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Abstract: Protein-ligand interactions are necessary for majority protein functions. Adenosine- 5’-triphosphate (ATP) is one such ligand that plays vital role as a coenzyme in providing energy for cellular activities, catalyzing biological reaction and signaling. Knowing ATP binding residues of proteins is helpful for annotation of protein function and drug design. However, due to the huge amounts of protein sequences influx into databases in the post-genome era, experimentally identifying ATP binding residues is costineffective and time-consuming. To address this problem, computational methods have been developed to predict ATP binding residues. In this review, we briefly summarized the application of machine learning methods in detecting ATP binding residues of proteins. We expect this review will be helpful for further research.

Concentration detection sensor owing ability of ion detection is very important in health monitoring. The traditional sweat sensors often possess a complex structure, fabrication process with chemical reactions dependent performance. In this work, we present an electrical double layer (EDL)-based iontronic sensor using a simple planar double electrodes structure without employing chemical reaction for electrolytes concentration detection. When the two working electrodes are connected via an electrolyte solution, the EDL-based capacitance changes with the concentration of the electrolyte and can be used in the detection of both inorganic and organic electrolytes. The electrical measurements show that the capacitance has a good linear relationship with the concentration of NaCl solution with a range of 0.05-10 mM, with the R-square value of 99.9%. The sensor shows a high concentration resolution of 0.01 mM and possesses both concentration detection and molecular size identification upon combining a microporous membrane. The capacitive iontronic sensor shows great potential for applications in the detection of the salinity of seawater, biological ionic liquid, and assistance for disabled people who lose their sense of taste.

The soil carbon (C) and nitrogen (N) dynamic was usually considered as a minor change based on a static process in the sealed soil under decades of impervious surface (IS). However, no systematic studies concerning the soil organic carbon (SOC) and nitrogen (SON) dynamic were conducted under IS in contrast with urban vegetation (i.e., forest, grass). Here we utilized fractional distillation of soils as well as stable isotopic analysis to examine soil C&N cycles after 20 and 30 years of vegetation planting and IS construction in Guangzhou and Shenzhen, Pearl River Delta, China. Soil samples including bare soil (CK) and four land use treatments were split into different chemical fractions. Then we analyzed the C&N content, C/N ratio, δ13C, δ15N, C&N recalcitrant indices (RIC, RIN), and the mean residence time (MRT). We found that the soil C&N increased first (i.e., 20 years) because of enhanced C&N stocks in both labile (LP) and recalcitrant pool (RP), and then stabilized or decreased (i.e., 30 years) with the IS ages in both cities. IS had a lower SOC decomposition rate and thus resulted in the five to ten times longer MRT (about 259–465 years) than that in vegetated soils (about 39–55 years). Moreover, the SOC&SON always showed a decoupling relation in labile pools (i.e., LC and LN) in forests in both cities. The study showed the IS remarkably altered the soil C&N dynamics, showing a great difference in SOC&SON fractions composition and turnover compared with vegetation.

This study assessed the effect and potential molecular mechanism of tanshinone IIA on fracture healing. Mice model with fracture were established. Digital radiographic photographic system was used to detect callus formation after treatment with tanshinone II A (Tan IIA) and alkaline phosphatase (ALP) staining analyzed ALP activity. Osteoblast proliferation was also measured. Western blot and Quantitative real-time PCR (qRT-PCR) measured osteogenic markers expression. Compared with control group, Tan IIA treatment could increase callus formation, stimulate osteoblast proliferation, osteogenic proteins and genes expression, and activate mTORC1 signaling pathway. However, Tan IIA’s effects were significantly inhibited after rapamycin treatment. Tan IIA regulates osteoblast differentiation by mTORC1 signaling and promotes intramembranous ossification in the process of callus formation, which accelerates bone healing.

Sepsis and sepsis‐induced skeletal muscle atrophy are common in patients in intensive care units with high mortality, while the mechanisms are controversial and complicated. In the present study, the atrophy of skeletal muscle was evaluated in sepsis mouse model as well as the apoptosis of muscle fibres. Sepsis induced atrophy of skeletal muscle and apoptosis of myofibres in vivo and in vitro. In cell‐based in vitro experiments, lipopolysaccharide (LPS) stimulation also inhibited the proliferation of myoblasts. At the molecular level, the expression of polo‐like kinase 1 (PLK1) and phosphorylated protein kinase B (p‐AKT) was decreased. Overexpression of PLK1 partly rescued LPS‐induced apoptosis, proliferation suppression and atrophy in C2C12 cells. Furthermore, inhibiting the AKT pathway deteriorated LPS‐induced atrophy in PLK1‐overexpressing C2C12 myotubes. PLK1 was found to participate in regulating apoptosis and E3 ubiquitin ligase activity in C2C12 cells. Taken together, these results indicate that sepsis induces skeletal muscle atrophy by promoting apoptosis of muscle fibres and inhibiting proliferation of myoblasts via regulation of the PLK1‐AKT pathway. These findings enhance understanding of the mechanism of sepsis‐induced skeletal muscle atrophy.

Background Chemical exchange saturation transfer (CEST) is an emerging metabolic MRI technique to map creatine distribution in the myocardium. Purpose To investigate the feasibility of using a contrast-free CEST technique to evaluate cardiac involvement in amyloid light-chain (AL) amyloidosis. Study type Prospective. Population Forty patients with biopsy-proven AL amyloidosis (age 57.6 ± 9.1 years, 31 males) and 20 healthy controls (age 42.8 ± 13.8 years, 13 males). Field strength/sequence A 3.0 T, CEST imaging using a single-shot FLASH sequence, T1 mapping with a modified Look-Locker inversion recovery sequence and late gadolinium enhancement (LGE) imaging with a phase-sensitive inversion recovery gradient echo sequence. Assessment The average CEST was calculated in the basal short-axis slice of the entire left ventricle and septum. LGE was assessed subjectively (none/patchy/global) and extracellular volume (ECV), CEST and T1 maps generated. Statistical tests Comparison between patient groups and healthy controls was performed by one-way analysis of variance with post hoc Bonferroni correction. Correlation was assessed using the Pearson's r correlation or Spearman ρ correlation. Statistical significance was defined as P Results Global (0.09 ± 0.03 vs. 0.11 ± 0.02) and septal (0.09 ± 0.03 vs. 0.11 ± 0.03) basal short-axis CEST was significantly decreased in patients with AL amyloidosis compared to the controls. Global CEST correlated significantly with Mayo stage (ρ = -0.508), NYHA Class (ρ = -0.430), LVEF (r = 0.511), mass index (r = -0.373), LGE (ρ = -0.537), ECV (r = -0.544), and T2 (r = -0.396). Septal CEST correlated significantly with LVEF (r = 0.395), LGE (ρ = -0.330), and ECV (r = -0.391). Data conclusions This study highlights the potential of CEST MRI to identify cardiac involvement and evaluate disease burden and to give insight into cellular changes intermediary between function and structure in AL amyloidosis patients. Evidence level 2 TECHNICAL EFFICACY: Stage 2.

