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Background: Clinically, gouty arthritis is associated with severe inflammation, such as pain, swelling and erythema of the joints. Gelatinase A and B (matrix metalloproteinase-2 and -9, MMP-2 and -9) participate in the degradation of the extracellular matrix (ECM) components in a variety of arthritis, especially in the inflammatory arthritis. Methods: We examined the levels of MMP-2 and -9 in 40 synovial fluids (SFs) from the knee joints of 24 patients with gouty arthritis and compared them with the clinical and laboratory variables of inflammation. Results: Gelatin zymography revealed that not only activated MMP-2 levels but also proMMP-9 levels in SF from the knee joints of gouty arthritis were associated with the local arthritis activity scores (LAS) (p<0.001) and correlated well with the neutrophil counts in SF as well (p<0.001). A similar correlation between proMMP-9 levels and LAS was also found within the individual patients before and during treatment with nonsteroidal antiinflammatory drugs (NSAIDs; p<0.001). ProMMP-2 appeared in all SFs irrespective of LAS and neutrophil counts. Conclusions: The analysis of MMP-9 in SF samples can reveal the inflammatory condition of the knee joints with gouty arthritis. Joint aspiration may decrease the amount of MMPs in SF to attack the ECM of joint whether it is normal or not. [Copyright &y& Elsevier]

Rotaviruses (RV) are a common cause of severe diarrhea in young children, resulting in nearly one million deaths worldwide annually. Rotavirus VP7 was the rotavirus neutralizing protein. Previous study reported that VP7 DNA vaccine can induce high levels of IgG in mice but cannot protect mice against challenge (Choi, A.H., Basu, M., Rae, M.N., McNeal, M.M., Ward, R.L., 1998. Virology 250, 230–240). We found that rotavirus VP7 could maintain its neutralizing immunity when it was transformed into the potato genome. Mice immunized with the transformed tubers successfully elicited serum IgG and mucosal IgA specific for VP7. The mucosal IgA titer was as high as 1000, while serum IgG titer was only 600. Neutralizing assays indicated that IgA could neutralize rotavirus. These results indicate the potential usefulness of plants for production and delivery of edible rotavirus vaccines. [Copyright &y& Elsevier]

Sequences of the chloroplast trnL-F region and 3′ end ndhF gene were used to elucidate phylogenetic relationships and the delimitation of families within Dipsacales s.l. Parsimony analyses of individual and combined data were conducted using maximum parsimony method. The most parsimonious tree based on combined trnL-F and 3′ end ndhF data set recognizes seven major clades of Dipsacales s.l. with the following relationships: Apiales (Adoxaceae ((Diervillaceae, Caprifoliaceae s.str.) (Linnaeaceae (Morinaceae (Dipsacaceae, Valerianaceae))))). Both Sambucus and Viburnum have close relationships with Adoxaceae, supporting their inclusion in this family. Caprifoliaceae s.l. (excluding Sambucus and Viburnum) is polyphyletic, and comprises three clades or families, i.e., Linnaeaceae (Abelia, Dipelta, Kolkwitzia, and Linnaea), Diervillaceae (Weigela and Diervilla) and Caprifoliaceae s.str. (Heptacodium, Leycesteria, Lonicera, Symphoricarpos, and Triosteum). This study focuses on the systematic position of Heptacodium, Triplostegia, and Morinaceae; and suggests that Heptacodium is closely related to the other Caprifoliaceae s.str.; Triplostegia is a sister to Dipsacaceae; Morinaceae, which has an affinity with Dipsacaceae, is possibly a sister group with Dipsacaceae–Valerianaceae clade. Our results are highly congruent with those of and . [Copyright &y& Elsevier]

: ObjectiveThe aim of this study was to further define the signal transduction pathways leading to hypoxia-inducible factor-1 (HIF-1) erythropoietin (EPO) gene expression.: Materials and MethodsHuman hepatocellular carcinoma cells (Hep3B) were exposed to hypoxia (1% oxygen) and examined for mRNA expression, as well as gene transactivation with RT-PCR and luciferase reporter gene assays, respectively.: ResultsTreatment with LY294002 (a selective pharmacological inhibitor of phosphatidylinositol 3-kinase) significantly inhibited EPO protein and mRNA expression in Hep3B cells exposed to hypoxia for 24 hours, while treatment with PD098059 or SB203580 (selective pharmacological inhibitors of the MEK and p38 mitogen-activated protein kinase pathways, respectively) had no significant effects. The activity of AKT, a downstream target of PI3K, was increased by hypoxia and was also inhibited by LY294002. Genetic inhibition of AKT resulted in significant inhibition of NF-κB and HIF-1-mediated transactivation, as well as EPO gene expression, in response to hypoxia. Overexpression of constitutively active AKT resulted in increased NF-κB and HIF-1 transactivation. The selective inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), significantly blocked HIF-1 protein expression. Inhibition of NF-κB with a superrepressor dominant negative IκBα genetic construct also significantly blocked NF-κB and HIF-1 transactivation, as well as EPO gene expression.: ConclusionWe propose a key role for NF-κB in EPO gene regulation in response to hypoxia. [Copyright &y& Elsevier]

We present a non-Markovian master equation for a qubit interacting with a general reservoir, which is derived according to the Nakajima--Zwanzig and the time convolutionless projection operator technique. The non-Markovian solutions and Markovian solution of dynamical decay of a qubit are compared. The results indicate the validity of non-Markovian approach in different coupling regimes and also show that the Markovian master equation may not precisely describe the dynamics of an open quantum system in some situation. The non-Markovian solutions may be effective for many qubits independently interacting with the heated reservoirs. [ABSTRACT FROM AUTHOR]

By modulating the substitution on the oxamide ligand, a mononuclear tetrahedral Co(II) complex (HNEt 3) 2 [CoL 2 ] (1) (H 2 L = N , N ′-bis(methanesulfonyl)oxamide) with subtle variation in the CoN 4 coordination environment was successfully synthesized, which displays zero-field slow magnetic relaxation and a hysteresis loop at 1.8 ​K. The complex adopts distorted tetrahedral coordination geometries with acute N–Co–N bite angle imposed by two mutually perpendicular oxamide ligands. Magnetic studies and computational results reveal that the acute N–Co–N bite angle seems to govern the overall magnetic anisotropy of tetrahedral Co(II) complexes with two bidentate chelated ligands containing N 4 -donor set. Upon reducing the bite angle, the D parameter increases gradually and reaches the maximum at about 81°, and then show a significant decrease as the angle continuing to decline. This research demonstrates that the easy-axial magnetic anisotropy can be maximized by reducing the bite angle to a certain extent, which is also feasible for tetrahedral cases with other donor sets. Magnetic studies and theoretical calculations indicate the D value of tetrahedral Co(II) complexes can be increased by appropriately reducing the bite angle of N-Co-N. [Display omitted] • A tetrahedral Co(II) complex with CoN 4 coordination environment was successfully synthesized. • The complex displays zero-field slow magnetic relaxation and a hysteresis loop at 1.8 K. • Magnetic and computational studies reveal that the N-Co-N bite angle seems to govern the overall magnetic anisotropy. • The D value of tetrahedral Co(II) complexes can be maximized by reducing the N-Co-N bite angle to a certain extent. [ABSTRACT FROM AUTHOR]

LA-ICP-MS U Pb dating of garnet has become one of the important geochronometric methods in recent years. Both the matrix-matched and non-matrix-matched external standards were used for dating. However, under which conditions reliable ages can be obtained and the difference between the matrix-matched and non-matrix-matched methods have not been well constrained. In this contribution, a series of ablation experiments (including spot analysis and line scanning) were conducted on different grandite garnets using various ablation parameters (spot size, repetition rate and fluence) under both the matrix-matched (garnet as external standard) and non-matrix-matched (zircon as external standard) conditions, with the aim to obtain the optimal conditions for precise LA-ICP-MS garnet U Pb dating. The results show that U Pb fractionation associated with downhole depth, intrinsic properties of U (more refractory) and Pb (more volatile) and radiation damage (alpha dose) of crystal lattice occurs in zircon and garnet. The fractionation can be minimized or even eliminated by optimizing the ablation parameters (e.g., large spot size and low repetition rate) or the analytical modes (e.g., line scanning). This makes it feasible to use zircon as external standard for garnet U Pb dating. Line scanning is most favorable for garnet U Pb dating at broad ablation parameters regardless of matrix-matched or non-matrix-matched. In spot analysis mode, all the garnets can be precisely dated using a large spot size (e.g., ≥90 μm) coupled with moderate-low repetition rate (e.g., 2–5 J/cm2) and fluence (e.g., 2–5 J/cm2) under matrix-matched condition. Under non-matrix-matched condition, all the garnets can also be precisely dated when a larger spot size (e.g., ≥120 μm) coupled with moderate repetition rate (e.g., 5 Hz) and fluence (e.g., 5 J/cm2) is used. Too high or too low repetition rates (e.g., <2 Hz and > 10 Hz) and fluences (e.g., <2 J/cm2 and > 10 J/cm2) were found to be unsuitable for garnet U Pb dating. Low-U and high-U samples are best treated differently due to their different U Pb fractionation coefficients, especially at the high fluence and repetition rate conditions. Equally, U-concentration matched garnet standards are required to improve the accuracy and precision of the U Pb dating Natural grandite garnets selected from Fe, W and Cu Mo skarn deposits can be precisely dated using the optimized methods. These garnets have compositions varying widely between andradite and grossular with variable U (1–100 ppm) and common Pb (f 206 of 0–0.7) concentrations, indicating that the methods are reliable and thus suitable for wide applications. [Display omitted] [ABSTRACT FROM AUTHOR]

