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Objective. The role of coiled-coil domain-containing protein 45 (CCDC45) in the development of hepatocellular carcinoma (HCC) has not been reported. The present study is aimed at investigating the expression and prognosis of CCDC45 in HCC and its relevance to immune infiltration. Methods. We conducted CCDC45 expression analysis using The Cancer Genome Atlas (TCGA) tumor database, the Human Protein Atlas (HPA) database, and the Tumor Immunological Evaluation Resource (TIMER). We used the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN) database to show the correlation of CCDC45 with clinical features. We examined the prognostic impact of CCDC45 expression levels on HCC patients with the Kaplan-Meier mapper database. Genes coexpressed with CCDC45 and its regulators were also identified using LinkedOmics. The enriched Gene Ontology (GO) categories and associated signaling pathways were estimated using GO, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Assay (GSEA) pathway data. Correlations between CCDC45 and cancer immune infiltration was analyzed through the TIMER and an integrated repository portal for Tumor-Immune System Interactions (TISIDB) databases. Results. The expression of CCDC45 was elevated in HCC tissues compared to adjacent liver tissues, and overexpression of CCDC45 was significantly correlated with tumor stage. Furthermore, HCC patients with CCDC45 overexpression had a shorter overall survival (OS). Functional network analysis indicated that CCDC45 was involved in homologous recombination, spliceosome, and DNA replication. Interestingly, CCDC45 expression was positively correlated with the level of immune cell infiltration. Conclusions. CCDC45 is associated with prognosis and immune infiltration of HCC and may be a potential therapeutic target for HCC.

Highly efficient NIR-II luminescent nanoprobes of AgInTe2:Zn/ZnS QDs were successfully synthesized with the maximum quantum yield of 25.2%, and were employed for sensitive biodetection of xanthine oxidase with the limit of detection down to 25 nU L−1.

Huangkui capsule (HKC), a Chinese patent medicine, has been widely used in China as adjuvant therapy for chronic kidney disease (CKD). It displays superior anti-proteinuria efficacy than losartan in patients with CKD at stages 1-2, however, the mechanism of HKC alleviating proteinuria has not been well elucidated.This study aims to confirm the therapeutic effect and investigate associated underlying mechanism of HKC against proteinuria by in vivo and in vitro experiments.We established an adriamycin (ADR) induced proteinuria mouse model to evaluate kidney function by biochemical markers measurement and to observe histopathological alterations by hematoxylin and eosin (HE), Masson's trichrome and Periodic Acid-Schiff (PAS)-stained sections of renal, respectively. Moreover, the expressions of Nephrin and Podocin were measured by immunohistochemistry (IHC) and western blotting analysis to investigate podocyte damage. Furthermore, we established Mouse Podocyte Clone-5 (MPC-5) injury model to identify the active components of HKC against podocyte damage by detecting the expressions of Nephrin, Podocin, and ZO-1 proteins. At last, the key protein levels of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway were assessed by western blotting analysis to explore the underlying mechanism of HKC against proteinuria.Our results showed that HKC administration for three consecutive weeks dose-dependently ameliorated both renal function and histopathological damages, elevated the expressions of Nephrin and Podocin, the pivotal molecules maintaining filtration function of the podocyte, indicating the promising protective effect against podocyte injury under ADR exposure. Consistently, in vitro experiments showed HKC administration effectively reversed the abnormal expressions of Nephrin and Podocin in MPC-5 cells treated with ADR, suggesting its protective effect against podocyte injury to maintain filtration barrier integrity. In addition, Hibifolin was identified as the most active ingredients in HKC, which suppressed upstream JAK2/STAT3 and PI3K/Akt pathway phosphorylation to maintain the structural and functional integrity of podocyte filtration barrier. Of note, AG490, a selective JAK2 inhibitor, was used to further affirm the role of Hibifolin involving in regulation JAK2/STAT3.Our study suggested that HKC may protect podocytes via JAK2/STAT3 and PI3K/Akt pathway to display its effects of ameliorating proteinuria.

