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Coal spontaneous combustion (CSC) often occurs in environments that are poorly ventilated or under lean-oxygen environments in coal mines or coal seam outcrops. The understanding of the thermodynamic properties of CSC under lean-oxygen conditions is important to avoid safety and environmental problems. In this paper, the mass variation and critical temperature (the minimum temperature required for coal reaction in each stage) of six coals during CSC under lean-oxygen conditions were investigated using thermogravimetric methods. Furthermore, the thermodynamics parameters and kinetic compensation processes during CSC under lean-oxygen conditions were analyzed. The results showed that the oxidation and combustion of coal under lean-oxygen conditions was affected by the coal rank and oxygen concentration. The increase in the critical temperature was more significant when the oxygen concentration was reduced from 10 to 5%. The mechanism functions most likely to cause CSC at different oxygen concentrations were similar. The reaction mechanisms of high-rank coals at a low-temperature oxidation stage were more influenced by oxygen concentration than low-rank coals. Evaluations of kinetic behavior showed that activation energy decreased in a linear manner as the oxygen concentration decreased. The mathematical relationship between the activation energy and the pre-exponential factor indicated that there was a kinetic compensation process during CSC under lean-oxygen conditions. It is also worth noting that the effect of the coal rank on the thermodynamic characteristics of CSC is better than that of oxygen concentration. This work is helpful for enhancing the prediction and prevention of CSC.

Hen egg white lysozyme (HEWL) is frequently applied as a model protein for research on protein folding, unfolding, and fibrillization identified by featured fluorescent probes. Here, a series of hydrophilic, pH-sensitive tetraarylethene (TAE)-type AIEgens are synthesized via a geminal cross-coupling (GCC) reaction and evaluated for their capabilities of fluorescence sensing and super-resolution localization imaging of HEWL fibrils. With superior optical and sensing properties, the selected TAE-type AIEgen probe is weakly emissive in aqueous media, without dependence on the pH value and buffer concentration, but exhibits "turn-on" fluorescence upon interaction with HEWL amyloid fibrils in a spontaneous and reversible way that just meets the requirement of fluorescence random switching for super-resolution imaging. The selected probe has the strongest fluorescence response to HEWL amyloid fibrils exhibiting a limit of detection of 0.59 nmol/L and enables super-resolution fluorescence imaging of amyloid aggregates with a high resolution of 40 nm.

A uniform diffusion layer is essential for non-dendritic deposition of lithium in high-density lithium batteries. However, natural pristine solid electrolyte interface (SEI) is always porous and inhomogeneous because of repeated breakdown and repair cycles, whereas ideal materials with excellent mechanical property for artificial SEIs remain a challenge. Herein, a robust and stable interface is achieved by spinning soft polymer associated with few MoO3 into fibers, and thus mechanical property of fibers other than materials determines mechanical performance of the interface which can be optimized by adjusting parameters. Furthermore, lithium deposited underneath the layer is enabled by constructing an optimal resistance to make the membrane serve as an artificial SEI rather than lithium host. As a result, dendrite-free lithium was observed underneath the membrane, and stable interface for long-term cycling was also indicated by EIS measurements. The lithium iron phosphate (LiFePO4) full-cell with coated electrode demonstrated an initial capacity of 155.2 mAh g−1, and 80% of its original capacity was retained after 500 cycles at 2.0 °C without any additive in carbonate-based electrolyte.

In accordance with the fourth industrial revolution (4IR), thin-film all-solid-state batteries (TF-ASSBs) are being revived as the most promising energy source to power small electronic devices. However, current TF-ASSBs still suffer from the perpetual necessity of high-performance battery components. While every component, a series of a TF solid electrolyte (i.e., lithium phosphorus oxynitride (LiPON)) and electrodes (cathode and Li metal anode), has been considered vital, the lack of understanding of and ability to ameliorate the cathode (or anode)-electrolyte interface (CEI) (or AEI) has impeded the development of TF-ASSBs. In this work, we suggest an ensemble design of TF-ASSBs using LiPON (500 nm), an amorphous TF-V2O5-x cathode with oxygen vacancies (Ovacancy), a thin evaporated Li anode (evp-Li) with a thickness of 1 μm, and an artificial ultrathin Al2O3 layer between evp-Li and LiPON. Well-defined Ovacancy sites, such as O(II)vacancy and O(III)vacancy, in amorphous TF-V2O5-x not only allow isotropic Li+ diffusion at the CEI but also enhance both the ionic and electronic conductivities. For the AEI, we employed protective Al2O3, which was specially sputtered using the facing target sputtering (FTS) method to form a homogeneous layer without damage from plasma. In regard to the contact with evp-Li, interfacial stability, electrochemical impedance, and battery performance, the nanometric Al2O3 layers (1 nm) were optimized at different temperatures (40, 60, and 80 °C). The TF-ASSB cell containing Al2O3 (1 nm) delivers a high specific capacity of 474.01 mAh cm-3 under 60 °C at 2 C for the 400th cycle, and it achieves a long lifespan as well as ultrafast rate capability levels, even at 100 C; these results were comparable to those of TF Li-ion battery cells using a liquid electrolyte. We demonstrated the reaction mechanism at the AEI utilizing time-of-flight secondary ion mass spectrometry (TOF-SIMS) and molecular dynamics (MD) simulations for a better understanding. Our design provides a signpost for future research on the rational structure of TF-LIBs.

Increasing evidence suggests that abnormal regulation of neurotrophic factors is involved in the etiology and pathogenesis of Autism Spectrum Disorder (ASD). However, clinical data on neurotrophic factor levels in children with ASD were inconsistent. Therefore, we performed a systematic review of peripheral blood neurotrophic factors levels in children with ASD, and quantitatively summarized the clinical data of peripheral blood neurotrophic factors in ASD children and healthy controls. A systematic search of PubMed and Web of Science identified 31 studies with 2627 ASD children and 4418 healthy controls to be included in the meta-analysis. The results of random effect meta-analysis showed that the peripheral blood levels of brain-derived neurotrophic factor (Hedges’ g = 0.302; 95% CI = 0.014 to 0.591; P = 0.040) , nerve growth factor (Hedges’ g = 0.395; 95% CI = 0.104 to 0.686; P = 0.008) and vascular endothelial growth factor (VEGF) (Hedges’ g = 0.097; 95% CI = 0.018 to 0.175; P = 0.016) in children with ASD were significantly higher than that of healthy controls, whereas blood neurotrophin-3 (Hedges’ g = − 0.795; 95% CI = − 1.723 to 0.134; P = 0.093) and neurotrophin-4 (Hedges’ g = 0.182; 95% CI = − 0.285 to 0.650; P = 0.445) levels did not show significant differences between cases and controls. Taken together, these results clarified circulating neurotrophic factor profile in children with ASD, strengthening clinical evidence of neurotrophic factor aberrations in children with ASD.

