTF1, targeted by miR-125b, participated in cell-mediated immunity regulation. MiR-320-related circRNAs and SATB1-AS1 serving as the sponge of miRNAs, such as has-circ-0129245, has-circ-0138746, and has-circ-0139786, were hub genes in ceRNA network. In conclusion, AAA patients might be benefit from EVAR based on various pathways and some molecules, such as miR-125b and SATB1-AS1, related with shear stress.

Supramolecular Combination Cancer Therapy Based on Macrocyclic Supramolecular Materials.

Supramolecular combination therapy adopts supramolecular materials to design intelligent drug delivery systems with different strategies for cancer treatments. Thereinto, macrocyclic supramolecular materials play a crucial role in encapsulating anticancer drugs to improve anticancer efficiency and decrease toxicity towards normal tissue by host-guest interaction. In general, chemotherapy is still common therapy for solid tumors in clinics. However, supramolecular combination therapy can overcome the limitations of the traditional single-drug chemotherapy in the laboratory findings. In this review, we summarized the combination chemotherapy, photothermal chemotherapy, and gene chemotherapy based on macrocyclic supramolecular materials. Finally, the application prospects in supramolecular combination therapy are discussed.

Adaptive optimal output regulation for wheel-legged robot Ollie: A data-driven approach.

The dynamics of a robot may vary during operation due to both internal and external factors, such as non-ideal motor characteristics and unmodeled loads, which would lead to control performance deterioration and even instability. In this paper, the adaptive optimal output regulation (AOOR)-based controller is designed for the wheel-legged robot Ollie to deal with the possible model uncertainties and disturbances in a data-driven approach. We test the AOOR-based controller by forcing the robot to stand still, which is a conventional index to judge the balance controller for two-wheel robots. By online training with small data, the resultant AOOR achieves the optimality of the control performance and stabilizes the robot within a small displacement in rich experiments with different working conditions. Finally, the robot further balances a rolling cylindrical bottle on its top with the balance control using the AOOR, but it fails with the initial controller. Experimental results demonstrate that the AOOR-based controller shows the effectiveness and high robustness with model uncertainties and external disturbances.