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Drug-induced hepatotoxicity (DIH) is a common cause of acute liver injury, endangering human health. Intracellular adenosine triphosphate (ATP) content in hepatocytes is related to hepatotoxicity. Thus, monitoring the dynamic changes in lysosomal ATP is promising to further understand the pathogenesis and accurate evaluation of DIH. Herein, we developed a lysosomal ATP-activated upconversion nanoprobe by decorating ATP-sensitive carbon dots (CDs) on the surface of upconversion nanoparticles (UCNPs) for ratiometric imaging of hepatotoxicity. Owing to the excellent optical characteristics of UCNPs as well as the high selectivity and biocompatibility of CDs, this nanoprobe showed robust reversibility and good sensitivity to ATP in an acidic environment. Noticeably, it was successfully applied in imaging the lysosomal ATP levels fluctuation in living cells and deep tissues and used for studying the production and remediation pathways of acetaminophen-induced hepatotoxicity. This nanoprobe is significant for further understanding the pathogenesis of DIH and may be a potentially effective tool for the clinical evaluation of DIH.

Based on non-equilibrium Green’s function combined with density functional theory (NEGF-DFT), we theoretically investigate the spin-related photogalvanic effect (PGE) in topological insulator BiBr and SbBr nanoribbons from atomic first-principles calculations....

The spark plasma-sintered Ti-6Al-4V alloy was used as experimental specimens to perform the multi-pass hot compression. The deformation temperature was 950, 900, 850 °C, and the compressed amount was 20, 30, 20% corresponding to one pass, two passes and three passes, respectively. The flow behaviors revealed that the curve with the strain rate of 5 s−1 appeared obvious oscillatory phenomenon after peak. Additionally, the curve with strain rate of 0.1 and 1 s−1 almost kept constant after peak stress during the process of two-pass compression. The microstructures showed that the sintered voids with the average diameter of 7.53 μm could be observed in initial Widmanstatten structures with the aspect ratio of 11.49 ± 0.5. The deformed inhomogeneity had prominent influence on the microstructures. For three-pass deformation with the strain rate of 0.1 s−1, the microstructures of severe plastic deformation area were equiaxial microstructures with the grain diameter of 3.82 μm, while the microstructures for medial and small plastic deformation area were dual and Widmanstatten, respectively. With the strain rate of 0.1 s−1, the fraction of dynamic recrystallization (fDRX) increased from 0.034 through 0.112 to 0.440 with the passes increased, and the variation tendency toward average diameter of grain size versus compressed passes shifted reversely. The β→α phase transformation was the main reason for the misorientation angle nearby 60° for one pass with the strain rate of 0.1 s−1. The fDRX declined from 0.440 through 0.225 to 0.297 with raising the strain rate for three-pass deformation, but the grain size changed oppositely. The CDRX and DDRX were both appeared during multi-pass hot deformation.

Heavy ion therapy is currently recognized as the most advanced cancer radiotherapy approach in the world. This article introduces a high-precision and non-contact measurement method based on close-...

In this paper, a third order gas kinetic scheme is developed on the three dimensional hybrid unstructured meshes for the numerical simulation of compressible inviscid and viscous flows. A third-order WENO reconstruction is developed on the hybrid unstructured meshes, including tetrahedron, pyramid, prism and hexahedron. A simple strategy is adopted for the selection of big stencil and sub-stencils. Incorporate with the two-stage fourth-order temporal discretization and lower-upper symmetric Gauss-Seidel methods, both explicit and implicit high-order gas-kinetic schemes are developed. A variety of numerical examples, from the subsonic to supersonic flows, are presented to validate the accuracy and robustness for both inviscid and viscous flows.

