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Microcystins (MCs) are hepatotoxic heptapeptides identified in cyanobacterial bloom-impacted waters and soils. However, their environmental fate in soils is poorly understood, preventing reliable site assessment. This study aims to clarify the variant-specific adsorption, desorption, and dissipation of MC-LR and MC-RR in agricultural soils. Results revealed that their adsorption isotherms followed the Freundlich model (R2 ≥ 0.96), exhibiting a higher nonlinear trend and lower adsorption capacity for MC-LR than for MC-RR. The soils had low desorption rates of 8.14-21.06% and 3.06-34.04%, respectively, following a 24 h desorption cycle. Pairwise comparison indicated that soil pH and clay played key roles in MC-LR adsorption and desorption, while organic matter and cation exchange capacity played key roles in those of MC-RR. MC-LR dissipation half-lives in soils were 27.18-42.52 days, compared with 35.19-43.87 days for MC-RR. Specifically, an appreciable decrease in MC concentration in sterile soils suggested the significant role of abiotic degradation. This study demonstrates that the minor structural changes in MCs might have major effects on their environmental fates in agricultural soil and indicates that the toxic effects of MCs should be of high concern due to high adsorption, low desorption, and slow dissipation.

Perfluorooctanesulfonate (PFOS) as an accumulative emerging persistent organic pollutant in crops poses severe threats to human health. Lettuce varieties that accumulate a lower amount of PFOS (low-accumulating crop variety, LACV) have been identified, but the regarding mechanisms remain unsolved. Here, rhizospheric activation, uptake, translocation, and compartmentalization of PFOS in LACV were investigated in comparison with those of high-accumulating crop variety (HACV) in terms of rhizospheric forms, transporters, and subcellular distributions of PFOS. The enhanced PFOS desorption from the rhizosphere soils by dissolved organic matter from root exudates was observed with weaker effect in LACV than in HACV. PFOS root uptake was controlled by a transporter-mediated passive process in which low activities of aquaporins and rapid-type anion channels were corrected with low expression levels of PIPs (PIP1-1 and PIP2-2) and ALMTs (ALMT10 and ALMT13) genes in LACV roots. Higher PFOS proportions in root cell walls and trophoplasts caused lower root-to-shoot transport in LACV. The ability to cope with PFOS toxicity to shoot cells was poorer in LACV relative to HACV since PFOS proportions were higher in chloroplasts but lower in vacuoles. Our findings provide novel insights into PFOS accumulation in lettuce and further understanding of multiprocess mechanisms of LACV.

The effects of hydrogen treatment on electrical properties of detector-grade cadmium manganese telluride (CdMnTe:In) crystals were investigated. The results showed that the resistivity of the crystals was improved from $10^{9}$ to $10^{10} ~\Omega \cdot $ cm after annealing. With the increase of annealing time, the resistivity first increased and then decreased. Hydrogen passivation reduced the carrier concentration and enhanced mobility. The disappearance of A1 phonon mode of Te in Raman spectroscopy suggested that Te was decreased in crystal surface. The energy resolution and mobility–lifetime product of CdMnTe detectors were significantly improved. The CdMnTe:In crystal annealed for 30-h hydrogen treatment with greatest energy resolution and highest ( $\mu \tau $ )e value had the best detector performance.

To enhance structural stability and explore energy storage mechanisms for sodium-ion batteries, Ni3S2 nanoparticles anchored on d-Ti3C2 nanosheets (Ni3S2/d-Ti3C2) are designed and synthesized throu...

Bone is the most common late metastasis of breast cancer. Bone metastasis causes not only severe bone pain, but also bone-related diseases such as pathological fractures, which are closely related to osteoclasts. The effects of demethoxycurcumin (DMC) on osteoclast biology has not been investigated. In this study, we explored the effects of DMC on MDA-MB-231 cells, MCF-7 cells, and osteoclasts induced by RANKL in vitro, as well as the protective effect on bone destruction of tumor bone metastasis in vivo. DMC showed inhibitory effect on the migration and promotes the apoptosis of MDA-MB-231 and MCF-7 cells. At the same time, DMC inhibited osteoclast maturation and mature osteoclast bone resorption in a dose-dependent manner, and suppressed the expression of osteoclast marker genes TRAP, CTSK, MMP9, V-ATPase-d2 and DC-STAMP significantly. Biochemical data showed that DMC inhibited tumor cells and osteoclasts by inhibiting the early activation of ERK and JNK MAPK pathway. Consistent with the results in vitro, we confirmed that DMC protects bone destruction caused by tumor metastasis in vivo. In short, our study confirmed that DMC could be used as a potential drug for the treatment of tumor bone destruction.

When the hot oil pipeline is running at a low throughput, it easily enters into an unstable condition, which seriously threatens the safety of the hot oil pipeline operation. In this study, the unsteady heat transfer and flow mathematical models for the hot oil pipeline system were established first by comprehensively considering the uncertainty of parameters during pipeline operation, such as the operating parameters (throughput and oil temperature), physical properties of crude oil (freezing point, viscosity, and thixotropic parameters), and environmental parameters (buried deep soil temperature and soil thermal conductivity). Then, the efficient Latin hypercube sampling (LHS) stochastic numerical algorithm was applied and further developed to quantitatively describe the operation safety of hot oil pipelines with low throughput in the form of probability. On the basis of the abovementioned research, the qualitative relationship between pipeline flowrate and friction loss is obtained. Finally, taking an actual crude oil pipeline as an example, the failure probabilities of the pipeline under different operating conditions were analyzed in detail. Combined with the target safety level of pipeline operation, the minimum allowable throughput of pipelines was determined. This study revealed the flow and heat transfer law of hot oil pipelines with low throughput and determined its operation safety and reliability under different operating conditions.

