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Gliomas originating in the neuroepithelium account for about 80% of brain malignancies and are the most common cancer of the central nervous system. Clinical management of gliomas remains challenging despite significant advances in comprehensive therapies, including radiotherapy, chemotherapy, and surgery. The ITGB4 (Integrin subunit beta 4) gene encodes a receptor for laminins and its upregulation in tumor tissues is associated with poor prognosis. However, its role in glioma is not well understood. First, we performed a pan cancer analysis of ITGB4 expression in The Cancer Genome Atlas (TCGA) dataset. Survival analysis was done on Chinese Glioma Genome Atlas (CGGA) and TCGA. Immunohistochemistry was then used to validate the expression and role of ITGB4 in glioma. We finally analyzed the possible mechanism by immune infiltration and single-cell sequencing analysis. Here, we found that ITGB4 is upregulated in glioma and accurately predicts the prognosis of lower grade glioma (LGG). Univariate and multivariate Cox regression analyses showed that ITGB4 is a risk factor for LGG. Immunohistochemical analysis confirmed that ITGB4 accurately predicts LGG prognosis. Non-negative matrix factorization (NMF) cluster analysis showed that ITGB4 was closely related to immune related genes. Immune cell infiltration and single cell sequencing analyses indicated that ITGB4 may be closely related to the microenvironment of gliomas, especially tumor-associated fibroblasts. ITGB4 is a promising diagnostic and therapeutic factor in LGG patients. [ABSTRACT FROM AUTHOR]

Two types of retrograded eclogite (phengite‐bearing eclogite and garnet pyroxenite) within eclogite‐facies granitic gneisses are reported for the first time from the Younusisayi area of the South Altyn high to ultrahigh pressure (HP–UHP) metamorphic belt. These eclogites were studied using petrology, mineral chemistry, phase equilibrium modelling, and geochronology. The phengite‐bearing eclogite records five stages of metamorphism: (1) early prograde (Grt + Cpx + Amp + Rt + Qz) at conditions of P = 11.50–17.5 kbar, T = 665–740°C; (2) peak eclogite‐facies (Grt + Omp + Ph + Rt + Qz) at conditions of P > 24.2 kbar, T = 710–1000°C; (3) overprinting during retrograde transition to HP granulite‐facies conditions (Grt + Cpx ± Kfs + Pl + Rt + Qz) at P = 12.1–16.9 kbar and T = 760–890°C; (4) retrogression at granulite‐facies conditions (Grt + Cpx + Amp + Pl + Ilm + Qz) of P = 9.1–11.4 kbar, T = 730–840°C; and (5) amphibolite‐facies metamorphism (Amp + Pl + Ilm + Qz) during cooling and decompression. The garnet pyroxenite records four stages of metamorphism: (1) eclogite‐facies at conditions of P > 23.2 kbar, T = 775–965°C; (2) HP granulite‐facies conditions of P = 13.2–17.8 kbar and T = 836–912°C; (3) granulite‐facies conditions of P = 8.6–9.7 kbar, T = 739–783°C; and (4) amphibolite‐facies metamorphism. Zircon U–Pb dating and trace element analysis constrain eclogite‐facies metamorphism to c. 500 Ma, consistent with the age of the surrounding eclogite‐facies granitic gneiss (497.8 ± 2.7 Ma). Retrograde metamorphism ages of c. 460 Ma are interpreted as recording zircon growth after granulite‐facies metamorphism. The P–T–t path defines the integrated process of deep subduction and multistage exhumation and places constraints on the early Palaeozoic geodynamics of the South Altyn belt. Well‐preserved major and trace element zoning of garnets in the Ph‐bearing eclogites lacks evidence of significant thermal diffusion and may record garnet growth during deep subduction, immediately followed by very rapid exhumation. [ABSTRACT FROM AUTHOR]

• A novel peristaltic micropump integrated on a microfludic chip was developed. • The microfluidic chip was disposable and separated from the piezoelectric actuators. • High frequency (larger than 100Hz) and fast response. • Tiny dead volume (less than 300nL). Micropump is extremely useful in miniature biochemical analysis systems for its abilities of manipulating and transporting minute liquid. We developed a novel peristaltic micropump to pump fluids in microfluidic chip in this article. The micropump consists of three piezoelectric actuators, and part of a microfluidic chip as a compressible microchannel. The fluid in the microchannel is transported owning to a series of impacting actions on the microchannel by the piezoelectric actuators. The microchannel is integrated fabricated with the microfluidic chip, which ensures a tiny dead volume less than 300 nL. Being beneficial from the plug-and-play design of the microfluidic chip, there is no cross-contamination for the reagent has no contact with the reusable actuators. Calibration shows the micropump can transport liquid at a high resolution of 8.4 nL/s, a maximum flow rate of 102 nL/s, and backpressure of up to 2.0 K Pa. A demonstration of mixing liquids on a chip was carried out using two micropumps, indicating its great potential for manipulating microamount reagent in biochemical application. [ABSTRACT FROM AUTHOR]

