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Oxidative stress contributes significantly to the development of neurodegenerative diseases, thus developing nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent neuroprotectors is highly required for either prevention or treatment of these diseases. This work highlights an electrophilicity-based strategy that allows finding more active Nrf2-dependent neuroprotectors than natural piperlongumine (PL). Electrophilic modification was applied on both the exocylic and endocyclic Michael acceptors of PL, which includes placement of an electron-withdrawing trifluoromethyl group on its aromatic ring in the ortho, meta, or para position to the exocyclic olefin, and further introduction of an electron-withdrawing α-chlorine on its lactam ring. From a panel of PL analogs, we identified PLCl-4CF

Developing nuclear factor erythroid-2 related factor 2 (Nrf2)-dependent cytoprotectors against oxidative damage is of concern because they can effectively reduce the risk of oxidative stress-related diseases, such as cancer and inflammation. This work was aimed to develop more active Nrf2-dependent cytoprotectors than curcumin, a well-known dietary Nrf2 activator and cancer chemopreventive agent. Herein we designed a panel of curcumin-inspired mono-carbonyl piperidinone analogs differentiated by placing distinct electron-withdrawing and electron-donating groups on its two aromatic rings in the ortho, meta, or para position to the linker of α, β-unsaturated piperidinone. Among these, the ortho-fluorine-substituted CN-2F surfaced as a promising lead molecule, which was significantly superior to the parent curcumin in protecting HepG2 cells from oxidative damage induced by tert-butyl hydroperoxide. Mechanically, by virtue of its Michael receptor units and ortho-substituted mode, CN-2F activated Nrf2 signaling by covalently modifying Cys-151 and Cys-288 residues at Keap1, promoting phosphorylation of JNK, ERK and p38, as well as inhibiting Nrf2 degradation. This work reveals the structural determinants and the activity mechanisms of CN-2F as an Nrf2-dependent cytoprotector, and gives useful information on how to design curcumin-inspired Nrf2 activators and cytoprotectors.

The human serotonin transporter (SERT) terminates neurotransmission by removing serotonin from the synaptic cleft, which is an essential process that plays an important role in depression. In addition to natural substrate serotonin, SERT is also the target of the abused drug cocaine and, clinically used antidepressants, escitalopram, and paroxetine. To date, few studies have attempted to investigate the unbinding mechanism underlying the orthosteric and allosteric modulation of SERT. In this article, the conserved property of the orthosteric and allosteric sites (S1 and S2) of SERT was revealed by combining the high resolutions of x-ray crystal structures and molecular dynamics (MD) simulations. The residues Tyr95 and Ser438 located within the S1 site, and Arg104 located within the S2 site in SERT illustrate conserved interactions (hydrogen bonds and hydrophobic interactions), as responses to selective serotonin reuptake inhibitors. Van der Waals interactions were keys to designing effective drugs inhibiting SERT and further, electrostatic interactions highlighted escitalopram as a potent antidepressant. we found that cocaine, escitalopram, and paroxetine, whether the S1 site or S2 site, were more competitive. According to this potential of mean force (PMF) simulations, the new insights reveal the principles of competitive inhibitors that lengths of trails from central SERT to an opening were ~18Å for serotonin and ~22Å for the above-mentioned three drugs. Furthermore, the distance between the natural substrate serotonin and cocaine (or escitalopram) at the allosteric site was ~3Å. Thus, it can be inferred that the potent antidepressants tended to bind at deeper positions of the S1 or S2 site of SERT in comparison to the substrate. Continuing exploring the processes of unbinding four ligands against the two target pockets of SERT, this study observed a broad pathway in which serotonin, cocaine, escitalopram (at the S1 site), and paroxetine all were pulled out to an opening between MT1b and MT6a, which may be helpful to understand the dissociation mechanism of antidepressants.

