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The banana (Musa spp.) industry experiences dramatic annual losses from Fusarium wilt of banana disease, which is caused by the fungus Fusarium oxysporum f. sp. cubense (FOC). Pisang Awak banana ‘Fenza No. 1’ (Musa spp. cultivar Fenza No. 1), a major banana cultivar with high resistance to F. oxysporum f. sp. cubense race 4, is considered to be ideal for growth in problematic areas. However, ‘Fenza No. 1’ is still affected by F. oxysporum f. sp. cubense race 1 in the field. TR21 is an endophytic Bacillus subtilis strain isolated from orchids (Dendrobium sp.). Axillary spraying of banana plants with TR21 controls Fusarium wilt of banana, decreasing the growth period and increasing yields in the field. In this study, we established that TR21 increases root growth in different monocotyledonous plant species. By axillary inoculation, TR21 induced a similar transcriptomic change as that induced by F. oxysporum f. sp. cubense race 1 but also upregulated the biosynthetic pathways for the phytohormones brassinosteroid and jasmonic acid in ‘Fenza No. 1’ root tissues, indicating that TR21 increases Fusarium wilt of banana resistance, shortens growth period, and increases yield of banana by inducing specific transcriptional reprogramming and modulating phytohormone levels. These findings will contribute to the identification of candidate genes related to plant resistance against fungi in a nonmodel system and facilitate further study and exploitation of endophytic biocontrol agents.

The development of ultra-sensitive methods for detecting anions is limited by their low charge to radius ratios, microenvironment sensitivity, and pH sensitivity. In this paper, a magnetic sensor is devised that exploits the controllable and selective coordination that occurs between a magnetic graphene quantum dot (GQD) and fluoride anion (F–). The sensor is used to measure the change in relaxation time of aqueous solutions of magnetic GQDs in the presence of F‒ using ultra-low-field (118 μT) nuclear magnetic resonance relaxometry. The method was optimized to produce a limit of detection of 10 nmol/L and then applied to quantitatively detect F– in domestic water samples. More importantly, the key factors responsible for the change in relaxation time of the magnetic GQDs in the presence of F‒ are revealed to be the selective coordination that occurs between the GQDs and F‒ as well as the localized polarization of the water protons. This striking finding is not only significant for the development of other magnetic probes for sensing anions but also has important ramifications for the design of contrast agents with enhanced relaxivity for use in magnetic resonance imaging.

Graphical Abstract Stimulus-responsive therapy that allows precise imaging-guided therapy is limited for osteoarthritis (OA) therapy due to the selection of proper physiological markers as stimulus. Based on that the over-production of Reactive Oxygen Species (ROS) is associated with the progression in OA, we selected ROS as markers and designed a cartilage targeting and ROS-responsive theranostic nanoprobe that can be used for effective bioimaging and therapy of OA. This nanoprobe was fabricated by using PEG micelles modified with ROS-sensitive thioketal linkers (TK) and cartilage-targeting peptide, termed TKCP, which was then encapsulated with Dexamethasone (DEX) to form TKCP@DEX nanoparticles. Results showed that the nanoprobe can smartly “turn on” in response to excessive ROS and “turn off” in the normal joint. By applying different doses of ROS inducer and ROS inhibitor, this nanoprobe can emit ROS-dependent fluorescence according to the degree of OA severity, helpful to precise disease classification in clinic. Specifically targeting cartilage, TKCP@DEX could effectively respond to ROS and sustained release DEX to remarkably reduce cartilage damage in the OA joints. This smart, sensitive and endogenously activated ROS-responsive nanoprobe is promising for OA theranostics. Supplementary Information The online version contains supplementary material available at 10.1186/s12951-021-01136-4.

The cellulose synthase gene superfamily is vital for cell wall biogenesis during plant growth, particularly for flax fiber development. This study performed asequencing search of key CESA and CSL g...

Purpose The low-temperature sintering of silica glass combined with additive manufacturing (AM) technology has brought a revolutionary change in glass manufacturing. This study aims to carry out in an attempt to achieve precious manufacturing of silicate glassy matrix through the method of slurry extrusion. Design/methodology/approach A low-cost slurry extrusion modelling technology is used to extrude silicate glassy matrix inks, composed of silicate glass powder with different amounts of additives. Extrudability of the inks, their printability window and the featuring curves of silicate glassy matrix are investigated. In addition, the properties of the low-temperature sintering green part as a functional part are explored and evaluated from morphology, hardness and colour. Findings The results showed that the particle size was mainly distributed from 1.4 µm to 5.3 µm, showing better slurry stability and print continuity. The parameters were set to 8 mm/s, 80% and 0.4 mm, respectively, to achieve better forming of three-dimensional (3D) samples. Besides, the organic binder removal step was concentrated on 200°C–300°C and 590°C–650°C was the fusion bonding temperature of the powder. The hardness values of 10 test samples ranged from 588 HL to 613 HL, which met the requirements of hard stones with super-strong mechanical strength. In addition, the mutual penetration of elements caused by temperature changes may lead to a colourful appearance. Originality/value The custom continuous AM technology enables the fabrication of a glass matrix with 3D structural features. The precise positioning technology of the glass matrix is expected to be applied more widely in functional parts.

Double-strand break (DSB) repair choice is greatly influenced by the initial processing of DNA ends. 53BP1 limits the formation of recombinogenic single-strand DNA (ssDNA) in BRCA1-deficient cells, leading to defects in homologous recombination (HR). However, the exact mechanisms by which 53BP1 inhibits DSB resection remain unclear. Previous studies have identified two potential pathways: protection against DNA2/EXO1 exonucleases presumably through the Shieldin (SHLD) complex binding to ssDNA, and localized DNA synthesis through the CTC1-STN1-TEN1 (CST) and DNA polymerase α (Polα) to counteract resection. Using a combinatorial approach of END-seq, SAR-seq, and RPA ChIP-seq, we directly assessed the extent of resection, DNA synthesis, and ssDNA, respectively, at restriction enzyme-induced DSBs. We show that, in the presence of 53BP1, Polα-dependent DNA synthesis reduces the fraction of resected DSBs and the resection lengths in G0/G1, supporting a previous model that fill-in synthesis can limit the extent of resection. However, in the absence of 53BP1, Polα activity is sustained on ssDNA yet does not substantially counter resection. In contrast, EXO1 nuclease activity is essential for hyperresection in the absence of 53BP1. Thus, Polα-mediated fill-in partially limits resection in the presence of 53BP1 but cannot counter extensive hyperresection due to the loss of 53BP1 exonuclease blockade. These data provide the first nucleotide mapping of DNA synthesis at resected DSBs and provide insight into the relationship between fill-in polymerases and resection exonucleases.