Literaturstra��e. Chinesisch-deutsche Zeitschrift f��r Sprach- und Literaturwissenschaft, Bd. 19 Nr. 2 (2018)

In ischemia/reperfusion (I/R) injury, both inflammation and apoptosis play a vital role, and the inhibition of excessive inflammation and apoptosis show substantial clinical potential in the treatment of I/R disease. The role of sacubitril/valsartan (SAC/VAL)-a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI)-in inflammation regulation and apoptosis in the context of I/R injury needs to be further explored. In this study, we investigate the short- and long-term effects of SAC/VAL administration in treating adult murine I/R injury both in vivo and in vitro. Our results verified that the application of SAC/VAL could reduce infarct size and suppress apoptosis and the inflammatory response in the acute phase post I/R. Long-term application of SAC/VAL for four weeks significantly improved ventricular function and reversed pathological ventricular remodeling. Mechanistically, SAC/VAL treatment induces the inhibition of the GSK3β-mediated NF-κB pathway through synergistically blocking angiotensin 1 receptor (AT1R) and activating natriuretic peptide receptor (NPR). In summary, we reported the therapeutic role of SAC/VAL in regulating the GSK3β/NF-κB signaling pathway to suppress the inflammatory response and apoptosis, thereby reducing cardiac dysfunction and remodeling post I/R.

The gaseous plant hormone ethylene influences many physiological processes in plant growth and development. Plant ethylene responses are mediated by a family of ethylene receptors, in which the N-terminal transmembrane domains are responsible for ethylene binding and membrane localization. Until now, little structural information was available on the molecular mechanism of ethylene responses by the transmembrane binding domain of ethylene receptors. Here, we screened different constructs, fusion tags, detergents, and purification methods of the transmembrane sensor domain of ethylene receptors. However, due to their highly hydrophobic transmembrane domain (TMD), only a KSI-fused LeETR21–131 from tomato yielded a good-quality nuclear magnetic resonance (NMR) spectrum in the organic solvent. Interestingly, a dimer model of LeETR21–131 built by the AlphaFold2 algorithm showed greatly converged structures. The interaction analysis of ethylene and LeETR21–131 using molecular docking and molecular dynamics (MD) simulations demonstrated the potential binding sites of ethylene in LeETR21–131. Our exploration provides valuable knowledge for further understanding of the ethylene-perception process in ethylene receptors.

The installation spacing of thin quadrupole group is very small, the traditional base support adjustment support is changed to suspension regulating bracket, which meets the stability and adjustment accuracy of thin quadrupole. The motion and force, transmission efficiency, self-locking conditions of wedge mechanism for small spacing direction adjustment are studied, and the parametric design of wedge mechanism is studied.

Professional learning communities are recognized as one of the most effective approaches for promoting the professional development of teachers. In the current complex and rapidly changing era, to facilitate the implementation of interdisciplinary curricula, Chinese schools have made tremendous efforts to enhance teacher professional development, particularly by establishing professional learning communities. Aiming to understand the operation of professional learning communities in interdisciplinary subjects in Chinese K-12 schools and to examine factors impacting the sustainable development of these professional learning communities, we conducted a case study on professional learning communities in the interdisciplinary subject of Education for International Understanding in Chengdu Horsens Primary School. As part of this study, we interviewed the principal, course director, seed teachers and teachers participating in the selected case. The research results demonstrated that the major factors impacting the sustainable development of professional learning communities in interdisciplinary subjects in Chinese K-12 schools include school structures and policies, school leadership, teachers’ professionalism and learning capacity and their sense of community. In addition, compared to traditional subject-based professional learning communities in China, professional learning communities in interdisciplinary subjects highlight a sense of community, which presents three distinctive features: a conflict-inclusive atmosphere, the coexistence of individual and shared visions and an emotional bonding identity. These three features also have a considerable impact on the sustainable development of professional learning communities in interdisciplinary subjects in Chinese K-12 schools.

Necroptosis is a type of programmed cell death executed through the plasma membrane disruption by mixed lineage kinase domain-like protein (MLKL). Previous studies have revealed that an N-terminal four-helix bundle domain (NBD) of MLKL is the executioner domain for the membrane permeabilization, which is auto-inhibited by the first brace helix (H6). After necroptosis initiation, this inhibitory brace helix detaches and the NBD can integrate into the membrane, and hence leads to necroptotic cell death. However, how the NBD is released and induces membrane rupture is poorly understood. Here, we reconstituted MLKL2–154 into membrane mimetic bicelles and observed the structure disruption and membrane release of the first brace helix that is regulated by negatively charged phospholipids in a dose-dependent manner. Using molecular dynamics simulation we found that the brace region in an isolated, auto-inhibited MLKL2–154 becomes intrinsically disordered in solution after 7 ns dynamic motion. Further investigations demonstrated that a cluster of arginines in the C-terminus of MLKL2–154 is important for the molecular conformational switch. Functional mutagenesis showed that mutating these arginines to glutamates hindered the membrane disruption of full-length MLKL and thus inhibited the necroptotic cell death. These findings suggest that the brace helix also plays an active role in MLKL regulation, rather than an auto-inhibitory domain.