BackgroundTumor-associated macrophages (TAMs) promote key processes in the modulation of tumor microenvironment (TME). However, the clinical significance of heterogeneous subpopulations of TAMs in hepatocellular carcinoma (HCC) remains unknown.MethodsHCC tissues from Zhongshan Hospital and data from The Cancer Genome Atlas were obtained and analyzed. Immunohistochemistry and flow cytometry were performed to detect the characteristics of sialic acid-binding immunoglobulin-like lectin 10high(Siglec-10hi) TAMs and explore their impact on the TME of HCC. The effect of Siglec-10 blockade was evaluated in vitro based on fresh human tumor tissues.ResultsOur data revealed that Siglec-10 was abundant in a large proportion of HCC specimens and prominently distributed on macrophages. Kaplan–Meier curves and Cox regression analysis showed that intratumoral Siglec-10+cell enrichment was associated with unfavorable prognosis in patients with HCC. Notably, multiple anti-inflammatory cytokines and inhibitory receptors were enriched in Siglec-10hiTAMs. RNA sequencing data also revealed that numerous M2-like signaling pathways were significantly upregulated in Siglec-10hiTAMs. High infiltration of Siglec-10hiTAMs was associated with impaired CD8+T cell function in HCC. Of note, blocking Siglec-10 with the competitive binding antibody Siglec-10 Fc led to decreased expression of immunosuppressive molecules and increased the cytotoxic effects of CD8+T cells against HCC cells. Moreover, blocking Siglec-10 promoted the anti-tumor efficacy of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab.ConclusionsSiglec-10hiTAMs are associated with immune suppression in the TME, and indicate poor prognosis in patients with HCC. Targeting Siglec-10hiTAMs may serve as a promising immunotherapy approach for HCC.

CD74 was initially thought to participate mainly in antigen presentation as an MHC class II chaperone. Recent studies have shown that CD74 plays an important role within the cell and throughout the immune system in a wide spectrum of neoplasms. However, the role of CD74 in hepatocellular carcinoma (HCC) remains elusive. In this study, HCC tissues from Zhongshan Hospital and data from The Cancer Genome Atlas (TCGA) were obtained and analyzed. Immunohistochemistry, flow cytometry, and single-cell RNA sequencing (scRNA-seq) were performed to detect the characteristics of CD74+ cells and explore their impact on the tumor microenvironment (TME) of HCC. Our data revealed that stromal CD74+ cell enrichment was associated with favorable prognosis in patients with HCC. CD74 was abundant in a large portion of HCC specimens and prominently distributed on stromal macrophages. scRNA-seq data also indicated that the pathways related to immune response were significantly upregulated in CD74+ macrophages. High infiltration of CD74+ macrophages was associated with increased infiltration of CD8+ cytotoxic T lymphocytes (CTLs) with enhanced effector functions in HCC. Besides, blocking CD74 weakened the antitumor activity and proliferation ability of CD8+ CTLs in HCC. Our findings highlight the critical role of CD74 in HCC. New drugs and antibodies targeting CD74 may be effective strategies for HCC therapy.

Objective The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. Methods Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. Results A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. Discussion Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. Clinical trial registration ClinicalTrials.gov number: NCT02430259

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key enzymes in the process of lipid transport, is involved in the disease progression of various types of tumors. This article is to study the role of PCSK9 in the progression of hepatocellular carcinoma (HCC). Methods Immunohistochemistry was used to assess the expression of PCSK9 in tumor specimens from 105 HCC patients who underwent curative resection. Western blotting and quantitative real-time PCR were used to test the protein and mRNA expression levels in HCC cell lines. Cell Counting Kit-8 (CCK-8) and clone formation assays were performed to evaluate the proliferation ability of different kinds of cells in vitro. Flow cytometry was used to analyze cell cycle distribution and apoptosis rate. A xenograft model was established to study the effect of PCSK9 on HCC growth in vivo. TUNEL and immunofluorescence assays were used to detect cell apoptosis. Results High expression of PCSK9 in tumor tissues was related to microvascular invasion (p = 0.036) and large tumor size (p = 0.001) in HCC patients. Overall survival and disease-free survival after surgery were poor in patients with high expression of PCSK9 (p = 0.035 and p = 0.007, respectively). In vivo and in vitro experiments showed that PCSK9 promoted the growth of HCC by inhibiting cell apoptosis. A mechanistic study revealed that PCSK9 increases FASN expression, thereby inhibiting apoptosis of HCC cells via the Bax/Bcl-2/Caspase9/Caspase3 pathway. Conclusions PCSK9 expression level in HCC is an indicator of poor prognosis for patients with HCC. FASN-mediated anti-apoptosis plays an important role in PCSK9-induced HCC progression.

