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One of the effective methods to simultaneously achieve the thermal protection and friction reduction requirement of a scramjet engine is the usage of fuel film cooling. As the combustion process inside the combustor proceeds, the oxygen concentration in the burnt gas gradually decreases and will influence the thermal and friction characteristics of the hydrocarbon film. Therefore, the effects of oxygen concentration in the mainstream on the hydrocarbon film are evaluated by numerical simulations based on RANS framework. The results indicate that the cooling performance of the hydrocarbon film is not sensitive to the oxygen concentration, although the fuel film burns more intense as the oxygen concentration increases. While the friction reduction performance is sensitive to the oxygen concentration. Specifically, about 10% friction reduction can be obtained for 10% oxygen in the mainstream compared to that of inert cases, and the wall friction can be further reduced by 30% for 20% oxygen. Further analysis reveals that the mechanism of the above two drag reductions is different. For weak boundary layer combustion, the decrease of the molecular viscosity contributes to the reduction of friction. While for significant boundary layer combustion, a lower near-wall velocity gradient is the main reason.

Closed-Brayton-cycle (CBC) is a potential scheme to provide high-power electricity for hypersonic vehicles, but finite cold source onboard limits its power level. A thermoelectric generator (TEG) combined with CBC is a feasible power enhancement approach by extending the available temperature range of cold source. In this study, a performance assessment of the CBC-TEG combined power generation system coupled with hydrocarbon-fueled scramjet is performed to exhibit its possible operation characteristics and performance limitations on hypersonic vehicles. Results indicate that, at a fixed flight Mach number, a larger fuel equivalence ratio (φ) leads to a higher total electric power and CBC power but a lower TEG power. There are three limitations on the fuel equivalence ratio, TEG temperature difference, and combustion heat dissipation adjustment for the operation of CBC-TEG. The total power of CBC-TEG can be adjusted by φ, but the adjustable range becomes smaller at higher Ma. The electric quantity at unit fuel mass increases with φ, mainly due to the higher thermoelectric conversion efficiency. Moreover, the maximum value of the electric quantity at unit fuel mass for CBC-TEG reaches 277.0 kJ/kg, which is about 33.4% higher than that of standalone CBC.

Multiphoton excitation allows one to access high energy excited states and perform valuable tasks in biological systems using tissue penetrating near-infrared (NIR) light. Here, we describe new photoactive manganese tricarbonyl complexes incorporating the ligand 4'-p-N,N-bis(2-hydroxyethyl)amino-benzyl-2,2':6',2″-terpyridine (TPYOH), which can serve as an antenna for two photon NIR excitation. Solutions of Mn(CO)3(TPYOH)X (X = Br- or CF3SO3-) complexes are very photoactive toward CO release under visible light excitation (405 nm, 451 nm). The same responses were also triggered by multiphoton excitation at 750 and 800 nm. In this context, we discuss the potential applications of these complexes as visible/NIR light photoactivated carbon monoxide releasing moieties (photoCORMs). We also report the isolation and crystal structures of the TPYOH complexes Mn(TPYOH)Cl2 and [Mn(TPYOH)2](CF3SO3)2, to illustrate a possible photolysis product(s).

Gastric cancer remains one of the most common deadly diseases and lacks effective targeted therapies. In the present study, we confirmed that the signal transducer and activator of transcription 3 (STAT3) is highly expressed and associated with a poor prognosis in gastric cancer. We further identified a novel natural product inhibitor of STAT3, termed XYA-2, which interacts specifically with the SH2 domain of STAT3 (Kd = 3.29 μM) and inhibits IL-6-induced STAT3 phosphorylation at Tyr705 and nuclear translocation. XYA-2 inhibited the viability of seven human gastric cancer cell lines with 72-h IC50 values ranging from 0.5 to 0.7 μΜ. XYA-2 at 1 μΜ inhibited the colony formation and migration ability of MGC803 (72.6% and 67.6%, respectively) and MKN28 (78.5% and 96.6%, respectively) cells. In the in vivo studies, intraperitoneal administration of XYA-2 (10 mg/kg/day, 7 days/week) significantly suppressed 59.8% and 88.8% tumor growth in the MKN28-derived xenograft mouse model and MGC803-derived orthotopic mouse model, respectively. Similar results were obtained in a patient-derived xenograft (PDX) mouse model. Moreover, XYA-2 treatment extended the survival of mice bearing PDX tumors. The molecular mechanism studies based on transcriptomics and proteomics analyses indicated that XYA-2 might exert its anticancer activity by synergistically inhibiting the expression of MYC and SLC39A10, two downstream genes of STAT3 in vitro and in vivo. Together, these findings suggested that XYA-2 may be a potent STAT3 inhibitor for treating gastric cancer, and dual inhibition of MYC and SLC39A10 may be an effective therapeutic strategy for STAT3-activated cancer.

