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BackgroundIn the nuclear industry, zirconium alloys, employed as structural materials, undergo irradiation-induced deformation owing to the combined effects of thermo, mechanical stress, and neutron irradiation during the irradiation process, thereby affecting their reliability in use.PurposeThis study aims to explore and predict the irradiation deformation of zirconium alloys to ensure the safety and economical operation of reactors.MethodsFirst of all, a database of experimental data on irradiation deformation of zirconium alloys from publicly available literature was developed by collection, cleaning, re-organization and placement of these data into a well-designed database, accompanied by detailed descriptions of these data. Then, data patterns, model validation and data mining were conducted by combining the database with our own developed mesoscopic model. Specifically, over fifty sets of preliminary data from the data mining library were subjected to data mining to analyze the correlation between model parameters and control variables.ResultsData mining results indicate that the critical resolved shear stress (CRSS) of the slip system increases with Nb content whilst the irradiation creep compliance of zirconium alloys increases with temperature.ConclusionsCompared with conventional data induction methods, this study introduces a novel approach for fitting and data mining using a physics-based mesoscopic model, offering fresh perspectives and methodologies for studying irradiation-induced deformation in zirconium alloys. The impact of this approach will be boosted as the collected dataset expands.

At present, coal-fired power plants are still the main source of carbon dioxide (CO_2) emissions in China. The development and transformation of CO_2 capture technologies for coal-fired powerplants is an urgent problem to be solved. Using carbonic anhydrase (CA) can improve CO_2 absorption efficiency and effectively solve the problem of energy consumption in traditional carbon capture technol⁃ogy, which has attracted increasing attention in CO_2 capture research. Although CA enzyme has the advantages of high catalytic efficiency and environmental friendliness, the poor stability and reusability ofthe free form enzyme make it not be widely used in the actual industrial carbon capture technology. Therefore, it is necessary to select suitable carriers and immobilization methods to prepare stable immobilized CA enzyme. This paper introduces the mechanism of CA enzyme as a biocatalyst to enhance CO_2 absorption and the carbon capture technology based on enzymatic reaction, and summarizes the immobilization methods of CA enzyme (adsorption, covalent bonding, cross-linking and encapsulation) and the latest research progress in its application to CO_2 capture. Finally, the future development direction of the carbon capture technology based on enzymatic reaction is proposed. It focuses on: (1)developing engineering CA enzyme with high activity and stability; (2) constructing high-performance and cheap biomimetic catalyst with simulating the structure of CA enzyme; (3) developing more economical and efficient carrier materials and processes for immobilization of CA enzyme; (4) further evaluating the application and cost-effectiveness of immobilized CA enzyme in the actual carbon capture process.

The substitutions of the chlorine atoms in p-dichlorobenzene (DCB) or the chlorine end-groups of polyphenylene sulfide (PPS) by sodium N-methyl-4-aminobutyrate (SMAB) are important reactions in the polymerization of PPS. The reaction process of DCB with SMAB was studied under conditions similar to the polymerization of PPS. The molecular structures of the products were analyzed through high-performance liquid chromatography, liquid chromatography-mass spectroscopy, gas chromatography-mass spectrometry, and other methods. Several pairs of para- and meta-isomer products were found, which indicates the coexistence of both nucleophilic addition–elimination (SN2Ar) mechanism and aryne intermediate mechanism. Based on mechanism analysis, the networks of reactions of DCB with SMAB were proposed and the effects of the ratio of SMAB to DCB, water content, and temperature on the reaction process were studied.