A η*-Ni 6 (Al,Ti)Nb strengthened CoCrNi-based medium-entropy alloy with partially recrystallized and heterogeneous grain microstructure was prepared. Block and lamellar η*-Ni 6 (Al,Ti)Nb phases were present in different regions. Excellent tensile properties were achieved with yield strength of 1.34 GPa, ultimate tensile strength of 1.55 GPa and ductility of 9.2%. The deformation mode was dominated by stacking faults in all grains at the beginning of deformation and then relied on dislocation slip in the recrystallized grains. The high strain hardening rate is due to the intense obstruction effect of the η*-Ni 6 (Al,Ti)Nb phase for dislocation movement and the hard-deformed non-recrystallized grains. Our findings provide a wider range of options for the selection of the precipitation phase. • A new complex microstructure was obtained in a medium-entropy alloy. • The MEA shows outstanding strength and ductility. • Deformation mechanism was deeply discussed. • A high strain hardening rate was achieved. [ABSTRACT FROM AUTHOR]

Grasses and shrubs occupy large areas of fragile ecosystems following ecological restoration. Therefore, it is increasingly important to assess and monitor the environmental safety of pastures. However, previous studies on this topic lacked systematicity and directionality. In this study, we reviewed the literature on runoff and erosion to summarise the core issues for future research, resolve the current research bottleneck, and promote the balance of soil, water, and energy in fragile ecological areas. The results of the review indicate that coverage remained the main vegetation feature considered when characterising rangeland slope erosion and runoff. Erosion energy should be comprehensively considered based on the influence of vegetation on rainfall distribution and runoff erosivity. Rangeland slope erosion and runoff changes can only be explained by integrating the above- and below-ground characteristics of vegetation. Additionally, the impact of vegetation on runoff separation and the sediment transport processes at different erosion stages under rainfall conditions vary. Therefore, studying the comprehensive indicators of vegetation at different erosion stages in response to erosion and runoff will be vital in rangeland erosion research. From the perspective of disciplinary development, this study can promote the further development of soil erosion, ecology, soil science, hydrology, hydraulics, and other disciplines. • Research on soil erosion and overland flow on rangeland slopes lacks systematicity. • Effect of plants on runoff separation under rainfall varies between erosion stages. • Vegetation also affects sediment transport differently under rainfall. • Responses of comprehensive vegetation indicators to erosion and runoff are important. • Vegetation indicators will offer a breakthrough in rangeland research. [ABSTRACT FROM AUTHOR]

Duoxuekang (DXK, ཁྲག་འཕེལ་བདེ་བྱེད།) is a clinical experience prescription of CuoRu-Cailang, a famous Tibetan medicine master, which has effective advantages in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, its underlying mechanisms remain unclear. Aim of the study : The present study was designed to investigate the effects of DXK on cerebrovascular function of HH-induced brain injury in mice. DSC-MR imaging was used to evaluate the effect of DXK on the brain blood perfusion of patients with hypoxic brain injury. HPLC analysis was used to detect the content of salidroside, gallic acid, tyrosol, corilagin, ellagic acid, isorhamnetin, quercetin and gingerol in DXK. The model of HH-induced brain injury in mice was established by an animal hypobaric and hypoxic chamber. The BABL/c mice were randomly divided into six groups: control group, model group, Hongjingtian oral liquid group (HOL, 3.3 ml/kg) and DXK groups (0.9, 1.8 and 3.6 g/kg). All mice (except the control group) were intragastrically administrated for a continuous 7 days and put into the animal hypobaric and hypoxic chamber after the last intragastric administration. Hematoxylin-eosin staining was employed to evaluate the pathological changes of brain tissue. Masson and Weigert stainings were used to detect the content of collagen fibers and elastic fibers of brain, respectively. Routine blood test and biochemical kits were used to analyze hematological parameters and oxidative stress indices. Immunofluorescence staining was applied to detect the protein levels of VEGF, CD31/vWF and α-SMA. The results of DSC-MR imaging confirmed that DXK can increased CBV in the left temporal lobe while decreased MTT in the right frontal lobe, right temporal lobe and right occipital lobe of the brain. DXK contains salidroside, gallic acid, tyrosol, corilagin, ellagic acid, isorhamnetin, quercetin and gingerol. Compared with the model group, DXK can ameliorate the atrophy and deformation, and increase the number of pyramidal neurons in hippocampal CA3 area and cortical neurocytes. Masson and Weigert stainings results revealed that DXK can significantly increase the content of collagen fibers and elastic fibers in brain. Routine blood test results demonstrated that DXK can dramatically decrease the levels of WBC, MCH and MCHC, while increase RBC, HGB, HCT, MCV and PLT in the blood samples. Biochemical results revealed that DXK can markedly increase SOD, CAT and GSH activities, while decrease MDA activity. Immunofluorescence revealed that DXK can notably increase the protein levels of VEGF, CD31/vWF and α-SMA. In conclusion, this study proved that DXK can ameliorate HH-induced brain injury by improving brain blood perfusion, increasing the number of collagen and elastic fibers and inhibiting oxidative stress injury. The underlying mechanisms may be involved in maintaining the integrity of cerebrovascular endothelial cells and vascular function. However, further in vivo and in vitro investigations are still needed to elucidate the mechanisms of DXK on regulating cerebral blood vessels. Image 1 [ABSTRACT FROM AUTHOR]

[Display omitted] • ClyR is a chimeric lysin with high bactericidal activity against multiple streptococci. • ClyR harbors a novel internal CPP in the junction region of its two constitutive domains. • Internal CPP mediates the internalization of ClyR by epithelial cells to target intracellular pathogens. • Caveolin-dependent endocytosis of ClyR has minor effect on the transcription of epithelial cells. Intracellular pathogens pose serious challenges to the public health worldwide. Lysin, peptidoglycan hydrolase from phage, is promising alternative to conventional antibiotics because of its high bactericidal activity and low risk of resistance. However, most proteinaceous lysins cannot penetrate the mammalian cell membrane because of size exclusion. Previously, we reported a broad-spectrum chimeric lysin, ClyR, with a cysteine, histidine-dependent amidohydrolase/peptidase catalytic domain from PlyC lysin and an SH-3b cell-wall binding domain from PlySs2 lysin. Herein, we further report that a novel internal cell-penetrating peptide (CPP) is predicted in the junction region of the two constitutive domains of ClyR, mediated by which ClyR can be internalized by epithelial cells through caveolin-dependent endocytosis to target intracellular pathogens. Residues K153, P154, R169, and R188 of the internal CPP were found to be essential for ClyR-mediated internalization and intracellular killing. RNA-seq analysis further showed that there are minor differences in transcript and metabolic profiles from epithelial cells exposed to 100 μg/ml ClyR for 24 h. Taken together, our findings demonstrate a novel mechanism of internalization by ClyR, providing new insights into the rational designing of the next-generation lysins to target both extracellular and intracellular pathogens. [ABSTRACT FROM AUTHOR]

• A series of triangle bipyramid‒{Ln 3 TM 2 } are synthesized and characterized. • Complexes 1 ‒ 4 display effective antibacterial activities against E. coli and S. aureus. • Complexes 2 and 4 exhibits dominant CrIII•••ErIII and/or ErIII•••ErIII ferromagnetic couplings. Two pentanuclear {LnIII 3 CrIII 2 } clusters and the corresponding diamagnetic substituents‒{LnIII 3 AlIII 2 } were synthesized and characterized with the formulas of {Et 3 NH[Ln 3 TM 2 (OH) 6 (piv) 10 (H 2 O) 2 } (Hpiv = pivalic acid; TM = CrIII, Ln = HoIII (1), ErIII (2); TM = AlIII, Ln = HoIII (3), ErIII (4)). In complexes 1 ‒ 4 , five metal ions make up a triangular bipyramidal configuration. Dominant CrIII•••ErIII and/or ErIII•••ErIII ferromagnetic interactions were displayed in 2 and 4 , and effective antibacterial activities against E. coli and S. aureus were detected in 1 ‒ 4. The ferromagnetic molecular‒based magnets are the most promising substitutes of clinical antibiotics, and this study will provides a fundamental research for the development of antibacterial drugs. Image, graphical abstract [ABSTRACT FROM AUTHOR]

