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Human APOBEC3A (A3A) is a nucleic acid-modifying enzyme that belongs to the cytidine deaminase family. Canonically, A3A catalyzes the deamination of cytosine into uracil in single-stranded DNA, an activity that makes A3A both a critical antiviral defense factor and a useful tool for targeted genome editing. However, off-target mutagenesis by A3A has been readily detected in both cellular DNA and RNA, which has been shown to promote oncogenesis. Given the importance of substrate discrimination for the physiological, pathological, and biotechnological activities of A3A, here we explore the mechanistic basis for its preferential targeting of DNA over RNA. Using a chimeric substrate containing a target ribocytidine within an otherwise DNA backbone, we demonstrate that a single hydroxyl at the sugar of the target base acts as a major selectivity determinant for deamination. To assess the contribution of bases neighboring the target cytosine, we show that overall RNA deamination is greatly reduced relative to that of DNA, but can be observed when ideal features are present, such as preferred sequence context and secondary structure. A strong dependence on idealized substrate features can also be observed with a mutant of A3A (eA3A, N57G) which has been employed for genome editing due to altered selectivity for DNA over RNA. Altogether, our work reveals a relationship between the overall decreased reactivity of A3A and increased substrate selectivity, and our results hold implications both for characterizing off-target mutagenesis and for engineering optimized DNA deaminases for base-editing technologies.

The primary objectives of this study were to identify the effectiveness of hydrazine on partial nitrification in a sequencing batch reactor when treating low-strength ammonia wastewater and to inve...

1. The metabolism and excretion of cetagliptin were investigated in healthy male subjects after a single oral dose of 100mg/50μCi [14C] cetagliptin.2. The mean concentration-time profile of cetagliptin was similar to that of total radioactivity in plasma after oral administration of [14C] cetagliptin in healthy male subjects. Cetagliptin was rapidly absorbed after oral administration. Unchanged cetagliptin was the most abundant radioactive component in all matrices investigated. Approximately 53.13% of plasma AUC of total radioactivity was accounted for by cetagliptin. Each metabolite plasma AUC was not higher than 2.93% of plasma AUC of total radioactivity. By 336 h after administration, 91.68% of the administered radioactivity was excreted, and the cumulative excretion in the urine and feces was 72.88% and 18.81%, respectively. The primary route of excretion of radioactivity was via the kidneys.3. Four metabolites were detected at trace levels, and it involved hydroxylated (M436-1 and M436-3), N- sulfate (M500), and N-carbamoyl glucuronic acid conjugates (M640B) of cetagliptin. These metabolites were detected also in plasma, urine, and feces at low levels, except that metabolite M640B was not detected in feces. All metabolites were observed with < 10% of parent compound systemic exposure after oral administration.

In recent years, the treatment of dye wastewater has attracted widespread attention. Metal-organic frameworks (MOFs) adopt ordered porous structures and abundant active sites, which endorses them promising photocatalysts for the degradation of organic pollutants. In this work, two rare earth MOFs were successfully synthesized by solvothermal method from the reaction of of Eu3+ and Tb3+ salts with an aromatic tetracarboxylic acid H4TPTC (3,3',5,5'-terphenyl tetracarboxylic acid). X-ray single crystal diffraction indicated that the isostructural MOFs exhibited unique di-nuclear [Eu2(COO)4] or [Tb2(COO)4] clusters to construct three-dimensional coordination frameworks with solvent accessible channels along the [110] direction. These two MOFs had good thermal stability up to 400 °C and pH stability in the pH range of 3-9. The negative Zeta potential on the surface of these two complexes were conducive to the selective adsorption and degradation of cationic and neutral dyes, especially the high removal rate of large RhB molecules. For the photocatalytic degradation, mechanism studies showed that ·OH and ·O2- enhanced the sensitization of dyes and the separation of photogenerated carriers, and promoted the efficiency of photocatalytic degradation. This work provides two isomorphic rare earth MOFs adsorbents as well as photocatalysts for the purification of dye wastewater.

Background: Sanghuangporus baumii is a traditional Chinese medicine with anti- cancer, anti-tumor, and anti-inflammatory effects. Triterpenoids are one of the main medicinal ingredients found in S. baumii. However, the dynamic changes of triterpenoids content and its molecular regulation mechanism are still unclear. Objective: Some studies have shown that Lanosterol synthase (LS) is a key enzyme involved in the mevalonate pathway (MVA pathway) to produce lanosterol, which is a precursor for synthesizing S. baumii triterpenoids. Therefore, the study of LS gene and expression characteristics can provide clues for the further study of triterpenoids synthesis. Methods: The PCR, RACE PCR, RT-PCR, homologous recombination and prokaryotic expression technology were used to research the gene characteristic and dynamic changes of LS transcription level. Results: The S. baumii LS sequence included a 5’-untranslated region (129 bp), a 3’-untranslated region (87 bp), and an open reading frame (2,229 bp) encoding 734 amino acids. The S. baumii LS protein was expressed in E. coli BL21 (DE3). The transcription start site of the S. baumii LS promoter sequence ranged from 1 740 bp to 1790 bp. The LS promoter contained 12 CAAT-boxes, 5 ABREs, 6 G-Boxes, 6 CGTCA-motifs, and so on. The LS transcription levels were the highest on day 11 in mycelia (1.6-fold), and the triterpenoids content also gradually increased. The transcription levels began to decrease on day 13, but the triterpenoids content still increased. Results: The S. baumii LS sequence included a 5’-untranslated region (129 bp), a 3’-untranslated region (87 bp), and an open reading frame (2,229 bp) encoding 734 amino acids. The S. baumii LS protein was expressed in E. coli BL21 (DE3). The transcription start site of the S. baumii LS promoter sequence ranged from 1 740 bp to 1790 bp. The LS promoter contained 12 CAAT-boxes, 5 ABREs, 6 G-Boxes, 6 CGTCA-motifs, and so on. The LS transcription levels were the highest on day 11 in mycelia (1.6-fold), and the triterpenoids content also gradually increased. The transcription levels began to decrease on day 13, but the triterpenoids content still increased. Conclusion: The S. baumii LS was cloned and characterized to help to understand the mechanism of triterpenoids synthesis. In addition, we studied the relationship between LS transcription level and triterpenoid dynamic accumulation, and we found that they had a certain correlation.