Abstract Background As known, inhibition of phosphodiesterase 5 (PDE5) has the therapeutic effect on male erectile dysfunction (ED), and the processed folium of Epimedium sagittatum Maxim. (PFES) characterized by 8-isopentenyl flavonoids is a famous herb for treating ED. However, the main flavonoids inhibitory activities, structure–activity relationship (SAR) and signaling pathway have been not systematically studied so that its pharmacodynamic mechanism is unclear. Methods We aimed to initially reveal the PFES efficacy mechanism for treating ED. For the first time, 6 main 8-isopentenyl flavonoids (1–6) from PFES were isolated and identified. Then based on HPLC detection, we proposed a novel method to screen inhibitors among them. We further analyze the three-dimensional quantitative structure–activity relationship (3D-QSAR) for those inhibitors. Results The results were verified by cellular effects of the screened flavonoids. Among 6 compounds, Icariin: (1), 2-Oʹʹrhamnosylicaridide II (2) and Baohuoside I (3) were identified with significant activities (IC50 = 8.275, 3.233, 5.473 μM). Then 3D-QSAR studies showed that the replacement of C8 with bulky steric groups as isopentenyl, C3 with positive charge groups and C4' with a hydrogen bond acceptor substituent could increase inhibitory effects. In contrast, the substitution of C7 with bulky steric groups or hydrophilic groups tended to decrease the efficacies. And compounds 1, 2, 3 could increase cGMP level and decrease cytoplasmic Ca2+ of rat corpus cavernosum smooth muscle cells (CCSMCs)by activating PKG. Conclusion 8-isopentenyl flavonoids could be the main pharmacodynamic substances of PFES in the treatment for ED, and some had significant PDE5A1 inhibitory activities so as to activate cGMP/PKG/Ca2+ signaling pathway in CCSMCs, that was related to the substituents at the key sites such as C8, C3, C4ʹ and C7 in the characteristic compounds.

Triptolide (TP), a compound isolated from a Chinese medicinal herb, possesses potent anti-tumor, immunosuppressive, and anti-inflammatory properties, but was clinically limited due to its poor solubility, bioavailability, and toxicity. Considering the environment-friendly, low-cost mechanochemical techniques and potential dissolution enhancement ability of Na2GA, an amorphous solid dispersion (Na2GA&TP-BM) consisting of TP and Na2GA were well-prepared to address these issues. The performance of Na2GA&TP-BM was improved through ball milling, such as from crystalline state to an amorphous solid dispersion, suitable nano micelle size and surface potential, and increased solubility. This change had a significant improvement of pharmacokinetic behavior in mice and could be able to extend the blood circulation time of the antitumor drug. Moreover, in vitro and in vivo anti-tumor study showed that Na2GA&TP-BM displayed more potent cytotoxicity to tumor cells. The work illustrated an environment-friendly and safe preparation of the TP formulation, which was promising to enhance the oral bioavailability and antitumor ability of TP, might be considered for efficient anticancer therapy.

Background: Kidney-Yang deficiency syndrome (KDS) is a group of diseases related to hypothalamic-pituitary-adrenal (HPA) axis and sexual dysfunction. The folium of Epimedium brevicornu Maxim. (FEB) includes raw and prepared slices, named RFEB and PFEB, respectively. PFEB is traditionally believed to be good for tonifying kidney-Yang and improving sexual dysfunction. However, there are few studies comparing the pharmacological effects of RFEB and PFEB, and their underlying mechanisms. In this study, we aimed to compare the effects and safety of RFEB and PFEB on the HPA axis and sexual function. Additionally, the mechanisms of their roles in relation to the neuroendocrine-immune (NEI) network in the KDS model mice were explored.Methods: Male adult C57BL/6 mice were treated with corticosterone to establish a KDS mouse model, and RFEB and PFEB were administered intragastrically. Corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), testosterone levels and oxidative damage indexes were measured. The mRNA and protein levels of CRH and ACTH in hypothalamus and pituitary, endothelial nitric oxide synthase (eNOS) and phosphodiesterase 5 (PDE5) in corpus cavernosum were examined. TNFα, IL-6, NF-κB, eNOS and PDE5 were investigated in mouse corpus cavernosum.Results: Our results showed that PFEB was more effective than RFEB in increasing corticosterone-suppressed ACTH levels, enhancing CRH levels and cAMP/cGMP ratio, and reducing oxidative damage. In vivo, PFEB significantly increased eNOS and inhibited PDE5 expression in corpus cavernosum. PFEB showed stronger protective effect on normal spleen lymphocytes from apoptosis both in vitro and in vivo. Additionally, it noticeably inhibited the levels of inflammatory cytokines in corpus cavernosum. Both RFEB and PFEB were safe and did not cause any clinical signs of toxicity in mice at the dosage of 20 times dosages of that in the Chinese Pharmacopeia.Conclusion: We demonstrated that PFEB was better than RFEB at tonifying the kidney-Yang by comparing their effects on improving the NEI network, which includes the HPA axis, immune system and corpus cavernosum. This study revealed that PFEB could significantly improve the sexual function of KDS mice by regulating the HPA axis and activating the immune system through the NEI network.

Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poor prognosis. Here the authors report the characterization of a human IBC cell line recapitulating the clinical and histopathological features of the human disease, and implicating its high level of CCL2 in macrophage infiltration and tumor progression.

Nanoparticle delivery systems have been shown to improve the therapeutic efficacy of anti-cancer drugs, including a variety of drugs for the treatment of hepatocellular carcinoma (HCC). However, the current systems show some limitations, and the delivery of more effective nanoparticle systems for anti-HCC drugs with better targeting ability are needed. Here, we created paclitaxel (PTX)/norcantharidin (NCTD)-loaded core–shell lipid nanoparticles modified with a tumor neovasculature-targeted peptide (Ala-Pro-Arg-Pro-Gly, APRPG) and investigated their anti-tumor effects in HCC. Core–shell-type lipid nanoparticles (PTX/NCTD-APRPG-NPs) were established by combining poly(lactic-co-glycolic acid) (PLGA)-wrapped PTX with phospholipid-wrapped NCTD, followed by modification with APRPG. For comparison, PTX-loaded PLGA nanoparticles (PTX-NPs) and PTX/NCTD-loaded core–shell-type nanoparticles without APRPG (PTX/NCTD-NPs) were prepared. The in vitro and in vivo anti-tumor effects were examined in HepG2 cells and tumor-bearing mice, respectively. Morphological and release characterization showed that PTX/NCTD-APRPG-NPs were prepared successfully and achieved up to 90% release of PTX in a sustained manner. Compared with PTX/NCTD-NPs, PTX/NCTD-APRPG-NPs significantly enhanced the uptake of PTX. Notably, the inhibition of proliferation and migration of hepatoma cells was significantly higher in the PTX/NCTD-APRPG-NP group than those in the PTX-NP and PTX/NCTD-NP groups, which reflected significantly greater anti-tumor properties as well. Furthermore, key molecules in cell proliferation and apoptosis signaling pathways were altered most in the PTX/NCTD-APRPG-NP group, compared with the PTX-NP and PTX/NCTD-NP groups. Collectively, PTX/NCTD-loaded core–shell lipid nanoparticles modified with APRPG enhance the effectiveness of anti-HCC drugs and may be an effective system for the delivery of anti-HCC drugs.

Alloy elements can influence the microstructure evolution of aluminum alloys in the state of solid solute atoms or nano-precipitated silicon particles, but it is still a controversial subject which form has a more significant effect on the microstructure of aluminum alloys. Therefore, taking the Al-1%Si alloy as the research object, the ratio of precipitation state and the solid solution state of the silicon atoms was changed before deformation and a multi-pass accumulative roll-bonding method was used to achieve large deformation. In order to compare the influence of solid solute atoms and nano-precipitated silicon particles on the structure and properties of aluminum alloy during deformation, a comparative study was conducted on the evolution of nano-precipitated silicon particles, grain size, and dislocation density in the process of reaching the saturation state of the microstructure and mechanical properties. The results show that the initial samples with less nano-precipitated silicon particles and more solute silicon atoms have a higher saturated dislocation density and a smaller saturated grain size after deformation, corresponding to a higher saturated yield strength. Solid solute silicon atoms dispersed in the Al-1%Si alloy have a better overall effect than nano-precipitated silicon particles of the same volume in preventing the dynamic recovery of dislocations, which is consistent with the theoretical analysis of dislocations. The dislocation recovery ability in the material affects its saturated grain size. The stronger the dislocation recovery capacity, the larger the saturated grain size.