Bi2Se3 is a promising anode material for lithium-ion batteries (LIBs) due to its high capacity and weak van der Waals stacking for Li-ion insertion. However, it suffers from low conductivity and structural instability during the Li-ion insertion and extraction processes. Herein, a new carbon nanofiber (CNF) network decorated with Bi2Se3 nanoparticles (∼40 nm) was facilely prepared and directly used as a binder-free flexible anode in LIBs. The Bi2Se3/CNFs anode delivered a high reversible gravimetric capacity of 443 mA h g−1 after 260 cycles at 100 mA g−1 and a rate capability of 103 mA h g−1 at 16 A g−1. The full cell with LiCoO2 vs. Bi2Se3/CNFs has a discharge specific capacity of 261 mA h g−1 after 100 cycles at 100 mA g−1. The excellent Li-storage performance is attributed to the Bi2Se3 nanoparticles uniformly embedded in the unique conductive 3D CNFs network which effectively improves the conductivity and avoids the layer structure collapse of Bi2Se3 materials. The synergistic effect of the enhanced characteristics successfully improved the long-term cycling and rate capability of the Bi2Se3 anode. This flexible and binder-free Bi2Se3/CNFs electrode has great potential as a neoteric anode material for LIBs.

Supramolecular hydrogels attract extensive attention as waterborne biocompatible materials like biological tissues. Here we developed poly[N-(2-acetamidoethyl)acrylamide] (PAAE) supramolecular hydrogels with multiple hydrogen bonds, which exhibit ideal mechanical performances, such as strong resistance to compression and stretch, high stability in acidic or high ionic strength solution, excellent waterborne adhesiveness, self-healing and swelling behaviors. The small molecular precursor for PAAE hydrogels possesses great solubility up to 70 wt% in deionized water and superior infiltration capability to mouse brain tissues at 5 °C, and can be in situ polymerized at 30–45 °C and swollen in deionized water with a 1.75 times linear expansion factor. There is no noticeable loss of fluorescence intensity during the whole process from small molecular infiltration and polymerization to expansion. The mouse brain slices were embedded and used for expansion microscopy with enhanced optical resolution and preserved structure integrity.

Protein misfolding and denaturation, represented by amyloid fibrillation, are associated with many diseases. However, as a general chemical biological process, the dynamic structure information on amyloid fibrillation has not been demonstrated categorically. Herein, hen egg white lysozyme (HEWL) was used as the model protein of interest to realize in situ nanoscale imaging of protein fibrillation process using the fluorophores with aggregation-induced emission (AIE) activity. The AIE-active fluorophores exhibit the reversible capability of association and dissociation with β-sheet structure and thus dynamic binding-induced emission, which causes the spontaneous switching of fluorescence. The entire HEWL denaturation process induced by sodium dodecyl sulfate (SDS) at ambient conditions was demonstrated in detail by using two AIE-active fluorophores (TPE-NaSO3 and PD-BZ-OH) through reversible electrostatic interaction and specific labeling between AIE probes and β-sheet structures of amyloid fibrils, respectively. The results indicate that PD-BZ-OH is more specific AIE probe for amyloid fibrils than TPE-NaSO3. In comparison, the SEM and TEM results show the same denaturation process of protein fibrillation induced by SDS at different concentrations. The static super-resolution imaging of amyloid fibrils is performed with a resolution of 35 nm using PD-BZ-OH aqueous solution without additional auxiliary conditions. The dynamic evolution process of HEWL amyloid fibrillation is in situ visualized through super-resolution fluorescent microscopy with nanoscale resolution. Both static and dynamic super-resolution imaging of amyloid fibrillation provides detailed nanoscale structure information exceeding 50 nm resolution, which is of great significance in the exploration of amyloid fibrillation and related diseases.

Coronary artery spasm (CAS) causes serious ischaemic cardiac disease. The hyper-reactivity of vascular smooth muscle cells, which ascribe the up-regulation of endothelin receptor B type, is a key abnormality responsible for the pathological constriction of arteries in CAS. In this study, the nanocarriers were prepared and optimised for the delivery of U0126, which is an inhibitor of the mitogen-activated protein kinase, to treat pathological constriction of arteries. First, cationic amphipathic starch and hyaluronic acid were used in the encapsulation of U0126 to form U0126 nanoparticles (NPs). The shape of the U0126 NPs was spherical with a typical core–shell structure. The size was 94.1 ± 10.2 nm and the zeta potential was −20.3 ± 5.1 mV. Maximal encapsulation efficiencies and drug loading of U0126 in the NPs were 96.2 ± 3.1 and 8.2 ± 2.5%, respectively. U0126 NPs showed very great stability and could perform an effective targeted delivery. An arterial tissue culture model was used in the investigation of anti-constriction. In comparison with treatment with the free drug, the U0126 NPs significantly decreased the effective dosage, enhanced the effect of anti-constriction, and down-regulated the endothelin type B receptor in the culture model. These results suggest that U0126 NPs have a significant potential for the treatment of CAS.

We fabricated and evaluated four types of Li batteries, in this case a LTO/liquid electrolyte/Li battery, a LTO/LiPON/Li all-solid-state battery, and LTO/LiPON + liquid electrolyte/Li batteries with and without a separator to investigate and clarify the effects of each interface. Through the present research, it was found that a conventional polymer-based separator increases the impedance in the middle frequency region, resulting in an increase in the total cell resistance. After replacing the polymer-based separator with a thin-film solid electrolyte, the cycleability and capacity of the cell were comparable to those of a conventional Li-ion battery with a polymer separator. The all-solid-state Li thin-film battery without a liquid electrolyte exhibits the lowest capacity due to the large interfacial resistance between the Li metal and the LiPON solid electrolyte. However, we found that the insertion of an Al2O3 interlayer between the Li and LiPON improves the capacity.