In this paper, the structural, electronic and optical properties of vacancy-ordered double perovskites Cs 2 PtI 6 and Rb 2 PtI 6 were studied based on first-principles calculations. The stability of studied compounds is ensured by the negative formation enthalpy. The calculated results show that both Cs 2 PtI 6 and Rb 2 PtI 6 are indirect bandgap semiconductors. The bandgap values of Cs 2 PtI 6 and Rb 2 PtI 6 are 1.29 and 1.15 eV, respectively, which are suitable for photosensitive materials of solar cells. For both Cs 2 PtI 6 and Rb 2 PtI 6 , the valence band maximum (VBM) is dominated by the I-5p orbitals and the conduction band minimum (CBM) is mainly composed of the I-5p orbitals along with the Pt-5d orbitals. The optical properties of Cs 2 PtI 6 and Rb 2 PtI 6 in the photon energy range from 0 to 12 eV have been comprehensively studied by the HSE06 method. The results show that these two compounds exhibit excellent light absorption, especially in the ultraviolet range. Due to the suitable bandgaps and excellent light absorption, the vacancy-ordered double perovskites Cs 2 PtI 6 and Rb 2 PtI 6 can be effective candidates for lead-free photovoltaic materials. • First-principles method was used to study the structural, electronic and optical properties of Cs 2 PtI 6 and Rb 2 PtI 6. • The bandgap values of Cs 2 PtI 6 and Rb 2 PtI 6 are suitable for photosensitive materials of solar cells. • Both Cs 2 PtI 6 and Rb 2 PtI 6 show excellent light absorption in the ultraviolet range. • This work is meaningful for the development of lead-free double perovskites for photovoltaic applications. [ABSTRACT FROM AUTHOR]

Fusarium mycotoxins contaminated in maize are of serious threat to food security and safety. The main abiotic factors of mycotoxins-producing strains and circumstantial elements are crucial for mycotoxin production in the cereal matrix. In this current research work, Fusarium verticillioides and Fusarium graminearum are selected, which enable to produce the major mycotoxins in maize as common Fusarium isolates infecting maize. We first confirmed the constitution of mycotoxin profiles in 110 maize and derived feed samples collected from various provinces of China, through large-scale screening by the established high performance liquid chromatography-mass spectrometry (LC-MS/MS) approach. As indicated, the majority of mycotoxins was fumonisin, deoxynivalenol and zearalenone, frequently co-occurred with at least two kinds of mycotoxins. Interestingly, zearalenone-14-sulfate together with other masked forms of the target Fusarium mycotoxins were as co-contaminants there. Moreover, the circumstantial effects from a set of temperature and water activity (aw) are thoroughly demonstrated for potential contamination in maize flour and kernels. As revealed, the highest group factors were 0.99 and 25 °C while the relatively lower group factors were of temperature ≤20 °C or aw ≤ 0.95. Finally, a response surface analysis was performed to display the interaction of temperature-water activity interaction, required for potential contamination of Fusarium mycotoxins in maize and derived products. The risk group factors predicted by response surface equation were similar to the experimental results. This also could be valuable clues for pre-warning of mycotoxins occurrence, thus as reference data for control of mycotoxins in foods. • FBs, DON, ZEN and their masked forms co-occurred in maize and feed samples. • Temperature and aw significantly affected mycotoxins production. • Mycotoxins production at a lower level when temperature ≤ 20 °C or aw ≤ 0.95. • Response surface analysis model can predict mycotoxins risk level and guide the storage management of maize and feed. • These results provide reference data for the control of mycotoxins in food. [ABSTRACT FROM AUTHOR]

• Diagnosis and prognosis of gastric cancer remained a challenge. • Plasma Hsp90α was elevated in gastric cancer. • Plasma Hsp90α has moderate diagnostic value in gastric cancer. • Plasma Hsp90α has little prognostic value in gastric cancer. The role of plasma heat shock protein 90alpha (Hsp90α) in gastric cancers remains unclear. This study aimed to clarify the diagnostic and prognostic value of plasma Hsp90α in gastric cancer. Data regarding 976 gastric cancer, 50 gastric inflammatory diseases, and 100 healthy controls were collected. Plasma Hsp90α levels in gastric cancer were compared to those in controls. Its correlation with tumor biomarkers and immune cells was examined. The association of plasma Hsp90α with clinical features and the diagnostic and prognostic value in gastric cancer were also determined. Plasma Hsp90α levels were remarkably increased in gastric cancer, compared to those in gastric inflammatory diseases and healthy controls. Moreover, plasma Hsp90α was correlated with CEA, CA125, CA153, CA199, T cells, Th/Ts ratio, and B cells. Plasma Hsp90α was also associated with the metastasis stage. Multivariate logistic regression analysis revealed that Hsp90α, B cells, and T cells were significantly associated with gastric cancer. Plasma Hsp90α has a moderate diagnostic value, which increased when combined with B cell, T cells. Finally, plasma Hsp90α was not associated with the survival of gastric cancer patients. Plasma Hsp90α was elevated in gastric cancer and correlated with tumor biomarkers and immune cells. Plasma Hsp90α was associated with the metastasis stage and had moderate diagnostic performance but little prognostic value in gastric cancer. [ABSTRACT FROM AUTHOR]

• Oridonin, as well as MCC950 and CY-09, inhibits the NLRP3 inflammasome response. • Oridonin, found in traditional Chinese medicine, shows anti-inflammatory property in mice MI model. • Oridonin treatment reduces myocardial fibrosis and preserves cardiac function after MI. Myocardial infarction (MI) triggers a strong inflammatory response that is associated with myocardial fibrosis and cardiac remodeling. Interleukin (IL)-1β and IL-18 are key players in this response and are controlled by NLRP3-inflammatory bodies. Oridonin is a newly reported NLRP3 inhibitor with strong anti-inflammatory activity. We hypothesized that the covalent NLRP3 inhibitor Oridonin could reduce IL-1β and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in mice, improve poor heart remodeling, and preserve heart function. Male C57BL/6 mice were subjected to left coronary artery ligation to induce MI and then treated with Oridonin (1, 3, or 6 mg/kg), MCC950 (10 mg/kg), CY-09 (5 mg/kg) or saline three times a week for two weeks. Four weeks after MI, cardiac function and myocardial fibrosis were assessed. In addition, myocardial expressions of inflammatory factors and fibrotic markers were analyzed by western blot, immunofluorescence, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. Oridonin treatment preserved left ventricular ejection fraction and fractional shortening, and markedly limited the myocardial infarct size in treated mice. The myocardial fibrosis was lower in the 1 mg/kg group (15.98 ± 1.64)%, 3 mg/kg group (17.39 ± 2.45)%, and 6 mg/kg group (16.76 ± 3.06)% compared to the control group (23.38 ± 1.65)%. Moreover, similar with the results of Oridonin, MCC950 and CY-09 also preserved cardiac function and reduced myocardial fibrosis. The expression levels of NLRP3, IL-1β and IL-18 were decreased in the Oridonin treatment group compared to non-treated group. In addition, myocardial macrophage and neutrophil influxes were attenuated in the Oridonin treated group. The covalent NLRP3-inflammasome inhibitor Oridonin reduces myocardial fibrosis and preserves cardiac function in a mouse MI model, which indicates potential therapeutic effect of Oridonin on acute MI patients. [ABSTRACT FROM AUTHOR]