Osteoporosis is one of the most common metabolic bone diseases affecting millions of people. We previously found that harmine prevents bone loss in ovariectomized mice via increasing preosteoclast platelet‐derived growth factor‐BB (PDGF‐BB) production and type H vessel formation. However, the molecular mechanisms by which harmine promotes preosteoclast PDGF‐BB generation are still unclear. In this study, we revealed that inhibitor of DNA binding‐2 (Id2) and activator protein‐1 (AP‐1) were important factors implicated in harmine‐enhanced preosteoclast PDGF‐BB production. Exposure of RANKL‐induced Primary bone marrow macrophages (BMMs), isolated from tibiae and femora of mice, to harmine increased the protein levels of Id2 and AP‐1. Knockdown of Id2 by Id2‐siRNA reduced the number of preosteoclasts as well as secretion of PDGF‐BB in RANKL‐stimulated BMMs administrated with harmine. Inhibition of c‐Fos or c‐Jun (components of AP‐1) both reversed the stimulatory effect of harmine on preosteoclast PDGF‐BB production. Dual‐luciferase reporter assay analyses determined that PDGF‐BB was the direct target of AP‐1 which was up‐regulated by harmine treatment. In conclusion, our data demonstrated a novel mechanism involving in the production of PDGF‐BB increased by harmine, which may provide potential therapeutic targets for bone loss diseases.

One of the challenges of exploiting extracellular vesicles (EVs) as a disease biomarker is to differentiate EVs released by similar cell types or phenotypes. This paper reports a high-throughput and label-free EV microarray technology to differentiate EVs by simultaneous characterization of a panel of EV membrane proteins. The EsupplV microarray platform, which consists of an array of antibodies printed on a photonic crystal biosensor and a microscopic hyperspectral imaging technique, can rapidly assess the binding of the EV membrane proteins with their corresponding antibodies. The EV microarray assay requires only a 2 μL sample volume and a detection time of less than 2 h. The EV microarray assay was validated by not only quantifying seven membrane proteins carried by macrophage-derived EVs but also distinguishing the EVs secreted by three macrophage phenotypes. In particular, the EV microarray technology can generate a molecular fingerprint of target EVs that can be used to identify the EVs' parental cells, and thus has utility for basic science research as well as for point-of-care disease diagnostics and therapeutics.

The design of a powerful heterojunction structure and the study of the interfacial charge migration pathway at the atomic level are essential to mitigate the photocorrosion and recombination of electron-hole pairs of CdS in photocatalytic hydrogen evolution (PHE). A temperature-induced self-assembly strategy has been proposed for the syntheses of Prussian blue analogue (PBA)/CdS nanocomposites with beaded structure. The specially designed structure had evenly exposed CdS which can efficiently harvest visible light and inhibit photocorrosion; meanwhile, PBA with a large cavity provided channels for mass transfer and photocatalytic reaction centers. Remarkably, PB-Co/CdS-LT-3 exhibits a PHE rate of 57 228 μmol h-1 g-1, far exceeding that of CdS or PB-Co and comparable to those of most reported crystalline porous material-based photocatalysts. The high performances are associated with efficient charge migration from CdS to PB-Co through CN-Cd electron bridges, as revealed by the DFT calculations. This work sheds light on the exploration of heterostructure materials in efficient PHE.

Exosomes have been considered as high-quality biomarkers for disease diagnosis, as they are secreted by cells into extracellular environments as nanovesicles with rich and unique molecular information, and can be isolated and enriched from clinical samples. However, most existing exosome assays, to date, require time-consuming isolation and purification procedures; the detection specificity and sensitivity are also in need of improvement for the realization of exosome-based disease diagnostics. This paper reports a unique exosome assay technology that enables completing both magnetic nanoparticle (MNP)-based exosome extraction and high-sensitivity photonic crystal (PC)-based label-free exosome detection in a single miniature vessel within one hour, while providing an improved sensitivity and selectivity. High specificity of the assay to membrane antigens is realized by functionalizing both the MNPs and the PC with specific antibodies. A low limit of detection on the order of 107 exosome particles per milliliter (volume) is achieved because the conjugated MNP–exosome nanocomplexes offer a larger index change on the PC surface, compared to the exosomes alone without using MNPs. Briefly, the single-step exosome assay involves (i) forming specific MNP–exosome nanocomplexes to enrich exosomes from complex samples directly on the PC surface at the bottom of the vessel, with a >500 enrichment factor, and (ii) subsequently, performing in situ quantification of the nanocomplexes using the PC biosensor. The present exosome assay method is validated in analyzing multiple membrane proteins of exosomes derived from murine macrophage cells with high selectivity and sensitivity, while requiring only about one hour. This assay technology will provide great potential for exosome-based disease diagnostics.

Transcription factors play key roles in cell-fate decisions by regulating 3D genome conformation and gene expression. The traditional view is that methylation of DNA hinders transcription factors binding to them, but recent research has shown that many transcription factors prefer to bind to methylated DNA. Therefore, identifying such transcription factors and understanding their functions is a stepping-stone for studying methylation-mediated biological processes. In this paper, a two-step discriminated method was proposed to recognize transcription factors and their preference for methylated DNA based only on sequences information. In the first step, the proposed model was used to discriminate transcription factors from non-transcription factors. The areas under the curve (AUCs) are 0.9183 and 0.9116, respectively, for the 5-fold cross-validation test and independent dataset test. Subsequently, for the classification of transcription factors that prefer methylated DNA and transcription factors that prefer non-methylated DNA, our model could produce the AUCs of 0.7744 and 0.7356, respectively, for the 5-fold cross-validation test and independent dataset test. Based on the proposed model, a user-friendly web server called TFPred was built, which can be freely accessed at http://lin-group.cn/server/TFPred/., Graphical Abstract, Transcription factors binding to methylated DNA perform special and unclear functions. Lin and colleagues developed a machine-learning-based method to predict transcription factors and their preference for methylated DNA, which will help the discovery of methylated DNA-bound transcription factors and the study of their functions.

The sluggish kinetics and unclear mechanism have significantly hindered the development of Li-CO2 batteries. Here, a Li-CO2 battery cathode catalyst based on a porphyrin-based covalent organic framework (TTCOF-Mn) with single metal sites is reported to reveal intrinsic catalytic sites of aprotic CO2 conversion from the molecular level. The battery with TTCOF-Mn exhibits a low overpotential of 1.07 V at 100 mA/g as well as excellent stability at 300 mA/g, which is one of the best Li-CO2 battery cathode catalysts to date. The unique features of TTCOF-Mn including uniform single-Mn(II)-sites, fast Li+ transfer pathways, and high electron transfer efficiency contribute to effective CO2 reduction and Li2CO3 decomposition in the Li-CO2 system. Density functional theory calculations reveal that different metalloporphyrin sites lead to different reaction pathways. The single-Mn(II) sites in TTCOF-Mn can activate CO2 and achieve an efficient four-electron CO2 conversion pathway. It is the first example to reveal the catalytic active sites and clear reaction pathways in aprotic Li-CO2 batteries.