• A novel on-chip size-tunable droplet microfluidic system. • Size & frequency tunable without channel size change, droplet size can be changed from 81.5 µm to 345.5 µm. • Simple operation and small waste of reagent (<200 nL). [Display omitted] Droplet microfluidics has become widely employed in various chemical and biological analyses, by offering the capacity of high-efficiency generation of miniature droplets in accurate sizes and precise concentrations. In this article, a size-tunable droplet microfluidic system has been first developed, which includes an on-chip microfluidic peristaltic pump. In particular, both the sizes and frequencies of the generated droplets can be fine-tuned without requirement of changing the geometrical design of the microfluidic chip itself. By choosing proper parameters as driving voltage and frequency of the peristaltic pump, the desired droplet length (from 81.5 µm to 345.5 µm) and generation frequency can be easily obtained. Due to the on-chip design of the micropump, the size-tunable droplet microfluidic system has tiny dead volume as low as 1 μL. Moreover, less than 200nL reagent was wasted before getting into a stable droplet generating state, showing potential in the applications of capsulation of rare objects in small-volume sample and isovolumetric isolation for precise analysis. [ABSTRACT FROM AUTHOR]

Abstract: Huperzine A (Hup A) is a lycopodium alkaloid from Huperzia serrata, which has been used as a therapeutic agent in several neurological disorders. Despite the diverse pharmacological activities Hup A has, its role in hippocampal neurogenesis remains to be established. This study showed that Hup A not only promoted the proliferation of cultured mouse embryonic hippocampal neural stem cells (NSCs), but also increased the newly generated cells in the subgranular zone (SGZ) of the hippocampus in adult mice. Furthermore, the in vitro findings indicated that low concentrations of Hup A stimulated the proliferation of cultured NSCs, whereas extremely high concentration of it decreased the cell proliferation. Hup A activated mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, which was a well-known regulator of biological processes including cell proliferation and differentiation. ERK inhibitor dramatically inhibited the proliferative effect of Hup A on NSCs. Administration of Hup A to adult mice significantly enhanced the cell proliferation in dentate gyrus of hippocampus, and increased the remaining newborn cells 4 weeks after the drug administration. Moreover, the newly generated BrdU+/NeuN+ neurons were also increased by Hup A treatment. These findings suggest a novel role of Hup A in neurogenesis and provide a new insight into its therapeutic effects in neurological disorders via a neurogenesis-related mechanism. [Copyright &y& Elsevier]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. In the present study, the function of amyloid precursor protein (APP) in modulating capacitive calcium entry (CCE), a refilling mechanism for depleted intracellular calcium stores, was investigated. CCE in neural 2a (N2a) cells stably expressing wild-type human APP was lower than in wild-type N2a cells, while CCE in APP knockout mouse embryonic fibroblast (MEF) cells was higher than in their wild-type counterparts. We demonstrate that wild-type APP depresses CCE. Furthermore, using N2a cells transfected with C-terminal APP fragments, we show that these fragments anchored in the cell membrane play an important role in CCE depression. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondrial malfunction and calcium dyshomeostasis are early pathological events considered as important features of the Alzheimer’s disease (AD) brain. Recent studies have suggested mitochondrion as an active regulator of Ca2+ signaling based on its calcium buffering capacity. Herein, we investigated the mitochondrial involvement in the modulation of store-operated calcium entry (SOCE) in neural 2a (N2a) transgenic AD model cells. Results showed that SOCE was significantly depressed in N2a cells transfected with wild-type human APP695 (N2a APPwt) compared with empty vector control (N2a WT) cells. Pharmacological manipulation with mitochondrial function blockers, such as FCCP, RuR, or antimycin A/oligomycin, could inhibit mitochondrial calcium handling, and then impair SOCE pathway in N2a WT cells. Furthermore, mitochondria of N2a APPwt cells exhibited more severe swelling in response to Ca2+, which is an indication of mitochondrial membrane permeability transition (MPT), than the wild-type controls. Additionally, treatment with cyclosporin A, a potent inhibitor of cyclophilin D, which can block MPT, could significantly restore the attenuated SOCE in N2a APPwt cells. Therefore, inhibition of cyclophilin D might be a therapeutic strategy for Alzheimer’s disease. [Copyright &y& Elsevier]

Digital PCR enabled high-sensitivity and quantitative measurements of rare biological variants. A new digital droplet-enabled PCR technology was introduced in this paper, which partitioned genetic targets into a planar nanoliter droplet array by using a microfluidic impact printer (MIP) with a disposable microfluidic chip. The accuracy of this MIP-enabled PCR technology was verified by detecting a series of concentration gradients of GAPDH gene across spanning four orders of magnitude (from 0.464 copies/μL to 464 copies/μL). Furthermore, this technology was applied to detect the expressions of p53 gene in colon cancer tissues and adjacent nontumorous tissues, from which the copies of the nucleic acids could be absolute-quantitatively determined. The outcomes were consistent with the results of using the conventional real-time PCR, demonstrating a great potential of the MIP-enabled digital PCR in detecting gene expression in clinical samples. Image 1 • A droplet digital PCR technology based on microfluidic impact printing is proposed. • The reactions happen in a planar droplet array, easy to be measured. • The detection range is expanded by generating multi-volume droplets. • The MIP-ddPCR eliminates cross-contamination with disposable microfluidic chip. • The p53 gene in colon cancer tissues was absolutely quantified by the MIP-ddPCR. [ABSTRACT FROM AUTHOR]