Hydrate growth is influenced by many factors, including thermodynamics, kinetics, mass and heat transfer, and so on. There is thus a practical significance in establishing a model that comprehensively considers these influencing factors for hydrate crystal growth in multiphase transportation pipelines. On this basis, this paper presents a more practical and comprehensive bidirectional growth model of hydrate shells for an actual pipeline system. Thermodynamic phase equilibrium theory and water molecule penetration theory are applied in this model to develop a method for calculating the concentration change of hydrate-forming guest molecules and the permeation rate of water molecules. The temperatures on both sides of the hydrate shell are predicted by the heat transfer model. Simultaneously, decreasing the mass transfer coefficient with continuous hydrate growth is used to describe the problem in which the mass transfer efficiency decreases with a thickened hydrate shell. Then, the hydrate growth kinetic parameters of the pipeline system are optimized according to hydrate growth experiments conducted in a high-pressure flow loop and the microscopic characteristics of the particles were provided using the PVM and FBRM probes. The improved hydrate growth model can improve the prediction accuracy of hydrate formation in slurry systems.

Background Bacillus cereus is a foodborne pathogen commonly found in nature and food and can cause food spoilage and health issues. Although the prevalence of B. cereus in foods has been reported worldwide, the extent of contamination in edible fungi, which has become increasingly popular as traditional or functional food, is largely unknown. Here we investigated the prevalence, toxin genes’ distribution, antibiotic resistance, and genetic diversity of B. cereus isolated from edible fungi in China. Results Six hundred and ninety-nine edible fungi samples were collected across China, with 198 (28.3%) samples found to be contaminated by B. cereus, with an average contamination level of 55.4 most probable number (MPN)/g. Two hundred and forty-seven B. cereus strains were isolated from the contaminated samples. Seven enterotoxin genes and one cereulide synthetase gene were detected. The detection frequencies of all enterotoxin genes were ≥ 80%, whereas the positive rate of the cesB gene in B. cereus was 3%. Most isolates were resistant to penicillins, β-lactam/β-lactamase inhibitor combinations, cephems, and ansamycins, but were susceptible to penems, aminoglycosides, macrolides, ketolide, glycopeptides, quinolones, phenylpropanol, tetracyclines, lincosamides, streptogramins, and nitrofurans. Meanwhile, 99.6% of all isolates displayed multiple antimicrobial resistance to three or more classes of antimicrobials. Using genetic diversity analysis, all isolates were defined in 171 sequence types (STs), of which 83 isolates were assigned to 78 new STs. Conclusions This study provides large-scale insight into the prevalence and potential risk of B. cereus in edible fungi in China. Approximately one-third of the samples were contaminated with B. cereus, and almost all isolates showed multiple antimicrobial resistance. Detection frequencies of all seven enterotoxin genes were equal to or more than 80%. These new findings may indicate a need for proper pre-/post-processing of edible fungi to eliminate B. cereus, thereby preventing the potential risk to public health.

This work reports a molecularly imprinting polymer based on environmentally friendly and non-toxic ZnO quantum dots for the selective detection sulfadimidine. The MIP@ZnO was prepared by sol–gel method, which usedZnO quantum dots, TEOS, APTES, ammonia as signal materials, cross-linker, function monomer, and initiator, respectively. Result proved that MIP@ZnO exhibited excellent selective fluorescence quenching in the presence of sulfadimidine, good linear relationship in the range of 0–40 μmol L−1 with a correlation coefficient (R2) of 0.98547 was obtained, and the imprinting factor was 2.83. Furthermore, MIP@ZnO has been successfully applied for detection SM2 in real samples with the spiked recoveries ranging from 95.6 to 99.8% with RSD below 2.38%.

Although the crystal structures for many inorganic compounds are readily available, researchers are still working hard to understand the relations between the structures and chemical properties of solutions because most of the chemical reactions take place in solutions. A huge amount of effort has been put toward modeling the ion solvation structure from the perspectives of both experiments and theories. In this study, the solvation structures of Ca2+ ions in aqueous and alcoholic solutions at different concentrations were carefully evaluated by Ca K-edge X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analyses. Density functional theory (DFT) calculations were also performed to correlate the results with the experimental data and then further extended to other similar systems. It was found that the number of coordinating solvent molecules decreases with increasing Ca2+ concentration and increasing solvent molecule sizes. From the EXAFS data, it was observed that the first solvation shell of Ca2+ splits into two Ca-O distances in a methanol solution and the counter ion Cl- might also be within the first shell at high concentrations. For the first time, the effects of solvents with different polarities and sizes on the ion solvation environment were systematically evaluated.

Cadmium manganese telluride is a promising material for fabricating room-temperature nuclear radiation detectors widely used in medical imaging, environmental protection, nuclear security detection, astrophysics, and so on. The Cd0.9Mn0.1Te: V (V: CMT) crystal examined in this work was grown through the Te solution (10% excess) vertical Bridgman method. The low-temperature photoluminescence (PL) spectra indicated that the grown crystal has good quality. A simultaneous thermal excitation current spectrum was used to characterize the effect of vanadium doping on the level defects in the crystal. The current–voltage and Hall test results showed that the crystal resistivity was (3.781–6.185) × 1010 Ω cm. The conductivity was of n type. The carrier concentration was (1.69–9.94) × 106 cm−3. The Hall mobility was (3.08–9.29) × 103 cm−2 V−1 s−1. The maximum measured ratio of the light and dark currents, when the crystal was exposed to 5 mW white light, was 11. In addition, the room-temperature electron mobility-lifetime product of the middle sample was 6.925 × 10−4 cm2 V−1 using the 241Am@5.48 MeV α particle source.