Size uniformity of single tracks has a significant influence on the quality of parts in metal additive manufacturing. Herein, the 7075 aluminum alloy single tracks were fabricated by self-developed liquid metal flow rapid cooling additive manufacturing equipment. The forming process of single tracks was observed by a high-speed camera. The effects of process parameters on the size uniformity of the single tracks were analyzed. The influence mechanism of size uniformity of the single tracks was revealed. The results show that the size uniformity of 7075 aluminum alloy single tracks increases with increasing discharge pressure, melt superheat and deposition distance, or decreasing nozzle travelling speed. The variation of the inclination angle of the solid-liquid interface and the distance between solid-liquid interface and liquid flow under different process parameters results in the variety of size uniformity of the single tracks. The work would provide a new technical idea and theoretical basis for investigating the size uniformity of single tracks prepared by additive manufacturing.

Cytomegalovirus (CMV) is a β-herpesvirus that establishes lifelong latency in infected hosts. Following transplantation of a latently infected organ, reactivation can occur and consists of a spectrum of clinically apparent syndromes from mild symptoms to tissue-invasive, resulting in both direct and indirect sequelae. Before the advent of effective antiviral agents, the primary treatment was reduction in immunosuppression (IS). While antiviral agents provide effective prophylaxis, there are several important caveats associated with their use, including drug toxicity and resistance. The traditional view attributes CMV reactivation and the ensuing clinical disease primarily to IS, either intrinsic to disease-related immune compromise or from the extrinsic administration of IS agents. However, previous data from both animal models and human subjects showed that inflammatory signals could induce upregulation of latent viral gene expression. New data demonstrate that ischemia/reperfusion is necessary and sufficient to induce CMV reactivation following murine transplantation of a latently infected graft. In this article, we review a growing body of evidence that suggests that reactivation of both human CMV and murine CMV is first triggered by molecular events that activate CMV gene expression and lytic infection and viral dissemination are then facilitated by IS. The initial activation of viral gene expression may be mediated by oxidative stress, DNA damage, or inflammatory cytokines, and these factors may act synergistically. New therapeutic approaches are needed to capture this complex array of targets.

Most hepatocellular carcinoma (HCC) patients are diagnosed at an advanced stage; however, the effect of systemic therapy on advanced HCC remains undetermined. Therefore, new treatment targets must be identified. We analyzed Gene Expression Omnibus datasets from two HCC patient cohorts and found that NT5DC2 was associated with vascular invasion and poor survival. In two hepatoma cell lines, NT5DC2 overexpression promoted HCC cell proliferation and clone formation in vitro and promoted tumor growth in vivo. Coimmunoprecipitation assays and liquid chromatography with tandem mass spectrometry analysis revealed that NT5DC2 bound directly to epidermal growth factor receptor (EGFR). NT5DC2 upregulated EGFR expression by downregulating EGFR ubiquitination and preventing its degradation via the ubiquitin-proteasome pathway but did not upregulate its transcription. EGFR upregulation activated downstream signal transduction, which played a critical role in the protumor effects of NT5DC2. Erlotinib, a small-molecule inhibitor of EGFR, blocked the effect of NT5DC2 in promoting HCC cell proliferation. In a cohort of 79 patients who underwent curative resection for HCC, NT5DC2 expression in the tumors was associated with larger tumors and microvascular invasion. NT5DC2 expression was also independently associated with recurrence-free survival. The present study demonstrated for the first time that NT5DC2 promotes tumor cell proliferation in HCC and may serve as a potential molecular target for treating HCC. EGFR blockage could be used to treat selected patients with NT5DC2 upregulation.