Polyoxometalates (POMs), possessing multiple-electron redox ability, controllable size, and precise structure, hold much promise to be applied as anode materials in lithium-ion batteries (LIBs). Ho...

The Alzheimer's disease related peptide, Amyloid-beta (Aβ)1-40 and 1-42, has proven difficult to be purified as a recombinant monomeric protein due its expression in E. coli leading to the formation of insoluble inclusion bodies and its tendency to quickly form insoluble aggregates. A vast array of methods have been used so far, yet many have pitfalls, such as the use of tags for ease of Aβ isolation, the formation of Aβ multimers within the time frame of extraction, or the need to reconstitute Aβ from a freeze-dried state. Here, we present a rapid protocol to produce highly pure and monomeric recombinant Aβ using a one-step ion exchange purification method and to label the peptide using a maleimide dye. The washing, solubilization, and purification steps take only 3 h. We also present a protocol for the isolation of Aβ-mCherry from mammalian cells.

Here, we detected platelet extravasation from blood vessels in both mouse and human hepatocellular carcinoma (HCC) tissues. We show C‐X3‐C chemokine ligand 1 (CX3CL1) derived from HCC cells induces platelet infiltration through a CX3CR1/Syk/PI3K pathway and the infiltrated platelets promote the apoptosis of HCC cells. These findings confirm that platelets are important factors in tumor regulation., The mechanisms and biological functions of migrating platelets in cancer remain largely unknown. Here, we analyzed platelet infiltration in hepatocellular carcinoma. We detected platelet extravasation in both mouse and human HCC tissues. CX3CL1 directly induced platelet migration, and hypoxia enhanced platelet migration by upregulating CX3CL1 expression. Knocking down CX3CL1 in HCC cells reduced platelet migration in vitro, as well as infiltration of HCC tissue in an orthotopic HCC mouse model. Components of the CX3CR1/Syk/PI3K pathway were essential for CX3CL1‐induced platelet migration. Migrating platelets induced HCC cell apoptosis in vitro, as indicated by a reduced mitochondrial membrane potential and an increased percentage of apoptotic cells. In the orthotopic tumor implantation model, decreased platelet infiltration was associated with accelerated tumor growth. Taken together, our findings indicate that HCC cell‐derived CX3CL1 contributes to tumor infiltration by platelets, which in turn promotes apoptosis of HCC cells.

Graphical abstract, Highlights • Magnetic double-layer MOFs was prepared with porous crystal structure. • MMOFs have high adsorption capacity for fipronil pesticides. • Adsorption model analysis fitted the Freundlich adsorption model. • Removal rate of fipronil in water and cucumber were 70.9–99.7%., In this study, a novel metal-organic framework (M-ZIF-8@ZIF-67) was successfully prepared using the single layer Fe3O4-ZIF-8 as magnetic core and wrapped a layer of ZIF-67 outer. This M-ZIF-8@ZIF-67 was employed as an adsorbent for the adsorption and removal of fipronil and its metabolites from environmental water and cucumber samples. The characterization results suggested that M-ZIF-8@ZIF-67 has the double layer structure a polyhedral structure with uniform pores, while ZIF-67 was successfully coated on the surface of Fe3O4-ZIF-8. The unique structure endowed M-ZIF-8@ZIF-67 a high surface area (219 m2/g) and high adsorption capacity for fipronil, fipronil desulfinyl, fipronil sulfide and fipronil sulfone. To our knowledge, this is the first report detailing the adsorption properties of M-ZIF-8@ZIF-67 with double layer structure relating to the adsorption and removal of pesticides. Furthermore, the adsorption model analysis demonstrated that the static adsorption data fitted the Freundlich bimolecular layer adsorption model better than the Langmuir monolayer adsorption model. This study indicates that M-ZIF-8@ZIF-67 has significant potential in the adsorption and removal of fipronil and its metabolites in water and vegetable samples.

Mitochondrial dysfunction has long been implicated in the neurodegenerative disorder Parkinson's disease (PD); however, it is unclear how mitochondrial impairment and α-synuclein pathology are coupled. Using specific mitochondrial inhibitors, EM analysis, and biochemical assays, we report here that intramitochondrial protein homeostasis plays a major role in α-synuclein aggregation. We found that interference with intramitochondrial proteases, such as HtrA2 and Lon protease, and mitochondrial protein import significantly aggravates α-synuclein seeding. In contrast, direct inhibition of mitochondrial complex I, an increase in intracellular calcium concentration, or formation of reactive oxygen species, all of which have been associated with mitochondrial stress, did not affect α-synuclein pathology. We further demonstrate that similar mechanisms are involved in amyloid-β 1-42 (Aβ42) aggregation. Our results suggest that, in addition to other protein quality control pathways, such as the ubiquitin-proteasome system, mitochondria per se can influence protein homeostasis of cytosolic aggregation-prone proteins. We propose that approaches that seek to maintain mitochondrial fitness, rather than target downstream mitochondrial dysfunction, may aid in the search for therapeutic strategies to manage PD and related neuropathologies.

The structural modification of polysaccharides directly affects their physicochemical properties and applications. Dextran, a chained polysaccharide, consists of multiple d -glucose molecules with repetitive structures. In this study, the physicochemical properties of oxidized dextran (DO) at different concentrations of NaClO/NaBr and H2O2 were compared. The results showed that NaClO/NaBr oxidation is more conducive to the formation of carboxyl groups. Oxidized dextran with NaClO/NaBr (DOB) showed good iron (III) chelating ability, and the DOB‑iron (III) complex (DOBIC) had an iron content of 28.31%. According to structural analysis, NaClO/NaBr (2 g/100 g of active chlorine) and H2O2 (4 g/100 g), respectively, oxidize the C1 and C2 hydroxyl groups of dextran to carboxyl groups and open the ring when DO and iron have the strongest chelation ability. The complex is indeed a chelate iron complex, and iron core is composed of iron oxyhydroxide or the β-FeOOH mineral polymorph. These results indicate that DOBIC is expected to be a good iron supplement or food additive to strengthen iron.