Selenium has been shown to possess antioxidant and neuroprotective effects by modulating mitochondrial function and activating mitochondrial biogenesis. Our previous study has also suggested that selenium protected neurons against glutamate toxicity and hyperglycemia-induced damage by regulating mitochondrial fission and fusion. However, it is still not known whether the mitochondrial biogenesis is involved in selenium alleviating hyperglycemia-aggravated cerebral ischemia reperfusion (I/R) injury. The object of this study is to define whether selenium protects neurons against hyperglycemia-aggravated cerebral I/R injury by promoting mitochondrial biogenesis. In vitro oxygen deprivation plus high glucose model decreased cell viability, enhanced reactive oxygen species production, and meanwhile stimulated mitochondrial biogenesis signaling. Pretreated with selenium significantly decreased cell death and further activated the mitochondrial biogenesis signaling. In vivo 30 min of middle cerebral artery occlusion in the rats under hyperglycemic condition enhanced neurological deficits, enlarged infarct volume, exacerbated neuronal damage and oxidative stress compared with normoglycemic ischemic rats after 24 h reperfusion. Consistent to the in vitro results, selenium treatment alleviated ischemic damage in hyperglycemic ischemic animals. Furthermore, selenium reduced the structural changes of mitochondria caused by hyperglycemic ischemia and further promoted the mitochondrial biogenesis signaling. Selenium activates mitochondrial biogenesis signaling, protects mitochondrial structure integrity and ameliorates cerebral I/R injury in hyperglycemic rats.

Photoswitchable fluorescent diarylethenes are promisingly widely applied in the fields of optical memory, all-optical transistors, bioimaging, and super-resolution imaging, and so on. However, they face the problems of fluorescence quenching in an aggregated/solid state, the inadequate fluorescence ON/OFF switching ratio, and the necessity of UV-light irradiation. Herein, we report a novel kind of high-performance diarylethenes with aggregated-induced emission (AIE) by conjugating two diarylethene groups on one AIE-gen (i.e., TPE-2DTE (blue-green fluorescent) and OTPE-2DTE (orange fluorescence)). Their open forms show enhanced fluorescence in the aggregated and solid states. The closed form of TPE-2DTE/OTPE-2DTE was effectively generated upon short-wavelength visible-light (400 nm-450 nm) irradiation, whose fluorescence was dramatically quenched by intra- and inter-molecular energy transfer. Remarkably, 405 nm purple irradiation gives fluorescence ON/OFF ratios of 1196:1 and 1983:1 for TPE-2DTE and OTPE-2DTE, respectively. The reverse process can be accomplished after another longer wavelength irradiation such as 621 nm and shows considerable fatigue resistance. Taking advantage of superior photoswitching properties under visible-light irradiation, TPE-2DTE and OTPE-2DTE were used for super-resolution imaging with a high resolution of sub 50 nm. This work offers guidance to design bright-emitting and high-performance visible-light-controlled diarylethene photoswitches for practical applications.

A water-soluble probe, TPA-1OH, with aggregation-induced emission activity is synthesized and used for expedient real-time fluorescence in situ visualization of latent fingerprints (LFPs). A TPA-1O...

Lithium metal has been considered to be the most promising anode material for the new generation of energy-storage system. However, challenges still stand in protecting lithium metal from spontaneous reactions with electrolytes and preventing the dendritic propagation, both of which would lead to undesirable decrease in Coulombic efficiency. Polysulfone (PSf) membrane with high rigidity and free-volume cavities of approximately 0.3 nm was employed to provide a stable interface on the surface of anodic electrode. The isotropic channels were constructed by the interconnected and uniformly distributed free volumes in the polymer matrix, and were expected to be swelled by solvent molecules and anions of lithium salt and to allow Li+ ions to pass through onto the electrode surface. As a result, dendrite-free morphology of deposited lithium was observed. The stabilized interface arose from the PSf film was verified by the promoted performances of Cu|Li cells and steady voltage polarization of Li|Li cells. The full cell with PSf coated anode exhibited excellent cyclability (85% capacity retention rate over 400 cycles at 1 C) and an outstanding rate capability (117 mAh g−1 at 5 C). The beneficial performances were further verified by the EIS results. This work provides a new strategic idea to settle the dendritic problems of Li metal anodes.

Objective: Uncoupling protein 2 (UCP2) is a member of inner mitochondrial membrane proteins and deletion of UCP2 exacerbates brain damage after cerebral ischemia/reperfusion (I/R). Nevertheless, its functional role during cerebral I/R is not entirely understood. The objective of present study was to explore the influence of UCP2 deletion on mitochondrial autophagy (mitophagy) and mitochondria-mediated cell death pathway after cerebral I/R. Methods: UCP2-/- and wildtype (WT) mice were subjected to 60 min middle cerebral artery occlusion (MCAO) and allowed reperfusion for 24 hours. Infarct volume and histological outcomes were assessed, reactive oxygen species (ROS) and autophagy markers were measured, and mitochondrial ultrastructure was examined. Results: Deletion of UCP2 enlarged infarct volume, increased numbers of necrotic and TUNEL positive cells, and significantly increased pro-apoptotic protein levels in UCP2-/- mice compared with WT mice subjected to the same duration of I/R. Further, deletion of UCP2 increased ROS production, elevated LC3, Beclin1 and PINK1, while it suppressed p62 compared with respective WT ischemic controls. Electron microscopic study demonstrated the number of autophagosomes was higher in the UCP2-/- group, compared with the WT group. Conclusions: It is concluded that deletion of UCP2 exacerbates cerebral I/R injury via reinforcing mitophagy and cellular apoptosis in mice.

Three-dimensional (3D) and two-dimensional (2D) Ag-based zwitterionic metal–organic frameworks (MOFs) [Ag2(Cedcp)]n (1, 3D, H3CedcpBr denotes N-(carboxyethyl)-(3,5-dicarboxyl)-pyridinium bromide) a...

Porous polymer membranes have been widely used as matrixes of gel polymer electrolytes (GPEs) for lithium-ion batteries (LIBs). This work demonstrates the creation of lithium-ion-conducting channel...