The practical applications of lithium–sulfur (Li–S) batteries are greatly hindered by their low cycling stability and low efficiency, which mainly stem from the dissolution and diffusion of lithium polysulfides in the electrolyte. To tackle these challenges, here we construct an asymmetric polar Ti2CO/WS2 heterostructure to simultaneously trap lithium polysulfides and accelerate reaction kinetics. Van der Waals inclusive density-functional theory computations are carried out to uncover the unique role of the asymmetric heterostructure in the enhancement of the performance of Li–S batteries. In particular, we find higher adsorption energies of high-order lithium polysulfides on the O-terminal side, which helps to restrain the shuttle effect in Li–S batteries. Meanwhile, the S-terminal side of the heterostructure possesses a lower diffusion barrier and decomposition barrier, being specifically favorable for fast electrochemical processes. The analysis of the density of states of Ti2CO/WS2 shows the metallic character of the system; this guarantees the high conductivity and fast electron transfer of the proposed electrode. All these features illustrate that such asymmetric heterostructures could be promising anchoring materials for advanced Li–S batteries.

The Quasi-Biennial Oscillation (QBO) of tropical zonal wind is one of the most important modes of interannual variability in the stratosphere. It is well established that the QBO influences the distribution of trace gases throughout the global stratosphere. What has not been clearly shown thus far is whether the stratospheric QBO has a consistent and significant impact on tropospheric trace gases. Here we clearly demonstrate that the effects of QBO variability in stratospheric transport and trace gas distributions regularly and persistently extend into the troposphere, which influences the interannual variability of long-lived trace gas mole fractions at the Earth’s surface. We show that the variability in the surface mole fractions on one- to five-year timescales is primarily driven by the QBO. The QBO influence on tropospheric constituent mole fractions arises from the modulation of the stratosphere to troposphere mass flux and is apparent in surface measurements, as well as throughout the stratosphere and troposphere in chemistry–climate model simulations of chlorofluorocarbon-11, chlorofluorocarbon-12 and nitrous oxide. The global total emissions estimated from measured changes in the global mean surface mole fractions of these ozone-depleting species, as well as other long-lived trace gases, will be improved by accurately accounting for the QBO-driven variability. Interannual variations of long-lived trace gas mole fractions at the Earth’s surface are primarily driven by the stratospheric Quasi-Biennial Oscillation, according to surface measurements and model simulations. Ignoring this variability may induce errors in estimating emissions of trace gases.

This study aimed to explore the effects of Yiqi Huoxue Recipe (YQHXF) on the pathological changes, Th-17 lymphocyte infiltration, nucleus pulposus cell apoptosis, and the expression of extracellular matrix related proteins in degenerative intervertebral disc of rats. Thirty SD rats were randomly divided into 5 groups (Sham, Model, Low YQHXF, Medium YQHXF, and High YQHXF). In this paper, the annulus fibrosus was broken and arranged disorderly, nucleus pulposus cells apoptosis was increased, and the intervertebral discs were infiltrated by a large number of inflammatory cells in model group rats. However, YQHXF treatment group significantly attenuated these effects. Annulus fibrosus puncture caused increase in Th-17 lymphocyte infiltration and inflammatory factors in the model group, however, those effects were inhibited by YQHXF intervention. YQHXF treatment significantly reduced nucleus pulposus cell apoptosis, which was increased in the model group. The down-regulation of SOX-9 phosphorylation, type II collagen, BMP-2 and the up-regulation of β-catenin, MMP-3, MMP-13 and ADAMTS5 were found in the model group compared with sham group. However, those changes were significantly attenuated by YQHXF treatment. YQHXF could alleviate intervertebral disc degeneration in rats by reducing Th-17 lymphocyte infiltration, inhibiting nucleus pulposus cell apoptosis and promoting SOX-9/β-catenin-mediated ECM synthesis

To overcome the limitations of both LDHs and MXenes, we develop a self-sacrifice template strategy using a zeolite imidazolate framework-67 (ZIF-67) to derive Co-LDH anchored on an MXene conductive substrate (Co-LDH/MXene). In this process, ZIF-67 grows on the MXene nanosheets, then spontaneously transforms into Co-LDH/MXene in aqueous solution at room temperature. As the LIB anode, it shows a reversible capacity of 854.9 and 398.0 mAh g−1 at 0.1 and 1 A g−1, respectively. This work proposes a feasible synthesis method for the in situ construction of a Co-LDH/MXene hybrid, which may be suitable for other MXenes.

Background and Aims: Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver disease with high short-term mortality. The inclusion or exclusion of previously decompensated cirrhosis (DC) in the diagnostic criteria of ACLF defined by the Asian Pacific Association for the Study of the Liver (APASL-ACLF) has not been conclusive. We aimed to evaluate the prognostic impact of decompensated cirrhosis in ACLF.Methods: We retrospectively collected a cohort of patients with a diagnosis of APASL-ACLF (with or without DC) hospitalized from 2012 to 2020 at three liver units in tertiary hospitals. Baseline characteristics and survival data at 28, 90, 180, 360, 540, and 720 days were collected.Results: Of the patients assessed using APASL-ACLF criteria without the diagnostic indicator of chronic liver disease, 689 patients were diagnosed with ACLF, of whom 435 had no decompensated cirrhosis (non-DC-ACLF) and 254 had previously decompensated cirrhosis (DC-ACLF). The 28-, 90-, 180-, 360-, 540-, and 720-day mortality were 24.8, 42.9, 48.7, 57.3, 63.4, and 68.1%, respectively, in DC-ACLF patients, which were significantly higher than in non-DC-ACLF patients (p < 0.05). DC was independently associated with long-term (180/360/540/720 days) but not short-term (28/90 days) mortality in patients with ACLF. Age, total bilirubin, international normalized ratio, and hepatic encephalopathy were independent risk factors for short- and long-term mortality risk in ACLF patients (p < 0.05).Conclusions: Patients with DC-ACLF have a higher mortality rate, especially long-term mortality, compared to non-DC-ACLF patients. Therefore, DC should be included in the diagnostic criteria of APASL-ACLF and treated according to the ACLF management process.

