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Chiglitazar (Carfloglitazar) is a novel non-thiazolidinedione (TZD) structured peroxisome proliferator-activated receptor (PPAR) pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies. This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone. Eligible patients were randomly assigned to receive chiglitazar 32 mg (n = 167), chiglitazar 48 mg (n = 166), or placebo (n = 202) once daily. The primary endpoint was the change in glycosylated hemoglobin A1c (HbA1c) at week 24 with superiority of chiglitazar over placebo. The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA1c, and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were −0.87% (95% confidential interval (CI): −1.10 to −0.65; P

Electrochemical production of hydrogen peroxide (H2 O2 ) through two-electron (2 e- ) oxygen reduction reaction (ORR) is an on-site and clean route. Oxygen-doped carbon materials with high ORR activity and H2 O2 selectivity have been considered as the promising catalysts, however, there is still a lack of direct experimental evidence to identify true active sites at the complex carbon surface. Herein, we propose a chemical titration strategy to decipher the oxygen-doped carbon nanosheet (OCNS900 ) catalyst for 2 e- ORR. The OCNS900 exhibits outstanding 2 e- ORR performances with onset potential of 0.825 V (vs. RHE), mass activity of 14.5 A g-1 at 0.75 V (vs. RHE) and H2 O2 production rate of 770 mmol g-1 h-1 in flow cell, surpassing most reported carbon catalysts. Through selective chemical titration of C=O, C-OH, and COOH groups, we found that C=O species contributed to the most electrocatalytic activity and were the most active sites for 2 e- ORR, which were corroborated by theoretical calculations.

The level of circulating tumor cells (CTCs) in blood is a predictor of metastatic cancer progress, serving as an important biomarker for cancer diagnosis, prognosis, and therapy. Currently, there are mainly two conventional strategies to distinguish CTCs, including biological property-based affinity capture and physical property-based label-free isolation. Although great progress has been made in this field, the ability to distinguish CTCs still needs to be improved further due to the cell heterogeneity. Herein, a metabolism-based isolation approach was applied to identify tumor cells according to the "Warburg effect", and a bifunctional open-space platform with fluid walls was developed for real-time monitoring and in situ capture/analysis of tumor cells. A drop-on-demand inkjet printing technique was introduced to create a single cell-containing droplet array with high throughput and high encapsulation rate, and the homogeneous crystalline matrix spots ejected from the inkjet also provided high-quality and reproducible lipid profiling. This platform could combine both microscopic image and mass data, and it has been proven to be capable of isolating and identifying CTCs in complex blood samples, making it a promising tool for evaluating the efficacy of therapy and monitoring the disease progression.

Oedaleus decorus asiaticus (Bei-Bienko, 1941) has been regarded as one of the most dominant locusts in the northern grassland, the adjacent area of agriculture and animal farmland, in China. The aims of this study were to investigate the effects of vegetation type on the oviposition behavior of this pest in an open field and the hatching success of the offspring in the following year. The results showed that vegetation type did have a significant effect on whether any egg pods were laid by O. d. asiaticus. Once the females laid eggs, vegetation type and cage number had a significant effect on the number of egg pods laid. The highest number of egg pods was found in the Cleistogenes squarrosa treatment, followed by Stipa krylovii and then Leymus chinensis, while the Artemisia frigida treatment contained the lowest number of egg pods. The O. d. asiaticus eggs laid in S. krylovii and C. squarrosa treatments had a significantly higher hatching success rate (over 53%) than the other two grasses (below 40%). In short, habitats with C. squarrosa and S. krylovii grasses are likely to be preferred by ovipositing females, thus population monitoring efforts of O. d. asiaticus should focus on these habitats.

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are often present in newly diagnosed acute myeloid leukemia (AML) patients with an incidence rate of approximately 30%. Recently, many FLT3 inhibitors have been developed and exhibit positive preclinical and clinical effects against AML. However, patients develop resistance soon after undergoing FLT3 inhibitor treatment, resulting in short durable responses and poor clinical effects. This review will discuss the main mechanisms of resistance to clinical FLT3 inhibitors and summarize the emerging strategies that are utilized to overcome drug resistance. Basically, medicinal chemistry efforts to develop new small-molecule FLT3 inhibitors offer a direct solution to this problem. Other potential strategies include the combination of FLT3 inhibitors with other therapies and the development of multitarget inhibitors. It is hoped that this review will provide inspiring insights into the discovery of new AML therapies that can eventually overcome the resistance to current FLT3 inhibitors.

To avoid the formation of Ti-Ni intermetallics in a joint, three laser welding processes for Ti alloy–NiTi alloy joints were introduced. Sample A was formed while a laser acted at the Ti alloy–NiTi alloy interface, and the joint fractured along the weld centre line immediately after welding without filler metal. Sample B was formed while the laser acted on a Cu interlayer. The average tensile strength of sample B was 216 MPa. Sample C was formed while the laser acted 1.2 mm on the Ti alloy side. The one-pass welding process involved the creation of a joint with one fusion weld and one diffusion weld separated by the remaining unmelted Ti alloy. The mechanical performance of sample C was determined by the diffusion weld formed at the Ti alloy–NiTi alloy interface with a tensile strength of 256 MPa.