Solid oxide fuel cells (SOFC) have gradually become possible to be used in the aviation field because of their high efficiency and fuel flexibility. The number of internal combustion engines (ICE) that are already in use is large, which makes it difficult to completely abandon them in a short period. Hence, finding low-carbon alternative fuels is significant for the development of cleaner internal combustion engines. In this paper, different hybrid power systems configured with different fuels, i.e., hydrogen, methanol, liquid ammonia, isooctane, natural gas and gasoline, which consist of a solid oxide fuel cell and an internal combustion engine, are constructed to help find the optimal set of fuel and system structure by analyzing the power generation performance and weight of different systems. The results show that the hybrid power system with ammonia or methanol (except gasoline) as fuel presents the lowest actual fuel consumption rate (around 310 g/kWh). The hybrid power system with ammonia as fuel performs the highest power generation efficiency of 61.58%, and the corresponding power density is estimated at 0.556 kW/kg. In conclusion, the proposed system with ammonia as fuel has obvious advantages in fuel consumption rate, power generation efficiency, carbon emission reduction and fuel storage.

Platycodin D (PD) is a triterpene saponin extracted from the root of Platycodon grandiflorum. It has been reported to exhibit multiple pharmacological and biological properties. There is substantial evidence to support that PD displays a wide range of anti-tumor activities. However, the detailed molecular mechanism still needs further elaboration. In the present study, to explore whether PD inhibits gastric cancer (GC) cell viability, eight GC cell lines and the GES-1 cell line (a gastric mucosal cell line) were tested. We found that PD exhibited better inhibitory activity on GC cell lines than on the non-tumor cell line. Besides, treatment with PD led to a significant cell cycle arrest, thereby causing subsequent apoptosis. Regarding the cell growth inhibition mechanism, PD can downregulate the protein level of c-Myc rather than its mRNA level in a dose-dependent manner. Further studies revealed that PD disturbed the overall ubiquitination level in GC cell lines and enhanced the ubiquitination-dependent degradation of c-Myc. Interestingly, the inhibition of cell viability by PD could be restored to a certain extent when the expression of c-Myc was recovered, suggesting that PD-mediated GC cell growth inhibition is closely associated with c-Myc expression. Our study proposes a novel molecular mechanism for PD inhibiting GC cell proliferation and growth by destabilizing the c-Myc protein. This work may lay a preliminary foundation for developing PD as an anti-cancer therapy.

In this paper,the control characteristic of cascaded hybrid high voltage direct current (HVDC) system is studied. The influence mechanism of modular multilevel converter (MMC) inverters to the whole hybrid HVDC are investigated,and the complete voltage-current characteristic curves of the hybrid HVDC are obtained in droop control modes. Compared with the master-slave control,MMCs in droop control have ability to control both DC voltage and DC power,and the power reverse transmission will not occur. However,MMCs in droop control cannot control DC voltage accurately. Thus,an adaptive droop control strategy of cascaded hybrid HVDC system is proposed. The droop curve can be moved in real time adaptively according to DC current,which avoid the fluctuations of DC voltage due to the change of DC current. Finally,the simulation results verify the effectiveness of the proposed strategy based on PSCAD/EMTDC. This strategy can adjust the droop curves adaptively and realize accurate control of DC voltage in hybrid HVDC system,which improves the stability of the hybrid HVDC system.

Abstract Background Pancreatic cancer is one of the most lethal cancers worldwide. The IAPs function as E3 ubiquitin ligases and contribute to pancreatic cancer initiation, progression, and metastasis. Although IAP-targeted therapies have been developed and shown anticancer efficacy in preclinical settings, none of them has been approved yet. Methods Transcriptome data from public datasets were used to analyze the correlation of IAPs and E2s, and the biological function of E2 UbcH5c in pancreatic cancer. A structure-based virtual screen was used to identify UbcH5c inhibitor, and surface plasmon resonance analysis and cellular thermal shift assays were employed to evaluate the binding affinity. The anticancer activities were demonstrated through in vitro and in vivo assays, while the related mechanisms were explored through transcriptomic and proteomic analyses and confirmed by western blot, immunofluorescence, and qRT-PCR. Results UbcH5c is positively correlated with the expression of IAPs in pancreatic cancer. We further found that UbcH5c is overexpressed and associated with a poor prognosis in pancreatic cancer. We identified a small-molecule UbcH5c inhibitor, termed DHPO, which directly bound to UbcH5c protein. DHPO inhibited cell viability and colony formation, induced apoptosis, and suppressed migration and invasion of pancreatic cancer cells in vitro. The compound inhibited UbcH5c-mediated IκBα degradation and NF-κB activation, which is critical for its anticancer activity. Furthermore, DHPO suppressed the tumor growth and metastasis in two orthotopic pancreatic tumor mouse models. Conclusions These results indicated that inhibiting UbcH5c is a novel and effective strategy for treating pancreatic cancer and DHPO represents a new class of UbcH5c inhibitor and may be further developed as an anti-pancreatic cancer therapeutic agent.