SUMOylation, the covalent conjugation of small ubiquitin-like modifier (SUMO) proteins to protein substrates, has been reported to suppress type I interferon (IFN1) responses. TAK-981, a selective small molecule inhibitor of SUMOylation, pharmacologically reactivates IFN1 signaling and immune responses against cancers. In vivo treatment of wild type mice with TAK-981 upregulated IFN1 gene expression in blood cells and splenocytes. Ex vivo treatment of mouse and human dendritic cells promoted their IFN1-dependent activation, and vaccination studies in mice demonstrated stimulation of antigen cross-presentation and T cell priming in vivo. TAK-981 also directly stimulated T cell activation, driving enhanced T cell sensitivity and response to antigen ex vivo. Consistent with these observations, TAK-981 inhibited growth of syngeneic A20 and MC38 tumors in mice, dependent upon IFN1 signaling and CD8(+) T cells, and associated with increased intratumoral T and NK cell number and activation. Combination of TAK-981 with anti-PD1 or anti-CTLA4 antibodies improved the survival of mice bearing syngeneic CT26 and MC38 tumors. In conclusion, TAK-981 is a first in class SUMOylation inhibitor that promotes anti-tumor immune responses by activation of IFN1 signaling. TAK-981 is currently being studied in phase I clinical trials (NCT03648372, NCT04074330, NCT04776018 and NCT04381650) for the treatment of patients with solid tumors and lymphomas.

Perfluorooctane sulfonate (PFOS), normally present in groundwater and surface water, is an emerging environmental contaminants, but is extremely difficult to be degraded due to high energy of the C-F bond. Here, an electrocoagulation (EC) technique coupled with peroxymonosulfate (PMS) activation was used to deeply degrade PFOS. Results showed that approximately 100% PFOS was removed from the solution in the monopolar serial (MS) mode within 60 min and achieved a high kinetic rate of 0.074 min−1, which was significantly higher than those of reported studies (Table S3). Energy consumption (2.06 kWh/kg) in the MS mode was significantly lower than that of Al (52.30 kWh/kg) and Zn (213.50 kWh/kg) electrodes, which further confirmed the potential application prospects of EC technique. The quenching experiments, electron spin response (ESR) analysis, and DFT calculations can verify that ⚫OH was the main radical from the reaction of Fe2+–OH reaction site with PMS. In addition, results from fluorine balance and TOC removal also indicated the complete mineralization and degradation of PFOS in the EC process. Quantum chemical calculations can confirm the PFOS degradation mechanism and key active sites for direct electron transfer and radical attack. After five cycle operations of PFOS degradation, the EC process was still effective in degrading PFOS with a removal efficiency above 98%. Thus, this work provided a novel alternative for the high-effective treatment of PFOS from contaminated environmental water bodies.

The neurotrophic receptor tyrosine kinase (NTRK) genes including NTRK1, NTRK2, and NTRK3 encode the tropomyosin receptor kinase (Trk) proteins TrkA, TrkB, and TrkC, respectively. So far, two TRK inhibitors, larotrectinib sulfate (LOXO-101 sulfate) and entrectinib (NMS-E628, RXDX-101), have been approved for clinical use in 2018 and 2019, respectively. To overcome acquired resistance, next-generation Trk inhibitors such as selitrectinib (LOXO-195) and repotrectinib (TPX-0005) have been developed and exhibit effectiveness to induce remission in patients with larotrectinib treatment failure. Herein, we report the identification and optimization of a series of macrocyclic compounds as potent pan-Trk (WT and MT) inhibitors that exhibited excellent physiochemical properties and good oral pharmacokinetics. Compound 10 was identified via optimization from the aspects of chemistry and pharmacokinetic properties, which showed good activity against wild and mutant TrkA/TrkC in in vitro and in vivo studies.

This article shows that carbon dots (CQDs), polystyrene sphere (PS) or silica sphere (SiO2) assembled on MoS2 have been successfully synthesized as electrode materials (CQDs/MoS2, PS/MoS2 and SiO2/MoS2) for supercapacitors by a simple hydrothermal process. It can be observed that SiO2 is distributed in the periphery of the flower-like MoS2, and the special morphology has a positive effect on electrochemical performance. As expected, SiO2/MoS2 as a promising electrode material for supercapacitor, exhibiting a higher specific capacitance of 1448.53 F g−1 at a current density of 5 A g−1 and good cycle stability of 70.10% retention after 2000 cycles. This method also provides a reference for the electrode material of supercapacitors with better performance in the future.

In order to investigate the passivation effects of hydrogen, high-resistivity indium doped cadmium manganese telluride (CMT:In) single crystals were annealed in H2 atmosphere. The results indicated the concentration of Mn element and the density of Te inclusions did not change after annealing. Both the resistivity and IR transmittance increased because of the reduction of the carrier concentration. The intensity of (D0,X) peak and (D0,h) peak decreases remarkably because of the passivation of the indium donor. The donor–acceptor pair peak (DAP) peak disappeared, which was due to the dissociation of [VCd − InCd] complexes and the passivation of the impurities by hydrogen. Moreover, Dcomplex peak consisted of two peaks. The intensities of D1 peak increased and D2 peak decreased because the passivation of hydrogen on the donor and dislocation, respectively. The best condition of passivation for H2 atmosphere annealing is 573 K for 30 h.