CXXC Zinc finger protein 1 (CFP1) is a multitasking protein playing essential roles during various developmental processes. Its ability to interact with several proteins contribute to several epigenetic events. Here, we review CFP1's functions and its impact on DNA methylation and the post-translational modification of histone proteins such as lysine acetylation and methylation. We will also discuss the potential role of CFP1 in carcinogenesis and the impact of the mutations identified in patients suffering from various cancers.

Bax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. This might involve their embedding in the cytosolic leaflet of the lipid bilayer, thus generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, Bax proteins might comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determined a high‐resolution structure of the Bax core region, revealing a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but also creating polar interactions between charged residues and lipid heads. Structure‐guided mutations demonstrate the importance of both types of protein–lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria., NMR structures of membrane‐bound Bax core dimer reveal dual interactions with non‐polar tails and charged heads of bilayer lipids contributing directly to apoptotic mitochondrial permeabilization.

Wuwei heavy ion therapy center is the first Chinese heavy ion accelerator facility developed for cancer therapy, in which four terminals are distributed and the height of the vertical terminal is u...

Heterostructures have broad potential application in energy conversion material and optoelectronic device since of novel interface effect and enhanced electron transport dynamics at heterointerfaces. Herein, we report a heterostructured SnS/SnO2/spherical graphene composite, in which ultrafine SnS/SnO2 nanoparticles with heterostructures are sandwiched between multi-layers of graphene sheets, exhibiting a hollow spherical architecture as a whole. Detailed electrochemical studies indicate that the molar ratio of SnS to SnO2 has great influence on the charge transport efficiency. Theoretical calculation reveals that SnS and SnO2 exhibit different work functions and the Fermi level shift is affected by the SnS/SnO2 molar ratio, thus the hybrid with the ratio close to 1.0 owns the most adsorbed lithium ions, which leads to the highest specific charge-transfer kinetics and lowest ion-diffusion resistance than other samples. Electrochemical tests show that the composite with appropriate composition delivers the best lithium storage rate performance (620 and 312.7 mAh g−1 at 1 C and 10 C). A much stable and high reversible specific capacity of 850 mAh g−1 is obtained after 200 cycles at 0.1 C. The appropriate molar ratio of nano-heterostructures and the novel sandwich hollow spherical composite structure are attributed to the excellent electrochemical performances.

Efficient electrocatalysts for hydrogen evolution reaction (HER) are critical to reduce energy losses in alkaline water electrolysis. Herein, CoNiSe2 heteronanorods decorated with layered-double-hydroxides (LDHs) nanosheets are designed, in which the selenide-LDHs interfaces can boost H2O chemisorption to produce reactive H intermediate, resulting in fast HER kinetics. Such promotion in HER is further interpreted by theoretical calculation and in-situ Raman investigation. By contrast, it’s negligible for anodic oxygen evolution. Assembled as an electrolyzer for overall water splitting, the heteronanorods afford a quite low cell voltage of 1.44 V at a geometric current density of 10 mA cm−2 and remarkable stability for more than 48 h in 1.0 M KOH, performing among the best of non-precious electrocatalysts. Identifying efficient electrocatalysis on engineered heterointerfaces, this work is anticipated to open up new opportunities for catalyst design in energy chemistry.