The effects of interwire distance (d) and arc length correction coefficient (Cc) on the arc behaviors, droplet transfer and welding process stability in the double-wire narrow-gap gas metal arc welding (NG-GMAW) were investigated. With d changing from 10mm to 20mm, the arc deflection only occurs at the background stage of pulsed welding current, and the droplet transfer mode keeps unchanged. A large Cc (20%) leads to serious peak arc deflection and unstable droplet transfer, whereas a small Cc (− 10%) eliminates the arc deflection and brings about short-circuiting droplet transfer. The arc interruption frequently occurs when d is 20mm or Cc is 20%. Moreover, when d is 10mm or Cc is 20%, serious sidewall arcs occur in double-wire NG-GMAW. With the increase in d and/or decrease in Cc, the welding process stability can be improved at first and then gets worse. In general, the trailing arc is more stable than the leading arc. Increasing Cc will result in a serious surface depression defect on the left side of the weld bead because of the serious peak arc deflection. A sound weld bead is obtained when the interwire distance is 15mm.

Lanthanide ion (Ln

Owing to the ill-conditioned nature of electrical resistivity tomography and the measurement error of the hardware equipment, the reconstructed resistivity distribution image often contains artifacts of varying degrees. Other soft-field imaging technologies, such as electrical impedance tomography and electrical capacitance tomography, also encounter artifacts. Artifacts interfere with the assessment of damaged areas. To eliminate the influence of artifacts on the reconstructed image, a novel artifact elimination algorithm called the fast artifact filtering (FAF) algorithm is proposed. Based on the calculation results of existing algorithms, such as the Newton’s one-step error reconstructor (NOSER) algorithm, the FAF algorithm can remove the damaged areas with low confidence from the potentially damaged areas and only retain the damaged areas with high confidence for final imaging. Several simulation models were used to test the effectiveness of the artifact elimination algorithm proposed in this study. The test results show that the number of artifacts in the final reconstructed image is significantly reduced after the NOSER algorithm is combined with the FAF algorithm. In addition, when the number of finite element model division elements was 4802, the refresh time of a single image increased by approximately 1 ms. A structural health monitoring test for hollow structure is provided. The results show that the FAF also performs well on the measured voltage data.

The effects of interwire distance and angle on arc interaction behaviors and droplet transfer, as well as the weld undercut-defect formation mechanism in tandem pulsed gas metal arc welding (GMAW) with a novel welding torch were studied in this work. The arc interaction behaviors vary with the change of the interwire distance and angle. Generally, the background leading arc is much easier to deflect than the background trailing arc. When the interwire distance is 10 mm and the interwire angle is 10°, the arc climbing phenomenon occurs in the leading arc because of the strong electromagnetic attraction. The pulsed streaming spray and pulsed projected spray are two primary droplet transfer modes occurring in most welding cases. They are greatly influenced by the welding torch configuration. The interwire distance of 15 mm and the interwire angle of 10° are considered to be the best in the present work based on the comprehensive evaluation of arc behaviors, droplet transfer and weld bead formation. When the interwire angle is equal to or greater than 14°, and the interwire distance is kept to be 15 mm, the blocking effect of the trailing arc on the backward fluid driven by the leading arc gets weakened due to the increased inter-wire-tip transverse distance. For this reason, only a handful of molten metal exists under the leading arc. Moreover, the molten metal from the melting of trailing wire cannot reach the right edge of the welding pool that is formed by the leading arc. Thus, an undercut defect occurs in the weld bead.

Lanthanide (Ln3+)-doped upconversion (UC) nanocrystals have drawn tremendous attention because of their intriguing optical properties. Currently, it is highly desired but remains challenging to achieve efficient multiphoton UC emissions. Herein, we report the controlled synthesis of a new class of UC nanocrystals based on Cs2NaYF6:Yb/Tm nanoplatelets (NPs), which can effectively convert the 980 nm light to five-photon and four-photon UC emissions of Tm3+ without the fabrication of a complicated core/multishell structure required in traditional nanocrystals. Particularly, the as-prepared Cs2NaYF6:Yb/Tm NPs exhibit a maximal UV-to-NIR emission intensity ratio of 1.2, which is the highest among Tm3+-doped core-only UC nanocrystals. We reveal that the enhanced multiphoton UC emissions may benefit from the confined energy migration of Ln3+ dopants in the unique two-dimensional-like structure of Cs2NaYF6 NPs. As such, intense red and green UC emissions of Eu3+ and Tb3+ can further be generated via the cascade sensitization of Tm3+ and Gd3+ in Cs2NaYF6:Yb/Tm/Gd/Eu and Cs2NaYF6:Yb/Tm/Gd/Tb NPs, respectively. These results validate the superiority of Cs2NaYF6 for the future design of efficient UC nanocrystals towards versatile applications.