A novel bioflocculant, A-GS408, produced by Klebsiella oxytoca GS-4-08 cultured in acetonitrile (ACN) as sole nitrogen source was investigated in this study. A complete degradation of 1 g l−1 of ACN was achieved in 350 h, and 4.6 g of crude A-GS408 can be obtained in one litter of synthetic medium. The as-prepared bioflocculant exhibits good flocculation efficiency (over 90%) toward Kaolin solution with the aid of Fe3+. Chemical analysis showed that the bioflocculant was mainly composed of polysaccharides (46.3%) and proteins (20.6%). FTIR and XPS results indicated the abundant carboxyl, amine and hydroxyl groups in A-GS408 s, which play an important role on Pd2+ and Cu2+ adsorption. The adsorption of heavy metals can be well stimulated by Freundlich isotherm equation, and the Kf was up to 439.2 mg1-1/n l1/n g−1 and 112.2 mg1-1/n l1/n g−1 for Pb2+ and Cu2+, respectively. The kinetic fitting results proved that the adsorption of heavy metals by A-GS408 was chemisorption. This study may provide a new method for preparation of bioflocculant, which can not only degrade toxic compound i.e., acetonitrile, but also can reuse considerable nitrogen source from nitrile-containing wastewater.

Tetraphenylethylene (TPE) derivatives are typical aggregation-induced emission (AIE) molecules, which have been widely investigated and applicated. The Rathore’s procedures and McMurry reaction are the two frequently used methods for synthesizing the TPE derivatives. The complex processes and low tolerance of active function groups make the TPE with limited structures and properties in some degree. Very recently, a novel strategy, named geminal cross coupling (GCC) reaction, is developed for designing and synthesizing various topological small molecules and polymers with rich optical properties beyond simple TPE compounds, and becomes a powerful synthesis method to AIE materials. This review overviews the current progresses of AIE molecules and polymers prepared by GCC as well as their applications. We believe that GCC reaction will have a bright future in the development of the next generation of tetraarylethylene (TAE)-kind AIE materials.

Background Membrane-associated fibrinogen-like protein 2 (FGL2 prothrombinase, p FGL2) is abundantly expressed in activated microvascular endothelial cells (MVECs) and plays a crucial role in microthrombus formation in microcirculatory vasculature. It has been widely reported that coronary microvascular obstruction (CMVO) contributes to adverse outcomes following myocardial ischemia/reperfusion. However, the role of p FGL2 in CMVO is poorly understood. Methods and results We aimed to identify the effect of MVECs- p FGL2 in CMVO using FGL2 knockout mice. As results, the MVECs- p FGL2 expression progresses significantly over 3 days and then gradually decreases, which is positively correlated with the extent of CMVO as detected by HE staining in wild type mice. Furthermore, FGL2 deficiency is correlated with decreased areas of no-reflow and necrosis as detected by Evans Blue and TTC staining and that it ameliorates cardiac dysfunction detected by hemodynamics in the early stage of CMVO. Moreover, fibrin deposition in microvasculature is significantly reduced in FGL2-deficient mice as evidenced by immunohistochemistry, MSB and Carstairs staining, along with the down-regulation of leukocyte adhesion and infiltration. Additionally, we observed that the FGL2 deficiency decreases macrophage infiltration and shifts the macrophage phenotype from pro-inflammatory (M1,) to anti-inflammatory (M2,) pattern in the early stage of CMVO. Conclusion These findings highlight the MVECs- p FGL2-fibrin pathway in the early stage of CMVO and provide insights into coagulation and inflammation for the coronary artery disease therapeutics.

Three-dimensional palladium nanoflowers (Pd NF) composed of ultrathin Pd nanosheets had been synthesized by a solvothermal approach in our previous work. Here, the effects of preparation conditions on the morphology and electrochemical performance of palladium nanostructures were investigated. The explored conditions are as follows: the ratio of reducing agent to capping agent, the concentration of PdCl2 precursor, the amount of HCl (used for PdCl2 dissolution), the reaction temperature and time. Only when these conditions are strictly controlled, the obtained Pd material displays a uniformly nanoflower-like morphology, otherwise the Pd samples with nanoparticles or incomplete flowers can only be obtained. Then, the relationship between the morphology of Pd and its electrocatalytic activity was further studied. The results indicate that the Pd with perfect nanoflowers morphology possesses superior activity for formic acid electro-oxidation, while the Pd with incomplete flowers and ordinary (or irregular) particle morphology shows moderate and inferior activity. Therefore, the morphology-dependent electrocatalytic activity has been demonstrated in this work.

We herein report an efficient Ag+ and S2− dual sensing scenario by a three-dimensional (3D) Cu-based metal–organic framework [Cu(Cdcbp)(bpea)]n (MOF 1, H3CdcbpBr = 3-carboxyl-(3,5-dicarboxybenzyl)-pyridinium bromide, bpea = 1,2-di(4-pyridinyl)ethane) shielded with a 5-carboxytetramethylrhodamine (TAMRA)-labeled C-rich single-stranded DNA (ss-probe DNA, P-DNA) as a fluorescent probe. The formed MOF-DNA probe, denoted as P-DNA@1, is able to sequentially detect Ag+ and S2− in one pot, with detection limits of 3.8 nM (for Ag+) and 5.5 nM (for S2−), which are much more lower than the allowable Ag+ (0.5 μM) and S2− (0.6 μM) concentration in drinking water as regulated by World Health Organization (WHO). The detection method has been successfully applied to sense Ag+ and S2− in domestic, lake, and mineral water with satisfactory recoveries ranging from 98.2 to 107.3%. The detection mechanism was further confirmed by molecular simulation studies.

Nano silicon carbide was used separately and as an auxiliary absorber for the modification of the PAN precursor fibers to upgrade their microwave absorbability in order to undergo the subsequent pre-oxidization by using microwave. Surface coatings were successfully applied to the PAN precursor and the coated fibers were pre-oxidized over the microwave furnace for 60 min. To study the effect of the coatings on the pre-oxidized fibers, a series of characterizations were carried out. FTIR analysis results showed clear changes in the basic chemical structure of pre-oxidized fibers, which approved the occurrence of the cyclization and crosslinking reactions. Furthermore, the cyclization was confirmed by the thermal analysis results. According to the listed oxygen values, it can be suggested that the pre-oxidized fibers can resist the high temperatures in the following stage (carbonization). In addition, the crystalline analysis revealed a reduction in crystallinity, while the mechanical analysis demonstrated a reduction in tensile strength and elongation at break of pre-oxidized fibers.