Selective detection of antibiotics and MnO4− is crucial for human health improvement and protecting the environment. Two stable Zn(II)-based metal–organic frameworks (MOFs) {[Zn6(L1)2(NDC)5(μ2-OH)2]·0.5H2O}n (1), and {[Zn(L2)(NDC)]·2H2O}n (2) (H2NDC = 1,4-naphthalenedicarboxylic acid, L1 = 1,5-bis(1-(pyridine-4-ylmethyl)-1H-benzo[d]imidazol-2-yl)pentane, L2 = 1,6-bis(1-(pyridine-4-ylmethyl)-1H-benzo[d]imidazol-2-yl)hexane) were successfully synthesized by adopting the mixed ligands approach. 1 is a rare 3D 3,5,6T23 framework based polynuclear complex group. 2 possesses a 2D sql layer. The two MOFs exhibit excellent chemical and thermal stability. The title compounds are promising dual-functional fluorescent sensors for detecting enrofloxacin/MnO4− anions with high selectivity and sensitivity (Ksv values toward enrofloxacin: 4.29 × 106 L mol−1 for 1 and 4.59 × 106 L mol−1 for 2 and toward MnO4−: 1.05 × 104 for 1, 5.48 × 103 L mol−1 for 2, respectively), which are the first observations of fluorescent MOFs for the sensing of enrofloxacin and MnO4− anions.

Lithium–sulfur (Li–S) batteries have attracted much attention attributed to their high theoretical energy density, whereas the parasitic shuttling behavior of lithium polysulfides (LiPS) hinders th...

DNA deaminase enzymes play key roles in immunity and have recently been harnessed for their biotechnological applications. In base editors (BEs), the combination of DNA deaminase mutator activity with CRISPR-Cas localization confers the powerful ability to directly convert one target DNA base into another. While efforts have been made to improve targeting efficiency and precision, all BEs to date utilize a constitutively active DNA deaminase. The absence of regulatory control over promiscuous deaminase activity remains a major limitation to accessing the widespread potential of BEs. Here, we reveal sites that permit splitting of DNA cytosine deaminases into two inactive fragments, whose reapproximation reconstitutes activity. These findings allow for the development of split-engineered base editors (seBEs), which newly enable small-molecule control over targeted mutator activity. We show that the seBE strategy facilitates robust regulated editing with BE scaffolds containing diverse deaminases, offering a generalizable solution for temporally controlling precision genome editing.

Engleromyces sinensis (Xylariales, Xylariaceae) is an important medicinal fungus in China. In the present study, its taxonomic status was confirmed by muti-locus DNA (ITS-LSU-RPB2-TUB2) phylogenetic analysis for the first time. The main active components of the stromata and cultured mycelium of E. sinensis were analyzed by high-performance liquid chromatography (HPLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR) methods. Cytochalasin D was identified in stromata and mycelium, and no neoengleromycin was detected. Due to the lack of molecular data related to E. goetzei, the interspecific relationships of E. goetzei and E. sinensis need to be investigated further.

Dielectric ceramics capacitors (DCC) with excellent energy storage performance (ESP) and charge-discharge performance (CDP) is very critical in the field of advanced electronics and power systems. A strategy that improves the ESP of 0.6Ba(Zr0.2Ti0.8)O3-0.4(Na0.5Bi0.5)TiO3 (BZT-NBT) ceramics was proposed via Sr2+ doping. XRD and SEM results confirmed that 0.6(Ba1-xSrx)(Zr0.2Ti0.8)O3-0.4(Na0.5Bi0.5)TiO3 (x = 0, 0.1, 0.2, 0.3, 0.4) (BSZT-NBT) ceramics formed dense and stable perovskite solid solutions. The relaxor ferroelectric (RFE) properties of BSZT-NBT ceramics were also well proved by dielectric behaviors. A large recoverable energy storage density (Wrec) and large efficiency (η) of 3.72 J cm−3 and 94.03 % (x = 0.3) can be simultaneously obtained at 289 kV cm-1. ESP of BSZT-NBT (x = 0.3) ceramics at 180 kV cm-1 exhibit good frequency (1−100 Hz) and temperature (room temperature (RT)-120 °C) stability. BSZT-NBT (x = 0.3) ceramics at 120 kV cm−1 exhibit a prominent power density (PD) and rapid discharge rate (t0.9) of of 37.62 MW cm−3 and 70.6 ns. All evidences confirm that introduction of Sr2+ into A-site of barium titanate-based ceramics could effectively improve ESP.

Conductive hydrogels are promising multifunctional materials for wearable sensors, but their practical applications require combined properties that are difficult to achieve. Herein, we developed a flexible wearable sensor with double-layer structure based on conductive composite hydrogel, which included the outer layer of silicone elastomer (Ecoflex)/silica microparticle composite film and the inner layer of P(AAm-co-HEMA)-MXene-AgNPs hydrogel. Through covalently cross-linking silicone elastomer on the surface of the hydrogel polymer, we bonded a thin Ecoflex film (100 μm) on the P(AAm-co-HEMA)-MXene-AgNPs hydrogel with robust interface, which can easily adhere to the Ecoflex/SiO2 microparticle composite film by silicone glue. The Ecoflex/SiO2 microparticle composite film endows the strain wearable sensor with superhydrophobic function that could maintain the stability under stretching or bending. Moreover, it can effectively resist the interference of water droplets and water flow. The P(AAm-co-HEMA)-MXene-AgNPs hydrogel exhibits outstanding antibacterial activity to inhibit Staphylococcus aureus, Escherichia coli, and even drug-resistant Escherichia coli. In addition, the flexible wearable sensor exhibited good self-adhesive performance by changing the reaction temperature of hydrogel and can adhere strongly onto various materials. The conductive composite hydrogel reported in this work contributes an innovative strategy for the preparation of multifunctional flexible wearable sensor.