Garnet amphibolite is one of the common metabasic rocks exposed in collisional orogenic belt, the metamorphic evolution of which is associated closely with orogenic processes. The Yaganbuyang garnet amphibolites occur as blocks hosted by massive granitic gneiss, and consist mainly of hornblende, garnet, clinopyroxene, plagioclase, biotite, quartz with minor rutile/ilmenite and phengitic muscovite. These garnet amphibolites were interpreted to have experienced decompression-dominated evolution that can be divided into three generations (M1, M2, M3), based on the petrographic observations and phase equilibria modeling calculated by THERMOCALC. The assemblage of the first generation (M1) is inferred to possibly be dominated by garnet + omphacite + rutile + phengite + quartz, which is modeled to be roughly stable at P > 25 kbar and T > 800 °C. The second generation (M2) is characterized by the local symplectites of clinopyroxene + plagioclase produced from omphacite, indicating a near-isothermal decompression from ∼23.8 kbar/875 °C to ∼10 kbar/852 °C. The third generation (M3) is marked by the kelyphitic rims of plagioclase + hornblende around garnet and of hornblende + ilmenite around clinopyroxene, involving the late-stage retrogression from ∼9.8 kbar/848 °C to ∼5.8 kbar/645 °C. Zircon U-Pb dating yielded one group metamorphic age of c. 500 Ma that is interpreted to represent the timing of the peak eclogite-facies metamorphism. A combination of petrography observation, phase modeling results and geochronology data suggests that the Yaganbuyang garnet amphibolites have once undergone eclogite-facies metamorphism by continental subduction rather than crustal thickening. Therefore, the Yaganbuyang area is an eastward extension part of the South Altyn HP-UHP metamorphic belt. [ABSTRACT FROM AUTHOR]

Discontinuous dewetting is an attractive technique that can produce droplet array of specific volume, geometry and at predefined location on a substrate. Droplet array has great potential in bioanalysis such as high-throughput live cell screening, digital PCR, and drug candidates. Here, we propose a self-dispersing droplet array generation method, which has advantages of low cost, simple operation, and easy large-area production ability. Droplet array of specific volumes was generated on a polymethyl methacrylate (PMMA) substrate using a simple reusable polyimide (PI) adhesive mask. Experiment shows that the generated droplet array can be used to successfully capture single particles which obeys Poisson distribution in a high-throughput manner. Furthermore, a droplet-array sandwiching chip was created based on the self-dispersion method for rapid detection of human serum albumin (HSA) at wide range of 183–11,712 μg/mL with low reagent consumption of 2.2 μL, demonstrating its potential applications in convenient high-throughput bioanalysis and bioassays. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative stress has been demonstrated to be involved in the pathogenesis of Alzheimer''s disease (AD). Thus, antioxidant therapy may represent a promising avenue for the treatment of AD. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent free radical scavenger and has been shown to provide neuroprotection in both animal models of cerebral ischemia and stroke patients. In the present study, we investigated the protective effect of edaravone against AD-relevant insults in neuroblastoma N2a cells and explored the potential mechanisms involved. N2a/Swe.Δ9 cells were used as the AD model cells, which exhibited reduced cell viability, increased apoptosis and oxidative stress as well as decreased mitochondrial membrane potential compared with N2a/Wt cells. All of these phenotypes were significantly reversed by edaravone treatment. Edaravone treatment significantly elevated cell viability, reduced apoptotic rate, attenuated oxidative stress and improved mitochondrial membrane potential in N2a/Swe.Δ9 cells. Furthermore, edaravone treatment inhibited mitochondria-dependent apoptosis pathways in N2a/Swe.Δ9 cells through decreasing the Bax/Bcl-2 ratio, attenuating cytochrome c release and suppressing the activation of caspase-3. These results demonstrate that edaravone provides neuroprotection in an AD-related in vitro model and therefore, may be a potential complement for AD therapy. [Copyright &y& Elsevier]

Mafic dyke swarm is widely developed in Proterozoic continental lithosphere. The Gangou diabase dyke from the Xixia area, intruded into the Douling complex of the South Qinling belt, yields zircon UPb age of 731 Ma. It has low SiO2 content (49.02 wt.%-49.37 wt.%) and Mg# (34.0–37.7) and shows characteristics of subalkaline tholeiite series. They show high ΣREE (155.5×10 6–184.7×106), weak negative Eu anomaly (SEu=0.88-0.93), slight depletion of Nb and Ta, and enrichment of LILE. Their major and trace element, Sr-Nd-Pb isotope and clinopyroxene compositions indicate that it originated from the partial melting of the asthenospheric mantle within-plate extension setting and was slightly contaminated by crust compositions. The similarities of formation age, petrogenesis, source characteristic and tectonic setting for Gangou diabase with mafic dykes in Wudang Block and mafic volcanic rocks in Yaolinghe Group indicate that the South Qinling belt underwent strong continental extension in Neoproterozoic during 796–685 Ma most likely correspondence to the breaking-up of the Rodinia supercontinent. [ABSTRACT FROM AUTHOR]