The reunion of Sn is always a troublesome issue when it’s used as the energy storage materials, on the one hand it comes from the preparation process due to its low melting point, and on the other hand it comes from the Li-Sn alloying process because of its natural tendency of migration. The Sn/SnO2/spherical graphene composite prepared by one-step low temperature hydrothermal reduction method can effectively solve this problem. In the composite, Sn/SnO2 tiny nanoparticles with average diameter of 5 nm distribute evenly between multilayers of graphene sheets presenting a hollow spherical structure. The introduction of SnO2 can effectively restrain the agglomeration of Sn nanoparticles during alloying process since an amorphous Li2O matrix is formed to separate the adjacent active particles. The sandwich graphene hollow sphere skeleton effectively buffers the volume expansion of Sn/SnO2 and further restricts their migration and agglomeration. Due to the above advantages, the nano-Li2O generating from the decomposition of SnO2 can contact closely with excessive nano-Sn in restricted area, promoting facile conversed conversion reaction. Therefore, the composite exhibits high reversible capacity and excellent cycle performance. A stable and high specific capacity of 843.8 mAh g−1 is obtained after 100 cycles at 0.1 C.

Based on non-equilibrium Green's function combined with density functional theory (NEGF-DFT), we theoretically investigate the spin-related photogalvanic effect (PGE) in two anti-ferroelectric bilayer In

Background Chronic obstructive pulmonary disease (COPD) is characterized by limited airflow due to pulmonary and alveolar abnormalities from exposure to cigarette smoke (CS). Current therapeutic drugs are limited and the development of novel treatments to prevent disease progression is challenging. Isoforskolin (ISOF) from the plant Coleus forskohlii is an effective activator of adenylyl cyclase (AC) isoforms. Previously we found ISOF could attenuate acute lung injury in animal models, while the effect of ISOF on COPD has not been elucidated. Purpose In this study, we aimed to evaluate the efficacy of ISOF on COPD and reveal its potential mechanisms. Methods A rat model of COPD was established by long-term exposure to CS, then the rats were orally administered with ISOF (0.5, 1 and 2 mg/kg). The pulmonary function, lung morphology, inflammatory cells and cytokines in serum or bronchoalveolar lavage fluid (BALF) were evaluated. Transcriptomics, proteomics and network pharmacology analysis were utilized to identify potential mechanisms of ISOF. Droplet digital PCR was used to detect the mRNA expression of AC1-10 in donor lung tissues. AC activation was determined in recombinant human embryonic kidney 293 (HEK293) cells stably expressing human AC isoforms. In addition, ISOF caused trachea relaxation ex vivo were assessed in isolated trachea rings from guinea pigs. Results ISOF significantly ameliorated pathological damage of lung tissue and improved pulmonary function in COPD rats. ISOF treatment decreased the number of inflammatory cells in peripheral blood, and also the levels of pro-inflammatory cytokines in serum and BALF. Consistent with omics-based analyses, ISOF markedly downregulated the mTOR level in lung tissue. Flow cytometry analysis revealed that ISOF treatment reduced the ratio of Th17/Treg cells in peripheral blood. Furthermore, the expression levels of AC1 and AC2 are relatively higher than other AC isoforms in normal lung tissues, and ISOF could potently activate AC1 and AC2 in vitro and significantly relax isolated guinea pig trachea. Conclusion Collectively, our studies suggest that ISOF exerts its anti-COPD effect by improving lung function, anti-inflammation and trachea relaxation, which may be related to AC activation, mTOR signaling and Th17/Treg balance.

Based on non-equilibrium Green's function combined with density functional theory (NEGF-DFT), we theoretically investigate the spin-related photogalvanic effect (PGE) in two anti-ferroelectric bilayer In2Se3 structures by atomic first-principles calculations. It is found that, due to the absence of inversion symmetry and the presence of strong spin–orbital interaction (SOI) in anti-ferroelectric bilayer In2Se3, the photoinduced charge-to-spin conversion can be achieved via the PGE. The generated spin-dependent photocurrent is largely spin-polarized and the corresponding spin polarization can vary from 0% to 100% depending on the photon energies, polarization and incident angles. Furthermore, it is found that, by tuning the polarization and the incident angles of light, the fully spin-polarized and pure spin photocurrent can be obtained. Most importantly, the spin dependent photocurrent can be largely tuned through the transition between two anti-ferroelectric bilayer In2Se3 states by the gate voltage. The defined relative spin dependent photoresponse change ratio ns between two states is extremely large and its maximum value can be in the order of ∼104. Therefore, our work demonstrates the great potential of bilayer In2Se3's novel application in two-dimensional non-volatile opto-spintronic devices.