Background: Diabetes increases the risk for various cancers without established mechanisms. Centrosome amplification can initiate tumorigenesis in genetically modified cells. However, the findings from genetically modified experimental models may be far away from reality. We have reported that diabetes promotes the occurrence of centrosome amplification in different types of cells, implicating that centrosome amplification is a candidate mechanism underlying the diabetes-promoted tumorigenesis. In the present study, we investigated the molecular mechanisms of the centrosome amplification triggered by high glucose, insulin and palmitic acid using HCT116 colon cancer cells as an experimental model. Results: We found that KIF2A was localized in the centrosomes. The experimental treatment induced the binding between ROCK1 and KIF2A, although did not increase the protein level of KIF2A. The molecular docking modeling analysis also showed that the two proteins had the binding/interaction potential. We used siRNA of each protein to knockdown their expression level, as a tool to disrupt the ROCK1-KIF2A complex, which attenuated the treatment-induced centrosome amplification. Conclusions: Our results suggest that the binding between ROCK1 and KIF2A signals for the diabetes-associated centrosome amplification. This provides a molecular target for the inhibition of the centrosome amplification, which might be required for assessing the role of centrosome amplification in cancer in the nature, such as cancer in diabetes.

A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY., Normally, norepinephrine (NE) and acetylcholine (ACh) production is maintained at a balanced level in bone, so that osteocytes cannot generate excessive neuropeptide Y (NPY) to favor bone marrow mesenchymal stem/stromal cell adipogenesis rather than osteogenesis. With aging/estrogen deficiency, sympathetic overactivity, and decreased parasympathetic activity cause NE overproduction and ACh reduction, resulting in excess osteocyte NPY generation and subsequent bone‐fat imbalance.

Rheumatoid arthritis (RA) is a classic autoimmune disease characterized by uncontrolled synovial proliferation, pannus formation, cartilage injury, and bone destruction. The specific pathogenesis of RA, a chronic inflammatory disease, remains unclear. However, both key glycolysis rate-limiting enzymes, hexokinase-II (HK-II), phosphofructokinase-1 (PFK-1), and pyruvate kinase M2 (PKM2), as well as indirect rate-limiting enzymes, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), are thought to participate in the pathogenesis of RA. In here, we review the latest literature on the pathogenesis of RA, introduce the pathophysiological characteristics of HK-II, PFK-1/PFKFB3, and PKM2 and their expression characteristics in this autoimmune disease, and systematically assess the association between the glycolytic rate-limiting enzymes and RA from a molecular level. Moreover, we highlight HK-II, PFK-1/PFKFB3, and PKM2 as potential targets for the clinical treatment of RA. There is great potential to develop new anti-rheumatic therapies through safe inhibition or overexpression of glycolysis rate-limiting enzymes.

Efficient conversion of carbon dioxide (CO2) into value-added products is essential for clean energy research. Design of stable, selective, and powerful electrocatalysts for CO2 reduction reaction (CO2RR) is highly desirable yet largely unmet. In this work, a series of metalloporphyrin-tetrathiafulvalene based covalent organic frameworks (M-TTCOFs) are designed. Tetrathiafulvalene, serving as electron donator or carrier, can construct an oriented electron transmission pathway with metalloporphyrin. Thus-obtained M-TTCOFs can serve as electrocatalysts with high FECO (91.3%, −0.7 V) and possess high cycling stability (>40 h). In addition, after exfoliation, the FECO value of Co-TTCOF nanosheets (~5 nm) is higher than 90% in a wide potential range from −0.6 to −0.9 V and the maximum FECO can reach up to almost 100% (99.7%, −0.8 V). The electrocatalytic CO2RR mechanisms are discussed and revealed by density functional theory calculations. This work paves a new way in exploring porous crystalline materials in electrocatalytic CO2RR., The study of covalent organic frameworks (COFs) in electrocatalytic CO2 reduction reaction (CO2RR) has drawn much attention. Here the authors show a series of tetrathiafulvalene based COFs designed and exfoliated into nanosheets which exhibit high electrocatalytic CO2RR performance.

The robust cell-in-shell structure is highly desirable for endowing living cells with an artificial exoskeleton to defend them from many environmental factors such as osmotic pressure, shear force, heat, UV radiation, and enzymes. Cell encapsulation has shown potential applications in many fields and attracted increasing interest. However, the influences of the precursors on the cell viability during the shell formation process are not clear and seldom investigated. Here, zinc nitrite, zinc acetate and zinc sulfate were applied individually to synthesize zeolitic imidazolate framework-8 (ZIF-8) shells on living cells. All the zinc salt precursors could convert to a ZIF-8 layer on the living cell surface. The zinc salts and organic ligand did not exhibit obvious toxicity to yeast cells when applied individually. However, dead cells were observed during the living cell encapsulation process using different zinc precursors. Compared with zinc nitrate and zinc acetate, ZIF-8 formed by zinc sulfate led to a higher percentage of cell death, especially under high concentrations of zinc sulfate. Cell division was suppressed by the ZIF-8 shell but restored fully upon shell removal by EDTA solution or pH 4.0 buffer. Escherichia coli (E. coli) cells showed a lower percentage of cell death, indicating excellent tolerance to the ZIF-8 encapsulation process. This work illustrates the cell toxicity during the formation of ZIF-8 cell shells by different zinc salts and engineering of the cell growth by MOF coating, which could provide a foundation for further quantitative analysis and potential applications in biomedicine and bioengineering.

Temperature is a major factor affecting physical and mechanical rock properties. With increasing temperature, a series of variations enlarge the internal defects within rocks, resulting in physical and mechanical rock property variations. To explore the influence of temperature on the physical and micro-structure of limestone, the weighing test and P-wave velocity test were conducted on limestone after exposure to high temperature to reveal the evolution of the limestone mass and P -wave velocity. XRD, XRF, SEM, and mercury intrusion tests were also carried out to examine the mineral composition and content, micro-fracture morphology, porosity, and fractal dimension. The limestone mass and P-wave velocity decrease with increasing temperature. When T ≤ 400 °C, there is no obvious change in chemical composition and crystal structure; when T = 400–500 °C, the diffraction intensity of partial calcite decreases, and dolomite decomposes gradually; when T > 500 °C, illite decomposes gradually, while dolomite decomposes completely; and the diffraction intensity of calcite is significantly reduced. When T ≤ 200 °C, changes in trace minerals or impurities containing K2O and Na2O and the decomposition of illite oxide are dominant; when T = 400–600 °C, illite oxide, trace minerals, or impurities containing K2O and calcium hydroxide begin to decompose. When T = 600–800 °C, magnesite and dolomite begin to decompose. When T ≤ 200 °C, micro-fracture surfaces change slightly. When T = 200–500 °C, micro-fractures begin to develop and propagate gradually, most of which are intergranular cracks with a small number of transgranular cracks. When T > 500 °C, transgranular cracks occur in samples with locally broken crystals, and the cracking of the crystal structure occurs with increasing pore size. With increasing temperature, the limestone pore fractal dimension decreases gradually, and the higher the temperature, the greater the decrease. 400 °C to 500 °C is the temperature threshold interval that causes the pore structure change. These new pores, resulting from the increasing temperature, are primarily mesopores with a pore diameter of 1.0–10.0 μm. This research provides a scientific basis for the design and construction of rock engineering projects to be subjected to high temperatures, deep geological radioactive nuclear waste disposal sites, deep mines, and the exploitation of geothermal resources.