Prostate cancer (PC) is the most common non-cutaneous malignancy among men in the western world. However, heterogeneity remains a pressing clinical problem.The least absolute shrinkage and selection operator (LASSO) was used to screen the prognostic signature. Weighted correlation network analysis (WGCNA) was used to identify the target genes associated with high-risk characteristics. Gene set enrichment analysis was used to suggest the molecular mechanism ofTen DNA methylation sites were selected as the prognostic signature. A high expression ofWe developed a DNA methylation 10-CpG prognostic signature to predict the prognosis of PC patients. And the high expression of

Suhua Wang,1,2 Siyuan Han,1,2 Weiyan Cheng,1,2 Ruoyang Miao,1,2 Shasha Li,1,2 Xin Tian,1,2 Quancheng Kan1,2 1Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Henan Key Laboratory of Precision Clinical Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Xin Tian; Quancheng Kan, Email tianx@zzu.edu.cn; kanqc@zzu.edu.cnPurpose: To enhance the cytotoxicities of our obtained CDK4 inhibitors and get CDK4/HDACs inhibitors with potent enzymatic inhibitory and anti-proliferative activities.Methods: A series of novel CDK4/HDACs inhibitors were designed and synthesized by incorporating the HDAC pharmacophores (hydroxylamine or o-diaminoaniline) into the basic structure of our newly obtained 2-anilino-4-triazolpyrimidine based CDK4 inhibitors. The enzymatic inhibitory (HDAC1, CDK2, CDK4, and CDK6) activities and cytotoxicities of these compounds were evaluated. Moreover, HDAC isoforms inhibitory activity, cell cycle arrest assay, cell apoptosis analysis, cell migration, and cell colony formation assay were performed for the representative compound 11k.Results: Most of these compounds showed excellent HDAC1 inhibitory activities (IC50s: 0.68∼ 244.5 nM) and anti-proliferative activities against cancer cell lines. Some compounds displayed potent CDK4 inhibitory activities and a certain selectivity towards CDK2 and CDK6. Compound 11k exhibited potent enzymatic (CDK4: IC50=23.59 nM; HDAC1: IC50=61.11 nM; HDAC2: IC50=80.62 nM; HDAC6: IC50=45.33 nM) and anti-proliferative activities against H460, MDA-MB-468, HCT116, and HepG2 cell lines with IC50 values 1.20, 1.34, 2.07, and 2.66 μM, respectively. Further mechanistic studies revealed that compound 11k could arrest the cell cycle in G0/G1 phase and induce apoptosis in HCT116 and MDA-MB-468 cells. In addition, compound 11k significantly inhibited the migration and cell colony formation of H460 and HCT116 cells.Conclusion: This study suggested that the incorporation of the HDAC pharmacophore into CDK4 inhibitor scaffold to design CDK/HDAC inhibitors might be a tractable strategy to enhance the antitumor potency of compounds.Keywords: CDK4, HDAC, inhibitor, 2-anilino-4-triazolpyrimidine, cancer