A successful growth of Cd0.9Mn0.1Te (CMT) ingot (vanadium doping concentration of 1 × 1017 atoms/cm3) was achieved by using the Tellurium (Te) solution vertical Bridgman method. Using diffraction in the transmission electron microscope (TEM), the cell parameter of grown crystal was reckoned at 0.6496 nm. The [1 1 2 ¯ ] zone-axis diffraction pattern (DP) was obtained and indexed as the (1 1 1), the (1 3 ¯ 1 ¯ ), the (2 2 ¯ 0) and the ( 3 ¯ 1 1 ¯ ), respectively. Bright field (BF) image of the [1 1 2 ¯ ] zone-axis showed bend contours which caused by the lattice planes physically rotate and the lattice defects. A screw dislocation was assigned according to the changes characteristic of the bend contour when crossing the 1 3 ¯ 1 ¯ bend contour. And by imaging technique of high-resolution TEM (HRTEM), an edge dislocation and a set of stacking faults were recognized in the interfaces between Te precipitates and CMT: V. Then through the selected area diffraction (SAD) method, an array of rod-shape monoclinic-phase Te precipitates was identified parallel to the [1 1 ¯ 0] direction, i.e. the slip direction of the dislocation. The [1 0 0] zone-axis diffraction spots of the Te precipitates were superimposed on the [ 1 ¯ 1 2] zone-axis of CMT: V. 020 spot of the Te precipitates was a double diffraction spot produced by interactions of the Te precipitates and CMT: V reflections. Moreover, the results indicated the moire fringes were formed in the area of misfitted and rotational lattices of the Te precipitates and CMT: V. They were interference interactions which magnified the differences of lattice spacing and relative orientation.

Methamphetamine (METH) abusing contributes to dopaminergic neurons degeneration, resulting inParkinson's disease (PD)-like changes. More recently, the association between METH exposure and the Alzheimer's disease (AD)-like changes gained more attention, however, the underlying mechanisms remain poorly understood. In the present study, we aimed to investigate whether METH exposure promotes the formation of Aβ42, one of the key AD-like pathological proteins. With the cell model PC-12 cell line, it showed that METH treatment significantly increased the level of the precursor protein APP and its hydrolysates CTFs expression in a dose-dependent manner. In parallel, with the ELISA assay, we found that METH exposure contributed to an obvious elevation of the Aβ1-42 excretion in the cell culture supernatant. Therefore, we examined the expression of p-GSK3α and BACE-1, which were responsible for APP and Aβ1-42 generation respectively, it suggested in that METH obviously activated the p-GSK3α and increased the level of BACE-1, and the expression of BACE-1 was also detected by the immunofluorescence, with the significant elevation of the BACE-1 fluorescence intensity. In conclusion, METH treatment promotes the expression of Aβ precursor protein APP and its hydrolysis product CTFs and Aβ1-42, and p-GSK3α as well as BACE-1 may be involved in this process.

Adopting inorganic solid electrolytes (ISEs) is a promising approach to assemble batteries using Li metal anodes because of their superior Li-ion conductivity and high mechanical strength. This approach greatly improves the energy density and the safety of batteries. However, lithium dendrites still can pierce the bare ISE because of inhomogeneous current distributions at interfaces, leading to serious short circuits. This work proposes to reduce the interfacial resistance and prevent lithium dendrite growth simultaneously through in situ formation of interlayers enabled by a conversion reaction of MoS2 layers coated on a bare Li6.5La3Zr1.5Ta0.5O12 (LLZO) pellet. The interfacial resistance is reduced to only 14 Ω cm2, with the overpotential decreasing notably. The critical current density of cells is improved from 0.7 mA cm−2 to 2.2 mA cm−2. Furthermore, short circuits are significantly suppressed above the critical current density with the potential diverging quickly. The cell can be recovered to some extent by applying an inverse potential for a short time. The comparison between XPS and XAS measurements reveals that the nanoscale thin MoS2 layer in contact with the Li anode can be converted into an interlayer composed of Mo and Li2S through the conversion reaction. The sluggish kinetics of the conversion reaction resulting from the poor electronic conductivity makes the in situ-formed interlayer kinetically stable, which can hinder further reaction of MoS2 with Li effectively. Moreover, the in situ reaction could suppress the local tip electric field effect efficiently and make the current distribution more even. This study provides a new strategy to optimize the interface of anodes by screening for more candidates which undergo a conversion reaction.

Methamphetamine (METH) is a potent and highly addictive central nervous system stimulant. The association between METH exposure and Alzheimer's disease (AD) has gained more attention, but, the mechanisms behind METH-induced neuron-related adverse outcomes remain poorly understood. With the western blot assay, our results revealed that METH exposure significantly increased the expression of AD-associated pathological proteins, including the amyloid precursor protein (APP) and the phosphorylated tau protein (p-tau). Meanwhile, the insulin signaling was disturbed after the administration of METH, since the key insulin signaling proteins, such as p-AKT, p-GSK3α, p-GSK3β and p-ERK, were reduced. Additionally, the linking between the pathological proteins and the insulin signaling mediated by METH in the present work was verified by the treatment with the insulin signaling enhancer rosiglitazone, which was shown to improve the insulin signaling and decrease APP and p-tau expression. Thus, targeting insulin signaling may provide novel insights into potential therapeutic intervention for METH-mediated AD-like neurodegeneration.