Abstract Introduction In this study, a new agent consisting of HER2-specific affibody Z HER2:V2 and chemotherapy drug pemetrexed was synthesized to develop a new targeted drug. Its biological characteristics and anticancer efficacy were assessed in cells level and xenografts models by radiolabeling with technetium-99m. Methods After the Z HER2:V2 -pemetrexed conjugate was synthesized, radiolabeling of the conjugate was performed using its C-terminal 4 amino acids (Gly-Gly-Gly-Cys) as the chelating moiety. The radiochemical yield of the [99mTc]Tc-Z HER2:V2 -pemetrexed was identified by instant thin-layer chromatography (ITLC). Stability of the radiolabeled conjugate was investigated both in vitro and in vivo. In vitro binding affinity and cell internalization study of the probe were performed in A549 cells (HER2-positive). Tumor uptake was evaluated by in vitro uptake assay in A549 cells and H23 cells (HER2-negative), and by in vivo biodistribution and SPECT imaging in A549 and H23 tumor-bearing mice. The antitumor efficacy of the Z HER2:V2 -pemetrexed conjugate was evaluated in cells and xenograft models. Results The Z HER2:V2 -pemetrexed was successfully synthesized and conjugated with technetium-99 m, and acquired the radiochemical yield of 97.0 ± 0.3%. The stability of [99mTc]Tc-Z HER2:V2 -pemetrexed was good in both physiological saline and human serum. The radiolabeled agent displayed excellent HER2-binding specificity and affinity in vitro , and was gradually internalized into the cells. Biodistribution study revealed obvious tumor uptake in A549 xenografts (percentage injected dose per gram, 2.6 ± 1.0%ID/g at 4 h postinjection), while the uptake in HER2-negative H23 tumors was much lower (0.2 ± 0.1%ID/g at 4 h postinjection, P < 0.01). SPECT imaging exhibited an intensity in the A549 xenograft which could be blocked by excess Z HER2:V2 -pemetrexed. Treatment with Z HER2:V2 -pemetrexed significantly impaired the tumor growth (P < 0.05), with less weight loss than pemetrexed. Conclusion [99mTc]Tc-Z HER2:V2 -pemetrexed showed desirable property and HER2-specificity. The Z HER2:V2 -pemetrexed conjugate could inhibit tumor growth of HER2-positive lung adenocarcinoma and may have the potential to become a targeted drug for lung cancer. Advances in knowledge and implications for patient care The compound described herein performs HER2-targeting with favorable anticancer efficacy and offers the potential of novel targeting strategies for further tumor therapy. [ABSTRACT FROM AUTHOR]

• Aloe-emodin α -amino phosphate derivatives with targeting DNA were synthesized. • The introduction of phosphoramidate can increase lipophilicity the compounds and promote them to enter the nucleus. • The main interaction mode of Aloe-emodin α-amino phosphate derivatives with DNA is intercalation. • Aloe-emodin α-amino phosphate derivatives could increase the DNA fragmentation of cancer cells and possessed strong anti-tumor potential. Square-planar aromatic compounds (such as aloe emodin) have been widely studied for their anti-tumor potential. However, It still suffer from poor cells membrane permeability and low bioavailability. To solve this problem, we introduced α-amino phosphate on the anthraquinone scaffold to increasing the permeability of the cancer cells. 13 aloe emodin α-amino phosphate derivatives were synthesized. Among them, compounds 2a and 2b showed better anti-tumor activity than aloe-emodin in different tumor cells. The interaction between compounds 2a, 2b and calf thymus DNA (Ct-DNA) was studied via UV–vis absorption, fluorescence spectrum, viscosity measurements and molecular docking. The results show that the interaction mode of 2a and 2b with DNA is intercalation. Under confocal microscopy, 2a and 2b can effectively penetrate the cell membrane, nuclear membrane and enter the nucleus. Comet assay showed that compound 2b could increase the DNA fragmentation of cancer cells.Contain α-amino-phosphate anthraquinone scaffold emerges as a promising anticancer activity structure and our results may provide a structural modification direction for improving the membrane permeability of anthraquinones and other drugs. Aloe-emodin α-amino phosphate derivatives were synthesized. It is worth noting that the compounds 2a and 2b can enter the nuclear membrane and bind to DNA by intercalating mode to inhibit the proliferation of tumor cells. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Magmatism formed during the initial stage (ca. 480Ma) and advanced stage (ca. 450Ma) of exhumation of subducted continental crust have been recognized in South Altyn western China. • Two stages of magmatism exhibits evidence for the partial melting of subducted continental crust during differential exhumation process of South Altyn in Palaeozoic. The early Palaeozoic continental subduction–collisional belt in South Altyn (SA) western China distributes a large amount of (ultra)-high-pressure ((U)HP) metamorphic and granitic rocks associated with subduction, collision, and exhumation. In this study, four granitic rocks were collected from Bashenwake located in eastern SA. The ages of the garnet-bearing alkali-feldspar granite (GAFG), garnet-bearing granitic gneiss (GGG), alkali-feldspar granite (AFG), and syenogranite (SG) are 458.0 ± 4.1, 483.0 ± 4.1, 450.0 ± 2.4, and 482.0 ± 4.9 Ma, respectively. Whole-rock major and trace elements and Sr–Nd–Pb isotope, and zircon Hf isotope compositions for all samples exhibit characteristics of a continental crustal source. Based on partial melting modeling, the source temperature of the GGG, GAFG, AFG and SG was concluded as 750–780 °C, 730–760 °C, 730–770 °C and ca. 800 °C, respectively. The source pressure was estimated as ca. 0.8 GPa for the GGG, GAFG and AFG, and ca. 1.2 GPa for SG. Combined with studies on (U)HP metamorphic rocks in SA, this study reveals that GGG is formed by metamorphism while SG is formed from partial melting of upper crustal rocks heated by upwelling mantle during the initial stage of exhumation (ca. 480 Ma) of subducted continental crust in SA. During further stage of exhumation of the subducted continental crust at ca. 450 Ma, the GAFG and AFG were formed from partial melting of GGG as a result of decreased pressure and further mantle upwelling. Consequently, the exhumation age of subducted continental crust in eastern SA is ca. 30 Myr earlier than that in western SA. Thus, the geochronology and petrogenesis of four granitic samples in this study exhibit one of very few evidence for partial melting of subducted continental crust during the exhumation and also provide magmatism exhibits evidence for the differential exhumation model of eastern SA in Palaeozoic. [ABSTRACT FROM AUTHOR]