• ANXA3 is positively associated with infiltrated neutrophil-lymphocyte ratio (iNLR) in HCC. • HCC patients with a high iNLR and high ANXA3 expression confer the highest risk of death. • ANXA3 regulates the chemokine CXCL8 and CCL25 to remodel the iNLR and promotes tumourigenicity in HCC. Accumulating evidence has indicated that inflammation is required for the initiation and progression of hepatocellular carcinoma (HCC). The annexin family protein, which has a highly similar structure, has been demonstrated to participate in pro- or anti-inflammatory regulation in the developing of tumours. However, the potential effects of ANXA3 in the immune microenvironment of HCC remain unknown. In present study, we found that increased ANXA3 expression is associated with a higher infiltrated neutrophil-lymphocyte ratio (iNLR) in HCC. Moreover, HCC patients with a high iNLR and high ANXA3 expression confer the highest risk of death. ANXA3 can be detected in both cell lysates and culture supernatants. However, the secretory ANXA3 did not directly regulate the iNLR. Further study demonstrated that ANXA3 upregulated the iNLR by inducing chemokine CXCL8 and CCL25 release from HCC cells. We further confirmed that ANXA3 promotes tumourigenesis and detected the same associations between ANXA3 and the iNLR or chemokines in vivo. Our findings indicate that ANXA3 regulates the chemokine to remodel the iNLR and promotes tumourigenicity in HCC. These results further expanded our understanding of ANXA3 in the microenvironment of HCC and might provide novel targets for the investigation of molecular treatments for HCC patients. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignant tumor in China and even in the world. DNA repair genes can lead to tumor metastasis by affecting cancer cell resistance. Studies have preliminarily shown that DNA repair genes are related to breast cancer metastasis, but it is not clear whether they can be used as a prediction of the risk of breast cancer metastasis. Therefore, this study mainly discusses the predictive value of DNA repair genes in postoperative metastasis of breast cancer. The nested case–control method was used in patients with breast cancer metastasis after surgery (n = 103) and patients without metastasis after surgery (n = 103). The proteins and mRNA of DNA repair genes were detected by immunohistochemistry and Real-time PCR respectively. In protein expression, PARP1 (OR 1.147, 95% CI 1.067 ~ 1.233, P < 0.05), XRCC4 (OR 1.088, 95% CI 1.015 ~ 1.166, P < 0.05), XRCC1 (OR 1.114, 95% CI 1.021 ~ 1.215, P < 0.05), ERCC1 (OR 1.068, 95% CI 1.000 ~ 1.141, P < 0.10) were risk factors for postoperative metastasis of breast cancer. In addition, we used the ROC curve to study the optimal critical values of MSH2, MLH1, PARP1, XRCC1, XRCC4, 53BP1, ERCC1 and XPA combined with the Youden index, and the effects of MSH2, MLH1, PARP1, XRCC1, XRCC4, 53BP1, ERCC1 and XPA on breast cancer metastasis were verified again. Among them, the risk of metastasis in the PARP1 high expression group was 3.286 times that of the low expression group (OR 3.286, 95% CI 2.013 ~ 5.364, P < 0.05). The risk of metastasis in the XRCC4 high expression group was 1.779 times that of the low expression group (OR 1.779, 95% CI 1.071 ~ 2.954, P < 0.05). The risk of metastasis in patients with ERCC1 high expression group was 2.012 times that of the low expression group (OR 2.012, 95% CI 1.056 ~ 3.836, P < 0.05). So we can conclude that protein expression of PARP1 (cut-off value = 6, Se = 76.70%, Sp = 79.61%), XRCC4 (cut-off value = 6, Se = 78.64%0, Se = 79.61%), ERCC1 (cut-off value = 3, Se = 89.32%, Sp = 50.49%), suggesting that when the PARP1 score is higher than 6 or the XRCC4 score is higher than 6 or the ERCC1 score is higher than 3, the risk of metastasis will increases. Due to PARP1, XRCC4 and ERCC1 belong to a part of DNA repair gene system, and the three proteins are positively correlated by correlation analysis (rPARP1-XRCC4 = 0.343; rPAPR1-ERCC1 = 0.335; rXRCC4-ERCC1 = 0.388). The combined diagnosis of the PARR1, XRCC4 and ERCC1 have greater predictive value for the risk of metastasis of breast cancer (Se = 94.17%, Sp = 75.73%; OR 11.739, 95% CI 2.858 ~ 40.220, P < 0.05). The postoperative metastasis of breast cancer could be effectively predicted when the immunohistochemical scores met PARP1 (IHC score) > 6, XRCC4 (IHC score) > 6 and ERCC1 (IHC score) > 3. In addition, the combined diagnosis of PARP1, XRCC4 and ERCC1 has great predictive value for the risk of breast cancer metastasis. [ABSTRACT FROM AUTHOR]

A dinuclear CoII cluster with octahedral geometries has been synthesized, which exhibits dominant ferromagnetic couplings between the two CoII ions. • A dinuclear CoII cluster constructed by benzimidazole ligands is synthesized and characterized. • Complex 1 contributes a rare perfect linear Co–NNN–Co unit. • Complex 1 exhibits dominant ferromagnetic couplings between the two CoII ions. A dinuclear CoII cluster, [Co 2 (L) 8 (N 3)(H 2 O) 2 Cl 3 ·3CH 3 OH·5H 2 O (1 , L = 1-methyl--1 H -benzo d imidazole) is constructed. Singe-crystal X-ray diffraction reveals that azido contributes a rare linear coordination mode of Co–NNN–Co in complex 1 , and both of CoII ions are located in {N 5 O} environments with octahedral geometries. Magnetic properties exhibit dominant ferromagnetic couplings between the two CoII ions. [ABSTRACT FROM AUTHOR]

• Most Nb-bearing minerals in Bayan Obo ore-hosting dolomite has hydrothermal origin. • Both Mesoproterozoic and Paleozoic Nb mineralization postdate REE of same stage. • Mesoproterozoic Nb mineralization was due to carbonatite-derived hydrothermal fluids. • The Permian granite magmatism might cause Nb mineralization independent from REE. • Extreme Nb-Ta fractionation at Bayan Obo was inherited from primary carbonatite. The Bayan Obo REE-Nb-Fe deposit, which reserves the current largest REE resources globally, also hosts over 70% of China's Nb resources. Unlike many world-class carbonatite-related Nb deposits (e.g. Morro dos Seis Lagos and Araxá, Brazil) with igneous or secondary origin, Nb was mainly stored in Nb-bearing minerals (aeschynite, ilmenorutile, baotite, fergusonite etc.) of hydrothermal origin at Bayan Obo, supported by evidence from petrography, element and isotopic geochemistry. Although igneous fersmite and columbite were occasionally discovered in local carbonatite dykes, the Mesoproterozoic and Paleozoic hydrothermal metasomatism occurred in the ore-hosting dolomite, related to carbonatite intrusion and the closure of Paleo-Asian Ocean respectively, has played a more significant role during the ultimate Nb enrichment. REE, however, was significantly enriched during both the carbonatite-related magmatic and hydrothermal processes. Consequently, there was differentiated mineralization between REE and Nb in the carbonatite dykes and the ores. Niobium mineralization at Bayan Obo is rather limited in Mesoproterozoic carbonatite, whereas more extensive in the metasomatized ore-hosting dolomite, and generally postdating the REE mineralization at the same stage. According to mineral geochemistry, Bayan Obo aeschynite was classified into 3 groups: aeschynite-(Nd) with convex REE patterns (Group 1); aeschynite-(Ce) (Group 2) and nioboaeschynite (Group 3) with nearly flat REE patterns. Aeschynite (Group 1), ilmenorutile and fergusonite precipitated from Paleozoic hydrothermal fluids with advanced fractionation of Ce-rich REE minerals. The Mesoproterozoic hydrothermal Nb mineralization, represented by aeschynite (Group 3) and baotite, occurred postdating REE mineralization at same stage. Besides, fersmite and aeschynite (Group 2) precipitated from the Mesoproterozoic REE-unfractionated melt and hydrothermal fluids, respectively. All above Nb-bearing minerals exhibit extreme Nb-Ta fractionation as a primary geochemical characteristic of mantle-derived carbonatite. The forming age of the aeschynite megacrysts (Group 1) has not been accurately determined. However, the potential age was constrained to ~430 Ma or alternatively ~270–280 Ma subjected to subduction and granite activity, respectively. These aeschynite crystals inherited REEs from multiphase former REE mineralization, with an intermediate apparent Sm-Nd isochron age between the Mesoproterozoic and the Paleozoic REE mineralization events. [ABSTRACT FROM AUTHOR]

In this work, using a bulky anion, a mononuclear five-coordinate Co(II) complex [Co(12-TMC)(CH 3 CN)][B(C 6 F 5) 4 2 ·CH 2 Cl 2 (12-TMC ​= ​1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane) (1) has been constructed. X-ray single crystal diffraction shows that the central Co(II) ion of 1 binds with five N atoms, generating a distorted square pyramidal geometry. The direct-current (dc) magnetic data of 1 displayed a gradual and incomplete spin-crossover behaviour. Compared with reported complexes [Co(12-TMC)(CH 3 CN)](X) 2 (X ​= ​BF 4 −, 2 ; and PF 6 −, 3), complex 1 exhibited much slower magnetic relaxation under an applied dc field of 1000 ​Oe, which originated from the low-spin state (S ​= ​1/2) of Co(II) ion. A mononuclear Co(II) complex with a bulky anion has been successfully prepared and characterized, which exhibits excellent spin-crossover behavior and SIM properties. Image 1 • A mononuclear Co(II) complex with a bulky anion was prepared and characterized. • DC magnetic data showed a gradual and incomplete spin-crossover behaviour. • AC magnetic measurement exhibited slow magnetic relaxation. • The slow magnetic relaxation is originated from the low-spin state of Co(II) ion. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA), a common biopolymer found in the extracellular fluid, was grafted with β-cyclodextrin (β-CD) to form a composite polymer that could form inclusion complexes with tocopherol (VE), enhancing its water-solubility and serving as a model drug delivery system. Herein, different copolymers were prepared with varying HA:β-CD ratios and characterized. VE loading capacity was directly correlated with increased β-CD composition in the polymers and morphological changes were observed upon VE binding. The host materials and their VE inclusion complexes are not cytotoxic, and are thus useful for VE and drug delivery. [ABSTRACT FROM AUTHOR]