BACKGROUND Drug extravasation is a complication of totally implantable access port (TIAP) use and could cause tissue injury and sustained organ dysfunction. Therefore, the clinical management of children with TIAP is challenging. CASE SUMMARY This was a case of extravasation of a chemotherapeutic drug (paclitaxel) from an implantable infusion port in a 23-mo old child. After fully evaluating the skin at the site of extravasation, the nurse continued to use the infusion port to complete the follow-up chemotherapeutic course. The skin around the infusion port was red, and showed no ulceration, swelling, or induration at discharge. CONCLUSION Since children are more active and often noncompliant, it is necessary to appropriately train pediatric nurses caring for individuals with TIAPs, and any abnormal situation should be timely addressed.

Background: Although Semaphorin 3A (Sema3A)/ Neuropilin-1(NRP1)/Plexin A1 is one of the important targets in bone metabolism, few studies are performed on this target in the glucocorticoids- induced osteoporosis. Luteolin is a chemical component of Honeysuckle and it has various bioactivities. The effect of Luteolin on the glucocorticoids-induced osteoporosis (primary osteoblasts model) remain unknown. Objective: The aim of this study was to investigate the action of Sema3A/ NRP1/Plexin A1 in Luteolin- induced osteoprotection against high-dose Dexamethasone. Methods: The effect of Luteolin on the proliferation, late differentiation, and apoptosis of primary osteoblasts model of glucocorticoids-induced osteoporosis in vitro as well as the expression of Sema3A/ NRP1/Plexin A1 are investigated by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide, Cell Counting Kit-8, reverse transcription-quantitative real-time polymerase chain reaction, western bolting and so on. Results: Suckling SD rats’ calvarial osteoblasts were isolated and identified. The glucocorticoidsinduced primary osteoporosis cell model was established by 100 μM Dexamethasone in 48 h (P Conclusion: The thesis concludes that Luteolin promoted the proliferation of osteoblast and inhibited its apoptosis and late differentiation in this glucocorticoids-induced primary osteoporosis cell model. This function may be related to the expression of up-regulated Sema3A/NRP1/Plexin A1. Therefore, Luteolin may be a potential medicine for the glucocorticoids-induced osteoporosis.

Intra-articular (IA) injection is an efficient treatment for osteoarthritis, which will minimize systemic side effects. However, the joint experiences rapid clearance of therapeutics after intra-articular injection. Delivering system modified through active targeting strategies to facilitate localization within specific joint tissues such as cartilage is hopeful to increase the therapeutic effects. In this study, we designed a nanoscaled amphiphilic and cartilage-targeting polymer-drug delivery system by using formononetin (FMN)-poly(ethylene glycol) (PEG) (denoted as PCFMN), which was prepared by PEGylation of FMN followed by coupling with cartilage-targeting peptide (CollBP). Our results showed that PCFMN was approximately regular spherical with an average diameter about 218 nm. The in vitro test using IL-1β stimulated chondrocytes indicated that PCFMN was biocompatible and upregulated anabolic genes while simultaneously downregulated catabolic genes of the articular cartilage. The therapeutic effects in vivo indicated that PCFMN could effectively attenuate the progression of OA as evidenced by immunohistochemical staining and histological analysis. In addition, PCFMN showed higher intention time in joints and better anti-inflammatory effects than FMN, indicating the efficacy of cartilage targeting nanodrug on OA. This study may provide a reference for clinical OA therapy.

Inspired by the chemistry and biology of butyrolactones, pyrrolidines, and chromanones, we successfully developed a simple domino 1,3-dipolar cycloaddition of homoserine-lactone-derived azomethine ylides for the construction of biologically important spiro[butyrolactone–pyrrolidine–chromanone] hybrids in the presence of Et3N as a catalyst under mild conditions. The reaction is based on the application of carboxylic-acid-activated chromones as dienophiles, followed by a decarboxylation process. This reaction displayed good substrate tolerance and gave the desired products in moderate to good yields with high diastereoselectivities (up to 85% yield and >20:1 diastereomeric ratio) via an exo-transition state. This is the first example of an introduction of a chromanone moiety into a spiro[butyrolactone-pyrrolidine] framework, which might be valuable in medicinal chemistry.

The application of fuel cells boosts the hydrogen demand particularly for distributed hydrogen production facility. As a potential candidate of hydrogen supply, microchannel autothermal methane steam reactor operates at high temperature and results in high thermal impact, which would decrease its stability and lifespan. A three-dimension numerical model based on finite element method was developed to evaluate the thermal characteristic and thermo-mechanically induced stress behavior of the reactor. Three different potential manufacturing materials, Fe–Cr–Al alloy, ceramic and quartz, were chosen. The results indicate that the cold-spot temperature appears near reactor inlet while the hotspot temperature appears near reactor outlet for reactor manufactured by different materials. Corresponding to the hot spot temperature, the maximum Von Mises stress appears near reactor outlet. The difference is the maximum Von Mises stress appears in catalyst layer for quartz reactor while it appears in interconnect rib for both Fe–Cr–Al alloy reactor and ceramic reactor. Meanwhile the maximum Von Mises stress reaches 1830 MPa for ceramic reactor. While the maximum Von Mises stress is 1197 MPa for quartz reactor and 1760 MPa for Fe–Cr–Al alloy reactor respectively. It implies the outlet catalyst layer region is vulnerable for quartz reactor. While the outlet interconnect rib is most vulnerable for both Fe–Cr–Al alloy reactor and ceramic reactor.

Ferroptosis is a new type of programmed cell death characterized by intracellular iron accumulation and lipid peroxidation that leads to oxidative stress and cell death. The metabolism of iron, lipids, and amino acids and multiple signalling pathways precisely regulate the process of ferroptosis. Emerging evidence has demonstrated that ferroptosis participates in the occurrence and progression of various pathological conditions and diseases, such as infections, neurodegeneration, tissue ischaemia-reperfusion injury and immune diseases. Recent studies have also indicated that ferroptosis plays a critical role in the pathogenesis of acute lung injury, chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary infection and asthma. Herein, we summarize the latest knowledge on the regulatory mechanism of ferroptosis and its association with iron, lipid and amino acid metabolism as well as several signalling pathways. Furthermore, we review the contribution of ferroptosis to the pathogenesis of lung diseases and discuss ferroptosis as a novel therapeutic target for various lung diseases.

Tyrosinase (TYR) is an important polyphenolic oxidase enzyme and usually regards as a biomarker of melanoma cancer. Highly effective tracking TYR activity in vivo will help to study the mechanism of TYR in living organisms and forecasts related diseases. In this study, we present a novel TYR-activatable fluorescent probe (CHMC-DOPA) for tracking TYR activity in vitro and in vivo. CHMC-DOPA is constructed by incorporating dopamine (DOPA) moiety into a fluorescent chloro-hydroxyl-merocyanine (CHMC) scaffold. Upon exposure to TYR, the dopamine unit in CHMC-DOPA is oxidized to a dopaquinone derivative, and an intramolecular photo-induced electron transfer (PET) process between CHMC fluorophore and o-dopaquinone will take place, the fluorescence of CHMC-DOPA is quenched rapidly. Therefore, the evaluation of TYR activity is established in terms of the relationship between fluorescence quenching efficiency and TYR activity. In our experiments, CHMC-DOPA shows various advantages, such as fast response (8⬰min), low concentration of TYR activation (0.5 U/mL), good water-solubility, as well as the lowest detection limit (0.003 U/mL) compared with previously reported works. Furthermore, CHMC-DOPA also exhibits excellent cell membrane permeability and low cytotoxicity, which is successfully used to monitor endogenous TYR activity in living cancer cells and zebrafish models. CHMC-DOPA performs well, and we anticipate that this newly designed novel platform will provide an alternative for high effective monitoring TYR activity in biosystems.