Direct production of biodiesel by both esterification and transesterification of renewable oils with acid value (AV) of 9.6-28.9 mg KOH/g using calcined blast furnace dust is studied. Blast furnace dust calcined at 600-700 degrees C obviously promotes efficient biodiesel production because of the crystal form transformation from lead sulfate particles in dust into active lead oxide, lead sulfide, and lead particles. It is found for the first time that lead oxide, lead sulfide and lead particles can resist saponification from fatty acids to catalyze raw renewable oils to biodiesel with catalytic activity order as follows: lead oxide > lead > lead sulfide > lead sulfate. Biodiesel production process is optimized according to an orthogonal design with biodiesel yield of 92 wt% obtained at AV of 9.6 mg KOH/g (82 wt% after 5 cycles). Biodiesel yield of 84 wt% is achieved at AV of 28.9 mg KOH/g with acidity of 0.18 mmol/g. Calcined blast furnace dust presents potential applications in the production of biodiesel from renewable oils with high AVs. (C) 2021 Elsevier Ltd. All rights reserved.

An efficient synthesis of indolo[2,1-a]benzazepinones through rhodium-catalyzed cascade reactions of 2-arylindoles with allyl alcohols has been developed. This work expands the scope of products that are available through C-H activation/intramolecular annulation reactions of 2-arylindoles in organic synthesis.

The Rh(III)-catalyzed dual directing group assisted C-H activation/annulation of 3-arylisoxazolones with propargyl alcohols has been developed, which expands the application scope of isoxazolones in organic synthesis. This protocol also worked well with 3-aryl-1,4,2-dioxazol-5-ones to produce synthetically and biologically important 4-arylisoquinolones.

Objectives To establish the epidemiological cut-off values (ECOFFs) for cefoselis against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis and Pseudomonas aeruginosa. Methods We collected 2288 non-repetitive clinical isolates from five laboratories throughout four cities in China. The cefoselis MICs and inhibition zone diameters for all isolates were established using the broth microdilution method and the disc diffusion method following EUCAST guidelines. MIC ECOFFs were determined by visual estimation and ECOFFinder software. Zone diameter ECOFFs were set if a high correlation of MICs and inhibition zone diameters was found by Pearson correlation. Zone diameter ECOFFs were finally determined by the visual estimate method. Results MICs of cefoselis were distributed from 0.008 to >256 mg/L for the four Enterobacterales species and from 0.25 to >256 mg/L for P. aeruginosa. MIC ECOFFs were 0.125 mg/L for E. coli, K. pneumoniae and P. mirabilis, 0.25 mg/L for E. cloacae and 32 mg/L for P. aeruginosa. A high correlation of MICs and zone diameters was observed for all Enterobacterales (|r| > 0.8, P Conclusions We determined MIC and zone diameter ECOFFs for cefoselis against four Enterobacterales species and P. aeruginosa. The establishment of ECOFFs for cefoselis provides clinicians with helpful guidance to differentiate WT and non-WT pathogens.

Cross-linked polymer microspheres have potential applications in many fields. Compared with seed polymerization, two-part dispersion polymerization is a very attractive method for preparing micron-sized cross-linked microspheres. However, the current dispersion polymerization would be adversely affected by the addition of more than 1 wt% of cross-linker at a time and even agglutination occurred. In this study, a facile method for the preparation of highly cross-linked microspheres by two-step dispersion polymerization of a chain transfer agent has been developed. The relationship between cross-linker and transfer has been studied in detail, and microspheres can be simultaneously maintained by adding the cross-linker ethylene glycol dimethacrylate (EGDMA) at concentrations of up to 10%.

Poor utilisation efficiency of carbohydrate always leads to metabolic phenotypes in fish. The intestinal microbiota plays an important role in carbohydrate degradation. Whether the intestinal bacteria could alleviate high-carbohydrate diet (HCD)-induced metabolic phenotypes in fish remains unknown. Here, a strain affiliated to Bacillus amyloliquefaciens was isolated from the intestine of Nile tilapia. A basal diet (CON), HCD or HCD supplemented with B. amy SS1 (HCB) was used to feed fish for 10 weeks. The beneficial effects of B. amy SS1 on weight gain and protein accumulation were observed. Fasting glucose and lipid deposition were decreased in the HCB group compared with the HCD group. High-throughput sequencing showed that the abundance of acetate-producing bacteria was increased in the HCB group relative to the HCD group. Gas chromatographic analysis indicated that the concentration of intestinal acetate was increased dramatically in the HCB group compared with that in the HCD group. Glucagon-like peptide-1 was also increased in the intestine and serum of the HCB group. Thus, fish were fed with HCD, HCD supplemented with sodium acetate at 900 mg/kg (HLA), 1800 mg/kg (HMA) or 3600 mg/kg (HHA) diet for 8 weeks, and the HMA and HHA groups mirrored the effects of B. amy SS1. This study revealed that B. amy SS1 could alleviate the metabolic phenotypes caused by HCD by enriching acetate-producing bacteria in fish intestines. Regulating the intestinal microbiota and their metabolites might represent a powerful strategy for fish nutrition modulation and health maintenance in future.

We successfully synthesized nanoflower-like δ-MnO2, rod-shaped MnOOH, nano-small granular Mn3O4, and the cuboidal and spindle shaped MnCO3 via a facile one-pot hydrothermal method by adjusting the concentration of two sorts of short-chain surfactants with special catechol structures (3-Hydroxytyramine hydrochloride (DA) and 3,4-dihydroxybenzenepropanoic acid (DHCA)) in KMnO4 solution. The XRD and FTIR data demonstrated that the crystal form, morphology and size of the crystal were controlled by small molecule ligands. Afterwards, the relationship between manganese oxides and electrochemical properties was further explored. The results illustrated that nanoflower-like δ-MnO2 with layer structures have the highest specific capacitance of 307.4 F g−1 at a scan rate of 5 mV s−1.