Here, we report our trials to regulate the luminescence performance of the macrocyclic samarium(III) complex and prepare four excellent luminescent Sm(III) complex-doped poly(methylmethacrylate) (PMMA) composites. Four 23-membered [1 + 1] Schiff-base macrocyclic mononuclear Sm(III) complexes, Sm-2a–Sm-2d, originating from dialdehydes with different pendant arms and 1,2-bis(2-aminoethoxy)ethane, have been constructed by the template method. Crystal structures reveal that every Sm(III) ion with the coordination geometry of a distorted bicapped square antiprism is capsulated by the macrocyclic cavity environment forming the “lasso-type” protection. Relative photophysical properties of macrocyclic Sm(III) complexes are carefully investigated in solid-state, methanol solution, and doped PMMA film, and all these show characteristic emissions of the Sm(III) ion associated with satisfactory lifetimes and quantum yields in all media, which could be comparable to reported outstanding examples. Especially, the luminescence performance for this type of Sm(III) complex could be regulated in the solid state by the use of different functional groups in the pendant arm while it is not achieved in solution and the doped PMMA composite. High emitting and air-stable plastic materials could be obtained when these Sm(III) complexes are doped in PMMA with 0.1 wt % mixing ratio, and the corresponding maximum lifetime and quantum yield are 61.2 μs and 0.63% in the case of complex Sm-2a, respectively. We believe that these highly luminescent “lasso-type” Sm(III) complexes and doped PMMA composites are valuable references in the design of luminescent lanthanide(III) hybrid materials.

Photocatalytic conversion of CO2 into energy carriers has been recognized as a highly promising strategy for achieving the virtuous carbon cycle in nature. The realization of this process depends on an efficient catalyst to reduce the reaction barrier. Herein, we report a series of transition metal ion modified crystalline covalent organic frameworks (COFs) for the heterogeneous photocatalytic reduction of CO2. By coordinating different kinds of open metal active species into COFs, the resultant DQTP (2,6-diaminoanthraquinone - 2,4,6-triformylphloroglucinol) COF-M (M = Co/Ni/Zn) exerts a strong influence on the activity and selectivity of products (CO or HCOOH). Significantly, DQTP COF-Co exhibits a high CO production rate of 1.02 × 103 μmol h−1 g−1, while DQTP COF-Zn has a high selectivity (90% over CO) for formic acid generation (152.5 μmol h−1 g−1). This work highlights the great potential of using stable COFs as platforms to anchor earth-abundant metal active sites for heterogeneous CO2 reduction.

Purpose This observational study aimed to identify the independent risk factors for both the acquisition and mortality of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) bacteremia and further assess the in vitro antimicrobial activities of ceftazidime–avibactam (CAZ/AVI) and aztreonam–avibactam (ATM/AVI) against recent CRE bacteremic isolates. Patients and methods This observational study was conducted to reveal the risk factors and mortality rate for CP-CRE bacteremia between 2012 and 2018 and also evaluate the in vitro antimicrobial activities of CAZ/AVI and ATM/AVI against recent CRE bacteremic isolates from 2016 to 2018. Results A total of 81 non-repetitive isolates were collected from 2012 to 2018, with 67.90% (55/81) being CP-CRE. Old age (P = 0.01), transfusion [odds ratio (OR): 17.19; 95% CI: 3.15–93.72; P = 0.001], longer ICU stay (P = 0.02), cancer (OR: 15.91; 95% CI: 3.56–71.37; P < 0.001), and previous carbapenem exposure (OR: 27.86; 95% CI: 5.03–154.19; P = 0.001) were identified as independent risk factors for the acquisition of CP-CRE bacteremia compared with the ESBL bacteremia. The in vitro antimicrobial activities of CAZ/AVI and ATM/AVI against the CRE bacteremic isolates from 2016 to 2018 showed a respective susceptibility rate of 70.68% (41/58) and 100.00% (58/58). Conclusion The findings indicated that both CP-CRE/non-CP-CRE stratification and CRE resistance mechanism determination were necessary for better guiding the clinical management of CRE bacteremia: ATM/AVI probably works with both non-CP-CRE and CP-CRE bacteremia, even the most notorious double-carbapenemase producer with porin loss/deficiency, whereas CAZ/AVI works with most of the non-CP-CRE and KPC-producers in the region.

An environmentally friendly iodofunctionalization of olefins for the synthesis of various iodinated products was developed via the oxidative umpolung of iodide using I2O5 as the inorganic oxidant. ...

Solar energy-driven conversion of CO2 into fuels with H2 O as a sacrificial agent is a challenging research field in photosynthesis. Herein, a series of crystalline porphyrin-tetrathiafulvalene covalent organic frameworks (COFs) are synthesized and used as photocatalysts for reducing CO2 with H2 O, in the absence of additional photosensitizer, sacrificial agents, and noble metal co-catalysts. The effective photogenerated electrons transfer from tetrathiafulvalene to porphyrin by covalent bonding, resulting in the separated electrons and holes, respectively, for CO2 reduction and H2 O oxidation. By adjusting the band structures of TTCOFs, TTCOF-Zn achieved the highest photocatalytic CO production of 12.33 μmol with circa 100 % selectivity, along with H2 O oxidation to O2 . Furthermore, DFT calculations combined with a crystal structure model confirmed the structure-function relationship. Our work provides a new sight for designing more efficient artificial crystalline photocatalysts.

Liquid chromatography-mass spectrometry based profiling of microbial metabolites has been a challenging task due to their diverse physicochemical properties and wide concentration ranges. This study is aimed to develop a systematic platform for the broad-scale profiling of microbial metabolites by integrating aqueous-lipophilic biphasic extractions and chemical derivatizations with a data-dependent automatable metabolite annotation algorithm. This complementary strategy of detection will not only largely expand the metabolite coverage, but also facilitate the drawing out of interested submetabolome using designed chemical derivatizations. Then, the data-dependent metabolite annotation algorithm is able to automatically match the raw MS/MS data with those of compounds in the self-collected databases. The performance of this platform is illustrated through the analysis of two representative bacteria (Escherichia coli and Pseudomonas aeruginosa) and intestinal contents samples from experimental colitis mice. As a result, 292 metabolites corresponding to 875 annotated features distributing over 25 chemical families were putatively annotated in a short time. Of these metabolites, 197 and 218 are respectively from the bacteria and intestinal contents, and 107 are identified in all three biological samples. This systematic platform could be used to accomplete high-coverage detection and high-quality data processing of microbial metabolites. At the same time, chemical derivatization design and the establishment of self-collected databases will facilitate self-driven untargeted analysis.