Natural sources are a valuable reserve of chemical diversity for drug development. However, creative screening assays are required to unlock this potential. A high-content screen was developed to isolate anti-mitotic and polyploidy-inducing activity in mammalian cancer cells from plant extracts. The assay was utilized in an analysis of more than 2000 medicinal plants and activity was identified in a rhizome extract from Corydalis longicalcarata. Two bioactive benzophenanthridine alkaloids, corynoline and its close analog acetylcorynoline, were purified. These compounds display pleiotropic effects on cell division, including prevention of chromosome congression, compromise of the spindle checkpoint response, and blockade of cytokinesis. Corynoline and acetylcorynoline are known entities but the potential for development as anti-mitotic drugs has never been ascribed to these two phytochemicals. This study highlights the requirement and ability of novel bioassays to unlock novel function for known phytochemicals.

Oxytocin (OXT) is an important peptide that is mainly used as a therapeutic drug to induce labor or strengthen uterine contractions, or to control bleeding after childbirth. OXT has also been reported as a biomarker linked to emotion, and as a potential biomarker for cancer diagnosis. The accurate purity characterization of OXT calibrators is critical for quality control of pharmaceuticals and the development of reference measurement systems for this analyte in laboratory medicine. OXT possesses the particular analytical measurement challenge of a disulfide bond. Accurate value assignment of the purity of oxytocin calibrators can be carried out by applying the mass balance approach or alternative approaches such as amino acid analysis, quantitative nuclear magnetic resonance spectrometry, and nitrogen determination. In order to avoid biases, all these approaches require a correction for structurally related peptide impurities. Structurally related peptide impurities present in a synthetic OXT material have been identified and quantified by a newly developed and in-house-validated liquid chromatography–high-resolution mass spectrometry (LC-hrMS) method. This method was adopted for the measurement of the study material used for an international comparison evaluating the competencies of laboratories to perform peptide characterization. Eighteen structurally related impurities were identified, confirmed, and accurately quantified in the OXT study material by using LC-hrMS. The study material contained a total mass fraction of 31.1 mg/g structurally related OXT impurities with an associated expanded uncertainty of 1.7 mg/g.

Synechococcus accounts for a considerable proportion of oceanic carbon fixation and has close relation with heterotrophic bacteria at sub-micrometre scales. However, the relationship between Synechococcus and heterotrophic bacteria and their impacts on oceanic carbon flow is not well understood. Here, we separately co-cultured the heterotrophic bacterial community with two different axenic Synechococcus strains, i.e. Synechococcus sp. PCC7002 and Synechococcus sp. CCMP1334. The dissolved organic carbon (DOC) released by Synechococcus promoted the rapid growth of heterotrophic bacteria. Due in part to the slight differences in the Synechococcus-derived DOC composition, the starting heterotrophic bacterial community was reshaped by the two Synechococcus strains into significantly divergent community structures, suggesting that different heterotrophic bacterial communities may gather around different Synechococcus strains and interact with each other in the oceans. Interestingly, the two Synechococcus strains also released some very stable humic-like DOC components that resisted use by heterotrophic bacteria and were gradually accumulated in seawater, implying that in addition to photosynthetic carbon fixation, Synechococcus may also play an important role in long-term ocean carbon sequestration by producing relatively recalcitrant DOC. Moreover, the interactions of Synechococcus and the heterotrophic bacterial communities could increase aggregate formation and particle sinking, which can likely enhance the contribution of Synechococcus to the magnitude of the sinking biological carbon pump in the oceans.

With the development of biomedical technology, epitope mapping of proteins has become critical for developing and evaluating new protein drugs. The application of hydrogen-deuterium exchange for protein epitope mapping holds great potential. Although several reviews addressed the hydrogen-deuterium exchange, to date, only a few systematic reviews have focused on epitope mapping using this technology. Here, we introduce the basic principles, development history, and review research progress in hydrogen-deuterium exchange epitope mapping technology and discuss its advantages. We summarize the main hurdles in applying hydrogen-deuterium exchange epitope mapping technology, combined with relevant examples to provide specific solutions. We describe the epitope mapping of virus assemblies, disease-associated proteins, and polyclonal antibodies as examples of pattern introduction. Finally, we discuss the outlook of hydrogen-deuterium exchange epitope mapping technology. This review will help researchers studying protein epitopes to gain a more comprehensive understanding of this technology.