Purpose: Variants in NUS1 are associated with a congenital disorder of glycosylation, developmental and epileptic encephalopathies, and are possible contributors to Parkinson’s disease pathogenesis. How the diverse functions of the NUS1-encoded Nogo B receptor (NgBR) relate to these different phenotypes is largely unknown. We present three patients with de novo heterozygous variants in NUS1 that cause a complex movement disorder, define pathogenic mechanisms in cells and zebrafish, and identify possible therapy. Methods: Comprehensive functional studies were performed using patient fibroblasts, and a zebrafish model mimicking NUS1 haploinsufficiency. Results: We show that de novo NUS1 variants reduce NgBR and Niemann-Pick type C2 (NPC2) protein amount, impair dolichol biosynthesis, and cause lysosomal cholesterol accumulation. Reducing nus1 expression 50% in zebrafish embryos causes abnormal swim behaviors, cholesterol accumulation in the nervous system and impaired turnover of lysosomal membrane proteins. Reduction of cholesterol buildup with 2-hydroxypropyl-ß-cyclodextrin significantly alleviates lysosomal proteolysis and motility defects. Conclusions: Our results demonstrate that these NUS1 variants cause multiple lysosomal phenotypes in cells. We show that the movement deficits associated with nus1 reduction in zebrafish arise in part from defective efflux of cholesterol from lysosomes, suggesting that treatments targeting cholesterol accumulation could be therapeutic.

There is growing evidence that pillaring up a densely packed ultramicroporous two-dimensional (2D) structure is an effective strategy to reduce their internal diffusion. Reliable pillaring paradigms, however, is rather challenging. Here we report a one-pot multi-component sequential assembly method for the preparation of a new self-pillared 2D polymer and ultramicroporous carbon with integrated surface protrusions. The molecular level pillaring process is surprisingly fast, that is, in 10 min. The thickness of nanoplate edge and the density (roughness), angle as well as height of protrusions can be precisely tuned. Exemplified in coal bed methane purification/separation, this unique pillared 2D carbons exhibit a CH4 /N2 selectivity up to 24 at a low CH4 partial pressure and two orders of magnitude faster CH4 diffusion kinetics than the commercial carbon molecular sieves. This solution synthesis methodology is generalizable for creation and fine tuning of pillared 2D heterostructures.

Cancer cells need to generate large amounts of glutathione (GSH) to buffer oxidative stress during tumor development. A rate-limiting step for GSH biosynthesis is cystine uptake via a cystine/glutamate antiporter Xc−. Xc− is a sodium-independent antiporter passively driven by concentration gradients from extracellular cystine and intracellular glutamate across the cell membrane. Increased uptake of cystine via Xc− in cancer cells increases the level of extracellular glutamate, which would subsequently restrain cystine uptake via Xc−. Cancer cells must therefore evolve a mechanism to overcome this negative feedback regulation. In this study, we report that glutamate transporters, in particular SLC1A1, are tightly intertwined with cystine uptake and GSH biosynthesis in lung cancer cells. Dysregulated SLC1A1, a sodium-dependent glutamate carrier, actively recycled extracellular glutamate into cells, which enhanced the efficiency of cystine uptake via Xc− and GSH biosynthesis as measured by stable isotope-assisted metabolomics. Conversely, depletion of glutamate transporter SLC1A1 increased extracellular glutamate, which inhibited cystine uptake, blocked GSH synthesis, and induced oxidative stress-mediated cell death or growth inhibition. Moreover, glutamate transporters were frequently upregulated in tissue samples of patients with non–small cell lung cancer. Taken together, active uptake of glutamate via SLC1A1 propels cystine uptake via Xc− for GSH biosynthesis in lung tumorigenesis. Significance: Cellular GSH in cancer cells is not only determined by upregulated Xc− but also by dysregulated glutamate transporters, which provide additional targets for therapeutic intervention.

Electrically responsive electrochemical actuators that contain a polymer electrolyte membrane laminated between two electrodes have attracted great attention due to their potential applications in smart electronics, wearable devices, and soft robotics. However, some challenges such as the achievement of large bending strain under low applied voltage and fast ion diffusion and accumulation still exist to be resolved. The key to the solution lies in the choice of electrode materials and the design of electrode structures. In this study, an engineering electrochemical actuator that presents large bending strain under low applied voltage based on MXene/polystyrene-MXene hybrid electrodes is developed. The developed electrochemical actuator based on the MXene/polystyrene-MXene 3D-structure is found to exhibit large bending strain (ca. 1.18%), broad frequency bandwidth, good durability (90% retention after 10,000 cycles) and considerable Young’s modulus (ca. 246 MPa). The high-performance actuation mainly stems from the excellent properties of MXene and 3D-structure of the electrode. The MXene provides excellent mechanical strength and high electrical conductivity which facilitate strong interaction and rapid electron transfer in electrodes. The 3D architectures formed by polystyrene microspheres generate unimpeded ion pathways for ionic short diffusion and fast injection. This study reveals that the 3D-structure hybrid electrodes play a crucial role in promoting the performance of such electrochemical actuators.

Owing to the boundedness of conventional remedies upon articular cartilage for self-rehabilitation and the incrementally senior citizens, the incidence of osteoarthritis (OA) is increasing worldwide. Empirical studies have revealed the advantageous and promising potentials of mesenchymal stem/stromal cells (MSCs) on the refractory OA, whereas the deficiency of systematic and detailed exploration of MSC-based therapy largely hampers the large-scale applications in regenerative medicine. Herein, we initially utilized the monosodium iodoacetate- (MIA-) induced OA rabbit models and investigated the therapeutic effect of human umbilical cord-derived UC-MSCs at serial dose gradients with the splendid hyaluronic acid and/or propylene glycol hydrogels (HA, HA/PG), respectively. Afterwards, we turned to a dual-luciferase reporter tracing system and evaluated the spatiotemporal distribution and metabolokinetics of bifluorescence expressing UC-MSCs (BF-MSCs) in OA rats. Of the aforementioned trials, we verified that the combination of HA/PG and middle-dose MSCs ( 0.5 × 10 7 cells/ml) eventually manifested the optimal efficacy on OA rabbits. Furthermore, with the aid of the bioluminescence imaging (BLI) technology for dynamic in vitro and in vivo tracking, we intuitively delineated the spatiotemporal distribution and therapeutic process of BF-MSCs in OA rats, which substantially confirmed the reinforcement of HA/PG on BF-MSCs for OA treatment. Collectively, our data conformably demonstrated that the middle dose of UC-MSCs combined with HA/PG hydrogel was sufficient for optimal MSC-based formulation for blocking OA progression and promoting cartilage repair, which supplied overwhelming new references and enlightened MSC-based therapeutic strategies for cartilage defects.