[Display omitted] • Clockwise P–T evolution is recorded by the South Altyn Tagh felsic gneiss. • The felsic gneiss was exhumed from eclogite-facies to granulite-facies within 20 Myr. • HP–HT eclogite-facies records were preserved in the weakly deformed felsic gneiss. • The HP mineralogical records were further eliminated by the strong deformation. Felsic gneisses are usually the dominant rock types in most high-pressure (HP) and ultrahigh-pressure (UHP) terranes, although their peak metamorphic conditions and complete P–T paths are rarely known. This lack of knowledge is attributed to the high variance of mineral assemblages at HP/UHP conditions of the felsic gneisses, or to the effects of retrograde-related overprinting. Thus, it is difficult to distinguish whether felsic gneisses underwent HP/UHP metamorphism. In this paper, we focus on the felsic gneiss that has been previously documented as having formed under HP granulite-facies metamorphism with peak P–T of > 1.15 GPa and > 860 °C from the Danshuiquan locality in the South Altyn HP – UHP belt. The Danshuiquan felsic gneiss is strongly deformed and is spatially associated with weakly deformed garnet-rich felsic gneiss. On the basis of detailed microstructure observations on mineral assemblages and phase equilibria modelling, three stages of metamorphic evolution for the weakly deformed garnet-rich felsic gneiss are identified. The first stage is represented by garnet cores, revealing a prograde P–T path from 1.5 GPa/750 °C to 2.1 GPa/900 °C. The second stage is characterized by garnet mantles with multiphase inclusions, defining HP eclogite-facies metamorphic conditions of 2.2–2.6 GPa/950–1100 °C. The third stage is represented by the composition of garnet rims, biotite, and plagioclase, suggesting an HP granulite to amphibolite facies decompression cooling process to 1.1–1.3 GPa/710–770 °C. In contrast, the strongly deformed felsic gneiss just records a deformation-related decompression process from 1.1 to 1.2 GPa/750–760 °C to 0.87–0.98 GPa/760–770 °C, and finally to 0.83 GPa/740 °C. Zircon U–Pb dating yields c. 920 Ma protolith ages, c. 500 Ma eclogite-facies ages, and c. 480 Ma granulite to amphibolite facies retrograde ages for the Danshuiquan felsic gneisses. Our results show that the Danshuiquan felsic gneisses underwent a similar metamorphic evolution process to that of Yinggelisayi HP–UHP rocks in the eastern segment of the South Altyn Tagh. Most HP mineralogical records tend to be eliminated by the strong deformation at crustal depths (∼30 km), meaning that the peak metamorphic conditions of the studied felsic rocks in UHP metamorphic terranes are previously underestimated. [ABSTRACT FROM AUTHOR]