Eph receptors and the corresponding Eph receptor-interacting (ephrin) ligands jointly constitute a critical cell signaling network that has multiple functions. The tyrosine kinase EphA2, which belongs to the family of Eph receptors, is highly produced in tumor tissues, while found at relatively low levels in most normal adult tissues, indicating its potential application in cancer treatment. After 30 years of investigation, a large amount of data regarding EphA2 functions have been compiled. Meanwhile, several compounds targeting EphA2 have been evaluated and tested in clinical studies, albeit with limited clinical success. The present review briefly describes the contribution of EphA2-ephrin A1 signaling axis to carcinogenesis. In addition, the roles of EphA2 in resistance to molecular-targeted agents were examined. In particular, we focused on EphA2's potential as a target for cancer treatment to provide insights into the application of EphA2 targeting in anticancer strategies. Overall, EphA2 represents a potential target for treating malignant tumors. [ABSTRACT FROM AUTHOR]

Based on the first principle, this paper explores the energy band structure and density of state of single-layer and nanotubes NBAs, analyzes their properties in terms of conductivity and band gap structure by comparing with graphene carbon nanotubes and nano sheets. We further add electric field to NBAs single-layer, and discuss the influence of electric field according to its energy band structure and density of state. Finally, the three-dimensional surface of Young's modulus is obtained by calculating the elastic modulus. The properties of Weyl material NbAs are studied based on first principles in this paper. Firstly, the Visualizer module of Material Studio software is used to construct NbAs single-layer nanotube and nanobelt, and then CASTEP module is used to optimize and calculate the band structure, density of states and conductivity curves. The energy band, density of states and conductivity curves of carbon nanotube and nanobelt are compared. The results show that the energy band structure of NbAs has conduction band and valence band crossing at Fermi energy level, which shows obvious metallicity and is more conductive than graphene. Secondly, DMOL3 package is used to calculate and analyze the energy band and state density of NbAs nano-ribbon after adding positive and negative voltage along the armchair direction and zigzag direction, respectively. The results show that the valence band of NbAs nanobelt decreases when positive voltage is applied along the direction of the armchair, while increases when negative voltage is applied. When the voltage is applied at 0.05a.u., the peak values of the distribution curve of density of states increase from about 30 eV to 800 eV, and the peak values of the electron density of states increase significantly. When voltage is applied along the zigzag direction, either positive or negative voltage will cause the valence band to move down. When the negative voltage is −0.10a.u., the peak values of the density of states change obviously. Finally, the stability of NbAs is calculated and analyzed. It is found that NbAs nanobelt meet the requirement of stability of elastic modulus of hexagonal crystal system, but have weak shear resistance in plane (001). This indicates that the structure of NbAs is layered, similar to graphene, which is easier to be separated and detached in layers. This study can provide certain theoretical basis for our future experimental exploration of NbAs material properties. [ABSTRACT FROM AUTHOR]

• HLJDZD32-1901 with no recombination belong to sublineage 1.5. • HLJDZD32-1901 shared same100-aa deletion in the NSP2 protein with NADC34-Like PRRSV. • HLJDZD32-1901 is a mild pathogenicity strain to piglets but may be high pathogenicity to pregnant sows. Porcine reproductive and respiratory syndrome virus (PRRSV) causes a substantial economic loss to the swine industry. Recently, NADC34-like PRRSV was reported in the USA, China and Peru and consistently attributed to a large number of abortions in the clinic. In the USA, the pathogenicity of NADC34-like PRRSV in piglets is highly variable. However, the pathogenicity of NADC34-like PRRSV in China is unclear. In this study, an NADC34-like PRRSV strain, HLJDZD32-1901, was isolated in primary alveolar macrophage (PAM) cells from a sow blood sample collected from an abortive farm in China. HLJDZD32-1901, with no recombination, has a 100-aa deletion in the NSP2 protein corresponding to positions 328–427 in the VR2332 strain. Phylogenetic analysis based on open reading frame 5 (ORF5) indicated that HLJDZD32-1901 belongs to sublineage 1.5. Animal experiments showed that the weight loss of HLJDZD32-1901-infected piglets was significantly different from that of control piglets at 8–14 dpi. In addition, the challenge group had obvious histopathological lesions, including interstitial pneumonia and enlarged lymph nodes, and increased viremia and viral loads in three tissues. However, piglets in the challenge group had only mild clinical symptoms, with no death or fever. Our results showed that NADC34-like PRRSV HLJDZD32-1901 is a mildly pathogenic strain in piglets. However, we speculate that HLJDZD32-1901 may be a highly pathogenic strain in pregnant sows based on clinical morbidity. [ABSTRACT FROM AUTHOR]

Active particles are widely recognized to potentially revolutionize technologies in numerous biomedical applications. However, the physical origin behind cellular uptake of these particles in the nonequilibrium state remains scarcely understood. Here we combine Brownian dynamics simulation as well as theoretical analysis to provide the criterion for cellular uptake of active particles, related to various physical attributes. Upon enhancing the activity, the uptake efficiency for the active particles with tilted orientation is examined to be nonmonotonic, in stark contrast to the monotonic dependence for active particles orientated normally to the membrane. This can be attributed to the interplay between membrane adhesion energy and kinetic energy of active particles, resulting in unique kinetic pathways. Furthermore, a theoretical model that captures the essential physics of the cellular endocytosis process is developed to reproduce this nonmonotonic feature. The results are of immediate interest to understand and tune activity-mediated cellular interaction and internalization of such emerging colloids. [ABSTRACT FROM AUTHOR]

A pentanuclear {Cr 2 Gd 3 } cluster has been successfully synthesized, which exhibits dominant ferromagnetic interactions and a considerable large −Δ S m of 27.0 J kg−1 K−1 among 3 d -4 f clusters. • A triangle bipyramid-{Cr 2 Gd 3 } based on pivalic acid is synthesized and characterized. • Complex 1 exhibits dominant ferromagnetic interactions between CrIII and GdIII ions. • Complex 1 displays a considerable large magnetic entropy value of 27.0 J kg−1 K−1 among low-nuclearity 3d -4 f clusters. A pentanuclear {Cr 2 Gd 3 } cluster (1) and its diamagnetic substituent-{Al 2 Gd 3 } (2) based on pivalic acid (Hpiv) were obtained with the formulas of {Et 3 NH[M 2 Gd 3 (OH) 6 (piv) 10 (H 2 O) 2 ]} (M = CrIII, 1 ; AlIII, 2). The metallic core shows a triangle bipyramid-{Cr 2 Gd 3 } held together by six µ 3 -OH groups, and the piv- ligands located at the periphery. Magnetic studies for complex 1 exhibit dominant ferromagnetic interactions between CrIII and GdIII ions. Furthermore, ferromagnetic {Cr 2 Gd 3 } cluster (1) displays a considerable large magnetic entropy value (−Δ S m = 27.0 J kg−1 K−1) at high temperature among low-nuclearity 3d -4 f clusters. [ABSTRACT FROM AUTHOR]

Utilizing quinaldichydroxamic acid (H 2 quinha), a tetranuclearity YbIII−based complex with the formula [Yb 4 (Hquinha) 8 (C 2 H 5 OH) 2 (H 2 O) 6 ](ClO 4) 4 ·4C 2 H 5 OH·2H 2 O (1) was synthesized and characterized. In 1 , there are two coordination geometries of YbIII ion, pentagonal bipyramid and trigonal dodecahedron. Magnetic properties of 1 show slow magnetic relaxation, representing the first polynuclear YbIII complex with single−molecule magnet behavior. In addition, complex 1 displays an emission peak at 530 ​nm originated from organic ligand. A polynuclear YbIII−based complex with two coordination geometries has been synthesized, which exhibits single−molecule magnet behavior and luminescence property. Image 1 • A tetranuclearity YbIII−based cluster based on quinaldichydroxamic acid is synthesized and characterized. • Complex 1 represents the first polynuclear YbIII complex with single−molecule magnet behavior. • Complex 1 displays the luminescence properties, which stems from organic ligand. [ABSTRACT FROM AUTHOR]