Background The interpretation system for prostate MRI is largely based on qualitative image contrast of different tissue types. Therefore, a fast, standardized, and robust quantitative technique is necessary. Synthetic MRI is capable of quantifying multiple relaxation parameters, which might have potential applications in prostate cancer (PCa). Purpose To investigate the use of quantitative relaxation maps derived from synthetic MRI for the diagnosis and grading of PCa. Study type Prospective. Subjects In all, 94 men with pathologically confirmed PCa or benign pathological changes. Field strength/sequence T1 -weighted imaging, T2 -weighted imaging, diffusion-weighted imaging, and synthetic MRI at 3.0T. Assessment Four kinds of tissue types were identified on pathology, including PCa, stromal hyperplasia (SH), glandular hyperplasia (GH), and noncancerous peripheral zone (PZ). PCa foci were grouped as low-grade (LG, Gleason score ≤6) and intermediate/high-grade (HG, Gleason score ≥7). Regions of interest were manually drawn by two radiologists in consensus on parametric maps according to the pathological results. Statistical tests Independent sample t-test, Mann-Whitney U-test, and receiver operating characteristic curve analysis. Results T1 and T2 values of PCa were significantly lower than SH (P = 0.015 and 0.002). The differences of T1 and T2 values between PCa and noncancerous PZ were also significant (P ≤ 0.006). The area under the curve (AUC) of the apparent diffusion coefficient (ADC) value was significantly higher than T1 , T2 , and proton density (PD) values in discriminating PCa from SH and noncancerous PZ (P ≤ 0.025). T2 , PD, and ADC values demonstrated similar diagnostic performance in discriminating LG from HG PCa (AUC = 0.806 [0.640-0.918], 0.717 [0.542-0.854], and 0.817 [0.652-0.925], respectively; P ≥ 0.535). Data conclusion Relaxation maps derived from synthetic MRI were helpful for discriminating PCa from other benign pathologies. But the overall diagnostic performance was inferior to the ADC values. T2 , PD, and ADC values performed similarly in discriminating LG from HG PCa lesions. Level of evidence 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;52:552-564.

Low-cost poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives have been widely used as hole-transporting materials (HTMs) in p–i–n perovskite solar cells (PSCs). However, reports on the use of PEDOT-based HTMs in regular PSCs have been rather limited up till now due to the low solubility of PEDOT in organic solvents. In this work, we report three PEDOT derivatives, namely, PEDOT-C6 (P6), PEDOT-C10 (P10), and PEDOT-C14 (P14), with a simple synthetic process by tailoring the length of the alkyl side-chains, and apply them as dopant-free HTMs in mesoscopic n–i–p structured PSCs. It is revealed that the alkyl side-chain length has a significant impact on the film morphology, hole transport capability, and thus the overall solar cell performance. The devices with P10 afford a champion PCE of 16.2% at one sun illumination (100 mW cm−2, AM 1.5G), which is significantly higher compared to those based on P6 (12.1%) and P14 (14.8%) under identical conditions. This has been the highest PCE reported so far for dopant-free PEDOT-based HTMs in conventional PSCs. The greatly enhanced photovoltaic performance observed for the P10-based devices is mainly attributed to the superior film formation property and hole transport capability of P10. Furthermore, the devices utilizing P10 also show excellent ambient stability, retaining 75% of their initial performance at a relative humidity (RH) of 80% after 120 h due to the high moisture resistivity of the HTM. The present work provides a new avenue for further developing low-cost, efficient, and stable HTMs in PSCs in the future.

Hypoxia is a hallmark of many solid tumors, and it causes the overexpression of a variety of proteins including the epidermal growth factor receptor (EGFR). Many antitumor prodrugs have been designed to target hypoxia. Here we report the identification of a kind of hypoxia-activated proteolysis targeting chimera (ha-PROTAC) by introducing the hypoxia-activated leaving group (1-methyl-2-nitro-1H-imidazol-5-yl)methyl or 4-nitrobenzyl into the structure of an EGFRDel19-based PROTAC. Among the obtained molecules, ha-PROTAC 13 exhibits a more potent degradation activity for EGFRDel19 in hypoxia than in normoxia in HCC4006 cells. This is the first example of identifying a PROTAC to selectively act on tumors utilizing the characteristic of tumor hypoxia and provides a new approach for PROTAC development.

ENKUR plays a crucial role in lung and colorectal cancers. Chemically synthesized cinobufotalin (CB) showed its significant anti-cancer effect in nasopharyngeal carcinoma. However, the roles of ENKUR and CB along with their correlation are still unknown in hepatocellular carcinoma (HCC). In this study, ENKUR expression in HCC tissue and cells were detected. The relationship between ENKUR expression and clinical pathology was also assessed.