The mechanisms underlying plant tolerance to boron (B) excess are far from fully understood. Here we characterized the role of the miR397-CsiLAC4/CsiLAC17 (from Citrus sinensis) module in regulation of B flow. Live-cell imaging techniques were used in localization studies. A tobacco transient expression system tested modulations of CsiLAC4 and CsiLAC17 by miR397. Transgenic Arabidopsis were generated to analyze the biological functions of CsiLAC4 and CsiLAC17. CsiLAC4's role in xylem lignification was determined by mRNA hybridization and cytochemistry. In situ B distribution was analyzed by laser ablation inductively coupled plasma mass spectrometry. CsiLAC4 and CsiLAC17 are predominantly localized in the apoplast of tobacco epidermal cells. Overexpression of CsiLAC4 in Arabidopsis improves the plants' tolerance to boric acid excess by triggering high-B-dependent lignification of the vascular system's cell wall and reducing free B content in roots and shoots. In Citrus, CsiLAC4 is expressed explicitly in the xylem parenchyma and is modulated by B-responsive miR397. Upregulation of CsiLAC4 in Citrus results in lignification of the xylem cell walls, restricting B flow from xylem vessels to the phloem. CsiLAC4 contributes to plant tolerance to boric acid excess via high-B-dependent lignification of cell walls, which set up a 'physical barrier' preventing B flow.

Background Cryptosporidium baileyi is an economically important zoonotic pathogen that causes serious respiratory symptoms in chickens for which no effective control measures are currently available. An accumulating body of evidence indicates the potential and usefulness of metabolomics to further our understanding of the interaction between pathogens and hosts, and to search for new diagnostic or pharmacological biomarkers of complex microorganisms. The aim of this study was to identify the impact of C. baileyi infection on the serum metabolism of chickens and to assess several metabolites as potential diagnostic biomarkers for C. baileyi infection. Methods Ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) and subsequent multivariate statistical analysis were applied to investigate metabolomics profiles in the serum samples of chickens infected with C. baileyi, and to identify potential metabolites that can be used to distinguish chickens infected with C. baileyi from non-infected birds. Results Multivariate statistical analysis identified 138 differential serum metabolites between mock- and C. baileyi-infected chickens at 5 days post-infection (dpi), including 115 upregulated and 23 downregulated compounds. These metabolites were significantly enriched into six pathways, of which two pathways associated with energy and lipid metabolism, namely glycerophospholipid metabolism and sphingolipid metabolism, respectively, were the most enriched. Interestingly, some important immune-related pathways were also significantly enriched, including the intestinal immune network for IgA production, autophagy and cellular senescence. Nine potential C. baileyi-responsive metabolites were identified, including choline, sirolimus, all-trans retinoic acid, PC(14:0/22:1(13Z)), PC(15:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PE(16:1(9Z)/24:1(15Z)), phosphocholine, SM(d18:0/16:1(9Z)(OH)) and sphinganine. Conclusions This is the first report on serum metabolic profiling of chickens with early-stage C. baileyi infection. The results provide novel insights into the pathophysiological mechanisms of C. baileyi in chickens. Graphic abstract

Objective: Platelet activation by stimulatory factors leads to an increase in intracellular calcium concentration ([Ca 2+ ] i ), which is essential for almost all platelet functions. Modulation of Ca 2+ influx and [Ca 2+ ] i in platelets has been emerging as a possible strategy for preventing and treating platelet-dependent thrombosis. Voltage-gated potassium 1.3 channels (Kv1.3) are highly expressed in platelets and able to regulate agonist-evoked [Ca 2+ ] i increase. However, the role of Kv1.3 channels in regulating platelet functions and thrombosis has not yet been elucidated. In addition, it is difficult to obtain a specific blocker for this channel, since Kv1.3 shares identical drug-binding sites with other K + channels. Here, we investigate whether specific blockade of Kv1.3 channels by monoclonal antibodies affects platelet functions and thrombosis. Approach and Results: In this study, we produced the anti-Kv1.3 monoclonal antibody 6E12#15, which could specifically recognize both human and mouse Kv1.3 proteins and sufficiently block Kv1.3 channel currents. We found Kv1.3 blockade by 6E12#15 inhibited platelet aggregation, adhesion, and activation upon agonist stimulation. In vivo treatment with 6E12#15 alleviated thrombus formation in a mesenteric arteriole thrombosis mouse model and protected mice from collagen/epinephrine-induced pulmonary thromboembolism. Furthermore, we observed Kv1.3 regulated platelet functions by modulating Ca 2+ influx and [Ca 2+ ] i elevation, and that this is mediated in part by P2X 1 . Interestingly, Kv1.3 −/− mice showed impaired platelet aggregation while displayed no abnormalities in in vivo thrombus formation. This phenomenon was related to more megakaryocytes and platelets produced in Kv1.3 −/− mice compared with wild-type mice. Conclusions: We showed specific inhibition of Kv1.3 by the novel monoclonal antibody 6E12#15 suppressed platelet functions and platelet-dependent thrombosis through modulating platelet [Ca 2+ ] i elevation. These results indicate that Kv1.3 could act as a promising therapeutic target for antiplatelet therapies.