Abstract Background Studies had shown many diseases affect the stability of human microbiota, but how this relates to benign prostatic hyperplasia (BPH) has not been well understood. Hence, this study aimed to investigate the regulation of BPH on gut microbiota composition and metabonomics. Methods We analyzed gut samples from rats with BPH and healthy control rats, the gut microbiota composition and metabonomics were detected by 16S rDNA sequencing and liquid chromatography tandem mass spectrometry (LC–MS/MS). Results High-throughput sequencing results showed that gut microbiota beta-diversity increased (P 0.05), Bacteroidetes (46.54% vs. 41.64%, P > 0.05), Clostridia (50.89% vs. 54.66%, P > 0.05), Ruminococcaceae (25.67% vs. 20.56%, P > 0.05). LC–MS/MS of intestinal contents revealed that differential metabolites were mainly involved in cellular processes, environmental information processing, metabolism and organismal systems. The most important pathways were global and overview maps, lipid metabolism, amino acid metabolism, digestive system and endocrine system. Through enrichment analysis, we found that the differential metabolites were significantly enriched in metabolic pathways, steroid hormone biosynthesis, ovarian steroidogenesis, biosynthesis of unsaturated fatty acids and bile secretion. Pearson correlation analysis (R = 0.94) showed that there was a strong correlation between Prevotellaceae, Corynebacteriaceae, Turicibacteraceae, Bifidobacteriaceae and differential metabolites. Conclusion Our findings suggested an association between the gut microbiota and BPH, but the causal relationship between the two groups is unclear. Thus, further studies are warranted to elucidate the potential mechanisms and causal relationships between BPH and gut microbiota.

After the AC system is short-circuited, voltage source converter-high voltage direct current (VSC-HVDC) can be equivalent to a current source with a certain amplitude and phase. In this paper, based on the equivalent model of VSC-HVDC when the receiving end grid fault occurs, the factors affecting the phase and amplitude of equivalent current source of VSC-HVDC are analyzed respectively. Studies show that the phase of the equivalent current source is mainly affected by the type of fault, and the amplitude is mainly affected by the control method, the amplitude limiter and the electrical distance. Because of the combination of different situations, the influence on the AC system short-circuit current is bceorning more complicated.The research results show that for AC side three-phase short-circuit fault, the influence of VSC-HVDC on short-circuit current can be divided into four situations, which contain zero feed in, limited amplitude of active control link, limited amplitude of reactive power control link and reference value of reactive power control link. The simulation results based on PSCAD software verify the relevant analysis.

Abstract Background Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. Methods Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. Results Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. Conclusions MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.

Carbon dot-based room-temperature phosphorescence materials have emerged as a shining new star in the carbon nanomaterial family in recent years due to their excellent optical properties. However, there still exists a significant challenge in obtaining carbon dots (CDs) with ultra-long phosphorescence lifetimes. In this study, tetraethyl orthosilicate (TEOS) was used to achieve in situ growth and encapsulation of CDs in a 3D SiO2 network using a one-pot hydrothermal method. It was demonstrated that Na+ is the key factor to achieve ultra-long afterglow lifetimes of CDs in dense SiO2 matrices, and the introduction of Na+ has a significant effect on extending the afterglow lifetime of various CDs. The designed Na/CDs@SiO2 nanomaterial exhibited an ultra-long afterglow lifetime of 6.69 s, which surpassed most reported CD-based afterglow lifetimes. This work provides a design principle and general strategy for achieving ultra-long afterglow lifetimes of CDs in dense SiO2 matrices. Due to the stable photoluminescence (PL) properties, low biotoxicity, and ultra-long afterglow lifetime of the Na/CDs@SiO2 nanomaterial, it was successfully applied in HeLa cell imaging. [ABSTRACT FROM AUTHOR]