The pelvic autonomic nerves control and regulate anorectal and urogenital function. The dysfunction of pelvic autonomic nerves lead to disorders of anorectum, bladder and male sex organs. Thus the intraoperative identification of pelvic autonomic nerves could be crucial in complications prevention and diseases treatment. Our clinical trial aims at estimating the effectiveness and validity of intraoperative indocyanine green fluorescence imaging in pelvic autonomic nerves identification. Intraoperative fluorescence imaging using indocyanine green was performed in ten patients and the feasibility was determined. From February 2019 to June 2019, the seven patients undergoing laparoscopic colorectal resection was administrated 4.5 mg/Kg indocyanine green 24 h before surgery. The near-infrared fluorescence imaging was conducted during surgery. A novel white light and near-infrared dual-channel laparoscopic equipment was applied. For each patient, signal–background ratio values for pelvic autonomic nerves were recorded and analyzed. We confirmed the dose and timing of indocyanine green administration was 4.5 mg/Kg and 24 h before surgery. Using the dual laparoscopic equipment, we could observe the splanchnic plexus, inferior mesenteric artery plexus, and sacral plexus successfully with a high signal background ratio value of 3.18 (standard deviation: 0.48). This pilot trial shows feasibility of intraoperative indocyanine green fluorescence imaging in pelvic autonomic nerves observation. It demonstrates that nerves can be visualized using alternative imaging techniques but it is not ready yet for prime time. This technique might aid observation with white light alone. Registration number: ChiCTR1900025336.

This study examined the effects of different sequential treatments of dextran glycation and succinic anhydride acylation on the structure and physicochemical properties of soy protein isolate (SPI). The tested properties included electrophoresis (SDS-PAGE), Fourier transform infrared spectroscopy, endogenous fluorescence spectroscopy, surface hydrophobicity (H0 ), free sulfhydryl (-SH), solubility, interfacial properties, rheological properties, and scanning electron microscope (SEM). The results show that the two treatments significantly improved the structure and functional characteristics of the SPI. The order of the methods had an important effect on the SPI. The lowest H0 (231.76 ± 11.92), the highest free -SH content (3.09 ± 0.09 µmol/g), and the highest solubility at pH = 7 (77 ± 3.97%) were obtained when the acylation treatment was followed by the glycation treatment. Emulsification, emulsion stability, foaming, and foam stability were also the highest. Glycation and acylation caused the viscosity coefficient (k) of the SPI solution to decrease compared with SPI alone, but the flow index (n) value increased, and the sum G' value of the conjugate system decreased as gel time increased. SEM showed that its microstructure has changed significantly. Therefore, this research provided an effective method for improving the functional characteristics of SPI and had potential industrial application prospects. PRACTICAL APPLICATION: Glycation and acylation of soybean protein isolate improved the chemical modification method of protein, improved the functional properties of soybean protein, widened its application in food and materials, and provided a new idea for the further development and utilization of soybean protein.

General control nonderepressible 2 (GCN2) is a serine/threonine protein kinase, detecting a variety of stresses including amino acid starvation, reactive oxygen species, etc. in eukaryotic cells. Activation of GCN2 requires the interaction of the N-terminal RWD domain with the upstream GCN1 protein and the dimerization by the kinase domain. In this study, we determined two crystal structures of the RWD domain of human GCN2 in two different crystal packing modes. These two different crystal structures reveal a same dimer of the RWD domain, which has not been reported in previous studies. We further confirmed this novel dimer interaction in solution using gel filtration experiments, and in human embryonic kidney (HEK) 293 cells using bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (co-IP) assays. Together, this study discovers a potential protein-protein interface on the RWD domain of human GCN2, and suggests a possible regulation between the interaction of GCN1 and the formation of GCN2 dimer.

All RecJ proteins are known to date only perform exonuclease activity. The present study reports that a novel RecJ protein obtained from Bacillus cereus isolated from marine sediments has both endonuclease and exonuclease activities. Analysis of the BcRecJ expression induction in E. coli BL21 revealed that the BcRecJ protein cleaved plasmids and genomic DNA in the host cell, and led to cell death and decreased the DNA content. Further, the BcRecJ protein had the ability to degrade supercoiled plasmid DNA into circular or linear forms in vitro. Meanwhile, the BcRecJ protein loaded with an S-modified guide facilitated plasmid linearization and reduced smear formation. The results suggested that this novel BcRecJ protein was different from any reported RecJs and had a longer C-terminus. Testing the BcRecJ mutants indicated that the endonuclease activity was affected by two residues of BcRecJ (D561, E637) after testing the BcRecJ mutants. The discovery of the type of protein is a new breakthrough for the RecJ proteins, which has both endonuclease and exonuclease activities.

Scavenging carbonylated proteins that are toxic substances inducing various diseases attract the most attention in the field of blood purification. In our study, functionalized cellulose beads modified by carbazate groups as affinity ligands of carbonyls were prepared for specific scavenging of carbonylated proteins based on the carbazate-aldehyde/ ketone reaction. Results showed that the carbazate-functionalized cellulose beads with different degrees of substitution (DS) maintained the original multi-porous structure with the diameter of about 50 μm and thermal stability. Spectroscopic and gel electrophoresis analysis indicated that the modified cellulose beads could effectively scavenge carbonylated proteins and the scavenging effects increased with the increase of DS. Thus, the carbazate functionalized cellulose beads may be developed as fillers in the column for the scavenging of carbonylated proteins.

Liver fibrosis is a major global health concern. Management of chronic liver disease is severely restricted in clinics due to ineffective treatment approaches. However, a lack of targeted therapy may aggravate this condition. Asiatic acid (AA), a pentacyclic triterpenoid acid, can effectively protect the liver from hepatic disorders. However, the pharmaceutical application of AA is limited by low oral bioavailability and poor targeting efficiency. This study synthesized a novel liver-targeting material from PEG-SA, chemically linked to ursodeoxycholic acid (UA), and utilized it to modify AA nanostructured lipid carriers (UP-AA-NLC) with enhanced targeting and improved efficacy. The formulation of UP-AA-NLC was optimized via the Box–Behnken Experimental Design (BBD) and characterized by size, zeta potential, TEM, DSC, and XRD. Furthermore, in vitro antifibrotic activity and proliferation of AA and NLCs were assessed in LX-2 cells. The addition of UP-AA-NLC significantly stimulated the TGF-beta1-induced expression of α-SMA, FN1, and Col I α1. In vivo near-infrared fluorescence imaging and distribution trials in rats demonstrated that UP-AA-NLC could significantly improve oral absorption and liver-targeting efficiency. Oral UP-AA-NLC greatly alleviated carbon tetrachloride-induced liver injury and fibrosis in rats in a dosage-dependent manner, as reflected by serum biochemical parameters (AST, ALT, and ALB), histopathological features (H&E and Masson staining), and antioxidant activity parameters (SOD and MDA). Also, treatment with UP-AA-NLC lowered liver hydroxyproline levels, demonstrating a reduction of collagen accumulation in the fibrotic liver. Collectively, optimized UP-AA-NLC has potential application prospects in liver-targeted therapy and holds great promise as a drug delivery system for treating liver diseases.