Background Neoadjuvant therapy plus oesophagectomy has been accepted as the standard treatment for patients with potentially curable locally advanced oesophageal cancer. No completed randomized controlled trial (RCT) has directly compared neoadjuvant chemotherapy and neoadjuvant chemoradiation in patients with oesophageal squamous cell carcinoma (ESCC). The aim of the current RCT is to investigate the impact of neoadjuvant chemotherapy plus surgery and neoadjuvant chemoradiotherapy plus surgery on overall survival for patients with resectable locally advanced ESCC. Methods This open label, single-centre, phase III RCT randomized patients (cT2-T4aN + M0 and cT3-4aN0M0) in a 1:1 fashion to receive either the CROSS regimen (paclitaxel 50 mg/m2; carboplatin (area under the curve = 2), q1w, 5 cycles; and concurrent radiotherapy, 41.4 Gy/23 F, over 5 weeks) or neoadjuvant chemotherapy (paclitaxel 175 mg/m2; and cisplatin 75 mg/m2, q21d, 2 cycles). Assuming a 12% 5-year overall survival difference in favour of the CROSS regimen, 80% power with a two-sided alpha level of 0.05 and a 5% dropout each year for an estimated 3 years enrolment, the power calculation requires 456 patients to be recruited (228 in each group). The primary endpoint is 5-year overall survival, with a minimum 5-year follow-up. The secondary endpoints include 5-year disease-free survival, toxicity, pathological complete response rate, postoperative complications, postoperative mortality and quality of life. A biobank of pre-treatment and resected tumour tissue will be built for translational research in the future. Discussion This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies. Trial registration NCT04138212, date of registration: October 24, 2019.

Bisphenol A (BPA) exposure can increase the risk of immune-related diseases in later life. Vitamin D3 (Vit D3) has been shown to have multiple immunomodulatory actions and has been used to treat immune diseases. However, the potential beneficial effects of Vit D3 on BPA-induced adverse effects in the immune system have not explored. We hypothesize that VitD3 may ameliorate BPA-induced side effects in the immune system, even in offspring of VitD3-supplemented mothers. Here, we established our experimental model by exposing pregnant dams with 1000 nM BPA with or without VitD3 (0.25 μg/kg, 1 μg/kg and 4 μg/kg) treatment. We show that mother’s exposure to BPA increases proliferation of the spleen T helper 17 (Th17) cells and serum protein level of IL-17 in the offspring; however, VitD3 supplementation in mothers dose-dependently ameliorated these BPA-induced side effects on the immune system in the offspring as evidenced by attenuated upregulation of Th17 proliferation, and RORγt, IL-17, IL-6, and IL-23 expressions in the offspring. Our data provide the first evidence that maternal VitD3 supplementation offers benefits to the offspring by attenuating BPA-induced side effects on the immune system through vitamin D receptor (VDR)-dependent regulation of transcription factors and cytokines, suggesting its translational potential.

Exogenous H2 S donor, sodium hydrosulfide (NaHS), can influence the bleomycin-induced pulmonary fibrosis by attenuating the epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, but whether NaHS affects paraquat (PQ)-induced EMT and the molecular mechanisms remain unclarified. The aim of the present study is to examine the effect of exogenous NaHS on PQ-induced EMT in human alveolar epithelial cells (A549 cells) and assess if this effect occurs through regulating transforming growth factor (TGF)-β1/Smad2/3 signaling pathway. The expressions of endogenous H2 S producing enzymes, namely cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulfur transferase, were detected by reverse transcription-polymerase chain reaction and western blotting. The induced EMT was assessed by morphological and phenotypic characterizations, and the protein level of E-cadherin and vimentin were detected by western blotting. To investigate the effect of NaHS on PQ-induced EMT and potential mechanism, A549 cells were pretreated with NaHS before incubating with PQ and then evaluated by morphological changes, cell migration ability, the expression of EMT markers and TGF-β1/Smad2/3 signaling pathway related proteins. PQ significantly downregulated the expression levels of cystathionine β-synthase and cystathionine γ-lyase, but not 3-mercaptopyruvate sulfur transferase, in a time-dependent manner in A549 cells. Exogenous NaHS could significantly retard PQ-induced morphological changes and cell migration ability. Furthermore, exogenous NaHS significantly upregulated the expression of E-cadherin, whereas it downregulated the expression of vimentin. In addition, exogenous NaHS could also significantly attenuates PQ-induced TGF-β1, phosphorylated Smad2/3 proteins expression, which induced by PQ in a time-dependent manner. This study provides the first evidence that exogenous NaHS attenuates PQ-induced EMT and migration of human alveolar epithelial cells through regulating the TGF-β1/Smad2/3 signaling pathway.

Mg deficiency affected only the differentiation zone in Citrus sinensis roots. Phloem impairment in Mg-deficient leaves resulted in cell wall lignifications of both vascular cambium and spongy parenchyma cells. Decrease of Mg content in the roots hampered secondary lignification of endodermal and protoxylem cell walls. Magnesium (Mg) is a vital nutrient for plant photosynthesis and biochemical reactions. Mg deficiency is a widespread problem in citrus production, directly affecting yield and quality. With the objective of investigating the relationship among root and leaf anatomy, photosynthetic efficiency and mineral nutrient uptake and transport in Mg-deficient citrus, the effects of Mg deficiency in ‘Xuegan’ (Citrus sinensis) seedlings on plant biomass, leaf gas exchange and chlorophyll, nutrient contents, root and leaf anatomy and lignin biosynthesis were studied. Mg deficiency decreased root and shoot dry weight, leaf CO2 assimilation, chlorophyll and Mg, phosphorus (P), boron (B), cupper (Cu) and iron (Fe) concentration in roots, stems and leaves, and increased potassium (K) and calcium (Ca) concentration. Mg deficiency in the leaves resulted in phloem disorder that blocked phloem transport, leading to carbohydrate accumulation in chloroplasts and secondary lignifications of both vascular cambium and spongy parenchyma cell walls. In contrast, decrease of Mg content in the roots hampered lignin deposition on the protoxylem and endodermal cell walls at the root differentiation zone. Poorly lignified Casparian strip and xylem cell walls in Mg-deficient root tips might decrease xylem loading efficiency of nutrients, lowering their contents in the above ground parts, which ultimately inhibited whole plant growth.