Chelerythrine (CHE) possesses broad pharmacological activities. In this study, the extract of Chelidonium majus L. were characterized by high performance liquid chromatography (HPLC), infrared radiation (IR) spectroscopy and nuclear magnetic resonance (NMR). It was proved that the extract was CHE. The antifungal activity of CHE against five fungal pathogens of rice was researched in vitro, revealing that CHE inhibited Ustilaginoidea virens (U. virens) and Cochliobolus miyabeanus (C. miyabeanus) with 50% effective concentrations (EC50) of 6.53 × 10−3 mg/mL and 5.62 × 10−3 mg/mL, respectively. When the concentration of CHE was 7.5 × 10−3 mg/mL, the inhibition rate of U. virens reached 56.1%. Moreover, CHE (4 × 10−3 mg/mL) exhibited the greatest efficacy in inhibiting spore of U. virens growth with an inhibition rate as high as 86.7%. CHE displayed the best inhibitory activity against U. virens at the concentration of 7.5 × 10−3 mg/mL, compared with the other two isoquinoline alkaloids and commercial fungicide validamycin. After treating U. virens mycelia with CHE, twisted and atrophied mycelia were observed by optical microscopy. SEM results demonstrated narrow and locally fractured mycelium. TEM observations showed that the cell wall had become thin and broken, and most organelles were difficult to recognize. Furthermore, membrane of mycelia was destroyed and reactive oxygen species (ROS) of spores was accumulated, which induced apoptosis of pathogenic fungi. From these results, our understanding of the mechanisms of antifungal activity of CHE against U. virens was enriched and this research is relevant for developing novel pesticides.

Background: Whether T-cell interferon-γ responses to Mycobacterium tuberculosis-specific antigens can be influenced by tuberculosis preventive treatment in a high-endemic country is uncertain. Methods: In this prospective, open-label, controlled study, 513 individuals with silicosis were randomly selected for TB preventive treatment with rifapentine and isoniazid or for observation. QuantiFERON-TB Gold in-tube (QFT-GIT) assay was used to measure IFN-γ response to M. tuberculosis antigens at baseline (T0) and at 6 (T1) and 33 (T2) months after completion of therapy. Results: A total of 220 subjects were included in the final analysis: 105 and 115 in the prevention and observation arms, respectively. The proportions of QFT-GIT reversion from baseline to T1 were similar in the prevention and observation arms (18.4% vs 12.8%, P = 0.566). However, reversion from baseline to T2 was more frequent in the prevention arm than in the observation arm, but the difference was not significant (24.2% vs 6.3%, P = 0.881). No significant difference was observed in the quantitative responses of QFT-GIT between the two arms during follow-up at T1 (P = 0.648) and T2 (P = 0.918). Conclusions: Preventive tuberculosis treatment has no effect on interferon-γ responses measured by serial QFT-GIT assays in a high tuberculosis-endemic country. Clinical Trials Registration: http://www.clinicaltrials.gov NCT02430259. Keywords: QuantiFERON TB-Gold in-tube, Tuberculosis preventive treatment, Serial tests, Randomized clinical trial

CD34+ myeloid lineage progenitor cells are an important reservoir of latent human cytomegalovirus (HCMV), and differentiation to macrophages or dendritic cells (DCs) is known to cause reactivation of latent virus. Due to its species-specificity, murine models have been used to study mouse CMV (MCMV) latency and reactivation in vivo. While previous studies have shown that MCMV genomic DNA can be detected in the bone marrow (BM) of latently infected mice, the identity of these cells has not been defined. Therefore, we sought to identify and enrich for cellular sites of MCMV latency in the BM haematopoietic system, and to explore the potential for establishing an in vitro model for reactivation of latent MCMV. We studied the kinetics and cellular characteristics of acute infection and establishment of latency in the BM of mice. We found that while MCMV can infect a broad range of haematopoietic BM cells (BMCs), latent virus is only detectable in haematopoietic stem cells (HSCs), myeloid progenitor cells, monocytes and DC-enriched cell subsets. Using three separate approaches, MCMV reactivation was detected in association with differentiation into DC-enriched BMCs cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) followed by lipopolysaccharide (LPS) treatment. In summary, we have defined the kinetics and cellular profile of MCMV infection followed by the natural establishment of latency in vivo in the mouse BM haematopoietic system, including the haematopoietic phenotypes of cells that are permissive to acute infection, establish and harbour detectable latent virus, and can be stimulated to reactivate following DC enrichment and differentiation, followed by treatment with LPS.