Cu(I)-based cyclic trinuclear complexes (CTCs) represent one of the most intensively investigated candidates in coinage metal-derived CTCs because of their rich photoluminescence properties. Beyond the molecular level, coordination polymers built upon Cu(I)-based CTCs have developed rapidly in recent times. However, most of the secondary building units (SBUs) on pyrazolyl moieties reported to-date have been centralized on pyrazoles, pyridines and carboxylates and most of the nodes for bridging linkers have been based on copper-halide clusters. This work presents the use of a thioether-functionalized pyrazole to construct Cu(I)-based CTC, 1, which was allowed to react with CuI and BiBr3 for constructing coordination polymers, 2 and 3, respectively. Successful isolation of 2 and 3 highlights that the thioether pendant on the pyrazole can act as a novel class of SBUs on Cu(I)-based CTCs to assemble coordination polymers with a soft Lewis acid and not limited to copper-halide clusters.

The cruciform linker molecule here features two designer functions: the pyrazole donors for framework construction, and the vicinal alkynyl units for benzannulation to form nanographene units into the Ni8-pyrazolate scaffold. Unlike the full 12 connections of the Ni8(OH)4(H2O)2 clusters in other Ni8-pyrazolate networks, significant linker deficiency was observed here, leaving about half of the Ni(II) sites capped by acetate ligands, which can be potentially removed to open the metal sites for reactivity. The crystalline Ni8-pyrazolate scaffold also retains the crystalline order even after thermal treatments (up to 300 °C) that served to partially graphitize the neighboring alkyne units. The resultant nanographene components enhance the electroactive properties of the porous hosts, achieving hydrogen evolution reaction (HER) activity that rivals that of topical nickel/palladium-enabled materials.

Two novel two-dimensional metal-organic frameworks (2D MOFs), 2D-M2 TCPE (M=Co or Ni, TCPE=1,1,2,2-tetra(4-carboxylphenyl)ethylene), which are composed of staggered (4,4)-grid layers based on paddlewheel-shaped dimers, serve as heterogeneous photocatalysts for efficient reduction of CO2 to CO. During the visible-light-driven catalysis, these structures undergo in situ exfoliation to form nanosheets, which exhibit excellent stability and improved catalytic activity. The exfoliated 2D-M2 TCPE nanosheets display a high CO evolution rate of 4174 μmol g-1 h-1 and high selectivity of 97.3 % for M=Co and Ni, and thus are superior to most reported MOFs. The performance differences and photocatalytic mechanisms have been studied with theoretical calculations and photoelectric experiments. This study provides new insight for the controllable synthesis of effective crystalline photocatalysts based on structural and morphological coregulation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

By having the potential to remove nitrogen oxide (NOx) air pollutants generated by vehicles and other anthropogenic combustion processes, particularly in urban areas, photocatalytic concrete has attracted significant commercial interests all over the world. In contrast to typical photocatalyst applications in concrete, in which titanium dioxide (TiO2) – the most utilised photocatalyst – is dispersed within the cementitious materials, the study reported here utilises titanium dioxide-coated aggregates. Used in an exposed-aggregate finish, this format aims to have a higher photocatalytic efficiency than titanium dioxide cement-bound materials. An exposed titanium dioxide-coated aggregate has the potential to provide a significantly higher proportion of catalyst to direct ultraviolet radiation and minimise lost performance due to occlusion. The exposed-aggregate surface area on the test mortar samples was measured with three-dimensional imaging techniques. Thereafter, photocatalytic efficiency was measured in comparison with that of the titanium dioxide cement mortar. The relationship between exposed area for photocatalytic reaction and photocatalytic efficiency was established. This indicated that the photonic efficiency increases with increasing exposed area, regardless of the method to support the catalyst – that is, either within the cement paste or externally mounted on the aggregate. The data confirm that exposing coated aggregate significantly enhances photonic efficiency.

Stimulus-responsive therapy permits precise control of therapeutic effect only at lesion of interest, which determines it a promising method for diagnosis and imaging-guided precision therapy. The acid environment and overexpressed matrix metalloproteinases-13 (MMP-13) are typical markers in osteoarthritis (OA), which enables the development of stimulus-responsive drug delivery system with high specificity for OA. We herein demonstrate a nano-micelle based stimuli-responsive theranostic strategy with reporting and drug release controlled by acidic pH and MMP-13 for OA therapy. Such nanoplatform is incorporated with a motif specifically targeting on cartilage, a motif responsive to matrix metalloproteinases-13 to specifically report OA condition and biodynamics of nano-micelles, an anti-inflammatory drug (e.g., psoralidin (PSO)) from traditional Chinese medicine, and a biocompatible polymeric skeleton for sustainable drug release in response to the acidic OA condition. The high effectiveness of this targeted precision therapy is demonstrated comprehensively by both in vitro and vivo evidences.

To examine whether urine kynurenine (KYN) levels were associated with early-stage Parkinson’s disease (PD), as well as the value of urine KYN as a potential biomarker in early-stage PD. Eighty-two participants including 41 PD patients and 41 healthy controls were enrolled into this study. Urine KYN levels were measured with a KYN enzyme-linked immunoassay kit. In order to explore the correlation between some clinical parameters and urine KYN, the clinical parameters for these participants were recorded. Diagnostic value and clinical relevance of urine KYN were assessed by using receiver operator characteristic (ROC) curve and correlation analysis. Urine KYN levels were significantly higher in the PD group than in the healthy group (891.95 ± 276.65 pg/ml vs. 640.11 ± 122.37 pg/ml, p = 0.000). The correlations between urine KYN levels and clinical parameters are as follows: Hoehn-Yahr stage (r = 0.676, p = 0.000), disease duration (r = 0.772, p = 0.000), Mini-Mental State Examination scores (r = −0.434, p = 0.005). There was no statistically significant correlation between urine KYN with age, low-density cholesterol (LDL), triglycerides (TG), cholesterol (TC), homocysteine (HCY), uric acid (UA), and glomerular filtration rate (GFR). The ROC analysis showed that urine KYN optimal cutoff value of 751.88 pg/ml had a sensitivity of 65.9% and a specificity of 90.2% for distinguishing between PD and controls, with an area under the curve (AUC) of 0.776. Urine KYN were significantly associated with PD severity and mild cognitive impairment. Urine KYN may be a new biomarker for early-stage PD.