The ability to characterize and predict tumor phenotypes is crucial to precision medicine. In this study, we present an integrative computational approach using a genome-wide association analysis and an Elastic Net prediction method to analyze the relationship between DNA copy number alterations and an archive of gene expression signatures. Across breast cancers, we are able to quantitatively predict many gene signatures levels within individual tumors with high accuracy based upon DNA copy number features alone, including proliferation status and Estrogen-signaling pathway activity. We can also predict many other key phenotypes, including intrinsic molecular subtypes, estrogen receptor status, and TP53 mutation. This approach is also applied to TCGA Pan-Cancer, which identify repeatedly predictable signatures across tumor types including immune features in lung squamous and basal-like breast cancers. These Elastic Net DNA predictors could also be called from DNA-based gene panels, thus facilitating their use as biomarkers to guide therapeutic decision making., Effective precision medicine strategies rely on the ability to predict tumour behaviour based on molecular characteristics. Here, the authors build models to predict multiple distinct gene expression patterns using DNA copy number alterations

Occupational trichloroethylene (TCE) exposure can induce hypersensitivity dermatitis and severe liver injury. Recently, several clinical investigations indicate that viral infection, such as human herpesvirus-6, is associated with hepatic dysfunction in patients with TCE-related generalized skin disorders. However, whether viral infection potentiates TCE-induced liver injury remains unknown. This study aimed to explore the contribution of viral infection to the development of TCE-sensitization-induced liver injury in BALB/c mice. Female BALB/c mice were randomly assigned into four groups: solvent control group (n = 20), TCE group (n = 80), poly(I:C) group (n = 20) and combination of TCE and poly(I:C) (poly(I:C)+TCE) group (n = 80). Poly(I:C) (50 μg) was i.p. administrated. TCE and poly(I:C)+TCE groups were further divided into sensitization and non-sensitization subgroup. Complement 3 and C3a protein levels, and complement factors were measured. Combination treatment significantly enhanced TCE-induced liver injury, decreased complement 3, but increased C3a in serum and liver tissues in sensitization group. These changes were not correlated with the hepatic complement 3 transcription. Moreover, combination treatment specifically promoted complement factor B, but not factor D and factor H expressions. These data provide first evidence that poly(I:C) potentiates liver injury in BALB/c mouse model of TCE-sensitization. Upregulated C3a and factor B contributes to the poly(I:C) action in TCE-induced liver injury. This new mode of action may explain increased risk of chemical-sensitization induced tissue damage by viral infection.

Occurrence and risk related to nitrosamines, a group of carcinogenic compounds found in some drinking waters and beer, are studied. An analytical method using a solid-phase micro-extraction (SPME) along with gas chromatography (GC) and mass spectrometry (MS) was developed to determine seven N-nitrosamines in drinking water and beer, including N-nitrosomethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), N-nitrosodi-n-propylamine (NDPA), N-nitrosopyrrolidine (NPyr), N-nitrosopiperidine (NPip), and N-nitrosodinbutylamine (NDBA). The analysis can be completed in 70 min, and only a 4 mL sample is required, with a detection limit of 0.1–0.8 ng/L for the seven nitrosamines in water and 6–15.7 ng/L in beer. The method was applied to analyze water samples collected from 11 reservoirs and their associated drinking water treatment plants in Taiwan and 10 beer samples from 6 brands with factories located in 6 countries. In the drinking water samples, all seven N-nitrosamines were detected, with NDMA having the highest level at 10.2 ng/L. In the beer samples, NDMA was detected at much lower concentrations (0.12–0.23 μg/L) than the 5 μg/L US standard, while NPip was detected at much higher concentrations (4.1–5.3 μg/L) compared to NDMA. The risk assessment indicates that the risk associated with NDMA is the highest among the studied N-nitrosamines in Taiwan's drinking water, with an average cancer risk of 6.4 × 10−06. For other nitrosamines, the risks are all below 10−6. For the risks associated with N-nitrosamines in beer, NDMA, NDEA, NDPA, and NPip are in the range of 1.5 × 10−05 to 4.6 × 10−04, while that for other nitrosamines are much lower. As for beer, no information for NPip and no modern information for NDEA and NDPA have previously been available, more studies about nitrosamines in beer are suggested for better estimation and control of the risks associated with consumption of beer.

Fluorescence microscopy is an intuitive detection method of β-amyloid (Aβ) fibrillation, which usually occurs in early-stage Alzheimer's disease. With the aid of single-molecular localization of reversibly-activated fluorogens, the limit of optical diffraction in fluorescence microscopy can be overcome and the imaging resolution can be promoted to the sub-100 nm boundary. Aggregation-induced emission (AIE) is the fluorogenic emission behavior in which fluorescence is significantly enhanced due to the restriction of intramolecular motion when the fluorogens aggregate together or bind with specific targets. Reversible binding events of AIE-active fluorogens cause fluorescence switching enabling single-molecular localization and super-resolution imaging. Here, we report a series of super-resolution fluorescent probes with AIE activity, which are used for the detection and super-resolution imaging of fibrillar amyloids. The AIE-active fluorogens show superior in vitro sensitivity to fibrillar amyloids of hen egg white lysozyme (HEWL), which is usually used as a model protein for amyloid studies, with the limit of detection down to 63.71 nM. The fluorescence colocalization imaging indicates the excellent ex vivo targeting capability of Aβ plaques in mouse brain slices, with the colocalization degrees more than 90%. Based on the reversible binding between AIE-fluorogens and Aβ fibrils, the AIE-based super-resolution imaging of in vitro Aβ fibrillation in tubes and ex vivo Aβ plaques in mouse brain slices is accomplished. The detailed structure information reveals that Aβ plaques in the mouse brain are composed of numerous radiant nanofibrils with an optical imaging resolution of about 30 nm.

The interfacial and micellization behavior of binary mixture of an amino sulfonate amphoteric 3-(N-dodecyl ethylenediamino)-2-hydropropyl sulfonate (C12AS) and a cationic octadecyltrimethyl ammonium bromide (OTAB) were investigated in aqueous solution without or with a 70 g/L alcohol (including methanol, ethanol, 1-propanol and 1-butanol) at 313.15 K by both the tensiometry and the conductometry. The surface excess concentration, the minimum area per surfactant molecule at the saturated interface and the standard free energy of adsorption at the air-liquid interface were adopted to be characteristic of the interfacial adsorption monolayer. Based on the pseudophase separation model and the regular solution theory, the Clint’s model and the Rubingh’s model was used to obtain the related parameters including the interaction parameters between two surfactant molecules, the compositions and the activity coefficients in mixed micelle and thermodynamic parameters. The effect of the alcohol chain length on the interfacial adsorption and the mixed micellization was discussed. The addition of short chain alcohol influences the properties of mixed cosolvent, the conformation of C12AS molecule and the electrostatic interaction between two surfactant molecules. Thermodynamic data shows that the presence of alcohol with a longer chain is beneficial to form the adsorption monolayer and the mixed micelle, and also it depresses the contribution of entropy to the process of micellization. These findings help with understanding the mechanism on the effect of short chain alcohol on the interfacial and micellization behavior of binary surfactant mixtures and further designing the surfactant formulations.