Six complexes including [Cd (bpt)(odc) 2 (1), [Ni(bpt)(odc) 2 (2), [Zn (bpt)(odc) 2 (3), [Zn (bpt)(1,4-ndc) 2 (H 2 O)] (4), [Cd (bpt)(1,4-ndc) 2 (5), [Cd (bpt)(Pta) 2 (H 2 O) 2 (6), {bpt = 2-(2 pyridyl)benzothiazole, H 2 odc = 4,4′-oxybisbenzoic acid, 1,4-H 2 ndc = naphthalene-1,4-dicarboxylic acid, Pta = terephthalic acid}, have been determined by single-crystal X-ray diffraction analysis, which shows that complexes 1–3 belong to monoclinic system with space group P2 1 /n, complex 4 and complex 6 belong to triclinic system with space group P-1, complex 5 belongs to monoclinic system with space group P2 1 /c. TD-DFT calculations for the complexes 3 was performed to explain the structures and electronic spectral properties. UV spectroscopy, fluorescence spectroscopy and viscosity were used to characterize the interaction of the CT-DNA complexes. The results indicate that complexes 1–6 have strong interaction with CT-DNA binding. All complexes exhibit an electrostatic or groove mode of binding with DNA. Furthermore, they also present that all complexes have strong ability to interact with DNA. It can effectively destroy the DNA acting on cancer cells. Therefore, we hope to provide a theoretical and scientific basis for the development of anti-cancer drugs. • Six new complexes have been synthesized and characterized. Complex 5 has special structures. • The fluorescence properties of complex 3 were calculated by TD-DFT method, while were consistent with the experimental results. • The CT-DNA binding with six new complexes were investigated by absorption, fluorescence spectroscopy and viscosity measurements. The experiment result shows that these complex can probably bind to CT-DNA via an electrostatic or groove mode. [ABSTRACT FROM AUTHOR]

The transcription factor NF-κB plays a critical role in diverse biological processes. The NF-κB pathway can be activated by incoming pathogens and then stimulates both innate and adaptive immunity. However, many viruses have evolved corresponding strategies to balance NF-κB activation to benefit their replication. Pseudorabies virus (PRV) is an economically important pathogen that belongs to the alphaherpesvirus group. There is little information about PRV infection and NF-κB regulation. This study demonstrates for the first time that the UL24 protein could abrogate tumor necrosis factor alpha (TNF-α)-mediated NF-κB activation. An overexpression assay indicated that UL24 inhibits this pathway at or downstream of P65. Furthermore, co-immunoprecipitation analysis demonstrated that UL24 selectively interacts with P65. We demonstrated that UL24 could significantly degrade P65 by the proteasome pathway. For the first time, PRV UL24 was shown to play an important role in NF-κB evasion during PRV infection. This study expands our understanding that PRV can utilize its encoded protein UL24 to evade NF-κB signaling. [ABSTRACT FROM AUTHOR]

The Yidun arc, located in the southeastern Tibetan Plateau, was formed by the westward subduction of the Ganze-Litang Paleo-Tethys ocean in Late Triassic. It is well-known for the formation of numerous Mesozoic porphyry-skarn Cu-Mo-(Au) deposits in the arc. To date, more than 20 Cu-Mo-(Au) deposits (>10 million tonnes Cu resources) have been discovered in the southern Eastern Yidun arc. However, few Cu-Mo deposits have been discovered in the northern Eastern Yidun arc. In recent years, some Cu-Mo deposits or occurrence are successively discovered in the northern Eastern Yidun arc, but their ore-forming ages are not well constrained. It remains unclear whether such Cu-Mo mineralization formed by similar metallogenic event and geodynamic setting as the Cu-Mo-(Au) mineralization in the south. In order to determine the metallogenic age and shed light on potential links between Cu-Mo mineralization and regional magmatic events, we present molybdenite Re-Os and zircon U-Pb ages to constrain the timing of two types of Cu-Mo mineralization in the northern Eastern Yidun arc (type I and type II). Molybdenite ICP-MS Re-Os dating results show that type I mineralization was formed at 217.7 ± 3.6 Ma, which is highly consistent with the formation ages of the host granite (218.1 ± 1.5 Ma, 2σ, n = 15, MSWD = 0.92) and aplite dyke (217.3 ± 1.3 Ma, 2σ, n = 16, MSWD = 0.50) within error. While the type II mineralization has a relatively younger formation age of 211.8 ± 4.7 Ma than the host granite (217.1 ± 1.5 Ma, 2σ, n = 14, MSWD = 0.96) and type I Cu-Mo mineralization. These data indicate that the Cu-Mo mineralization in the northern Eastern Yidun arc was temporally and spatially related to the Late Triassic magmatism in the region. Rhenium (Re) concentrations in the molybdenite from type I mineralization, ranging from 12.77 to 111.1 ppm (typically > 100 ppm), indicate that the ore-forming metals were derived mainly from a mantle source. However, Re contents in molybdenite from the type II mineralization, ranging from 7.983 to 10.40 ppm, indicate that the ore-forming metals were derived from a mixed mantle and crustal source with a predominantly crustal component. This study confirms that the northern Eastern Yidun arc exists Late Triassic Cu-Mo metallogenesis, and thus much attention should be paid on this region to find more Late Triassic Cu-Mo resources. [ABSTRACT FROM AUTHOR]

Selenium nanoparticles (SNP) were generally utilized as chemotherapeutic agents and environmental ameliorants, but without simultaneous biocontrol functionalities against fungal pathogens and mycotoxins, plus unknown recognition mechanism. Selenium nanoparticles derived from Trichoderma harzianum JF309 (TSNP) were herein synthesized, contrast to traditional SNP, where diverse metabolites co-occurred in TSNP including organic acids and their derivates, such as psoromic acid, β-decyloxybenzoic acid, glucaric acid lactone, etc., revealed by Triple TOF UPLC/HRMS. As hypothesized, this interaction of diverse recognition metabolites and selenium nanoparticles in TSNP might change the arrangement and movement of original state, form random, nondirective to regulated, directional, thus contributing to better antifungal effects and dramatically increasing control functionalities against Alternaria toxins (83% of TeA and 79% of AOH reduction), fumonisin B1 (63% of FB1 reduction) and deoxynivalenol (76% of DON reduction), respectively. Meanwhile, expression of key biosynthetic genes of FUM1, PA, TRI5 and TRI6 were substantially decreased. Finally, as convinced, the obtained nanoparticles had no significant side effects to the selected three human cells. In total, the achieved data supports the biogenic nanoparticles as valuable functional materials with great potential for practical plant protection and food safety prevention. • Selenium nanoparticles were friendly agents to control pathogens and mycotoxins. • The first attempt of combination of Trichoderma spp. and selenium nanoparticles. • The proposed recognition mechanism explained the damage of fungal hyphae. • Mycotoxin production and their genes were significantly reduced after treatment. • Trichoderma -derived nano-Se showed greater biocontrol effect than single nano-Se. [ABSTRACT FROM AUTHOR]

• ART attenuated rosacea-like dermatitis in LL37-induced mouse model. • ART reduced the expression of proinflammatory factors and infiltration of inflammation cells in LL37-induced rosacea-like mouse. • ART repressed pro-inflammatory factors release in HaCaT cells may partly via NF-kB signal pathways. • ART inhibited angiogenesis in vivo and migration of HUVECs in vitro. Rosacea is a facial chronic inflammatory skin disease with dysfunction of immune and vascular system. Artemisinin (ART), an anti-malaria drug, was reported to have several effects including anti-inflammation and anti-angiogenesis activities. However, the role of ART on rosacea remains unclear. To investigate the effects and molecular mechanism of ART on rosacea. In rosacea-like mouse model, the phenotype of rosacea lesions was evaluated by redness score, the inflammatory biomarkers were analyzed by qPCR, and the infiltration of inflammatory cells were assessed by IHC analysis and immunofluorescence. In vitro , LL37-induced expression of inflammatory factors in HaCaT cells was detected by qPCR, potential signaling pathways were detected by Western blotting or immunofluorescence. Migration ability of human umbilical vein endothelial cells (HUVECs) was evaluated by cell scratch and transwell assays. The skin erythema and histopathological alteration, as well as the elevated pro-inflammatory factors (IL-1β, IL6, TNFα) and TLR2 were significantly ameliorated by ART treatment in LL37-induced rosacea-like mice. In addition, ART reduced the infiltration of CD4+ T cells, macrophages and neutrophils, and repressed the expression of immune cells related chemokines (CXCL10, CCL20, CCL2 and CXCL2) in mouse lesions. In HaCaT cells, ART significantly decreased the LL37-induced expression of inflammatory biomarkers. Moreover, we found that ART inhibited rosacea-like inflammation via NF-kB signaling pathways in HaCaT cells. Finally, for vascular dysregulation, ART repressed the angiogenesis in mouse model and inhibited the LL37-induced HUVECs migration in vitro. ART ameliorated rosacea-like dermatitis by regulating immune response and angiogenesis, indicating that it could represent an effective therapeutic option for patients with rosacea. [ABSTRACT FROM AUTHOR]