Background: Adaptive resistance is one of the major hinderances for unresectable hepatocellular carcinoma (HCC) treated with lenvatinib and anti-programmed cell death protein 1 (anti-PD-1) therapy. Physical activity is known to have anti-cancer effects, including immunomodulatory actions, influencing patients’ outcomes. This study investigated the hypothesis that physical activity synergizes with combined lenvatinib plus anti-PD-1 therapy to enhance efficacy in patients with unresectable HCC.Methods: The physical activity levels of patients with unresectable HCC treated with combination therapy using lenvatinib plus anti-PD-1 antibodies were recorded by questionnaire. Patients were categorized according to physical activity levels (active vs. sedentary). The primary outcome was overall survival (OS), analyzed using the Kaplan-Meier method with a log-rank test. Secondary outcomes included objective response rate (ORR) and progression-free survival (PFS). Factors associated with survival and ORR were analyzed using regression analyses. A subcutaneous syngeneic HCC model was generated in C57BL/6 mice. Mice were randomized to receive placebo, combined lenvatinib plus anti-PD-1 antibodies or combination therapy plus physical activity. Tumors were measured every 3 days and harvested for immunohistochemistry analysis at 20 mm maximum diameter. Results: Fifty-nine patients with unresectable HCC were categorized to active (n=28) or sedentary (n=31) groups. The active group had higher albumin and des-γ-carboxy prothrombin levels and lower hepatitis B virus load at baseline; other clinical and oncologic characteristics were comparable between the two groups. Patients in the active group had significantly longer OS (HR = 0.220, 95% CI, 0.060-0.799) and PFS (HR = 0.158, 95% CI, 0.044-0.562) and higher ORR (OR = 4.571, 95% CI, 1.482-14.102) than patients in the sedentary group. Regular physical activity was independently associated with OS, PFS and ORR. The mouse model showed that physical activity significantly suppressed tumor growth and prolonged survival of tumor-bearing mice. Furthermore, physical activity inhibited Treg cell infiltration and immune checkpoint expression (including CTLA4, TIGIT and TIM3) induced by long-term combined lenvatinib plus anti-PD-1 therapy, improving efficacy. Conclusions: Regular physical activity was associated with improved outcomes in patients receiving combined lenvatinib plus anti-PD-1 therapy for unresectable HCC. Physical activity may improve therapeutic efficacy by reprograming the tumor microenvironment from an immunosuppressive to immunostimulatory phenotype.

Vitamin C (VC), widely found in vegetables and fruits, operates as an electron donor to perform various biological functions including anti-inflammatory activity. However, the mechanisms by which VC inhibits inflammation remain insufficiently understood. Accordingly, we performed a detail mechanistic study on anti-inflammatory activity of VC at millimolar (pharmacological) concentrations in lipopolysaccharides-stimulated RAW264.7 cells. It was found that VC and its two-electron oxidative product, dehydroascorbate (DHA) constructs an efficient redox cycle with the aid of intracellular glutathione and copper ions, thereby facilitating the generation of reactive oxygen species (ROS) and the ROS-dependent inhibition against the NF-κB-mediated inflammation.

The incidence of ulcerative colitis (UC), an inflammatory bowel disease (IBD), is drastically increasing globally, leading to greater economic hardship and patient morbidity. This study evaluated the effects of chelerythrine on acetic acid (AA)-induced UC in a mouse model. Mice received chelerythrine (25, 50, and 100 mg/kg, i.g.) and sulfasalazine (SASP) (500 mg/kg, i.g.) for 7 consecutive days following the induction of colitis via the intrarectal administration of AA (5% v/v). Disease activity index (DAI), tissue morphology, tissue damage, oxidative stress (OS), and inflammatory markers were then evaluated. The results revealed that the colonic levels of total antioxidant capacity (T-AOC), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) had decreased, while colonic myeloperoxidase (MPO), malondialdehyde (MDA), lipid peroxide (LPO) activity, colonic and serum interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) levels, and serum lactate dehydrogenase (LDH) had all increased significantly in the colitis untreated group compared to that of the normal control. Treatment with chelerythrine considerably improved most of these parameters, and a dose of 100 mg/kg, was found to be comparable to that of 500 mg/kg SASP. This alkaloid also markedly reversed body weight (BW), clinical activity score, gross lesion score, mucosal edema, and colon weight/length in a dose-dependent manner. In conclusion, the protective effect of chelerythrine could be attributed to its anti-inflammatory and antioxidant activities.