A lot of previous experimental studies on ultramafic rocks (SiO2 unsaturated system) (Ringwood and Major, 1971; Irifune et al., 1986; Gasparik, 1989; Ono and Yasuda, 1996) have demonstrated that characteristics of Si‐rich and Al‐deficient in garnet are resulted from coupled substitution of SiVI+MVI=AlVI+AlVI and SiVI+NaVII=AlVI+MVII (M=Mg, Fe, Ca) at ultrahigh pressures (UHP) (>5 GPa). The degree of substitution will be enhanced by increasing pressure which has a positive correlation with the content of SiVI, but a negative correlation with the content of AlVI in supersilic garnet. These experimental results established a theoretical foundation for further understanding the formation mechanism of the exsolution of pyroxene in garnet observed in deep mantle xenoliths and some ultrahigh pressure rocks, and also for estimating the pressure conditions of the formation of supersilic garnet before exsolution (Haggerty and Sautter, 1990; Sautter et al., 1991; van Roermund et al., 1998; Ye et al., 2000). Although some experimental studies on SiO2 saturated system have been reported (Irifune et al., 1994; Ono., 1998; Dobrazhinetskya and Green., 2007; Wu et al., 2009), the stability conditions of supersilic garnet are still lack of unified understanding. Therefore, HP‐HT experiments were carried out on felsic rocks under conditions of 6–12GPa and 1000°C–1400°C. Combined with previous experimental data, we try to figure out the minimum stable pressure and geological significants of supersilic garnet in SiO2 saturated system. Our experimental results from SiO2 saturated system show the minimum stable pressure of supersilic garnet should be ≥10 GP of stishovite stability field. These results are similar as that from experiments using starting composition similar to average upper continental crust reported by Irifune et al (1994) who yielded that garnet gradually became supersilic and Al‐deficient as pressures increased above 10 GPa, especially in a pressure interval between 13 and 18 GPa. Moreover, experiments with different starting materials (Ono, 1998; Dobrazhinetskya and Green, 2007; Wu et al. 2009) also indicate the stable pressure condition of supersilic garnet is mainly ≥9 –10 GPa in SiO2 saturated system if data of small‐size grains at low temperature are ignored due to measuring errors. Thus, it can be concluded that the minimum stable pressure of supersilic garnet in SiO2 saturated system is distinctly different from that in SiO2 unsaturated ultramafic rock system. The minimum pressure of the former is ≥9–10 GPa of stishovite stability field, while that of the latter is >5 GPa. Therefore, whether independent SiO2 phase exist or rock system is SiO2 saturated must be taken into considered when estimating the peak pressure of exsolutions in supersilic garnet in UHP rocks. Furthermore, pressure of >5 GPa directly estimated by supersilic garnet based on conclusion from SiO2 unsaturation system rather than SiO2 saturation in previous sdudies may have been underestimated and need to be re‐estimated. Supersilic garnets have been recognized by interior exsolutions of clinopyroxene in garnet pyroxene from Yinggelisayi South Altyn (Liu et al., 2005), and exsolutions of rodlike quartz+rutile in felsic gneiss from Songshugou North Qinling (Liu et al., 2003). According to the experimental results from SiO2 unsaturated system, the peak metamorphic pressure of the both SiO2 saturated rocks have been estimated to be >7Gpa and >5Gpa, respectively. However, combined with the new experimental results above, we re‐estimated that the peak metamorphic pressure of these SiO2 saturated rocks should be≥9 –10 GPa at least, implying an ultra‐deep subduction to mantle depth of stishovite stability field. This research, together with previous findings (Liu et al., 2007, 2018), shows that continental subduction to mantle depth (300km) of stishovite stability field and then exhumation to the surface is obviously more common than previously thought, and the rock types are also diverse. At the same time, it provides a new indicator and thought for recognizing the subduction to the mantle depth of stishovite stability field in UHP metamorphic belt. [ABSTRACT FROM AUTHOR]