Hydrogen (H2) plays a vital role both as a reactant in petrochemical processes and as an energy carrier and storage medium. When produced from carbon-containing feed stocks, such as fossil fuels and biomass, hydrogen is typically produced as a mixture with carbon dioxide (CO2), and must be subsequently separated by the associated energy, with an invertible energy penalty. In this study, the process for the removal of carbon dioxide from CO2 - H2 mixtures by de-sublimation was analysed. This process is particularly relevant to the production of liquid hydrogen (LH2) at cryogenic temperatures, for which cooling of the H2 stream is already necessary. The solid – gas equilibrium of CO2 - H2 was studied using the Peng-Robinson equation of state which provided a wide range of operating conditions for process simulation. The de-sublimation process was compared with selected conventional separation processes, including amine-based absorption, pressure swing adsorption and membrane separation. In the scenario in which the resulting products, carbon dioxide and hydrogen, were subsequently liquefied for transportation and storage at 10 bar and −46 °C, and 1 bar and −251.8 °C, respectively. The overall energy consumption per kg of CO2 separated (MJ/kgCO2), was found to follow the order: 8.19–11.21 for monoethanolamine (MEA) absorption; 1.81–8.93 for membrane separation; 1.53–5.69 for pressure swing adsorption; and 0.81–3.35 de-sublimation process. Each process was evaluated and compared on the bases of electricity demand, cooling water usage, high-pressure steam usage, and refrigeration energy requirements. Finally, the advantages and disadvantages were discussed and the feasibility and sustainability of the processes for application in the production of liquid hydrogen were assessed.

The uptake of CH4 by well-drained soil plays a vital role in mitigating the atmospheric CH4, but the impacts of shift in plant litter input on uptake of CH4 and the underlying mechanism are not fully understood. Here, we conducted in situ measurements of soil CH4 flux rates monthly throughout the year after the short-term litter input manipulations (i.e. Detritus Input and Removal Treatment-DIRT: control, CK; double litter, DL; no litter, NL; no roots, NR; and no aboveground litter and no roots, NRNL) in a coniferous forest (Platycladus orientalis (Linn.) Franco) ecosystem in subtropical China. The associated microclimates, soil properties and microbial PLFAs were also measured. Our results showed that soils acted as CH4 sink in all litter manipulation treatments, and the CH4 sink capacity significantly differed under litter manipulation treatments. Based on annual average values, net CH4 uptake rates decreased by 37.7 ± 4.9% and 41.7 ± 5.8% in the NL and NRNL treatments (i.e. litter layer removal), respectively, compared to the CK treatment. Thus, the net CH4 uptake induced by litter layer approximately accounted for 37.7 ± 4.9% of the total net CH4 uptake rate. The net CH4 uptake rate was not significantly influenced by the root exclusion (NR) treatment. In contrast, the effect of litter addition on net CH4 uptake rate was strongly depended on soil water content. During the dry season, litter addition did not significantly affect net CH4 uptake rate. In contrast, during the wet season, the net CH4 uptake rate decreased by 47.1 ± 4.9% in the DL treatment compared to the CK treatment. There was no significant difference in net CH4 uptake rate between dry and wet season under other litter input manipulation treatments. The net CH4 uptake rate was positively correlated with the abundance of methanotrophic bacteria across all litter input manipulation treatments, whereas the significant negative relationship between net CH4 uptake rate and water filled pore space (WFPS) was only found in the DL treatment. Overall, our results suggest that aboveground organic layer (i.e. litter) is more important in regulating the soils acting as atmospheric CH4 sink than roots, while the regulating function primarily depends on soil dry/wet conditions and the abundance of methanotrophic bacteria.

Nature of exosome-secreting cells determines exosome content and function. ALIX, involved in exosome biogenesis, promotes cell degeneration. Here, ALIX was knocked out (iPSC-ALIX-/-) and overexpressed (iPSC-ALIX3+) in induced pluripotent stem cells (iPSCs) using CRISPR-Cas9 and lentiviral transduction, respectively, and the secreted exosomes were analyzed. Exosomes from iPSC-ALIX-/- (exosome-KO), iPSC-ALIX3+ (exosome-over), and their corresponding controls contained 176, 529, 431, and 351 proteins, respectively. Exosome-over showed increased protein levels, while exosome-KO contained fewer protein types without differing in total protein content. ALIX knockout did not affect exosome uptake by endothelial cells. Exosome-over more effectively promoted cell viability than exosome-GFP, in a dose-dependent manner. All exosomes were protective for endothelial cells injured by hydrogen peroxide or cisplatin, as demonstrated by promotion of cell viability, horizontal migration, angiogenic sprouting from aortic rings, and formation of capillary-like structures, inhibition of apoptosis, and maintenance of permeability of endothelial monolayer, although exosome-over and exosome-KO had stronger and weaker effects, respectively. SNX2 was important for ALIX-mediated exosomal function. Beneficial functions of the exosomes were independent of experimental models, targeted cell types, causes of injury, exosome-producing iPSC passages, clones of ALIX knockout, and transfection batches of ALIX overexpression. Thus, we present a novel strategy to manipulate iPSCs for production of exosomes with beneficial ALIX-regulated protein composition for varied exosome functions. KEY MESSAGES: ALIX knockout and overexpression regulate protein profile in iPSC-derived exosome. ALIX knockout decreases therapeutic function of iPSC-derived exosomes. ALIX overexpression increases therapeutic function of iPSC-derived exosomes. Manipulating iPSCs can produce exosomes with more beneficial protein content.

Background Preterm birth and feeding are the most important pathogenic factors of neonatal necrotizing enterocolitis (NEC). Metabonomic has been widely used in the diagnosis and treatment of other diseases, but there is no research on the related diseases of premature infants. Compared with full-term infants, the metabolism of preterm infants has its own specificity, so it can easily lead to NEC and other digestive tract inflammatory diseases. Metabonomic may be applied to the diagnosis of preterm related diseases, such as NEC. Methods The model was established with premature infant serum samples from 19 premature infants in our hospital, which was compared with the full-term infant control group. Serum was analyzed by gas chromatography-mass spectrometry (GC-MS), coupled with the analysis of serum metabolic characteristics. The variable important in projection, P value and Pearson correlation coefficient of samples were analyzed by using SIMCA, SPSS and other multivariate statistical analysis software. Results Compared to the term infants, premature infants had significantly higher levels of luteolin, and lower levels of xylose, O-succinyl-L-homoserine and lauric acid in the serum. There were some correlations among several different metabolites and clinically related indices (albumin, total bilirubin) for premature birth related diseases. Conclusions There are metabolic alterations in the serum of premature infants, which make contribution to the diagnosis of NEC.