The present study aimed to examine the effects of 2.5 µm particulate matter (PM2.5) on airway inflammation and to investigate the possible underlying mechanism. Specifically, the focus was on the imbalance of T helper (Th)1/Th2 cells and the dysregulated expression of transcription factors, including trans‑acting T cell‑specific transcription factor 3 (GATA3), runt‑related transcription factor 3 (Runx3) and T‑box transcription factor TBX21 (T‑bet). In this study, ambient PM2.5 was collected and analyzed, male BALB/c mice were sensitized and treated with PBS, ovalbumin (OVA), PM2.5 or OVA + PM2.5. The effects of PM2.5 alone or PM2.5 + OVA on immunopathological changes, the expression of transcription factors GATA3, Runx3 and T‑bet, and the imbalance of Th1/Th2 were investigated. It was found that PM2.5 + OVA co‑exposure significantly enhanced inflammatory cell infiltration, increased higher tracheal secretions in lung tissue and upregulated respiratory resistance response to acetylcholine compared with PM2.5 or OVA single exposure and control groups. In addition, higher protein and mRNA expression levels of Th2 inflammatory mediators interleukin (IL)‑4, IL‑5 and IL‑13 in bronchoalveolar lavage fluid were observed in PM2.5 + OVA treated mice, whereas the expression levels of GATA3 and STAT6 were exhibited in mice exposed to OVA + PM2.5 compared with the OVA and PM2.5 groups. By contrast, PM2.5 exposure decreased the protein and mRNA expression levels of Th1 cytokine interferon‑γ and transcription factors Runx3 and T‑bet, especially among asthmatic mice, different from OVA group, PM2.5 exposure only failed to influence the expression of T‑bet. To conclude, PM2.5 exposure evoked the allergic airway inflammation response, especially in the asthmatic mouse model and led to Th1/Th2 imbalance. These effects worked mainly by upregulating GATA3 and downregulating Runx3. These data suggested that Runx3 may play an important role in PM2.5‑aggravated asthma in BALB/c mice.

Vitrification of Tellurium-based(Te) chalcogenid semiconductors is explored as a new route to enhance their thermoelectric properties by maximizing the degree of structural disorder to produce the minimum thermal conductivity. Ga2Te3-SnTe systems are focused in this paper and the optimized glass-forming composition is identified. Complete bulk (Ga2Te3)34(SnTe)66 glass is successfully prepared by a spark plasma sintering technique and exhibited an ultralow low thermal conductivity and high Seebeck coefficient. Together with the tunable electrical conductivity, the newly obtained Ga2Te3-SnTe glasses broaden the research scope of Te-based semiconductor glasses and also provide a new option for the development of high-performance thermoelectric materials.

The size of aerosol particles has fundamental effects on their chemistry and radiative effects. We explore those effects using aerosol size and composition data in the lowermost stratosphere along with calculations of light scattering. In the size range between about 0.1 and 1.0 µm diameter (accumulation mode), there are at least two modes of particles in the lowermost stratosphere. The larger mode consists mostly of particles produced in the stratosphere, and the smaller mode consists mostly of particles transported from the troposphere. The stratospheric mode is similar in the Northern and Southern Hemisphere, whereas the tropospheric mode is much more abundant in the Northern Hemisphere. The purity of sulfuric acid particles in the stratospheric mode shows that there is limited production of secondary organic aerosol in the stratosphere, especially in the Southern Hemisphere. Out of eight sets of flights sampling the lowermost stratosphere (four seasons and two hemispheres) there were three with large injections of specific materials: volcanic, biomass burning, or dust. The stratospheric and tropospheric modes have very different roles for radiative effects on climate and for heterogeneous chemistry. Because the larger particles are more efficient at scattering light, most of the radiative effect in the lowermost stratosphere is due to stratospheric particles. In contrast, the tropospheric particles can have more surface area, at least in the Northern Hemisphere. The surface area of tropospheric particles could have significant implications for heterogeneous chemistry because these particles, which are partially neutralized and contain organics, do not correspond to the substances used for laboratory studies of stratospheric heterogeneous chemistry. We then extend the analysis of size-dependent properties to particles injected into the stratosphere, either intentionally or from volcanoes. There is no single size that will simultaneously maximize the climate impact relative to the injected mass, infrared heating, potential for heterogeneous chemistry, and undesired changes in direct sunlight. In addition, light absorption in the far ultraviolet is identified as an issue requiring more study for both the existing and potentially modified stratosphere.

Perfluorooctanoic acid (PFOA) is bioaccumulative in crops. PFOA bioaccumulation potential varies largely among crop varieties. Root exudates are found to be associated with such variations. Concentrations of low-molecular-weight organic acids (LMWOAs) in root exudates from a PFOA-high-accumulation lettuce variety are observed significantly higher than those from PFOA-low-accumulation lettuce variety (p 80% attribution. Oxalic acid at rhizospheric concentrations (0.02-0.5 mM) can effectively inhibit PFOA sorption to soils by decreasing hydrophobic force, electrostatic attraction, ligand exchange, and cation-bridge effect. Oxalic acid enhances dissolution of metallic ions, iron/aluminum oxides, and organic matters from soils and forms oxalate-metal complexes, based on nuclear magnetic resonance spectra, ultraviolet spectra, and analyses of metal ions, iron/aluminum organometallic complexes, and dissolved organic carbon. The findings not only reveal the activation process of PFOA in soils by root exudates, particularly oxalic acid at rhizospheric concentrations, but also give an insight into the mechanism of enhancing PFOA accumulation in lettuce varieties.