Herein we report a Pd-catalyzed C–N bond cleavage strategy for the cycloaddition of pyrrolidines with azlactones or butenolides to construct the azepines. Leverage of the readily accessible 3-alkyl...

The design and construction of noble-metal free electrocatalysts with high efficiency for both hydrogen and oxygen evolution reactions holds promise for advancing the production of H2 fuels through the overall water splitting process. Herein, we report a novel hollow near-spherical superstructure of a cobalt sulfide electrocatalyst (h-CoxSy) via the accumulation of two-dimensional cobalt sulfide nanosheets in a sulfurization-pyrolysis process of hollow ZIF-67. Benefiting from the porous characteristics, a unique hollow superstructure and saw-toothed edges derived from the hollow ZIF-67 precursor, the h-CoxSy exhibited outstanding bifunctional electrocatalytic performances, with overpotentials of 320 and 295 mV to achieve 10 mA cm−2 for the OER and HER, respectively. When h-CoxSy was employed as both the anode and cathode for overall water splitting, a current density of 10 mA cm−2 can be obtained at a cell voltage of 1.88 V, along with impressive operation stability.

Surface modification by loading a water oxidation co-catalyst (WOC) is generally considered an efficient means to optimize the sluggish surface oxygen evolution reaction (OER) of a hematite photoanode for photoelectrochemical (PEC) water oxidation. However, the surface WOC usually exerts little impact on the bulk charge separation of hematite. Herein, an ultrathin citrate-Ni0.9Co0.1(OH)x [Cit-Ni0.9Co0.1(OH)x] is conformally coated on the fluorine-doped hematite (F-Fe2O3) photoanode for PEC water oxidation to simultaneously promote the internal hole extraction and surface hole injection of the target photoanode. Besides, the conformally coated Cit-Ni0.9Co0.1(OH)x overlayer passivates the redundant surface trap states of F-Fe2O3. These factors result in a superior photocurrent density of 2.52 mA cm−2 at 1.23 V versus a reversible hydrogen electrode (V vs. RHE) for the target photoanode. Detailed investigation manifests that the hole extraction property in Cit-Ni0.9Co0.1(OH)x is mainly derived from the Ni sites, while Co incorporation endows the overlayer with more catalytic active sites. This synergistic effect between Ni and Co contributes to a rapid and continuous hole migration pathway from the bulk to the interface of the target photoanode, and then to the electrolyte for water oxidation.

Objective: To investigate the correlation between monocyte to high-density lipoprotein ratio (MHR) and major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: In this retrospective study, 120 ACS patients who received PCI in our hospital from September 2014 to August 2019 were selected and divided into MACE group and normal discharge (ND) group. Their clinical data were collected, and MHR values were compared. Logistic regression analysis was conducted to analyze the correlations between various factors and ACS. The correlation between MHR and Gensini score was subjected to Pearson’s analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic value of MHR for MACE. Results: Hypertension degree, white cell count, Gensini score, MHR and the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), apolipoprotein A1 (ApoA1), ApoB, lipoprotein (a) [LP(a)] and uric acid (UA) in MACE group were significantly higher than those in ND group (P

Three-dimensional polyaniline (PANI) hydrogel was used as the conductive medium to improve the methane (CH4) production from the anaerobic degradation of organics in wastewater. The porous structure and hydrophilic surface of the PANI hydrogel promoted the adhesion of the anaerobes. The PANI hydrogel existed as a conductive emeraldine base (EB) form with a conductivity of 0.42 S/cm, and had a good biocompatibility with the microorganisms in the anaerobic system. The conductive PANI hydrogel was added into the anaerobic sludge as the conductive medium of the direct interspecies electron transfer (DIET) between bacteria and archaea, accelerating CH4 production during the biodegradation of organic pollutants. The results indicated that the CH4 production rate was increased by 10.50%, 14.21%, 28.77% and 19.30% from the anaerobic system with adding 1000, 2000, 3000 and 4000 mg/L of PANI hydrogel. The proportion of Methanosaeta in the anaerobic sludge with the ability of DIET was increased to 64.74% after adding the PANI hydrogel. The conductive PANI hydrogel served as an electronic channel to enrich the microorganism with the DIET ability, which was responsible for PANI hydrogel improved CH4 production.

Shape memory polymers (SMPs) that change shapes as designed by external stimuli have become one of the most promising materials as actuators, sensors, and deployable devices. However, their practical applications have been greatly limited due to the long recovery time, which mainly originates from their low recovery stress, inherent viscoelastic hysteresis effect and low heat transmission efficiency. In this work, a novel method is proposed to prepare fast responsive reduced graphene oxide/shape memory polyurethane/polyurethane foam (rGO/SMPU/PU foam) shape memory composites. The elastic PU foam is used as framework to be coated with SMPU and rGO by solution polymerization and self-assembly methods, which result in rGO/SMPU/PU foam with three-dimensional networks. The rGO/SMPU/PU foam exhibits a fast response (of less than 1 s) under a large compressing deformation (80%) due to the synergistic effect of the high elasticity of PU foam, the short energy transmission distance of the SMPU layer and the high thermal conductivity of the rGO layer. Moreover, owing to the outstanding shape fixity ratio (Rf) and shape recovery ratio (Rr) of SMPU and the mechanical properties of PU foam, the rGO/SMPU/PU foam shows an excellent shape memory effect (more than 98% Rf and Rr at 80% strain) and cyclic stability simultaneously. Such rGO/SMPU/PU foam material demonstrates the potential applications in high-sensitivity temperature sensors and temperature codes.