Background Fine ambient particle matter (PM2.5) induces inflammatory lung injury; however, whether intratracheal administration of PM2.5 increases pulmonary polymorphonuclear leukocyte (PMN) infiltration, the mechanism of infiltration, and if these cells exacerbate PM2.5-induced lung injury are unknown. Methods Using 32,704 subjects, the association between blood PMNs and ambient PM2.5 levels on the previous day was retrospectively analyzed. Neutropenia was achieved by injecting mice with PMN-specific antibodies. Inhibition of PMN infiltration was achieved by pretreating PMNs with soluble vascular cell adhesion molecule-1 (sVCAM-1). The effects of PMNs on PM2.5-induced lung injury and endothelial dysfunction were observed. Result Short-term PM2.5 (> 75 μg/m3 air) exposure increased the PMN/white blood cell ratio and the PMN count in human peripheral blood observed during routine examination. A significant number of PM2.5-treated PMNs was able to bind sVCAM-1. In mice, intratracheally-instilled PM2.5 deposited in the alveolar space and endothelial cells, which caused significant lung edema, morphological disorder, increased permeability of the endothelial-alveolar epithelial barrier, and PMN infiltration with increased VCAM-1 expression. Depletion of circulatory PMNs inhibited these adverse effects. Replenishment of untreated PMNs, but not those pretreated with soluble VCAM-1, restored lung injury. In vitro, PM2.5 increased VCAM-1 expression and endothelial and epithelial monolayer permeability, and promoted PMN adhesion to, chemotaxis toward, and migration across these monolayers. PMNs, but not those pretreated with soluble VCAM-1, exacerbated these effects. Conclusion VCAM-1-mediated PMN infiltration was essential for a detrimental cycle of PM2.5-induced inflammation and lung injury. Results suggest that drugs that inhibit PMN function might prevent acute deterioration of chronic pulmonary and cardiovascular diseases triggered by PM2.5.

A series of Ce3+, Dy3+ doped Ca3(P1-xBxO4)2 phosphors were synthesized by a high temperature solid-state reaction method, and their corresponding structure, morphology, and luminescence properties were investigated. It is found that the crystal phase transition from β-Ca3(PO4)2 to Ca5(PO4)3(OH) gradually occurs with increasing the boron content in the phosphors, which can provide various local environments for the doping ions and consequently affect the luminescence properties of the phosphors. A red shift of the emission peak of Ce3+ was revealed upon incorporation of boron into Ce/Dy co-doped phosphors. In addition, the luminescence properties could be well modulated by varying the excitation wavelength. The developed phosphors have great potential as a kind of single component white light-emitting phosphors for white light-emitting diodes.

Lysine crotonylation has been discovered in histone and non-histone proteins and found to be involved in diverse diseases and biological processes, such as neuropsychiatric disease, carcinogenesis, spermatogenesis, tissue injury, and inflammation. The unique carbon–carbon π-bond structure indicates that lysine crotonylation may use distinct regulatory mechanisms from the widely studied other types of lysine acylation. In this review, we discussed the regulation of lysine crotonylation by enzymatic and non-enzymatic mechanisms, the recognition of substrate proteins, the physiological functions of lysine crotonylation and its cross-talk with other types of modification. The tools and methods for prediction and detection of lysine crotonylation were also described.

BackgroundOsteoclast excessive activation was closely related to bone diseases such as osteoporosis and rheumatoid arthritis. Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of divaricate Saposhnikovia, was reported to exhibit analgesic, anti-inflammatory and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis and bone resorption remained unclear.MethodsOsteoclast formation, bone resorption pit area formation and F-actin ring formation were examined by TRAP staining, modified Vonkonsa staining and immunofluorescence, respectively. RT-Realtime PCR assay and western blot analysis were performed. siRNA transfection was conducted to silence the expression of 5-LO in cells. LPS-induced bone-loss mice model was prepared and the left and right femurs were collected for Micro-CT and histomorphometric analysis, respectively.ResultsSOG markedly attenuated RANKL-induced osteoclastogenesis through decreasing TRAP activity, F-actin ring formation and bone resorption with reduction of mRNA levels of osteoclastogenesis marker genes such as TRAP, CTSK and DC-STAMP. Our results further indicated that SOG markedly reduced the induction of key transcription factors NFATc1 and c-Fos at both mRNA and protein levels during osteoclastogenesis. In addition, SOG treatment did not alter the transient phosphorylation of NF-κB p65 subunit and MAPKs (p38, ERK1/2 and JNK), AKT and GSK3β by RANKL. Interestingly, our results showed that SOG significantly inhibited the phosphorylation of AKT and GSK3β at middle-late stage of osteoclastogenesis, but did not alter calcineurin catalytic subunit PP2B-Aα expression. GSK3β inhibitor SB415286 could partly reverse inhibition of osteoclastogenesis by SOG. 5-LO knockdown at BMMs also markedly reduced RANKL-induced osteoclastogenesis. In consistent with in vitro results，SOG could significantly improve bone destruction in LPS-induced mice model.ConclusionsSOG attenuated formation and function of osteoclast through suppressing AKT-mediated GSK3β inactivation, and 5-LO catalytic activity. Moreover, SOG prevented LPS-induced bone loss in mice through inhibiting osteoclastogenesis. Taken together, this study provided the evidence that SOG may have a potential therapeutic effect on osteoclast-related bone lysis disease.

Funder: Wellcome Trust, Oxidative stress results when the production of oxidants outweighs the capacity of the antioxidant defence mechanisms. This can lead to pathological conditions including cancer and neurodegeneration. Consequently, there is considerable interest in compounds with antioxidant activity, including those from natural sources. Here, we characterise the antioxidant activity of three novel peptides identified in protein hydrolysates from the sea cucumber Apostichopus japonicus. Under oxidative stress conditions, synthetic versions of the sea cucumber peptides significantly compensate for glutathione depletion, decrease mitochondrial superoxide levels, and alleviate mitophagy in human neuroblastoma cells. Moreover, orally supplied peptides improve survival of the Caenorhabditis elegans after treatment with paraquat, the latter of which leads to the production of excessive oxidative stress. Thus, the sea cucumber peptides exhibit antioxidant activity at both the cellular and organism levels and might prove attractive as nutritional supplements for healthy ageing.

Aim: Alcohol intake alters DNA methylation profiles and methylation might mediate the association between alcohol and disease, but limited number of positive CpG sites repeatedly replicated. Materials & methods: In total, 57 monozygotic (MZ) twin pairs discordant for alcohol drinking from the Chinese National Twin Registry and 158 MZ and dizygotic twin pairs in the Swedish Adoption/Twin Study of Aging were evaluated. DNA methylation was detected using the Infinium HumanMethylation450 BeadChip. Results: Among candidate CpG sites, cg07326074 was significantly correlated with drinking after adjusting for covariates in MZ twins in both datasets but not in the entire sample or dizygotic twins. Conclusion: The hypermethylation of cg07326074, located in the tumor-promoting gene C16orf59, was associated with alcohol consumption.