Profiling the chemical components of complicated herbal extracts using traditional analytical methods is time-consuming and laborious. In this study, an integrated data filtering and identification strategy was developed to efficiently identify the chemical constituents in Arnebiae Radix. The post-acquisition data processing steps with this strategy were as follows: (1) data acquisition by ultra-high performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-MS); (2) background subtraction on the basis of the total ion chromatogram (TIC) to obtain the background-subtracted ion chromatogram; (3) construction of a diagnostic ion database based on the measured MS/MS fragment ions of reference standards and auxiliary diagnostic information according to literatures; (4) mass defect filtering (MDF) to filter the background-subtracted ion chromatogram; and (5) rapid structural identification in the MDF-processed ion chromatogram on the basis of the diagnostic ion database and further structural confirmation by analysing the retention time, fragment behaviour, and online databases (Chemspider, PubChem, and SciFinder). In this study, the herbal medicine Arnebiae Radix was used to illustrate this strategy. A total of 96 compounds were efficiently exposed and characterized from Arnebiae Radix samples obtained from 20 sources, and 13 of these compounds were confirmed by comparison with the reference standards. Thirty components with a low abundance, that remained undetected in the TIC, were identified in the MDF-processed ion chromatogram. Nine of these compounds had not been identified from Arnebiae Radix previously, and were tentatively screened as unknowns. The chemical components in traditional Chinese medicine preparations are considered to be the material basis for the effectiveness of this medical system, and are closely related to the pharmacological activities of the drugs. The pharmacodynamics of these drugs are known to be influenced by the synergistic effects of various components. Therefore, comprehensive profiling of the chemical compositions of herbal extracts is essential for systematic elucidation of the pharmacodynamics of these medicines.

The non-receptor tyrosine phosphatase SHP2, encoded by PTPN11, plays an indispensable role in tumors driven by oncogenic KRAS mutations, which frequently occur in colorectal cancer. Here, PCC0208023, a potent SHP2 allosteric inhibitor, was synthesized to evaluate its inhibitory effects against the SHP2 enzyme, and the KRAS mutant colorectal cancer in vitro and in vivo, and its impart on the RAS/MAPK pathway. Consistent with an allosteric mode of inhibition, PCC0208023 can non-competitively inhibit the activity of full-length SHP2 enzyme, but lacks activity against the free catalytic domain of SHP2. Furthermore, PCC0208023 inhibited the proliferation of KRAS mutation-driven human colorectal cancer cells by inhibiting the RAS/MAPK signaling pathway in vitro. Importantly, PCC0208023 displayed good anti-tumor efficacy against KRAS-driven LS180 and HCT116 xenograft models in nude mice with the decreased Ki67 and p-ERK level, and increased cleaved caspase-3 expression in tumors. Interestingly, PCC0208023 maintained high levels in LS180 tumors within 24 h after administration and was mainly distributed in both intestines and lungs. Molecular docking studies revealed a higher affinity of PCC0208023 with key residues in the SHP2 allosteric pocket than RMC-4550. PCC0208023 deserves further optimization to identify additional low-toxic and potent SHP2 allosteric inhibitors with novel scaffolds for the treatment of patients with KRAS mutation-positive colorectal cancer.

Microbial fuel cell (MFC), a promising bio-electrochemical reactor could decompose organics in wastewater by redox processes of electro-active microorganism in anode and produce bio-energy, and the total MFC performance could mainly rely on electrochemical performance anode. Here, biomass carbon derived from municipal sludge was employed as low-cost and high-performance bio-anode for enhancing bioelectricity generation and wastewater treatment in MFC simultaneously. The electrochemical tests demonstrated that the large electrochemical active surface area, strong conductivity, and good biocompatibility in sludge carbon (SC) electrode resulted in higher power density (615.2 mW m−2) and lower power loss (5.4%) than those of none carbon (NC) electrode in long term operation. After 30-cycle of continuous running, the low loss of chemical oxygen demand (COD) removal was achieved up to 5.2%, which was smaller than that of NC electrode (14.1%), indicating that the MFC with SC anode could effectively treat wastewater and keep stable redox processes in anode electrode. After the formation of biofilm, the charge transfer resistance of SC electrode (16.38 Ω) was 72.4% lower than that of NC electrode (59.35 Ω). High-throughput analysis of biofilm exhibit Proteobacteria was the dominant electro-active bacteria, and the modification of SC could slightly change the bacterial community. Therefore, resource utilization of natural wastes provided the novel concept of anode catalyst fabrication for MFC in enhancing electron transfer, power output and wastewater decomposition.

Perinatal exposure to bisphenol A (BPA) contributes to neurological disorders in offspring, but the underlying mechanisms are still poorly understood. The abnormal release of neuroactive metabolites in the tryptophan (TRP) and dopamine (DA) pathways is considered to be closely associated with some disorders. Thus, in this study, TRP and DA pathways in adult female mouse offspring were investigated when the pregnant mice were given either vehicle or BPA (2, 10, or 100 μg/kg/d) from day 6 of gestation until weaning. Then, the serum and brain samples of offspring were collected at 3, 6 and 9 months, and 12 neuroactive metabolites in the TRP and DA pathways were detected. The results showed that, in the TRP pathway, TRP levels decreased, whereas kynurenine (KYN) levels and TRP turnover increased in the brain. In the serum, TRP, KYN and 5-hydroxytryptamine (5-HT) levels decreased significantly. For the DA pathway, DA and DA metabolites, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA), reduced significantly in the brain and serum. DA turnover decreased dramatically in the brain but enhanced in the serum. The disturbance of these two metabolic pathways might be one of the potential mechanisms of BPA-induced neuropsychiatric disorders.