A lot of previous experimental studies on ultramafic rocks (SiO2 unsaturated system) (Ringwood and Major, 1971; Irifune et al., 1986; Gasparik, 1989; Ono and Yasuda, 1996) have demonstrated that characteristics of Si‐rich and Al‐deficient in garnet are resulted from coupled substitution of SiVI+MVI=AlVI+AlVI and SiVI+NaVII=AlVI+MVII (M=Mg, Fe, Ca) at ultrahigh pressures (UHP) (>5 GPa). The degree of substitution will be enhanced by increasing pressure which has a positive correlation with the content of SiVI, but a negative correlation with the content of AlVI in supersilic garnet. These experimental results established a theoretical foundation for further understanding the formation mechanism of the exsolution of pyroxene in garnet observed in deep mantle xenoliths and some ultrahigh pressure rocks, and also for estimating the pressure conditions of the formation of supersilic garnet before exsolution (Haggerty and Sautter, 1990; Sautter et al., 1991; van Roermund et al., 1998; Ye et al., 2000). Although some experimental studies on SiO2 saturated system have been reported (Irifune et al., 1994; Ono., 1998; Dobrazhinetskya and Green., 2007; Wu et al., 2009), the stability conditions of supersilic garnet are still lack of unified understanding. Therefore, HP‐HT experiments were carried out on felsic rocks under conditions of 6–12GPa and 1000°C–1400°C. Combined with previous experimental data, we try to figure out the minimum stable pressure and geological significants of supersilic garnet in SiO2 saturated system. Our experimental results from SiO2 saturated system show the minimum stable pressure of supersilic garnet should be ≥10 GP of stishovite stability field. These results are similar as that from experiments using starting composition similar to average upper continental crust reported by Irifune et al (1994) who yielded that garnet gradually became supersilic and Al‐deficient as pressures increased above 10 GPa, especially in a pressure interval between 13 and 18 GPa. Moreover, experiments with different starting materials (Ono, 1998; Dobrazhinetskya and Green, 2007; Wu et al. 2009) also indicate the stable pressure condition of supersilic garnet is mainly ≥9 –10 GPa in SiO2 saturated system if data of small‐size grains at low temperature are ignored due to measuring errors. Thus, it can be concluded that the minimum stable pressure of supersilic garnet in SiO2 saturated system is distinctly different from that in SiO2 unsaturated ultramafic rock system. The minimum pressure of the former is ≥9–10 GPa of stishovite stability field, while that of the latter is >5 GPa. Therefore, whether independent SiO2 phase exist or rock system is SiO2 saturated must be taken into considered when estimating the peak pressure of exsolutions in supersilic garnet in UHP rocks. Furthermore, pressure of >5 GPa directly estimated by supersilic garnet based on conclusion from SiO2 unsaturation system rather than SiO2 saturation in previous sdudies may have been underestimated and need to be re‐estimated. Supersilic garnets have been recognized by interior exsolutions of clinopyroxene in garnet pyroxene from Yinggelisayi South Altyn (Liu et al., 2005), and exsolutions of rodlike quartz+rutile in felsic gneiss from Songshugou North Qinling (Liu et al., 2003). According to the experimental results from SiO2 unsaturated system, the peak metamorphic pressure of the both SiO2 saturated rocks have been estimated to be >7Gpa and >5Gpa, respectively. However, combined with the new experimental results above, we re‐estimated that the peak metamorphic pressure of these SiO2 saturated rocks should be≥9 –10 GPa at least, implying an ultra‐deep subduction to mantle depth of stishovite stability field. This research, together with previous findings (Liu et al., 2007, 2018), shows that continental subduction to mantle depth (300km) of stishovite stability field and then exhumation to the surface is obviously more common than previously thought, and the rock types are also diverse. At the same time, it provides a new indicator and thought for recognizing the subduction to the mantle depth of stishovite stability field in UHP metamorphic belt. [ABSTRACT FROM AUTHOR]

In this study, a series of chitosan films with different protonation degrees were prepared by deacidification with NaOH aqueous or ethanol solutions. The films were then used as a model to investigate the effects of the positive charge of chitosan on blood coagulation. The results showed that the positive charge of chitosan acted as a double-edged sword, in that it promoted erythrocyte adhesion, fibrinogen adsorption, and platelet adhesion and activation, but inhibited activation of the contact system. In contrast to prevailing views, we found that the positive charge of chitosan retarded thrombin generation and blood coagulation on these films. At least two reasons were responsible for this phenomenon. First, the positive charge inhibited the contact activation, and second, the positive charge could not significantly promote the activation of non-adherent platelets in the bulk phase during the early stage of coagulation. The present findings improve our understanding of the events leading to blood coagulation on chitosan films, which will be useful for the future development of novel chitosan-based hemostatic devices. [ABSTRACT FROM PUBLISHER]

Abstract: β- and γ-secretase cleave the amyloid precursor protein (APP) to release the amyloidogenic β-amyloid peptides (Aβ) and the APP intracellular domain (AICD). Aβ has been widely believed to initiate pathogenic cascades culminating in Alzheimer''s disease (AD). However, the physiological functions of the AICD remain elusive. In this study, we found the AICD to strongly inhibit Wnt-induced transcriptional reporter activity, and to counteract Wnt-induced c-Myc expression. Loss of the AICD resulted in an increased responsiveness to Wnt/β-catenin-mediated transcription. Mechanically, the AICD was found to interact with glycogen synthase kinase 3 beta (GSK3β) and promote its kinase activity. The subsequent AICD-strengthened Axin–GSK3β complex potentiates β-catenin poly-ubiquitination. Functional studies in N2a mouse neuroblastoma cells, rat pheochromocytoma PC12 cells and primary neurons showed that the AICD facilitated neurite outgrowth. And AICD antagonised Wnt3a-suppressed growth arrest and neurite outgrowth in N2a and PC12 cells. Taken together, our results identify the AICD as a novel inhibitory factor of the canonical Wnt signalling pathway and suggest its regulatory role in neuronal cell proliferation and differentiation. [Copyright &y& Elsevier]