Immobilizing heavy metals (HMs) from municipal solid waste incineration fly ash (MSWIFA) using shell coal gasification fly ash (SFA)-based geopolymer can solve the energy and environmental challenges simultaneously. In this study, we synthesized a geopolymer with SFA, metakaolin (MK), and steel slag (SS) to solidify and stabilize HMs (Pb, Cr, and Zn) and investigated the early immobilization mechanisms. The results show that the prepared geopolymer possessed high early-age mechanical strength and immobilization efficiency to HMs (>90%), even under the effect of excess HMs. The early immobilization mechanism of the geopolymer for the HMs could be described as follows. (1) Most of HMs were remained in the aluminosilicate. (2) The presence of amorphous zeolite precursor and clay minerals may contribute to restrain the HMs leaching; (3) Pb and Zn were trapped by the gel structure in M-O-Al and M-O-Si forms (M = Pb or Zn), whereas Cr (VI) was reduced to Cr (III). (4) Cr might involve in the geopolymerization of [SiO4] and [AlO4]− units. (5) The immobilization process of Pb and Zn in the geopolymer could be described as crystal growth (NG) - phase boundary reaction (I) - NG - I - diffusion (D), whereas that of Cr is prolonged to NG-I-NG-I-NG-I-D.

The design of selective and efficient covalent organic frameworks (COFs) based electrocatalysts with tunable morphology for efficient CO2 reduction reaction (CO2RR) to CH4 is highly desirable. Here, two kinds of anthraquinone-based COFs (i.e., AAn-COF and OH-AAn-COF) with tunable 1D superstructures (e.g., nanofibers (NF) and hollow tubes (HT)) have been produced via Schiff-base condensation reaction. Interestingly, a rarely reported nanosheet-based self-template mechanism and a nanosheet-crimping mechanism have been demonstrated for the production of COF-based nanofibers and hollow tubes, respectively. Besides, the obtained COF-based superstructures can be post-modified with transition metals for efficient CO2RR. Specifically, AAn-COF-Cu (NF) and OH-AAn-COF-Cu (HT) exhibit superior faradaic-efficiency with CH4 (FECH4) of 77% (−128.1 mA cm−2, −0.9 V) and 61% (−99.5 mA cm−2, −1.0 V) in a flow-cell, respectively. Noteworthy, the achieved FECH4 of AAn-COF-Cu (NF) (77%) the is highest one among reported crystalline COFs. This work provides a general methodology in exploring morphology-controlled COFs for electrocatalytic CO2RR.

Background: Soil heavy metal pollution is widespread around the world. Heavy metal pollutants are easily absorbed by plants and enriched in food chain, which may harm human health, cause the loss of plant, animal and microbial diversity. Plants can generally absorb soil heavy metal pollutants. Compared with hyperaccumulation plants, non-hyperaccumulator plant communities have many advantages in the remediation of heavy metals pollution in soil. However, the amount of heavy metals absorbed could be less, and the biomass would be reduced under heavy metal pollution. The application of nitrogen (N) and phosphorus (P) is inexpensive and convenient, which can increase the resistance of plants to adversity and promote the growth of plants of heavy metal polluted soils.Methods: We designed a comparative greenhouse experiment with heavy metal contaminated soils, and set up four treatments: CK treatment (soil without fertilizer), N treatment (soil with N addition), P treatment (soil with P addition), and N+P treatment (soil with N and P addition).Results: Our results showed that plant aboveground biomass were 231.17%, 14.84%, 269.86% greater than CK treatment, respectively. N and P fertilizer stimulated plants to allocate more biomass to the aboveground parts. In addition, N treatments significantly reduced the content of Cd in aboveground and belowground biomass of plants (P < 0.05); P fertilizer significantly decreased the content of Cu in aboveground biomass (P < 0.05). N+P treatments significantly reduced the content of Cd, Cu in aboveground and belowground biomass of plants (P < 0.05). Meanwhile, N and N+P significantly increased the accumulation (mg/m2) of Cd, Cu, and Pb in plant aboveground biomass (P < 0.05). N and N+P fertilizer increased aboveground-belowground heavy metals accumulation ratio (P < 0.05), promoting plants to uptake more heavy metal pollution out of soil.Conclusions: N and P fertilizer increased the accumulation of heavy metals in aboveground of the natural plant community and accelerated the absorption of heavy metals by plants, and N fertilizer had a better effect. Our results provide an inexpensive method for remediation of heavy metal pollution in low economic value soils, such as contaminated farmland, abandoned land and mine tailings, etc.

Sanguinarine, a benzophenanthridine alkaloid, has been described to have an antiplatelet activity. However, its antithrombotic effect and the mechanism of platelet inhibition have not thoroughly been explored. The current study found that sanguinarine had an inhibitory effect on thrombus formation. This inhibitory effect was quite evident both in the flow-chamber assays as well as in a murine model of FeCl3-induced carotid artery thrombosis. Further investigations also revealed that sanguinarine inhibited the collagen-induced human platelet aggregation and granule release. At the same time, it also prevented platelet spreading and adhesion to immobilized fibrinogen. The molecular mechanisms of its antiplatelet activity were found to be as follows: 1. Reduced phosphorylation of the downstream signaling pathways in collagen specific receptor GPVI (Syk-PLCγ2 and PI3K-Akt-GSK3β), 2. Inhibition of collagen-induced increase in the intracellular Ca2+ concentration ([Ca2+]i), 3. Inhibition of integrin αIIbβ3 outside-in signaling via reducing β3 and Src (Tyr-416) phosphorylation. It can be concluded that sanguinarine inhibits collagen-induced platelet activation and reduces thrombus formation. This effect is mediated via inhibiting the phosphorylation of multiple components in the GPVI signaling pathway. Current data also indicate that sanguinarine can be of some clinical value to treat cardiovascular diseases involving an excess of platelet activation.

BACKGROUND: Bupropion, one of the dual norepinephrine and dopamine reuptake inhibitors (NDRIs), is an aminoketone derivative performed effect in improving cognitive function for depression. However, its therapeutic effect is unsatisfactory due to poor clinical response, and there are only few derivatives in pre-clinical settings. OBJECTIVE: This work attempted to elucidate the essential structural features for the activity and designed a series of novel derivatives with good inhibitive ability, pharmacokinetic and medicinal chemistry properties. METHODS: The field-based QSAR of aminoketone derivatives of two targets were established based on docking poses, and the essential structural properties for designing novel compounds were supplied by comparing contour maps. RESULTS: The selected two models performed good predictability and reliability with R2 of 0.8479 and 0.8040 for training set, Q2 of 0.7352 and 0.6266 for test set respectively, and the designed 29 novel derivatives performed no less than the highest active compound with good ADME/T pharmacokinetic properties and medicinal chemistry friendliness. CONCLUSIONS: Bulky groups in R1, bulky groups with weak hydrophobicity in R3, and potent hydrophobic substituted group with electronegative in R2 from contour maps provided important insights for assessing and designing 29 novel NDRIs, which were considered as candidates for cognitive dysfunction with depression or other related neurodegenerative disorders.