The increased PD-L1 expression induces poorer prognosis in melanoma. The small molecule inhibitors of PD-1/PD-L1 pathways have been an encouraging drug development strategy because of good affinity and oral bioavailability without immunogenicity and immunotoxicities of PD-1/PD-L1 antibodies. In this study, we studied the effects of PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, on PD-1/PD-L1 binding and the cytokines secretion in human CD3+ cells in vitro. We also investigated the antitumor and immunomodulatory activity of PCC0208025 and the pharmacokinetics properties in B16-F10 melanoma-bearing mice. The results showed that PCC0208025 inhibited the PD-1/PD-L1 proteins binding, and rescued PD-L1-mediated inhibition of IFN-γ production in human CD3+ T cells in vitro. Furthermore, in B16-F10 melanoma-bearing mice, PCC0208025 presented the antitumor effects, enhanced IFN-γ levels in plasma, increased the frequency of CD3+CD8+ T and CD8+IFN-γ+ T and the ratios of CD8+/Treg, and deceased the CD4+CD25+CD127low/− (Treg) number in tumor. Pharmacokinetics study found that PCC0208025 was absorbed and distributed into the tumors with much higher concentrations than those of the blockade against PD-1/PD-L1 binding. Our work suggests that PCC0208025 exhibited anti-tumor effects through inhibiting Treg expansion and increasing cytotoxic activity of tumor-infiltrating CD8+ T cells by the blockade of PD-1/PD-L1 binding, which may provide the pharmacological basis to develop small molecule inhibitors of PD-1/PD-L1 binding for PCC0208025 as a lead compound.

High-effective catalyst for activating peroxymonosulfate (PMS) to degrade pollutant in wastewater and minimize its toxicity is crucial. Herein, CoFe2O4/montmorillonite composites (CF/MO) were synthesized and used as high-effective PMS catalysts for the degradation of tetracycline (TC). The CoFe2O4 nanoparticles were firmly loaded on the surface of MO with Fe O Al bonds, preventing the leaching of metal ions and bringing superior reusability and stability. It was optimized that the 20%-CF/MO showed superior catalytic activity to activate PMS for TC degradation, and SO4 − was the dominant active species for TC complete degradation within 30 min and achieved high kinetic rate of 0.178 min−1. The ultrahigh catalytic performance toward TC degradation was ascribed to the cycles and regeneration of Co(III)/Co(II) and Fe(III)/Fe(II) synthergetic surface redox couples in the catalysts. The TC degradation pathway and reaction mechanism in the 20%-CF/MO/PMS system were also proposed based on DFT calculation. The ecotoxicity of degradation products was assessed using proteomics, and the toxicity of TC was found to decrease significantly as the reaction progressed.

BACKGROUND: Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury. Mesenchymal stem cell (MSC) transplantation is used to reduce tissue damage, but exosomes are more stable and highly conserved than MSCs. This study was conducted to investigate the therapeutic effects of MSC-derived exosomes (MSC-Exo) on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R), and to explore the underlying mechanisms. METHODS: Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment, with or without MSC-Exo treatment. Exosomal integration, cell viability, mitochondrial membrane potential, and generation of reactive oxygen species (ROS) were examined. Terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate nick-end labeling (TUNEL) staining was performed to detect neuronal apoptosis. Moreover, mitochondrial function-associated gene expression, Nrf2 translocation, and expression of downstream antioxidant proteins were determined. RESULTS: MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation (P

Microbial fuel cell (MFC) utilizes electro-active microorganisms to generate electricity from organic waste, promising a clean and sustainable energy source. However, the low power output severely restricts the scale of their application. Here, resazurin (RZ), a phenoxazine, is used as an electron shuttling mediator to enhance electrical transport at the anode electrode. Nearly a fourfold increase in power density of 1026.8 ± 1.6 mW/m2 (RZ-5) was obtained compared to the control MFC (272.7 ± 1.5 mW/m2). RZ transforms into resorufin (RR) and dihydroresorufin (DHRR) in the anode, responsible for the electron shuttling. It has the desired effects of shortening electrons’ diffusion path, decreasing the cell resistance, and enhancing bioelectricity production. It also has the added effect of promoting the growth of electro-active bacteria from Pseudomonas and Geobacter genus on the anode. Both genera are known for their efficient conversion of organics through direct and indirect electron transfer pathways.

All-solid-state lithium-ion battery is considered to be one of the most promising next-generation battery technologies. Understanding the interfacial evolution of a solid electrolyte and a cathode electrode during mixing and sintering is of great importance and can provide guidance to avoid forming unwanted compounds and decrease the interfacial resistance. In this work, chemical compatibilities are investigated between a Ta-doped Li7La3Zr2O12 (LLZO) solid electrolyte and major commercial metal-oxide cathodes LiCoO2 (LCO) and Li(NiCoMn)1/3O2 (NCM) through ball-milling and cosintering processes. As revealed by X-ray absorption spectroscopy and transmission electron microscopy, LLZO spontaneously covers the majority of the large LCO and NCM particles with a thickness of ∼100 nm after ball milling. The thickness of LLZO layer on these cathodes decreases to about 10 nm after cosintering at 873 K, and an interfacial layer of approximately 3 nm is observed for NCM/LLZO. LCO shows a higher thermal stability than...

Sorption of perfluorooctanoic acid (PFOA), a toxic and persistent organic pollutant, by various size fractions of an agricultural soil at environmentally relevant concentrations was evaluated. PFOA sorption to all fractions involved both film diffusion and intraparticle diffusion with the rate-limiting step by the latter. PFOA isotherm data fitted a linear model. Organic matter (OM), cation exchange capacity, pore volume, and the Brunauer-Emmett-Teller area played key roles in PFOA sorption. The sorption capacity followed the order of humic acid > clay (0.15-4.4 mm) > fine silt (1.9-39.8 mm) > coarse silt (17.3-79.4 mm) > fine sand (45.7-316.2 mm) > coarse sand (120-724.4 mm), opposite to their contributions to overall PFOA sorption due to the influence of their percentage weight in the original soil. Percentage OM content was the dominant factor controlling the fraction contributions to overall PFOA sorption, demonstrating influence of the hydrophobic force on sorption. PFOA should be highly mobile and bioavailable in soil-crop systems due to the low log Koc values.