SummaryBax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. They may embed in the cytosolic leaflet of the lipid bilayer generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, they may comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determine a high-resolution structure of the Bax core region that forms a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but creating polar interactions between charged residues and lipid heads. Structure-guided mutations demonstrate the importance of both protein-lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria.

Based on non-equilibrium Green's function combined with density functional theory (NEGF-DFT), we investigate the spin dependent transport in the ferromagnetic 6,6,12/γ-graphyne zigzag nanoribbon (GYZNR) heterojunction under different magnetic configurations. It is found that, at low bias ([−0.05, 0.1] V), the junction presents metallic transport with negligible spin polarization in parallel configuration (PC) while it behaves as an insulator in anti-parallel configuration (APC), which results in giant magnetoresistance. Interestingly, when we increase the bias voltage beyond [−0.05, 0.1] V, dual spin filtering characterized by electron transport of different spin channels under different polarity of bias is observed in APC but not in PC. All these findings are understood from the symmetry matching of wave functions in two nanoribbons at equilibrium or finite bias. Furthermore, dual spin filtering can also be achieved in PC by applying a gate voltage on the central interface region, which arises from the shift of different single spin channel of the central gate region into the bias window at a different polarity of the gate voltage. Thus, our work demonstrates the great potential of the 6,6,12/γ-GYZNR heterojunction as a multi-functional device and its great perspectives in carbon-based nanoelectronics and spintronics.

The discharge caused by metals triggered by microwave radiation is a key issue, whereas little attention was paid to the pyrolysis of waste tires by using the interaction between microwave and meta...

SnS is widely studied as anode materials since of its superior structural stability and physicochemical property comparing with other Sn-based composites. Nevertheless, the inconvenience of phase morphology control and excessive consumption of sulfur sources during synthesis hinder the scalable application of SnS nanocomposites. Herein, we report a facile in-situ sulfuration strategy to synthesize sandwiched spherical SnS/sulfur-doped graphene (SnS/S-SG) composite. An ultra-low sulfur content with approximately stoichiometric ratio of Sn:S can effectively promote the sulfuration reaction of SnO2 to SnS and simultaneous sulfur-doping of graphene. The as-prepared SnS/S-SG composite shows a three-dimensional interconnected spherical structure as a whole, in which SnS nanoparticles are sandwiched between the multilayers of graphene sheets forming a hollow sphere. The sandwiched sphere structure and high S doping amount can improve the binding force between SnS and graphene, as well as the structural stability and electrical conductivity of the composite. Thus, a high reversibility of conversion reaction, promising specific capacity (772 mAh g−1 after 100 cycles at 0.1 C) and excellent rate performance (705 and 411 mAh g−1 at 1 C and 10 C, respectively) are exhibited in the SnS/S-SG electrode, which are much higher than that of the SnS/spherical graphene synthesized by traditional post-sulfuration method.

Using the test system for the microwave pyrolysis of scrap tires, the effects of different factors on the production characteristics of limonene in oils were investigated. The results showed that the optimum processing parameters for the production of limonene were the specific microwave power of 15 W/g, the weight hourly space velocity of 3.75 h−1, the tire particle size of 0.6 mm, and the absence of steel wires. The yield of limonene in the pyrolysis oil under this set of conditions was up to 23.4%. According to the pyrolysis process and the product composition, the mechanism of limonene production under microwave pyrolysis conditions was predicted. The content of limonene in the pyrolysis oil was quantitatively analyzed by an external standard method (ESM) and the peak area normalization method (PANM) separately. The numerical values of the test results obtained by multiplying PANM by the calibration factor of 1.5 equal the corresponding results obtained using the ESM method. Compared with conventional pyrolysis, the microwave pyrolysis of waste tires has a higher yield of limonene under optimized conditions. The results provide an important reference for the high-value utilization of waste tires and the utilization of resources, especially the subsequent production of limonene.