Background: A sequential combination of radiochemotherapy/endocrinotherapy and cytokine-induced killer cell (CIK) infusion has been shown to be an effective therapy for post-mastectomy breast cancer based on statistical analysis of the patient population. However, whether an individual could obtain an improved prognosis from CIK cell-based treatment remains unknown. In the present study, we focused on immune microenvironment regulation and specifically investigated the relationship between PD-L1 expression and survival benefit from CIK immunotherapy in breast cancer. Methods: A total of 310 postoperative breast cancer patients who received comprehensive treatment were enrolled in this retrospective study, including 160 patients in the control group (received chemotherapy/radiotherapy/endocrinotherapy) and 150 patients in the CIK cell treatment group (received chemotherapy/radiotherapy/ endocrinotherapy and subsequent CIK infusion). Results: We found that overall survival (OS) and recurrence-free survival (RFS) were significantly better in the CIK group than that in the control group. PD-L1 expression in tumor tissue sections was showed to be an independent prognostic factor for patients in the CIK treatment group using multivariate survival analysis. Further survival analysis in the CIK group showed that patients with PD-L1 tumor expression exhibited longer OS and RFS. In addition, among all patients who were enrolled in this study, only the patients with PD-L1 expression experienced survival benefits from CIK treatment. Conclusions: Our study showed the relationship between PD-L1 expression and CIK therapy and revealed that PD-L1 expression in the tumor is as an indicator of adjuvant CIK therapy for postoperative breast cancer. [ABSTRACT FROM AUTHOR]

Background: We examined the correlations between living arrangement and the physical activity (PA) levels of youth aged 9-19 years while accounting for demographic factors such as age, sex, and socioeconomic status in Shanghai, China.Methods: Cross-sectional analyses of data from the 2014 Physical Activity and Fitness in Shanghai China-The Youth Study was conducted. Participants were 33,213 primary (9-11-year-olds; n = 13,237), junior middle (12-14-year-olds; n = 11,157), and junior high school students (15-19-year-olds; n = 8819). Youth (boys = 49%) and their guardians were randomly sampled from 17 districts in Shanghai, China. Youths' moderate-to-vigorous PA (MVPA) levels, information about living arrangement, and guardians' sociodemographic factors were collected via questionnaires.Results: Only 17.8% of school-aged youths in Shanghai met MVPA recommendations, with significantly more boys (20.6%) meeting recommendations than girls (p < .001). Youths living in rural areas showed an overall significantly higher percentage of meeting MVPA recommendations (20.3%) than those living in urban areas (p < .001). Youths who lived with single parents showed an overall significantly lower percentage of meeting MVPA recommendations (15.3%) than those living with their grandparent(s) or with both parents (p < .001). A logistic regression analysis revealed that, among 9-11-year-olds, children who live with their grandparent(s) were less likely to meet MVPA recommendations than those who lived with both parents (boys: adjusted odds ratio (aOR) = 0.72, 95% confidence interval (CI) = 0.61-0.84; girls: aOR = 0.84, 95%CI = 0.72-0.98).Conclusions: Type of living arrangement was associated with the PA of youth in Shanghai, with no significant gender difference. Youth aged 9-19 years who lived with single parents had the lowest percentage of meeting MVPA recommendations. The probability of achieving 60 min/day MVPA recommendations was significantly lower among 9-11-year-old children living with their grandparent(s) than children living with both parents; however, no such difference was observed among adolescents. Our findings suggest that living arrangement may be an important consideration for promotion of PA among youth in China. [ABSTRACT FROM AUTHOR]

Oxytocin (OT) release by axonal terminals onto the central nucleus of the amygdala exerts anxiolysis. To investigate which subpopulation of OT neurons contributes to this effect, we developed a novel method: virus-delivered genetic activity-induced tagging of cell ensembles (vGATE). With the vGATE method, we identified and permanently tagged a small subpopulation of OT cells, which, by optogenetic stimulation, strongly attenuated contextual fear-induced freezing, and pharmacogenetic silencing of tagged OT neurons impaired context-specific fear extinction, demonstrating that the tagged OT neurons are sufficient and necessary, respectively, to control contextual fear. Intriguingly, OT cell terminals of fear-experienced rats displayed enhanced glutamate release in the amygdala. Furthermore, rats exposed to another round of fear conditioning displayed 5-fold more activated magnocellular OT neurons in a novel environment than a familiar one, possibly for a generalized fear response. Thus, our results provide first evidence that hypothalamic OT neurons represent a fear memory engram. • A novel method, vGATE, selectively tagged fear-activated oxytocin (OT) neurons • A subset of tagged OT neurons encodes for context-specific memory engram • Fear learning induces long-term plasticity in OT neurons • vGATE-tagged OT neurons predominantly operate by glutamate Hasan et al. developed a novel genetic method, vGATE, to tag a context-specific fear memory engram in the hypothalamic oxytocin system that participates in rapid unfreezing, extinction, and enhanced glutamatergic transmission. [ABSTRACT FROM AUTHOR]

Colloidal Janus spheres in the bulk typically spontaneously assemble into plastic crystalline phases, while particle orientations exhibit glasslike dynamics without long-range order. Through Brownian dynamics simulations, we demonstrate that shear can trigger a phase transition from an isotropic crystal with orientational disorder to an orientationally ordered crystal with lamellae along the shear direction. This nonequilibrium transition is accompanied with the orientational ordering following a nucleation and growth mechanism. By performing a phenomenological extension of free energy analysis, we reveal that the nucleation originates from the orientation fluctuations induced by shear. The growth of the orientationally crystalline cluster is examined to be disklike, captured by developing a lattice model with memoryless state functions. These findings bring new insights into the mechanisms for the ordering transition of anisotropic particles at nonequilibrium states. [ABSTRACT FROM AUTHOR]

Background: The effect of hydrogen sulfide (H2S) on visceral nociception is elusive. The conflicting evidence of its pro‐ and antinociceptive effects raises a series of questions with respect to the effect of H2S on colonic afferent activity and the underlying mechanism, which was further elucidated in this study. Methods: Colonic mesenteric afferent nerve spikes of normal male C57BL/6J mice, Cbs+/− mice, and Wistar rats were recorded in vitro. The abdominal withdrawal reflex (AWR) induced by colorectal distension (CRD) was evaluated in Cbs+/− mice and WT littermates. Key Results: Sodium hydrosulfide (NaHS) significantly decreased colonic afferent spontaneous discharge, chemosensitivity to bradykinin, mechanosensitivity to ramp distention, and intraluminal pressure in mice. Reducing the relaxant action of NaHS on intestinal smooth muscle using the nonspecific K+ channel blocker TEA (10 mmol/L) did not block the inhibition of NaHS on afferent nerve activity. The inhibitory effects of NaHS (0.5 mmol/L) on colonic afferent sensitivity were largely eliminated by the pretreatment with nonspecific NOS inhibitor NG‐Methyl‐l‐arginine acetate salt (1 mmol/L), the specific nNOS inhibitor NPLA (1 μmol/L), or N‐type Ca2+ channel blocker ω‐conotoxin GVIA (1 μmol/L). Compared with WT mice, Cbs+/− mice showed increased mesenteric afferent sensitivity to colonic distention and enhanced hyperalgesic response to CRD. Intraperitoneal administration of NaHS (60 μmol/kg) alleviated the nociception response to CRD in both Cbs+/− and WT mice. Conclusions and Inferences: H2S downregulates colonic mesenteric afferent sensitivity by a nNOS‐dependent mechanism in mice. Our findings may demonstrate a new mechanism for the antinociceptive effect of H2S in colon. The effect of H2S on visceral nociception is elusive. The aim of this study was to investigate the mechanism underlying the effect of H2S on colonic afferent sensitivity. Sodium hydrosulfide reduced the colonic afferent sensitivity in nNOS‐dependent way, including spontaneous activity, chemosensitivity, and mechanosensitivity. Cbs+/− mice exhibited visceral hypersensitivity to colonic distention. Our findings demonstrated the antinociceptive effect of H2S in the periphery. H2S and the donors might be the potent candidates for the development of analgesic drugs. [ABSTRACT FROM AUTHOR]