[Display omitted] • The mafic granulites in the Kuruksayi area were derived from overprinted eclogites. • Phase modeling suggests that such mafic granulites have undergone UHP metamorphism. • P - T conditions recorded in mafic granulites are comparable to that in HP/UHP eclogites. The South Altyn high-pressure–ultrahigh-pressure (HP–UHP) metamorphic belt in West China records the processes of deep continental subduction (>150–300 km). The HP mafic granulite pods hosted by massive granitic gneiss were for the first time discovered in the Kuruksayi area of the South Altyn Orogen, and they consist mainly of garnet, clinopyroxene, plagioclase, hornblende, biotite, and quartz, with minor rutile, ilmenite, and K-feldspar. The garnets vary in grain size and chemical zoning, and can be divided into three types: subhedral porphyroblastic (g 1), anhedral porphyroblastic (g 2), and neoblastic fine (g 3) grains. Four generations of mineral assemblage (M1–M4) are recognized, and are used to constrain the P–T evolution of the mafic granulites using phase equilibria modeling calculated by THERMOCALC. The first generation (M1) is represented by the core domains of g 1 (g 1C) that have inclusions of rutile and quartz and conspicuous chemical zoning. A pre-peak prograde stage of metamorphism from ~ 15.8 kbar/600 °C to ~ 19.2 kbar/655 °C is recorded by g 1C. The second generation (M2) is inferred to consist of garnet + omphacite + phengite + rutile + quartz and is recorded in the mantle domains of g 1 (g 1M). Modeling suggests that this is representative of conditions that reached a maximum P–T of ~ 36.2 kbar/920 °C. The third generation (M3) is characterized by intergrowths of clinopyroxene + plagioclase and biotite + plagioclase, and this stage is recorded by the compositions of g 2 with modeling suggesting an evolution from ~ 17.8 kbar/820 °C to ~ 11.5 kbar/826 °C, consistent with near-isothermal decompression. The last generation (M4) is characterized by kelyphitic rims of plagioclase + hornblende around garnet and the hornblende coronas that encompass symplectitic clinopyroxene, and is recorded by the compositions of g 3. Modeling suggests evolution from ~ 11.5 kbar/826 °C to ~ 8.7 kbar/735 °C, compatible with near-isobaric cooling. These four stages of metamorphism together establish a clockwise P–T path, which indicates a series of tectonic processes that took the continental slab from subduction to exhumation. Zircon U–Pb dating by LA–ICP–MS yielded two distinct clusters of ages: c. 897 Ma magmatic protolith ages and c. 494 Ma metamorphic ages. The metamorphic ages are interpreted to represent the timing of the eclogite-facies metamorphism, and are similar to the metamorphic ages of other HP/UHP rocks elsewhere in the South Altyn Orogen. Accordingly, we propose that the Kuruksayi mafic granulites underwent UHP metamorphism similar to that recorded in other South Altyn eclogites exposed in Jianggalesayi and Danshuiquan to the west and Yinggelisayi to the east. [ABSTRACT FROM AUTHOR]

The Qilian orogeny formed by subduction of the proto-Tethyan ocean along the northern margin of Gondwana. In this paper we report geochemical, zircon U-Pb-Hf, and mapping data of the Duoruonuoer volcanic rocks from the western Qilian Orogen. Based on distinct geochemical compositions, four melt types can be distinguished: boninite-like basalt, OIB-like basalt, MORB, and high-K to shoshonitic volcanic rocks (HKSV). Field relationships show a compositional change from HKSV, MORB, OIB to boninite-like basalt, from north to south. The boninite-like basalt is low to medium-K calc-alkaline, with low TiO 2 (0.13–0.18 < 0.5 wt%) and high CaO/Al 2 O 3 ratio (0.72–0.80), similar to high-Ca back-arc boninite. The geochemical characteristics of Duoruonuoer OIB-like basalt, MORB, and HKSV are similar to those of the Izu-Bonin (IB) back-arc magmatic assemblages. Boninite-like basalt is enriched in LILEs, and has low Ce/Pb, and high Sr/Nd, Ba/Nb ratios, indicating an addition of a shallow subduction-derived fluid phase. Inferred pressures of magma segregation are 0.9–1.4 GPa with temperatures of 1200–1370 °C consistent with melting of a highly depleted, low pressure hydrous mantle source. The MORB-like rock formed by mixing of depleted mantle and a subduction component, and is identical to back-arc basin floor basalt (BABB). The HKSV, dated at 475 Ma, shares the characteristics with lava from the IB back-arc seamount chains (rear-arc). Their low Ce/Pb and high Th/Yb and Th/Nb ratios are compatible with contributions from melts of deep subducting sediment and oceanic crust. High pressure (1.8–2.0 GPa) may reflect sourcing from a mantle melt at the base of thickened arc crust. The OIB-like basalts have high TiO 2 , Zr/Yb, Nb/Yb and Ce/Pb ratios, suggesting an enriched component from partial melting of the asthenosphere. The high-Fe 8 and Ti 8 composition of the Duoruonuoer OIB-like basalt is produced by fractional melting, similar to a spreading ridge segment developed a deeper source. The variety of Duoruonuoer back-arc magmatism highlights the importance of changes to the melt source region linked to replenishment of the mantle wedge by material extracted from the subducting slab and influx of more fertile mantle material. It is also controlled by evolution of the mantle wedge over time in the building of the back-arc basin. These findings provide evidence for c.475 Ma back-arc basin developed on a thickened arc lithosphere at the western Qilian Orogen. [ABSTRACT FROM AUTHOR]