A new biflavonoid, (2″ S)-8″-C-methyl-2″,3″-dihydrorobustaflavone-4′-methyl ether (1) and 5 known robustaflavones (2-6) were isolated from the 70% EtOH extract of Selaginella braunii for the first time. The structures of 1 and the known compounds were identified by performing a comprehensive analysis of spectroscopic data including ultraviolet-visible, high-resolution electrospray ionization mass spectrometry, 1-dimensional and 2-dimensional nuclear magnetic resonance, and circular dichroism spectra. Compounds 1-6 were determined for cytotoxic activity against 3 human cancer cell lines (SMMC-7721, MCF-7, and A549). Compound 1 exerted apparent antiproliferative effects on SMMC-7721, MCF-7, and A549 cells, with IC50 values of 18.6, 16.7, and 25.5 μM, respectively.

For low-light or near-infrared absorption spectrum measurements, it is challenging to obtain high resolution spectra due to limitations of exotic array detectors. In this paper, a new spectral measurement method based on compressed sensing (CS) is reported. An experimental spectrometer is constructed and calibrated, and the absorption spectra of two liquid samples are measured. Along with a high resolution, the new method has a better signal-to-noise ratio (SNR) than the conventional scanning spectroscopy technique. The measurement resolution of our experimental system is 0.38 nm. The result of wavelength position calibration is accurate. The peak value of characteristic spectrum of red sample is 730 nm, and that of blue sample are 440 nm and 740 nm.

This report derives the exact solutions for the problem of a magneto-electro-elastic cylinder with a penny-shaped and embedded crack subjected to transient thermal load. Thermal cracking is analysed in the theoretical framework of linear magneto-electro-thermo-elasticity. The heat conduction equation for a magneto-electro-thermo-elastic cylinder with a finite size is solved using the standard method of separation variables. The coupling magneto-electro-thermo-elastic fields are determined in a stationary case via the Hankel integral transform. Based on Abel’s integral equation and the dual integral equation, the mathematical formulations for the permeable crack conditions are derived. Solutions to the elastic, electric, and magnetic intensity factors are obtained. Due to the explicitness of these solutions, they are very interesting for the design and analysis of magneto-electro-thermo-elastic composites.

High-flux measurement characteristics of compressed sensing (CS) imaging causes the imaging system prone to be disturbed by quantization. To realize high-quality CS imaging with limited detector bits, an improved imaging method combining sparse measurements and multiple dithers is proposed to reduce the dynamic range of the measured signals and increase that of effective detection. Simulations and experiments show that compared with traditional CS imaging, the proposed system decreases reconstruction errors caused by quantization distortions and may reduce the required number of detector bits to 1. The effects of detector noise and system parameters are discussed to validate the feasibility and performance of this method.

The Qinling-Daba Mountains area is the main producing areas of Gynostemma longipes for medicinal usage, and samples of wild whole plants in Pingli, Shaanxi Province and Qingchuan, Sichuan Province were collected. The ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS~E) was used to profile the chemical compositions and analyze the similarities and differences of G. longipes samples in these areas. Based on the accurate molecular weight and fragment information obtained from Q-TOF-MS~E, the structures of the main components were identified by combining with the mass spectra, chromatographic behaviors of reference standards and related literatures. The results showed that the components of wild G. longipes from different places among Qinling-Daba Mountains area were similar. Forty-five chemical components were identified in the whole plant of G. longipes from Pingli, Shaanxi Province, including 43 triterpenoid saponins and 2 flavonoids which contain all main peaks in its fingerprint. The main components are dammarane-type triterpenoid saponins, such asgypenoside ⅩLⅨ, gypenoside A and its malonylated product of glycosyl.

In this study, a thick plate with a shallow semi-elliptical surface crack subjected to a transient thermal load was investigated based on the non-Fourier heat conduction law. Using a Laplace transform and its numerical inversion transform methods, the non-Fourier temperature fields and associated thermal stress formulas in the solid uncracking were obtained. Then, using the weight function and analogy methods, the thermal stress intensity factor formula at the crack tip was determined. The effects of the thermal shock time, crack depth, and crack shape on the thermal stress intensity factor and the crack growth behavior were explored numerically by comparing the Fourier model with a non-Fourier model. The results demonstrate that the non-Fourier model is much safer for studying the thermal shock cracking and crack growth behavior of solids under high-temperature applications.