The growing demand for electricity in long-duration space missions has become a pressing concern. The space nuclear closed-Brayton-cycle (CBC) power generation system offers advantages in power output, operational lifespan, and range. However, a significant speed disparity exists between its compressor and alternator. To address this challenge, this paper proposes a double-rotor CBC configuration. A corresponding dynamic model that couples the nuclear reactor and radiator is formulated, and dynamic analysis is conducted to facilitate system control. The study delves into the dynamic start-up process of the double-rotor CBC system and examines how various component parameters impact its power generation performance. The findings indicate that through the introduction of suitable reactivity to regulate reactor power and the incorporation of a PID controller to manage flow distribution between two turbines, the system can achieve start-up within 5200 s. Moreover, the innovative double-rotor structure suggested in this paper enables the separation of compressor and alternator speeds. Consequently, the compressor and alternator can operate within their optimal speed ranges independently, which is a feature that holds potential benefits for the system’s practical implementation. In addition, the steady-state operation of the system showcases the recuperator’s heat transfer power at around 1127.60 kW, a parameter of significant importance. Following steady-state operation, the double-rotor CBC system demonstrated an electrical power output of 175.99 kW and a thermal efficiency of 32.38%.

Pancreatic cancer is a highly aggressive cancer with an exceedingly low rate of response to treatments, which calls for comprehensive molecular characterization of pancreatic cancer cell lines (PCCLs). We screened multi-layer molecular data of 36 PCCLs, including gene mutation, gene expression, microRNA (miRNA) expression, and protein profiles. Our comparative analysis of genomic mutations found that PCCLs recapitulated genomic alterations of the primary tumor and suggested potential therapeutic strategies for clinical interventions. The panel of 36 PCCLs was classified into 2 subgroups based on transcriptomic mRNA expression, wherein the C1 subgroup was characterized with differentiation, whereas C2 cell lines were featured with immunity, angiogenesis, epidermis, and proliferation. Transcriptomic classification was further recapitulated by miRNA and protein expression. Additionally, the differential proteins between C1 and C2 subgroups were prominently involved in epidermal growth factor receptor (EGFR) signaling, phosphatidylinositol 3-kinase (PI3K) signaling, and mitogen-activated protein kinase (MAPK) signaling pathways. Tumor samples from different subgroups exhibited distinct infiltration of CD4 naive cells and monocytes. Remarkably, patients in subgroups C1 showed longer survival, whereas those in C2 had worse clinical outcome. Further integrative analysis revealed that temozolomide and NVP-TAE684 showed higher sensitivity in the C1 subgroup, whereas the C2 cell lines were more sensitive to SR1001 and SRT-1720. Our results also showed that PCCLs with mutations in CDKN2A, TP53, and SMAD4 were more sensitive to certain anti-cancer drugs. Our integrative analysis identified molecular features of pancreatic cancer that were associated with clinical significance and drug sensitivity, providing potentially effective strategies for precision treatments of patients with pancreatic cancer.

Objective To investigate the effects of long non-coding RNA DUXAP8 on the proliferation, cell cycle and apoptosis of ovarian cancer cells by regulating miR-4677-3p. Methods The expression of DUXAP8 and miR-4677-3p in ovarian cancer tissues and cell lines (SKOV3, OV90 and CaOV3) was detected by RT-qPCR. Then SKOV3 cells were divided into 6 groups, namely, si-NC group, si-DUXAP8 group, miR-NC group, miR-4677-3p group, si-DUXAP8+anti-miR-NC group and si-DUXAP8+anti-miR-4677-3p group. CCK-8 assay and clone formation assay were adopted to detect cell viability, flow cytometry to observe cell apoptosis and cycle, Western blotting to measure the expression levels of Cyclin D1, Bcl-2 and Bax, and dual luciferase reporter assay system to analyze the relationship of DUXAP8 and miR-4677-3p. Results When compared with adjacent tissues and normal ovarian epithelial cells, the expression level of DUXAP8 was significantly lower in ovarian cancer tissues (0.98±0.25 vs 4.14±0.72) and that of SKOV3, OV90, CaOV3 was obviously higher (1.03±0.08 vs 3.26±0.33、2.75±0.29、2.54±0.26, all P < 0.05). Interference with DUXAP8 or overexpression of miR-4677-3p inhibited the proliferation, reduced the rate of apoptosis, and arrested the cell cycle of ovarian cancer cells (P < 0.05). DUXAP8 regulated the expression of miR-4677-3p, and inhibiting miR-4677-3p partially restore and interfere with the effects of DUXAP8 on the proliferation, cycle and apoptosis of ovarian cancer cells (P < 0.05). Conclusion Interference with DUXAP8 can inhibit the proliferation of ovarian cancer cells, induce cell apoptosis, and block cell cycle, the mechanism may be related to the up-regulation of miR-4677-3p.