Terahertz (THz) plasmonic sensors has been regarded as exciting advances in biomedical engineering, due to their real-time, label-free, and ultrasensitive monitoring features. But actually, its widespread application remains impeded by poor modulation properties of operating frequency, single amplitude characterization method, and limited to low-loss substances. In the work, an ultraprecision THz sensor is achieved with direct phase readout capacity via combining steerable plasmonic resonance and attenuated total reflection. Interestingly, the oft-neglected THz phase were found to be ideal for plasmonic sensing characterization. Detailed investigation shows that the reflected THz phase exhibits two entirely different jump responses to coupling gap. Remarkably, the Q-factor of phase spectra for optimal coupling gaps, are generally higher than that of fixed coupling gaps, which falls within the range of 9.7–43.4 (4–26 times higher than its counterpart in amplitude measurements) in liquids sensing. The unique phase-jump responses on metasurfaces pave the way for novel THz sensing methods.

Dichlorodiphenyldichloroethylene (DDE) is the major and most stable toxic metabolite of dichlorodiphenyltrichloroethane (DDT), a well-known organochlorine pesticide banned worldwide in the 1980s. However, it remains easy to detect in humans, and internal levels vary widely among individuals. In the present study, a genome-wide association study (GWAS) (511 subjects) and two replications (812 and 1030 subjects) were performed in non-occupational populations in eastern China. An estimated dietary intake (EDI) of p, p′-DDT and p, p′-DDE was calculated by a food frequency questionnaire (FFQ) and the determination of 195 food and 85 drinking water samples. In addition, functional verifications of susceptible loci were performed by dual-luciferase reporter, immunoblotting and metabolic activity assays in vitro. p, p′-DDT and p, p′-DDE were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). A common loci rs3181842 (high linkage equilibrium with rs2279345) in CYP2B6 at 19p13.2 were found to be strongly associated with low serum levels of p, p′-DDE in this population in GWAS and were verified by two replications and combined analysis of 2353 subjects (P = 1.00 × 10-22). In addition, p, p′-DDE levels were significantly lower in subjects with the rs3181842 C allele than in those carrying the normal genotype, even in individuals with similar EDIs of p, p′-DDT. Furthermore, the rs3181842 C allele functionally led to low CYP2B6 expression and activity, resulting in a low metabolic capacity for the formation of p, p′-DDE from p, p′-DDT. The study highlighted that CYP2B6 variants were more relevant than environmental exposure to internal p, p′-DDE exposure, which is important information for DDT risk assessments.

When the Modular Multilevel Converter (MMC) fails on the AC side, the operating characteristics of MMC will be damaged. If the system wants to retain stable for a long time in the process of operation, it is obliged to design the control strategy in case of asymmetric fault. In this article, the control strategy based on feedback linearization principle is adopted to diminish the negative sequence current caused by breakdown, and a DC voltage controller is devised to suppress the fluctuation of the double frequency component under asymmetric fault conditions. The validity of the control strategy requires to be verified, the running results on PSCAD platform indicate this method is effective and feasible.

The H3K9me3 repressive histone conformation of p53 target promoters is abrogated in response to p53 activation by MDM2-mediated SUV39H1 degradation. Here, we present evidence that the USP7 deubiquitinase protects SUV39H1 from MDM2-mediated ubiquitination in the absence of p53 stimulus. USP7 occupies p53 target promoters in unstressed conditions, a process that is abrogated with p53 activation associated with loss of the H3K9me3 mark on these same promoters. Mechanistically, USP7 forms a trimeric complex with MDM2 and SUV39H1, independent of DNA, and modulates MDM2-dependent SUV39H1 ubiquitination. Furthermore, we show that this protective function of USP7 on SUV39H1 is independent of p53. Finally, USP7 blocking cooperates with p53 in inducing apoptosis by enhancing p53 promoter occupancy and dependent transactivation of target genes. These results uncover a layer of the p53 transcriptional program mediated by USP7, which restrains relaxation of local chromatin conformation at p53 target promoters.