A novel additive system comprising bis-(sodium sulfopropyl)-disulfide, polyethylene glycol and hydroquinone (HQ) was developed and investigated to achieve high rate copper electrodeposition at high temperature. HQ, as the key additive compound in this system, refines the Cu grain, makes the coating surface bright and smooth at high current density. The underlying mechanism of the additive-assisted electroplating was investigated through electrochemical, morphological characterizations and molecular dynamics simulation. Nanocubical copper particles were found through chronoamperometry tests, which explains the fine crystalline Cu grains and the bright coating surface. Additionally, the formation of the nanocubical copper particles is caused by the different adsorption energies of HQ on (311), (111) and (220) crystal faces and further leads to a strong suppression on the (220) orient crystal faces. Moreover, the electroplating results of through-holes illustrate the feasibility of this additive system in practical applications.

BACKGROUND Sturgeon is popular for its nutritious value and its taste. However, sturgeon fillets are traditionally heated in 100 °C boiling water, resulting in unfavorable taste and with a negative effect on the quality. This study considered the effect of combinations of vacuum and low-temperature treatments (LTVH groups) on sturgeon fillets compared with the traditional heat treatment (TC groups). RESULTS The results show that the LTVH groups had lower cooking-loss rates. All LTVH fillets were changed to a white color, and appeared 'done', as did the TC fillets. The LTVH and TC methods gave rise to significant differences in texture: the springiness of the LTVH groups decreased with heating time, and decreased rapidly in the TC groups (P

Background Methotrexate (MTX) is an antiproliferative drug widely used to treat inflammatory diseases and autoimmune diseases. The application of percutaneous administration is hindered due to its poor transdermal penetration. To reduce side effects and enhanced percutaneous delivery of MTX, novel methotrexate (MTX)-loaded micelles prepared with a amphiphilic cationic material, N,N-dimethyl-(N',N'-di-stearoyl-1-ethyl)1,3-diaminopropane (DMSAP), was designed. Materials and methods DMSAP was synthesized via three steps using simple chemical agents. H nuclear magnetic resonance and mass spectroscopy were used to confirm the successful synthesis of DMSAP. A safe and non-toxic phosphatidylcholine, soybean phosphatidylcholine (SPC), was added to DMSAP at different ratios to form P/D-micelles. Then, MTX-entrapped micelles (M/P/D-micelles) were prepared by electrostatic adsorption. The physicochemical properties and blood stability of micelles were examined thoroughly. In addition, the transdermal potential of the micelles was evaluated by permeation experiments. Results In aqueous environments, DMSAP conjugates could self-assemble spontaneously into micelles with a low critical micelle concentration (CMC) of 0.056 mg/mL. Stable, spherical MTX-entrapped micelles (M/P/D-micelles) with a size of 100-120 nm and high zeta potential of +36.26 mV were prepared. In vitro permeation studies showed that M/P/D-micelles exhibited superior skin permeability and deposition of MTX in the epidermis and dermis compared with that of free MTX. Conclusion These special novel cationic M/P/D-micelles can enhance the permeability of MTX and are expected to be a promising percutaneous delivery system for therapy skin diseases.

Dyslipidemia is a risk factor for cardiovascular diseases and type 2 diabetes. Several adipokines play important roles in modulation of blood lipids. Metrnl is a recently identified adipokine, and adipose Metrnl participates in regulation of blood triglyceride (TG). In this study, we generated Metrnl global, intestine-specific and liver-specific knockout mice, and explored the effects of Metrnl on serum lipid parameters. Global knockout of Metrnl had no effects on serum lipid parameters under normal chow diet, but increased blood TG by 14%, and decreased total cholesterol (TC) by 16% and high density lipoprotein cholesterol (HDL-C) by 24% under high fat diet. Nevertheless, intestine-specific knockout of Metrnl did not alter the serum lipids parameters under normal chow diet or high fat diet. Notably, liver-specific knockout of Metrnl decreased HDL-C by 24%, TC by 20% and low density lipoprotein cholesterol (LDL-C) by 16% without alterations of blood TG and nonesterified fatty acids (NEFA) under high fat diet. But deficiency of Metrnl in liver did not change VLDL secretion and expression of lipid synthetic and metabolic genes. We conclude that tissue-specific Metrnl controls different components of blood lipids. In addition to modulation of blood TG by adipose Metrnl, blood HDL-C is regulated by liver Metrnl.

Linyuan Yu, Lihong Gong, Cheng Wang, Naihua Hu, Yunqiu Tang, Li Zheng, Xuyang Dai, Yunxia Li School of Pharmacy, Chengdu University of Traditional Chinese Medicine; Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education; National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu 611137, People’s Republic of ChinaCorrespondence: Yunxia LiSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine; Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education; National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, No. 1166, Liu Tai Avenue, Wenjiang District, Chengdu, Sichuan, People’s Republic of ChinaTel +86-13699021135Email lyxcdutcm@126.comPurpose: Nonalcoholic fatty liver disease (NAFLD) has become a predictor of death in many diseases. This study was carried out to investigate the therapeutic effect of Radix Polygoni Multiflori Preparata (RPMP) and its main component emodin on egg yolk powder-induced NAFLD in zebrafish. Further investigation was performed to explore whether emodin was the main component of RPMP for the treatment of NAFLD as well as the underlying therapeutic mechanism of RPMP and emodin.Methods: Zebrafish were divided into control group, egg yolk powder group, RPMP group and emodin group. The obesity of zebrafish was evaluated by body weight, body length and BMI. The content of lipid was detected by triglyceride (TG), total cholesterol (TC) reagent kit and the fatty acid was detected by nonesterified free fatty acids (NEFA) reagent kit. HE staining was used to detect the histological structure of liver. Whole-mount Oil red O staining and Frozen oil red O staining were carried out to investigate the lipid accumulation in liver. KEGG and STRING databases were performed to analyze the potential role of AMPK between insulin resistance (IR) and fatty acid oxidation. Western blot and RT-qPCR were carried out for mechanism research.Results: RPMP and emodin significantly reduced zebrafish weight, body length and BMI. Both RPMP and emodin treatment could reduce the lipid deposition in zebrafish liver. RPMP significantly reduced the content of TG. However, emodin significantly reduced the contents of TG, TC and NEFA in zebrafish with NAFLD. The protein interaction network indicated that AMPK participated in both IR and fatty acid oxidation. Further investigation indicated that RPMP and emodin reduced hepatic lipogenesis via up-regulating the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT2), amp-activated protein kinase alpha (AMPKα), proliferator-activated receptor alpha (PPARα), carnitine palmitoyl transferase 1a (CPT-1a) and acyl-coenzyme A oxidase 1 (ACOX1).Conclusion: These findings suggest that emodin is the main component of RPMP for the treatment of NAFLD, which is closely related to the regulation of AMPK signaling pathway which increases IR and fatty acid oxidation.Keywords: RPMP, emodin, zebrafish, AMPK, nonalcoholic fatty liver disease