The reason why elongation of copper bars with columnar grains drops significantly after small cold-drawing was explored. The copper bars were prepared by warm-mould continuous casting. Tensile test was interrupted at various tensile strains in order to detect crack origin. Electron backscattered diffraction (EBSD) was used to analyze dislocation slip bands. It is found that the as-cast microstructure contains sharp grain boundary (GB) corners nearly parallel to the solidification direction (SD). Elongation of the copper bars drops significantly from 68.8% in as-cast state to 18.8% in as-drawn state. It is revealed that plastic deformation becomes severer in the vicinity of sharp GB corners. Locally accumulated internal stress even activates a slip system with very low Schmid factor of 0.17. The localized plastic deformation near sharp grain boundary corner promotes crack initiation and propagation, which eventually leads to the significant drop of elongation.

The microstructure of two-phase zone continuous casting Cu–4.7Sn (in wt. % as default) alloy was investigated by optical microscope and electron backscattering diffraction. Numerical simulation sof...

Pure copper wires with 10 mm diameter are prepared by self-development warm mold continuous casting technology, at the casting speed of 20∼140 mm/min, cooling water flow of 400 L/h, and the tempera...

A convenient and efficient approach for copper pattern preparation on Al2O3 ceramic substrate has been developed. The anatase nano-TiO2 film was firstly deposited on the surface of Al2O3 ceramic su...

Sequential double extension twinning in AZ31 Mg alloy happens easily during sequential biaxial compressions. Widespread twin-twin interaction leads to the formation of intragranular cross-level twin pairs, each of which can be defined by a primary twin variant PVi (i = 1–6) and its nearby secondary twin variant PVj-SVk (j, k = 1–6, j ≠ i, k) across the twin-twin boundary between them. Theoretically, 9 possible misorientations exist between the two variants. Misorientation between two crystals can be expressed by a pair of rotation axis (r) and the minimum rotation angle (θ). The crystallography of a cross-level twin pair can be described unanimously by the misorientations between PVi and PVj-SVk (i.e., r1-θ1), PVi and PVj (i.e., r2-θ2), and the host grain and PVj-SVk (i.e., r3-θ3), resulting in 13 possible orientation relationships (ORs) that can be expressed explicitly by the three misorientation angles (θ1, θ2, θ3). A cross-level twin pair is a key element of a crossing or crossed twin structure, which is common in the deformed microstructure. Statistical electron backscatter diffraction analysis reveals that OR2 of (49.7°, 60°, 60°) appears the most frequently. Twinning shear transmission is almost irrelevant to the formation of a cross-level twin pair. Although the majority of the identified twins are high Schmid factor (SF) ones with SF > 0.3 and SF ratio > 0.8, SF analysis fails to explain the highly preference of OR2 and the abnormal absence of OR8 of (44.0°, 60°, 60.4°), probably due to the complexity of the formation of a cross-level twin pair.

Zn-Mn-Cu alloys with micro-alloying of Mn and Cu in Zn are developed as potential biodegradable metals. Although the as-cast alloys are very brittle, their ductilities are significantly improved through hot rolling. Among the as-cast and the as-hot-rolled alloys, as-hot-rolled Zn-0.35Mn-0.41 Cu alloy has the best comprehensive property. It has yield strength of 198.4 ± 6.7 MPa, tensile strength of 292.4 ± 3.4 MPa, elongation of 29.6 ± 3.8% and corrosion rate of 0.050-0.062 mm a−1. A new ternary phase is characterized and determined to be MnCuZn18, which is embedded in MnZn13, resulting in a coarse cellular/dendritic MnZn13-MnCuZn18 compound structure in Zn-0.75 Mn-0.40Cu alloy. Such a coarse compound structure is detrimental for wrought alloy properties, which guides future design of Zn-Mn-Cu based alloys. The preliminary research indicates that Zn-Mn-Cu alloy system is a promising candidate for potential cardiovascular stent applications.

C70250 copper alloy rod billets with O20 mm were prepared by a self-developed temperature controlled mold continuous casting (TCMCC) technique. The evolution of microstructure and mechanical proper...

Tin single tracks were formed by a self-developed liquid metal flow rapid cooling additive manufacturing equipment with different superheats. The forming process was simulated by Flow 3D software. ...