Enterovirus A71 (EVA71) is a human enterovirus belonging to the Picornaviridae family and mostly causes hand-foot-and-mouth disease in infants. Viperin is an important interferon-stimulated gene with a broad antiviral activity against various viruses. However, the effect of viperin on human enteroviruses and the interaction mechanism between EVA71 and viperin remains elusive. Here, we confirmed the EVA71-induced expression of viperin in a mouse model and cell lines and showed that viperin upregulation by EVA71 infection occurred on both the mRNA and protein level. Viperin knockdown and overexpression in EVA71-infected cells indicated that this protein can markedly inhibit EVA71 infection. Interestingly, immunofluorescent confocal microscopy and co-immunoprecipitation assays indicated that viperin interacts and colocalizes with the EVA71 protein 2C in the endoplasmic reticulum. Furthermore, amino acids 50–60 in the N-terminal domain of viperin were the key residues responsible for viperin interaction with 2C. More importantly, the N-terminal domain of viperin was found responsible for inhibiting EVA71 replication. Our findings can potentially aid future research on the prevention and treatment of nervous system damage caused by EVA71 and may provide a potential target for antiviral therapy. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence for the prevalence of the co-existence of physical activity (PA) and sedentary behavior (SED), and its correlates among children and adolescents. This study has two aims: 1) to investigate the prevalence of PA and SED, and their co-existence, and 2) to examine the associations between PA or SED, or both with gender and age among children and adolescents in Shanghai, China.Methods: Using a cross-sectional study design (conducted from September to December 2014), 50,090 children and adolescents (10-18 years old, 50.4% boys) were included in this study. A self-reporting questionnaire was used to measure participants' sociodemographic characteristics, PA, and SED. Descriptive statistics were used to describe sample characteristics, the prevalence of PA and SED, and their co-existence. A Generalized Linear Model was conducted to explore the associations between the prevalence of PA and SED, and their co-existence with gender and age separately.Results: Of the children and adolescents studied, only 18.4% met the guidelines for PA, 25.5% met the guidelines for SED, and 5.7% met the guidelines for both. Boys were more physically active (aOR = 1.43, 95% CI: 1.36-1.50), and girls were less sedentary (aOR = 1.29, 95%CI: 1.24-1.34). The prevalence of PA, SED, or both all declined as age increased (p < 0.001). Stratified analysis by gender revealed greater declining trends of meeting the PA or SED guidelines, or both in girls (all p < 0.005).Conclusion: Very few children and adolescents showed active lifestyles, and this was significantly related to age. Effective interventions aiming to promote PA and concurrently to limited SED among children and adolescents should be implemented as early as possible. [ABSTRACT FROM AUTHOR]

Background: Recent studies showed that benzimidazoleisoquinolinone derivatives exhibit anticancer activity against human cancer cell lines. The aim of this study is to evaluate the anti-tumor effects and mechanisms of benzimidazoleisoquinolinones in isocitrate dehydrogenase-wildtype subtype of human glioblastoma (GBM) cells. Methods: Human U87 and LN229 cell lines were used to perform the experiments. MTT was applied to screen the effective small molecular inhibitors suppressing growth of GBM cells. Colony formation and BrdU staining assays were performed to assess the inhibition effect of compound-1H on the proliferation of GBM cells. The cell cycle and apoptosis were measured by flow cytometry and western blot to analyze the changes of the relative protein expressions and their signal pathways. Results: Compound-1H could suppress GBM cells in a time- and dose-dependent manner. Treatment of compound-1H could arrest cell cycle in S phase through up-regulating P21 and P53, and down-regulating cyclin A and E in a dose-dependent manner. Compound-1H also induced mitochondrial-dependent apoptosis by increasing Bax, cleaved caspase-3, cleaved caspase-9 and poly ADP-ribose polymerase expression, and decreasing Bcl-2 expression. Moreover, phosphorylated (p)-AKT and p-ERK levels relating to cell proliferation were dramatically decreased in U87 and LN229 cells. Conclusions: Our results suggest that it is the first time to report the compound-1H with benzimidazoleisoquinolinone core playing antitumor activity in human glioblastoma cells by inhibiting Raf/MEK/ERK and PI3K/AKT signaling pathways, and it could be as a lead compound for the further development of targeted glioblastoma cancer therapy. [ABSTRACT FROM AUTHOR]

Slug is a fast-turnover transcription factor critical for controlling cell fate and cancer cell invasion and metastasis. The stability of Slug is important and maintained by diverse mechanisms. In this study, we presented a paradigm of this activity by identifying long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) that binds to and stabilizes Slug in colon cancer cells. LncRNA SNHG15 transcription is upregulated in a variety of human cancers according to The Cancer Genome Atlas. Here, ectopic expression of SNHG15 promoted colon cancer cell migration in vitro, accelerated xenografted tumor growth in vivo, and elevated levels of SNHG15 were associated with poor prognosis for colon cancer patients. Mechanistically, SNHG15 maintains Slug stability in living cells by impeding its ubiquitination and degradation through interaction with the zinc finger domain of Slug. These findings revealed a novel mechanism underlying the control of Slug stability by demonstrating that oncogenic lncRNA SNHG15 interacts with and blocks Slug degradation via the ubiquitin-proteasome system. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-17 has been reported to play a controversial role in tumor immunity. Our previous studies showed that infiltration of IL-17-producing cells in esophageal squamous cell carcinoma (ESCC) induced tumor protective immunity by recruiting CD8+T lymphocytes, natural killer (NK) cells, and B lymphocytes into the tumor microenvironment. However, the mechanism of IL-17 regulation of tumor-associated neutrophils remains elusive in ESCC. In this study, we therefore evaluated the accumulation of myeloperoxidase (MPO)+ neutrophils and its association with IL-17-producing cells within ESCC tumor nests. We also investigated the effects of IL-17 on the recruitment and antitumor activity of neutrophils. MPO+ neutrophil infiltration was found to predict a favorable prognosis in ESCC patients and was positively correlated with IL-17+ cell density. IL-17 stimulated ESCC tumor cells to release more of the CXC chemokines CXCL2 and CXCL3, which are involved in neutrophil migration. Furthermore, IL-17 potentiates the direct killing capability of neutrophils by enhancing the production of cytotoxic molecules, including reactive oxygen species (ROS), MPO, TNF-related apoptosis-inducing ligand (TRAIL), and IFN-γ. Experiments in mice suggested that IL-17 alone might not affect tumor progression in the tumor-bearing host, but IL-17 can inhibit tumor growth by promoting beneficial neutrophil infiltration and activation at tumor sites. As emerging evidence indicates that targeting tumor-associated neutrophils is a strategy for antitumor therapy, our findings reveal a positive contribution of IL-17 to the modulation of neutrophil-mediated antitumor immunity in ESCC. This study provides further understanding of the mechanisms that selectively regulate functional activities of neutrophils, which may be critical for developing new tumor immunotherapy. [ABSTRACT FROM PUBLISHER]

In this work, we report the complete mitochondrial genome sequence of Sus cebifrons (Visayan warty pig). The total length of the mitogenome was 16,475 bp, and its overall base composition was estimated to be 35.0% for A, 25.8% for T, 26.2% for C and 13.0% for G, indicating an A-T (60.8%)-rich feature in Sus cebifrons mitogenome. It contained the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and a noncoding control region (D-loop region). The arrangement of these genes was the same as that found in other pigs. The complete mitochondrial genome sequence of the Sus cebifrons would provide new genetic resources for pig domestication study. [ABSTRACT FROM AUTHOR]

Cytokine-induced killer (CIK) cell immunotherapy represents an effective treatment strategy for treating hepatocellular carcinoma (HCC). However, the therapeutic benefits of CIK cell treatment can be influenced by differences in complex immune microenvironment between patients. Herein, we investigated the relationship between PD-L1 expression and survival benefits of CIK cell immunotherapy in HCC patients. This retrospective study included 448 HCC patients: 217 cases underwent hepatectomy alone; 231 cases received hepatectomy and post-operative CIK cell transfusion. Immunohistochemistry was used to measure PD-L1 expression in tumor tissue sections from all patients. Meanwhile, flow cytometry was performed to explore the relationship between PD-L1 expression and localized inflammatory response in HCC microenvironment. We found a significantly improved prognosis in CIK treatment group compared with surgery alone group. In the CIK treatment group, higher PD-L1 expression was observed in patients who exhibited long-term survival benefit. Survival analysis showed patients with ≥5% PD-L1 expression had better overall survival (OS) and recurrence-free survival (RFS) than patients with 1–5% or <1% PD-L1 expression, particularly in the subgroup with high hepatitis B viral load. By contrast, PD-L1 expression did not show direct impact on the survival of patients in surgery alone group. Additionally, PD-L1 expression was found to be highly associated with hepatitis B viral load and the proportion of tumor-infiltrating lymphocytes in HCC patients. In conclusions, our study indicates that PD-L1 expression may reflect the presence of endogenous host immune response to tumor and serve as a biomarker for predicting survival benefits from adjuvant CIK cell immunotherapy in HCC patients. [ABSTRACT FROM AUTHOR]