Aminoacyl-tRNA synthetases, the essential enzyme family for protein translation, are attractive targets for developing antibacterial, antifungal, and antiparasitic agents and for treating other human diseases. The antimalarial natural product cladosporin was discovered recently as a novel lysyl-tRNA synthetase (LysRS) specific inhibitor. Here, we report a thorough analysis of cladosporin derivatives using chemical synthesis, biophysical, and biochemical experiments. A series of isocoumarin derivatives with only one nonhydrogen atom/bond change per compound was synthesized. These changes include replacements of methyltetrahydropyran moiety by methylcyclohexane or cyclohexane, lactone by lactam, hydroxyl groups by methoxyl groups, and dismission of the chiral center at C3 with a Δ3,4 double bond. We evaluated these compounds by thermal shift assays and enzymatic experiments and further studied their molecular recognition by the Plasmodium falciparum LysRS through total five high-resolution crystal structures. Our results showed that the methyltetrahydropyran moiety of cladosporin could be replaced by a more stable methylcyclohexane without reducing binding ability. Removing the methyl group from the methylcyclohexane moiety slightly decreased the interaction with LysRS. Besides, the replacement with a lactam group or a conjugated Δ3,4 double bond within the scaffold could be two more options to optimize the compound. Lastly, the two phenolic hydroxyl groups were critical for the compounds to bind LysRS. The detailed analyses at atomic resolution in this study provide a foundation for the further development of new antibiotics from cladosporin derivatives.

Two new chemically-stable metalloporphyrin-bridged metal-catechol frameworks, InTCP-Co and FeTCP-Co, are constructed to achieve artificial photosynthesis without additional sacrificial agents and photosensitizers. The CO 2 photoreduction rate over FeTCP-Co considerably exceeds that obtained over InTCP-Co, and the incorporation of an uncoordinated hydroxyl group per catechol into the network further greatly promotes the photocatalytic activity. It could be explained by the fact that the iron-oxo coordination chain helps the energy band alignment and provides a redox-active site, and the uncoordinated hydroxyl group contributes to the visible-light absorptance, charge carrier transfer, and CO 2 -scaffold affinity. With a formic acid selectivity of 97.8%, FeTCP-OH-Co affords CO 2 photoconversion with a reaction rate 4.3 and 15.7 times higher than those of FeTCP- Co and InTCP-Co, respectively. These findings are also consistent with the spectroscopic study and DFT calculation.

Di-(2-ethylhexyl) phthalate (DEHP), used as a popular plasticizer to enhance the flexibility of plastics, is a major pollutant in aquatic environments. DEHP poses severe risks to aquatic organisms since it is an endocrine-disrupting compound. To comprehensively evaluate the toxicity of DEHP on the growth and livers of male X. tropicalis, sexually mature male X. tropicalis were exposed to environmentally relevant concentrations of DEHP, 0.2, 0.6, 1.8, 5.4 mg/L, for 49 days. The results showed that DEHP had a severe toxic effect on the livers of male X. tropicalis. Histopathological analysis of livers in all the DEHP-exposed groups showed changes in terms of vacuolization, loose cell cords, and an increasing amount of melanin. Large lipid droplets were markedly formed, and there were changes in the mitochondrial morphology upon DEHP exposure. In addition, oxidative stress was induced through the suppression of biochemical indicators and the downregulation in the mRNA expression of genes (nrf2, cat, sod, gst, and gpx) related to oxidative stress. A reduction in expression of fatty acid metabolism-related genes (pparα) was seen post-DEHP exposure. Thus, our study suggests that the hepatotoxicity induced by DEHP could be attributed to oxidative stress and disordered fatty acid metabolism. In conclusion, long-term exposure to DEHP at environmentally relevant concentrations poses ecological risks to aquatic organisms, which serves as a reminder that the application of DEHP and other plasticizers should be limited.

We propose an effective approach for creating robust nonreciprocity of high-order sidebands, including the first-, second- and third-order sidebands, at microwave frequencies. This approach relies on magnon Kerr nonlinearity in a cavity magnonics system composed of two microwave cavities and one yttrium iron garnet (YIG) sphere. By manipulating the driving power applied on YIG and the frequency detuning between the magnon mode in YIG and the driving field, the effective Kerr nonlinearity can be strengthened, thereby inducing strong transmission non-reciprocity. More interestingly, we find the higher the sideband order, the stronger the transmission nonreciprocity marked by the higher isolation ratio in the optimal detuning regime. Such a series of equally-spaced high-order sidebands have potential applications in frequency comb-like precision measurement, besides structuring high-performance on-chip nonreciprocal devices.

Simple Summary Myzus persicae is a worldwide pest causing significant economic loss, especially to vegetables. However, the mainly applied insecticides were not effective, whilst also endangering the safety of pollinators. Harmonia axyridis and Aphidoletes aphidimyza are predators of aphids, but they are costly and affected by temperature and insecticides. We conducted toxicity tests and greenhouse trails to make an effective combination of neonicotinoid insecticides and predators. Both H. axyridis and A. aphidimyza effectively controlled aphids whether combined with thiacloprid or not, at above 20 °C temperature condition. Our results indicated that it is it is necessary to choose H. axyridis or A. aphidimyza to control aphids based on economic and thermal considerations. Practically, thiacloprid could be used either as an emergency option to control aphids’ abundance alone or in combination with natural enemies. Abstract Excessive insecticide application has posed a threat to pollinators and has also increased insecticide resistance of Myzus persicae Sulzer. Therefore, it is urgent to develop an economical and effective strategy, especially for greenhouse vegetables. Firstly, we selected a neonicotinoid insecticide that is specifically fatal to M. persicae but relatively safe to predators and bumblebees by laboratory toxicity tests and risk assessments. Then, we tested the effectiveness of the neonicotinoid insecticide under different temperature conditions. According to the LC50 values and the hazard quotients, thiacloprid met the requirements. Greenhouse trails indicated that thiacloprid was quite efficient, while control dropped to 80% without the application of thiacloprid. As for biological control, Harmonia axyridis effectively controlled 90% of aphids with thiacloprid or not. However, Aphidoletes aphidimyza performed better above 20 °C. Our results indicated that it is cost-effective to control M. persicae with A. aphidimyza in suitable temperature conditions and H. axyridis was more effective at low temperatures. Practically, thiacloprid could be used either as an emergency option to control aphids’ abundance alone or in combination with natural enemies.