Electrospun fiber-based composite polymer electrolyte membranes (PEMs) with artifically constructed long-range proton conductive channels have been drawn considerable attention due to their promising applications in fuel cells. Herein, high level of superacidic phosphotungstic acid (PWA) coated poly(vinylidene fluoride) (PVDF/PWA) electrospun mat as a new three-dimensional proton conducting network was prepared using a polydopamine-assisted coating method. Polydopamine can homogeneously adhere PWA on the PVDF nanofibers' surface. This new mat was then used to fabricate PEMs after filled with polycation chitosan. With the introduction of the PVDF/PWA network, the obtained chitosan filled composite membrane showed significantly improved proton conductivity, which was about one order of magnitude higher than that of the chitosan filled pure PVDF membrane. Moreover, the chitosan can not only effectively inhibit the leaching out of PWA through the strong static interaction between chitosan and PWA, but also act as an ionomer matrix to further increase the proton transport. The direct methanol fuel cell of the PVDF/PWA composite membrane exhibits a peak power density of 85.0 mW cm −2 , whereas it is only 47.5 mW cm −2 for the membrane without PWA coating. Consequently, this study provides a new strategy to design high-performance PEMs by utilization of solid superacid coated electrospun nanofibers.

The effects of CaO and Na2CO3 on the reduction of high silicon iron ores at 1 250 °C were studied. The experimental results showed that the metallization rate was significantly hindered by the addition of CaO and Na2CO3, particularly at the early stage of roasting, compared to the rate without additives. In the absence of additives, iron oxides were quickly reduced to metallic iron, and fayalite was difficult to form. When CaO and Na2CO3 were added, the low reducible iron-containing silicate compounds formed and melted, subsequently retarding the metallization process. The inhibition of Na2CO3 was more noticeable than that of CaO, and higher Na2CO3 doses resulted in stronger inhibition of the increased metallization rate. However, when Na2CO3 was added prior to CaO, the liquid phase formed, which facilitated the growth of the metallic phase. To reinforce the separation of the metallic phase and slag, an appropriate amount of liquid phase generated during the reduction is necessary. It was shown that when 10% CaO and 10% Na2CO3 were added, a high metallization rate and larger metallic iron particles were obtained, thus further decreasing the required Na2CO3 dosage.

A combination of high-energy ball milling and constant pressure chemical vapor deposition was used to prepare carbon-coated SiO/ZrO2 composites. It was found that the as-prepared composites were composed of amorphous carbon, amorphous SiO, and paracryslalline ZrO2. The electrochemical analysis results revealed excellent electrochemical performances for the composites, including a high initial discharge capacity (1737 mA h g−1), a remarkable cyclic stability (reversible capacity of 721 mA h g−1 at 800 mA g−1, after 100 cycles), and a good rate capability (870 mA h g−1 at 800 mA g−1). These features demonstrate that these composites are promising alternative candidates for high-efficiency electrode materials of Li-ion batteries.

Objectives: We aimed to confirm whether RASSF10 activated the p53 signalling pathway, thereby modulating cell proliferation, migration, invasion, and apoptosis in papillary thyroid carcinoma (PTC) cells. Methods: A total of 108 PTC tissue samples and normal adjacent tissues were obtained. RT-PCR and Western blotting analyses were performed to detect RASSF10 expression, and methylation levels of RASSF10 were estimated by methylation-specific PCR (MSP). We also detected the expression and methylation status of RASSF10 in both a human PTC cell line (K1) and a normal thyroid cell line (FRTL5). After transfection of cells with empty vector pcDNA3.1, pcDNA3.1-RASSF10, p53 siRNA and shRASSF10, Coulter counter, colony-formation, wound healing, Transwell and flow cytometry analyses were performed to examine the role of RASSF10 in cell proliferation, migration, invasion, and apoptosis. Finally, the expression of p53, p21, Bcl-2 and Bax were detected using Western Blotting analyses. Results: RASSF10 expression in PTC tissues was significantly lower and hyper-methylated compared to normal adjacent tissues. In addition, RASSF10 was significantly down-regulated and hyper-methylated in K1 cells compared to FRTL5 cells. In addition, suppressed proliferation and significantly induced apoptosis of K1 cells were observed after transfection with pcDNA3.1-RASSF10 (P < 0.05). Furthermore, RASSF10 activated the p53 signalling pathway and regulated the expression of p53, p21, Bcl-2 and Bax. Furthermore, p53 siRNA could antagonize the effects of RASSF10 in K1 cells. Conclusions: RASSF10 induces apoptosis in PTC cells by activating the p53 signalling pathway, indicating its role as a treatment target for PTC.

Protein hydroxylation affects protein stability, activity, and interactome, therefore contributing to various diseases including cancers. However, the transiency of the hydroxylation reaction hinders the identification of hydroxylase substrates. By developing an enzyme-substrate trapping strategy coupled with TAP-TAG or orthogonal GST- purification followed by mass spectrometry, we identify adenylosuccinate lyase (ADSL) as an EglN2 hydroxylase substrate in triple negative breast cancer (TNBC). ADSL expression is higher in TNBC than other breast cancer subtypes or normal breast tissues. ADSL knockout impairs TNBC cell proliferation and invasiveness in vitro and in vivo. An integrated transcriptomics and metabolomics analysis reveals that ADSL activates the oncogenic cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL proline 24 hydroxylation. Hydroxylation-proficient ADSL, by affecting adenosine levels, represses the expression of the long non-coding RNA MIR22HG, thus upregulating cMYC protein level. Our findings highlight the role of ADSL hydroxylation in controlling cMYC and TNBC tumorigenesis., The hydroxylase EgIN2 contributes to triple negative breast cancers. Here, using an enzyme-substrate trapping strategy, the authors identify ASDL as a bona fide substrate of EgIN2 promoting aggressive properties of TNBC via the activation of cMYC signaling.