A mild and selective Cp*Ir(III)- and Cp*Rh(III)-catalyzed direct C(sp2)–H amination of arenes and three types of nitrene precursor reagents is reported, with the assistance of a thioether directing group. This redox-neutral protocol proceeds under mild reaction conditions, has a broad substrate scope and high functional-group compatibility and generates the desired aminated products in moderate to excellent yields. The reaction represents the first example of a thioether-directed Cp*Ir(III)- and Cp*Rh(III)-catalyzed C(sp2)–H direct amination reaction. Moreover, azide compounds were employed as a diverse and robust aminating reagent for the first time in a thioether-directed C–H functionalization reaction.

The development of novel hemostatic agents with distinct modes of action from traditional ones remains a formidable challenge. Self-assembling peptide hydrogels have emerged as a new hemostatic material, not only because of their inherent biocompatibility and biodegradability but also their designability. Especially, rational molecular design can make peptides and their hydrogelation responsive to biological cues. In this study, we demonstrated that transglutaminase-catalyzed reactions not only occurred among designed short peptide I3QGK molecules but also between the peptide and a natural polysaccharide O-carboxymethyl chitosan. Because Factor XIII in the blood can rapidly convert into activated transglutaminase (Factor XIIIa) upon bleeding, these enzymatic reactions, together with the electrostatic attraction between the two hemostatic agents, induced a strong synergetic effect in promoting hydrogelation, blood coagulation, and platelet adhesion, eventually leading to rapid hemostasis. The study presents a promising strategy for developing alternative hemostatic materials and methods.

A high-carbohydrate diet could achieve a protein-sparing effect, but it may cause negative impacts on the growth condition of fish due to their poor utilisation ability of carbohydrate. How to reduce the adverse effects caused by a high-carbohydrate diet is important for the development of aquaculture. In the present study, we aimed to identify whether inulin could attenuate the metabolic syndrome caused by a high-carbohydrate diet in fish. Nile tilapia (Oreochromis niloticus) (1·19 (sd0·01) g) were supplied with 35 % carbohydrate (CON), 45 % carbohydrate (HC) and 45 % carbohydrate + 5 g/kg inulin (HCI) diets for 10 weeks. The results showed that addition of inulin improved the survival rate when fish were challenged withAeromonas hydrophila, indicating that inulin had an immunostimulatory effect. Compared with the HC group, the HCI group had lower lipid accumulation in liver and the gene expression analyses indicated that addition of inulin down-regulated genes related to lipogenesis and up-regulated genes relevant toβ-oxidation significantly (P< 0·05). Higher liver glycogen and glucose tolerance were found in the HCI group compared with the HC group (P< 0·05). These results indicated that inulin could alleviate the metabolic syndrome induced by a high-carbohydrate diet. Furthermore, addition of inulin to a high-carbohydrate diet changed the intestinal bacterial composition and significantly increased the concentration of acetic acid and propionic acid in fish gut which have the potential to increase pathogen resistance and regulate metabolic characteristics in fish. Collectively, our results demonstrated a possible causal role for the gut microbiome in metabolic improvements induced by inulin in fish.

Objective Sleep disorders as a preclinical symptom of synucleinopathies become more prevalent in older adults. Synucleinopathies might be caused by the abnormal aggregation of alpha‐synuclein in the brain, which was indicated by alpha‐synuclein levels in cerebrospinal fluid (CSF). We aimed to investigate associations of sleep characteristics with CSF alpha‐synuclein in older adults. Methods Our study recruited 536 cognitively intact individuals (aged between 40 and 90 years old) from the Chinese Alzheimer’s Biomarker and Lifestyle study. Sleep behaviors were assessed by Pittsburgh Sleep Quality Index and total alpha‐synuclein in CSF was measured by enzyme‐linked immune‐sorbent assay. We used multiple linear and non‐linear regression models for research. Results Significant non‐linear associations of CSF alpha‐synuclein with sleep time and duration were revealed. Individuals who went to bed and fell asleep too early or late tended to have lower CSF alpha‐synuclein (reflection point for time to bed and fall asleep were 10:26 p.m. and 10:40 p.m.). Lower CSF alpha‐synuclein was also observed in individuals with either excessive or insufficient sleep duration (reflection point: 7.24 hours). Besides, overall poor sleep quality (β = −0.0621; P = 0.0242), longer sleep latency (β = −0.0415; P = 0.0174) and lower sleep efficiency (β = 0.0036; P = 0.0017) showed linear associations with lower CSF alpha‐synuclein. Sleep disturbances and daytime dysfunction were not significantly associated with CSF alpha‐synuclein. Interpretation Poor sleep was associated with lower levels of CSF alpha‐synuclein in older adults, which may provide new insight into the prevention of synucleinopathies.

Two nonbiaryl axially chiral β-carboline-quinazoline dimers, pegaharmols A (1) and B (2), were isolated from the roots of Peganum harmala. Their planar structures were elucidated by the spectroscopic methods of high-resolution mass spectrometry and 1D and 2D nuclear magnetic resonance (NMR). The stereochemistry was established by a comparison between the experimental data of NMR and electronic circular dichroism and the computed data by quantum mechanical calculations. It is discovered for the first time that the β-carboline at the C-8 position is bonded to the vasicine at the C-9 position. 1 exhibited moderate cytotoxic activity against HL-60 and A549 cell lines.