To investigate the effects of temperature and hydration on the microstructure of polymer electrolyte membrane and the transport of water molecules and hydronium ions, molecular dynamics simulations are performed on Nafion 117 for a series of water contents at different temperatures. The interactions among the sulfonate groups, hydronium ions, and water molecules are studied according to the analysis of radial distribution functions and coordination numbers. The sizes and connectivity of water clusters are also discussed, and it is found that the hydration level plays a key role in the phase separation of the membrane. However, the effect of the temperature is slight. When the water content increases from 3.5 to 16, the size of water clusters in the membrane increases, and the clusters connect to each other to form continuous channels for diffusion of water molecules and hydronium ions. The diffusion coefficients are estimated by studying the mean square displacements. The results show that the diffusion of water molecules and hydronium ions are both enhanced by the increase of the temperature and hydration level. Furthermore, the diffusion coefficient of water molecules is always much larger than that of hydronium ions. However, the ratio of the diffusion coefficient of water molecules to that of hydronium ions decreases with the increase of water content.

C27H18NO9Zn, triclinic, P 1 ¯ $P\overline{1}$ (no. 2), a = 8.4357(10) Å, b = 10.1228(10) Å, c = 13.5186(10) Å, α = 83.830(7)°, β = 10.1228(10)°, γ = 13.5186(10)°, V = 1142.05(19) Å3, Z = 2, R gt (F) = 0.0665, wR ref (F 2) = 0.1427, T = 293(2) K.

Frankliniella occidentalis (Thysanoptera: Thripidae) is a notorious pest of horticultural crops, against which the predator Orius sauteri or neonicotinoid insecticides are commonly used in control programmes. Here, we carried out a series of indoor acute toxicity tests and a risk assessment of eight neonicotinoid insecticides (imidacloprid, nitenpyram, acetamiprid, thiacloprid, thiamethoxam, clothianidin, dinotefuran and flupyradifurone) for O. sauteri and F. occidentalis. For O. sauteri, the LC50 values of acetamiprid and flupyradifurone were 12.75 and 9.24 mg a.i. L−1, respectively, and their hazard quotients were ≤ 2. Their toxicities to F. occidentalis were in a similar range. When LC20 of acetamiprid or flupyradifurone was applied to the pest, predator or both, predation ability was slightly reduced with flupyradifurone (37, 59 and 18, respectively) having less impact compared to acetamiprid (18, 21 and 10, respectively). Furthermore, we performed a greenhouse efficacy trial which involved the selected neonicotinoids acetamiprid and flupyradifurone as well as O. sauteri. Our results showed that integrated pest management, i.e. the application of half the amount of O. sauteri together with low doses (LC20) of acetamiprid or flupyradifurone, significantly reduced the pest with 76% and 75%, respectively, during the trial time, similar to the biocontrol treatment and significantly better than for chemical control alone. The cost of the integrated pest control strategy was similar to chemical control alone and lower than for biocontrol, indicating its potential as an economically feasible thrips control strategy, with reduced environmental risks compared to using chemicals only.

Stroke is one of the leading causes of mortality and disability worldwide. Long noncoding RNAs (lncRNAs) including MALAT1 have been shown to have critical roles in cerebral ischemia reperfusion injury (CIRI). However, the underlying mechanism of MALAT1 in CIRI has not been elucidated. The present study aimed to investigate the function and potential regulatory mechanism of MALAT1 in cerebral ischemic reperfusion injury. We established the middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reoxygenation (OGD/RX) model in vivo and in vitro, and then Cell Counting Kit-8 (CCK-8), RT-qPCR, flow cytometry analysis, lactate dehydrogenase (LDH) analysis, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to examine cell viability, MALAT1, aquaporin-4 (AQP4) expression, LDH release, and infarct volume, respectively. The level of AQP4 was remarkably upregulated in CIRI 24 h/48 h or OGD/RX 24 h/48 h compared with the sham group. Knockdown of AQP4 could alleviate OGD/RX-induced injury through enhancing cell viability and reducing LDH release and the rate of apoptotic cells. Furthermore, we found that MALAT1 was also increased in OGD/RX 24 h/48 h and silencing of MALAT1 could decrease AQP4. Inhibition of MALAT1 could also protect OGD/RX-induced injury, while the protective effect of MALAT1 siRNA on cerebral ischemic reperfusion was disappeared after transfection with AQP4 plasmid, indicating that MALAT1 may play a protective role in brain stroke through regulating AQP4. Taken together, our study provides evidence that MALAT1 is involved in ischemic stroke by inhibiting AQP4. Therefore, MALAT1 may serve as a potential target for therapeutic intervention in ischemic brain injury.

Taking inspiration from skeletal muscle with highly oriented myofibers, we developed a tough wood aerogel/poly(ionic liquid) (WA/PIL) hydrogel directly from wood via delignification, impregnation and gelation for the formation of a tactile sensor of electric double-layer capacitive configuration. The WA/PIL hydrogels integrated the representative properties of both wood and ionic liquids, being a promising candidate for both polyelectrolyte and separator materials. The influences of the wood texture and cross-linker (Bis) content on the mechanical and sensing performances of the hydrogels were investigated. The results showed that the tangential hydrogel slice with a 1.0 mol% Bis content (tan 1.0) displayed the most significant improvement in compressive stress (1.65 MPa) and deformation (73.3%) at fracture, suggesting the best compressibility. Electrodes also played a significant role in the sensitivity and stability of the sensor devices. While tan 1.0 with reduced graphene oxide (rGO) electrodes displayed the largest sensitivities (1.13–19.70 MPa−1), tan 1.0 with Ni foams possessed much more stable ionic signals within the whole stress range with sensitivities of 0.33–9.67 MPa−1. Due to the wide-stress-range responsiveness of our hydrogel sensor from gentle finger contact to vigorous hitting modes, it will find promising applications in various human–machine interfaces in the fields of electronics, recreation, sports, etc.

Efficient photocatalytic conversion of CO2 into energy-rich chemicals is of great significance for both environmental conservation and alleviating the energy crisis. However, convenient synthesis of low-cost, durable and eco-friendly photocatalysts with a novel morphology or structure for highly selective photocatalytic CO2 reduction remains a challenge. Herein, Co3O4 hierarchical nanosheets were synthesized by calcination of novel cobalt metal-organic framework (MOF) nanosheets prepared by a facile oil bath method. In such Co MOF nanosheets, 1,4-naphthalenedicarboxylic acid was chosen as the organic linker, rather than the commonly used 2-methylimidazole for ZIF-67. After thermal treatment in air, the obtained Co3O4 inherited the 2D morphology of its MOF template and evolved into hierarchical nanosheets which were composed of small nanoparticles. Benefiting from the large surface area, abundant mesoporous structure and good capability towards the separation and transfer of photo-generated charge carriers induced by less internal oxygen vacancies, the Co3O4 hierarchical nanosheets showed a CO generation rate of 39.70 μmol h-1 in visible-light photocatalytic CO2 reduction, which was superior to that of Co3O4 nanoparticles and commercial Co3O4. What's more, a CO selectivity of 77.3% was achieved, which is among the highest of cobalt-based spinel oxide photocatalysts for CO2 conversion.