Lanthanide (Ln3+)-doped upconversion (UC) nanocrystals have drawn tremendous attention because of their intriguing optical properties. Currently, it is highly desired but remains challenging to achieve efficient multiphoton UC emissions. Herein, we report the controlled synthesis of a new class of UC nanocrystals based on Cs2NaYF6:Yb/Tm nanoplatelets (NPs), which can effectively convert the 980 nm light to five-photon and four-photon UC emissions of Tm3+ without the fabrication of a complicated core/multishell structure required in traditional nanocrystals. Particularly, the as-prepared Cs2NaYF6:Yb/Tm NPs exhibit a maximal UV-to-NIR emission intensity ratio of 1.2, which is the highest among Tm3+-doped core-only UC nanocrystals. We reveal that the enhanced multiphoton UC emissions may benefit from the confined energy migration of Ln3+ dopants in the unique two-dimensional-like structure of Cs2NaYF6 NPs. As such, intense red and green UC emissions of Eu3+ and Tb3+ can further be generated via the cascade sensitization of Tm3+ and Gd3+ in Cs2NaYF6:Yb/Tm/Gd/Eu and Cs2NaYF6:Yb/Tm/Gd/Tb NPs, respectively. These results validate the superiority of Cs2NaYF6 for the future design of efficient UC nanocrystals towards versatile applications.

Rapid and accurate detection of phosphate (Pi) in complex biological fluid is of critical importance for timely warning of Pi accumulation and monitoring Pi related pathological process. Up to date, various luminescent probes have been developed for Pi determination in aqueous media. However, the huge obstacles of the current probes suffer from the inherent issues such as time-consuming, tedious preparation and unavoidable background interference during Pi detection. To circumvent this limitation, we proposed a universal and facile strategy to fabricate a novel sensitizer-Ln3+@surfactant micelle probe with time-resolved luminescent (TRL) superiority through the self-assembly of sensitizer, Ln3+ and surfactant. Through this design, the sensitizer-Ln3+ chelate can be encapsulated into the surfactant constructed micelle and Ln3+ luminescence can be substantially lighted up through the effective energy transfer from the coordinated sensitizer and the assistance of Triton X-100. Such high TRL signal can be sensitively and specifically quenched by Pi, which was attributed to the specific coordination competition between sensitizer and Pi towards Ln3+. Benefitting from the background-free interference and highly sensitive TRL response of the sensitizer-Ln3+@surfactant probe, we achieved the rapid, selective and sensitive detection of Pi in the range of 0.5–120 μM with a limit of detection (LOD) of 0.19 μM. Furthermore, the accuracy of the proposed method based on the Ln3+ involved micelle probes was further verified through the quantitation of Pi in real biological samples.

In this paper, a dynamic economic dispatch problem (DEDP) considering wind turbine (WT) and battery energy storage system (BESS) in a smart grid is formulated, which aims at minimising the total cost and making economic use of distributed energy resources, while meeting the requirement of constraints. To solve this problem, we propose a distributed consensus algorithm based on alternating direction method of multipliers (ADMM) and projected gradient method on the assumption of strongly connected and balanced communication networks. What's more, on the basis of average consensus theory, each node estimates the total power demand which is usually regarded as a known variable to make the condition more practical. Besides, we adopt the idea of bisection to deal with the exponential term in cost function. Our algorithm is fully distributed via local computation and guarantees power balance at each time slot. The effectiveness of the proposed algorithm is verified in simulation example.

We implement a thermal-fluctuation driven logical bit reset on a superconducting flux logic cell. We show that the logical state of the system can be continuously monitored with only a small perturbation to the thermally activated dynamics at 500 mK. We use the trajectory information to derive a single-shot estimate of the work performed on the system per logical cycle. We acquire a sample of $10^5$ erasure trajectories per protocol, and show that the work histograms agree with both microscopic theory and global fluctuation theorems. The results demonstrate how to design and diagnose complex, high-speed, and thermodynamically efficient computing using superconducting technology., 9 pages, 7 figures