A novel, moderately thermophilic, Gram-stain-negative bacterium, designated strain J18T, was isolated from a water-flooded oil reservoir. Cells were aerobic, oxidase- and catalase-positive, with a polar flagellum. Growth occurred at 35–60 °C and at pH 6–8.5. The respiratory quinones were ubiquinone 8 and ubiquinone 9. The dominant cellular fatty acids were C16 : 0, C17 : 0 cyclo, C19 : 0 cyclo ω8c and summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c). The polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, an unidentified phospholipid and an unidentified aminophospholipid. The strain showed the highest 16S rRNA gene sequence similarities to Tepidiphilus margaritifer DSM 15129T (98.6 %), Tepidiphilus succinatimandens DSM 15512T (98.4 %) and Tepidiphilus thermophilus DSM 27220T (98.1 %), respectively, and the similarity to other species was lower than 93 %. In the phylogenetic trees, it constituted a unique sub-cluster within the genus Tepidiphilus . The DNA G+C content of strain J18T was 64.44 mol%. As compared with the type strains, the genome-to-genome distances of strain J18T were 34.7–40 %. These results confirmed the separate species status of J18T with its close relatives. On the basis of physiological, chemotaxonomic and phylogenetic analyses along with the low levels of identity at the whole-genome level, it can be concluded that strain J18T represents a new species of the genus Tepidiphilus , for which the name Tepidiphilus olei sp. nov. is proposed. The type strain of T. olei is J18T (=CGMCC 1.16800T=LMG 31400T).

Aims It has been reported that allopregnanolone (APα) promotes the neurogenesis of the neural progenitor cells (NPCs) in the subventricular zone (SVZ) and prevents the decrease of dopaminergic neurons in 6‐hydroxydopamine (6‐OHDA)‐treated mice by binding to γ‐aminobutyric acid A receptor (GABAAR) and then opening voltage‐gated L‐type Ca2+ channel, but the underlying mechanisms remain elusive. The aim of this study was to explore the possible involvement of GABAAR and calcium/calmodulin‐dependent protein kinase II delta 3 (CaMKIIδ3) in this process. Methods 6‐OHDA‐treated mice and primary cultured midbrain cells were administrated with APα and GABAAR antagonist bicuculline (Bic), and the proliferation and differentiation of NPCs, the tyrosine hydroxylase (TH)‐positive neurons and their fibers, the expression levels of CaMKIIδ3 and brain‐derived neurotrophic factor (BDNF), and motor functions were measured using ELISA, immunohistochemical staining, real‐time RT‐PCR, Western blot, and behavioral test. Results Allopregnanolone significantly promoted the phosphorylation of cytoplasmic CaMKIIδ3 and its nuclear translocation by binding to GABAAR, which, in turn, increased the expression levels of BDNF. This may account for the findings that the exogenous APα enhanced the proliferation and differentiation of NPCs, and ameliorated the nigrostriatal system and behavioral performance in 6‐OHDA‐treated mice. Conclusions Allopregnanolone may directly activate GABAAR, which, in turn, enhance the proliferation and differentiation of NPCs via upregulating the expression levels of CaMKIIδ3, and finally contribute to the restoration of dopaminergic neurons in 6‐OHDA‐treated mice., APα significantly promotes the phosphorylation of cytoplasmic CaMKIIδ3 and its nuclear translocation by binding to GABAAR, which, in turn, increases the expression levels of cell cycle protein and BDNF. This may account for the findings that APα enhances the proliferation and differentiation of NPCs, and ameliorates the deficiency of dopaminergic neurons in 6‐OHDA‐treated mice and primary cultured midbrain cells.

Anthocyanins and proanthocyanidins are among the most numerous and widely distributed pigments in land plants. Given that these pigments are the valuable compounds, as stress protectants and health-promoting components because of their potent antioxidant activity, several metabolic engineering approaches focusing on these compounds have been attempted. Currently, the difference in biological functions between flavonoid decorations is focused, because some aglycone decorations were found to be key factors rendering physiological functions against environmental stresses. Therefore, metabolic diversity and functional genomics approaches focusing on anthocyanin decoration should be reconsidered. Additionally, since the production of anthocyanins and proanthocyanidins in plants is often represented in a tissue-specific manner and by stress induction, elucidation of the specific regulatory mechanisms of how these pathways have been evolved, is highly important. Here, we review current knowledge of the diversity of chemical structure and regulators of anthocyanin/proanthocyanin biosynthesis with cross-species comparison to assess metabolic evolution.

Background There is a correlation between tumor and inflammation. The activity of 13-[CH2CO-Cys(Bzl)-OBzl]-berberine (13-Cys-BBR) slowing tumor growth is higher than that of BBR. Whether the anti-inflammation activity of 13-Cys-BBR is higher than that of BBR remains unknown. There is a correlation between thrombosis and inflammation. Whether 13-Cys-BBR is an inhibitor of thrombosis remains unknown. Purpose The object of this investigation is to compare the activities of 13-Cys-BBR inhibiting thrombosis and inflammation to those of BBR. Methods In vivo anti-thrombosis assay was performed on rat model of arterial and venous thrombosis. In vivo anti-inflammation assay was performed on mouse model of xylene induced ear edema. Results At oral dose of 66.7 nmol/kg, 13-Cys-BBR, but not BBR, inhibited the rats to form both venous thrombus and arterial thrombus. At oral dose of 2 μmol/kg, 13-Cys-BBR, but not BBR, inhibited the ears of the mice to occur edema. Conclusion The anti-venous thrombosis activity, anti-arterial thrombosis activity and anti-inflammation activity of 13-Cys-BBR were significantly higher than those of BBR. 13-Cys-BBR is a promising preclinical candidate.

Transition-metal oxides as electrocatalysts for the oxygen evolution reaction (OER) provide a promising route to face the energy and environmental crisis issues. Although palmeirite oxide A2 Mo3 O8 as OER catalyst has been explored, the correlation between its active sites (tetrahedral or octahedral) and OER performance has been elusive. Now, magnetic Co2 Mo3 O8 @NC-800 composed of highly crystallized Co2 Mo3 O8 nanosheets and ultrathin N-rich carbon layer is shown to be an efficient OER catalyst. The catalyst exhibits favorable performance with an overpotential of 331 mV@10 mA cm-2 and 422 mV@40 mA cm-2 , and a full water-splitting electrolyzer with it as anode catalyst shows a cell voltage of 1.67 V@10 mA cm-2 in alkaline. Combined HAADFSTEM, magnetic, and computational results show that factors influencing the OER performance can be attributed to the tetrahedral Co sites (high spin, t2 3 e4 ), which improve the OER kinetics of rate-determining step to form *OOH.