Purpose: This study was to perform preclinical evaluation of a novel class I and IIb HDAC-selective inhibitor, purinostat mesylate, for the treatment of Ph+ B-cell acute lymphoblastic leukemia (B-ALL). Experimental Design: Biochemical assays were used to test enzymatic activity inhibition of purinostat mesylate. Ph+ leukemic cell lines and patient cells were used to evaluate purinostat mesylate activity in vitro. BL-2 secondary transplantation Ph+ B-ALL mouse model was used to validate its efficacy, mechanism, and pharmacokinetics properties in vivo. BCR-ABL(T315I)–induced primary B-ALL mouse model and PDX mouse model derived from relapsed Ph+ B-ALL patient post TKI treatment were used to determine the antitumor effect of purinostat mesylate for refractory or relapsed Ph+ B-ALL. Long-term toxicity and hERG blockade assays were used to safety evaluation of purinostat mesylate. Results: Purinostat mesylate, a class I and IIb HDAC highly selective inhibitor, exhibited robust antitumor activity in hematologic cancers. Purinostat mesylate at low nanomolar concentration induced apoptosis, and downregulated BCR-ABL and c-MYC expression in Ph+ leukemia cell lines and primary Ph+ B-ALL cells from relapsed patients. Purinostat mesylate efficiently attenuated Ph+ B-ALL progression and significantly prolonged the survival both in BL-2 secondary transplantation model with clinical patient symptoms of Ph+ B-ALL, BCR-ABL(T315I)–induced primary B-ALL mouse model, and PDX model derived from patients with relapsed Ph+ B-ALL post TKI treatment. In addition, purinostat mesylate possesses favorable pharmacokinetics and low toxicity properties. Conclusions: Purinostat mesylate provides a new therapeutic strategy for patients with Ph+ B-ALL, including those who relapse after TKI treatment.

Electrocatalytic materials for hydrogen evolution reaction are crucial in water splitting. Developing low‒cost and highly active catalyst remains an enormous challenge. Herein, we reported a simple approach to synthesize a molybdenum disulfide/micrometer‒scale biomass carbon tube matrix (BCTM) which is derived from available and accessible plant wild celery. Molybdenum disulfide (MoS2) nanosheet could be well dispersed on the BCTM to form porous structure, while the BCTM can enhance the conductivity of MoS2 nanosheet. The synergistic effects between the MoS2 nanosheet and BCTM contribute to high hydrogen evolution reaction activity. MoS2/BCTM shows admirable catalytic ability with a low overpotential of 176 mV at 10 mA cm−2, a small Tafel slope 51 mV·dec−1, and outstanding stability over 2000 cycles under acidic conditions. This novel strategy provides a low‒cost route to synthesize excellent MoS2‒based catalyst, which may widely apply in the fields of electrocatalysis and photocatalysis.

Polydatin (PD), an active component of Chinese herbs, is reported to have many biological functions, such as cardioprotective actions, anti-inflammatory activities, and antitumor effects. In this study, we investigated the effects of PD on body weight control, glucose and lipid metabolic regulation, and anti-inflammation in a high-fat-diet- (HFD-) induced obese mice model. After treatment of PD (100 mg/kg/d for 4 weeks), HFD mice reduced body weight, retroperitoneal fat mass, and adipose cell sizes; significantly lowered serum total cholesterol triglyceride (TG) and low-density lipoprotein (LDL) levels; and increased high-density lipoprotein (HDL) levels compared with the HFD control mice. Further studies showed that PD downregulated the mRNA and protein expressions of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor involving in the regulation of adipocyte differentiation, in the retroperitoneal fat of HFD mice. Additionally, PD significantly upregulated the mRNA and protein expressions of leptin, an adipocyte-derived anorexic hormone that regulates food intake and energy expenditure, in the adipose tissues of HFD mice. Moreover, PD reduced the expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) in the retroperitoneal and epididymal tissues of HFD mice, suggesting that PD prevented adipose tissue inflammation. In conclusion, PD may serve as a pharmaceutic candidate for obesity-related lipid metabolism, anti-inflammation, and body weight loss.

The first application of α-d-galacturonic acid hydrate (GalA) is reported here, as a potential O-donor ligand. The C–N couplings of N-heterocycles with aryl halides or arylboronic acids could be readily conducted and exhibited good functional group tolerance with characters of selectivity. These N-arylazoles allow rapid access to several pharmaceutical intermediates and can be easily transformed into a variety of other interesting scaffolds as well.

Sucrose phosphorylase (SPase) is capable of specifically catalysing transglucosylation reactions and can be employed in the enzymatic synthesis of α-D-glycosides. In the present study, a putative Thermobacillus SPase gene (TSPase) was synthesised with optimised codons and overexpressed in Escherichia coli. The 1467 bp gene encodes a 488-amino acid protein with a calculated molecular mass of 55.8 kDa. The specific activity of the recombinant TSPase (rTSPase) was 6.42 U/mg for sucrose, and the optimum temperature and pH were 65 °C and pH 7.0. The T1/2 value of the rTSPase was 212 h at 50 °C and 98 h at 60 °C. A stimulating effect on the activity of the rTSPase was observed in the presence of 5 mM Co2+. The rTSPase showed increased stability against DMSO as organic co-solvent at 50 °C. The Km and kcat of the rTSPase with sucrose were determined as 6.24 mM and 5.73 s−1 respectively. The rTSPase produced 2-O-α-D-Glucopyranosyl-L-ascorbic acid (AA-2 G) from ascorbic acid in both crude extract and whole-cell forms. A maximum yield of 19.7% (39.94 ± 0.17 g/L) was achieved after incubation of ascorbic acid sodium salt and sucrose (1:2) with 19.76 U/mL of the rTSPase at pH 7.0 and 50 °C for 24 h.

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized with heterotopic ossification of the axis joints ligaments, resulting in joint disability. MicroRNAs (miRNAs) are regulators of mRNAs that play a crucial role in the AS pathological process. Here, we showed that the level of miR-17-5p was significantly higher in fibroblasts and ligament tissues from AS patients as compared to the non-AS individuals. Knockdown of the miR-17-5p from the fibroblasts derived from AS patients exhibited decreased osteogenic differentiation and ossification. On the other hand, AS patient-derived fibroblasts overexpressing miR-17-5p displayed the increased osteogenesis. Furthermore, inhibition of miR-17-5p ameliorated osteophyte formation, and the sacroiliitis phenotype in AS rats received emulsified collagen. Mechanistically, miR-17-5p regulated osteogenic differentiation by targeting the 3ʹ UTR of ankylosis protein homolog (ANKH). Also, downregulation of miR-17-5p slowed AS progression through regulation of cytokines, such as dickkopf-1 (DKK1) and vascular endothelial growth factor (VEGF). In conclusion, our findings reveal a role of the miR-17-5p-ANKH axis in the regulation of heterotopic ossification, which is essential for therapeutic intervention in heterotopic ossification in AS.