TET family enzymes are known for oxidation of the 5-methyl substituent on 5-methylcytosine (5mC) in DNA. 5mC oxidation generates the stable base 5-hydroxymethylcytosine (5hmC), starting an indirect, multi-step process that ends with reversion of 5mC to unmodified cytosine. While probing the nucleobase determinants of 5mC recognition, we discovered that TET enzymes are also proficient as direct N-demethylases of cytosine bases. We find that N-demethylase activity can be readily observed on substrates lacking a 5-methyl group and, remarkably, TET enzymes can be similarly proficient in either oxidation of 5mC or demethylation of N4-methyl substituents. Our results indicate that TET enzymes can act as both direct and indirect demethylases, highlight the active-site plasticity of these Fe(II)/α-ketoglutarate-dependent dioxygenases, and suggest activity on unexplored substrates that could reveal new TET biology.

Several studies have researched the short-term effect of sulfur dioxide (SO2) exposure on hypertension. However, no evidence has provided the relationship between long-term high pollution exposure of SO2 and morbidity of hypertension in cohort studies in China. This retrospective cohort study aimed to evaluate this association. We used Cox proportional hazards regression models to examine the hazard ratios (HR) for hypertension risks from 1998 to 2009 associated with accumulative exposure of air SO2 among adults in northern China. Annual average concentrations of sulfur dioxide (SO2) were obtained from 15 local environmental monitoring centers. Hypertension was identified according to self-reported diagnostic time and treatment for hypertension with anti-hypertensive medication. Among 37,386 participants, 2619 new cases of hypertension were identified during 426,334 person-years. In the fully adjusted model, HR and 95% confidence interval (CI) of hypertension incidence for each 10 μg/m3 increase in SO2 were 1.176 (1.163 and 1.189). Results from stratified analyses suggested that effects of SO2 on hypertension morbidity were more pronounced in participants

Organic contaminants have a destructive influence on the environment. Dye is a kind of serious organic pollutant. The aim of this project was to explore the adsorption of methylene blue (MB) to pur...

In this work, a novel glutathione and pH serial dual-responsive drug delivery system has been developed, which was constructed with chitosan (CS), carbon dots (CDs) and hyaluronic acid (HA) modified the mesoporous silica nanoparticles (MSNs). The system showed excellent drug loading efficiency, controlled release and targeted delivery. In addition, the platform (MSN-CS@HA-CDs) exhibited fluorescence imaging property. The prepared drug delivery system appeared to be a promising cancer treatment platform.

Successful application of microorganisms to heavy metal remediation depends on their resistance to toxic metals. This study contrasted the differences of tolerant mechanisms between Pb2+ and Cd2+ in Enterobacter sp. Microbial respiration and production of formic acid showed that Enterobacter sp. had a higher tolerant concentration of Pb (>1000 mg l-1 ) than Cd (about 200 mg l-1 ). Additionally, SEM confirmed that most of Pb and Cd nanoparticles (NPs) were adsorbed onto cell membrane. The Cd stress, even at low concentration (50 mg l-1 ), significantly enlarged the sizes of cells. The cellular size raised from 0.4 × 1.0 to 0.9 × 1.6 μm on average, inducing a platelet-like shape. In contrast, Pb cations did not stimulate such enlargement even up to 1000 mg l-1 . Moreover, Cd NPs were adsorbed homogeneously by almost all the bacterial cells under TEM. However, only a few cells work as 'hot spots' on the sorption of Pb NPs. The heterogeneous sorption might result from a 'self-sacrifice' mechanism, i.e., some cells at a special life stage contributed mostly to Pb sorption. This mechanism, together with the lower mobility of Pb cations, caused higher microbial tolerance and removal efficiency towards Pb2+ . This study sheds evident contrasts of bacterial resistance to the two most common heavy metals.

Caffeine is a purine alkaloid and is widely consumed in coffee, soda, tea, chocolate and energy drinks. To date, a growing number of studies have indicated that caffeine is associated with many diseases including colorectal cancer. Caffeine exerts its biological activity through binding to adenosine receptors, inhibiting phosphodiesterases, sensitizing calcium channels, antagonizing gamma-aminobutyric acid receptors and stimulating adrenal hormones. Some studies have indicated that caffeine can interact with signaling pathways such as transforming growth factor β, phosphoinositide-3-kinase/AKT/mammalian target of rapamycin and mitogen-activated protein kinase pathways through which caffeine can play an important role in colorectal cancer pathogenesis, metastasis and prognosis. Moreover, caffeine can act as a general antioxidant that protects cells from oxidative stress and also as a regulatory factor of the cell cycle that modulates the DNA repair system. Additionally, as for intestinal homeostasis, through the interaction with receptors and cytokines, caffeine can modulate the immune system mediating its effects on T lymphocytes, B lymphocytes, natural killer cells and macrophages. Furthermore, caffeine can not only directly inhibit species in the gut microbiome, such as Escherichia coli and Candida albicans but also can indirectly exert inhibition by increasing the effects of other antimicrobial drugs. This review summarizes the association between colorectal cancer and caffeine that is being currently studied.

There has been a great deal of interest in developing isolated dairy lipid fractions that are rich in phospholipids (PL), due to their health benefits and functional properties. Dairy by-products that contain elevated levels of PL and milk fat globule membrane (MFGM) proteins can be an excellent source for these isolates. The β stream, a by-product of anhydrous milk fat production, is an excellent candidate because it contains a higher concentration of PL than many other dairy by-products. In this study, we investigated an economically feasible processing method to obtain these valuable components from the β stream. The use of zinc acetate and calcium acetate, along with mild heat treatment and pH adjustment, was effective in precipitating PL and proteins into a pellet fraction. With an additional extraction from the pellet using ethanol (90% at 70°C), a PL-enriched lipid fraction was obtained. The effective precipitation conditions were zinc acetate of 25 mM concentration at pH greater than 6.5 at 30°C, and calcium acetate of greater than 75 mM concentration at pH greater than 6.5 at 60°C. With ethanol extraction, PL recovery of 97.7 ± 1.7% from the zinc acetate precipitate and 94.9 ± 3.7% from calcium acetate precipitate were achieved.