Intracellular Fe3+ amount is one of the critical determinants of human health. The development of simple and effective probes for the quantitative detection of Fe3+in vivo is of great significance for the early diagnosis of disease or disorder associated with iron deficiency or overload. In this study, remarkable carbon dots, which can serve as a biosensor for efficient intracellular Fe3+ detection, were synthesized by hydrothermal carbonization of Fusobacterium nucleatum, an anaerobic bacterium. The achieved F. nucleatum-carbon dots (Fn-CDs) possessed the features of strong fluorescence, high stability and excellent biocompatibility. The obtained Fn-CDs could easily internalize into both plant cells and human cells with excellent ability for cell tracking and biomedical labeling. The fluorescence of Fn-CDs could still remain for another 24 hours after penetrating into cells. Furthermore, the fluorescent Fn-CDs were very sensitive to the presence of Fe3+ ions even in cells, exhibiting great promising applications in in vivo detection of Fe3+ ions. In addition, the Fn-CDs posed no harm to the mice, being circulated and excreted within a short time, making the Fn-CDs an excellent candidate for bioimaging and biosensing in vivo.

The alkaline electrocatalytic hydrogen evolution reaction (HER) is a potential way to realize industrial hydrogen production. However, the sluggish process of H2O dissociation, as well as the accumulation of OH− around the active sites, seriously limit the alkaline HER performance. In this work, we developed a unique CoS2 needle array grown on a carbon cloth (NAs@C) electrode as an alkaline HER catalyst. Finite-element simulations revealed that CoS2 needle arrays (NAs) induce stronger local electric field (LEF) than CoS2 disordered needles (DNs). This LEF can greatly repel the local OH− around the active sites, and then promote the forward H2O dissociation process. The local pH changes of the electrode surface confirmed the lower OH− concentration and stronger local pseudo-acidic environment of NAs@C compared to those of DNs@C. As a result, the NAs@C catalyst exhibited a low HER overpotential of 121 mV at a current density of 10 mA cm−2 in 1 M KOH, with the Tafel slope of 59.87 mV dec−1. This work provides a new insight into nanoneedle arrays for the alkaline HER by electric field-promoted H2O dissociation.

C-reactive protein (CRP) is one of the most commonly used biomarkers for inflammation. The standardisation of a procedure for the detection of CRP has attracted significant attention globally, and primary reference materials of CRP based on the recombinant expression of E. coli that exist in the form of monomers have been developed. However, a primary reference material of natural CRP is still required to achieve the exact matching of CRP measurements in secondary reference materials (e.g. CRP in frozen human serum). Herein, the development process for a certified reference material of natural CRP is reported, namely GBW09228. The raw material employed in this study was CRP extracted and purified from human body fluid, and exhibits a natural and verified pentameric structure. Through the use of amino acid analysis isotope dilution mass spectrometry (AAA-IDMS) and signature peptide-IDMS, this reference material was certified, and its certification results can be traced to SI units. The developed method was evaluated for its accuracy using the international comparison tests of the National Metrology Institute of Japan (NMIJ) and the Korea Research Institute of Standards and Science (KRISS). Overall, a CRP primary certified reference material (CRM) of well-characterised purity was determined that could be used to calibrate an IDMS-based reference method, that could then be used to assign target values to secondary CRMs. These secondary CRMs could in turn be used to calibrate and verify the accuracy of immunoassays, thereby giving a good foundation for establishing a complete traceability chain for CRP.

High throughput sequencing of small RNA and RT-PCR revealed that Vitis vinifera ‘Kyoho’, the main grapevine cultivar in Hangzhou, China, was co-infected with at least three viruses, namely grapevin...

In this study, for the first time, Porphyromonas gingivalis, an anaerobic bacterium, was selected to synthesize carbon dots. The achieved P. gingivalis-carbon dots (Pg-CDs) exhibited strong fluorescence and high stability with capability for dual function as Fe3+ sensor and intracellular imaging agent. The detection limit for Fe3+ was as low as 1.85 µm. On the other hand, the prepared Pg-CDs were an excellent candidate for biosensor with high biocompatibility.

Separation of natural compounds directly from the crude extract is a challenging work for traditional column chromatography. In the present study, an efficient method for separation of three main compounds from the crude extract of Dracocephalum tanguticum has been successfully established by high-speed counter-current chromatography (HSCCC). The crude extract was directly introduced into HSCCC by using dimethyl sulfoxide as cosolvent. Ethyl acetate/n-butyl alcohol/0.3% glacial acetic acid (4: 1: 5, v/v) system was used and three target compounds with purity higher than 80% were obtained. Preparative HPLC was used for further purification and three target compounds with purity higher than 98% were obtained. The compounds were identified as chlorogenic acid, pedaliin and pedaliin-6″-acetate.

As two important industrial manufacturing materials, ceramics and metals have their own advantages and disadvantages in terms of physical, chemical, and mechanical properties. The field of material manufacturing has witnessed efforts to develop technical processes that can properly combine these two alloys, aiming to effectively use their respective advantages. The welding technology for ceramics and metals, as a research topic with broad prospects, is comprehensively and deeply analyzed in this review. The current research progress in this field is analyzed from different process perspectives such as fusion welding, brazing welding, diffusion welding. By using appropriate intermediate materials between these two materials, the residual stress and brittle intermetallics near the interface of the transition joint can be minimised by solving the thermal expansion mismatch, reducing the bonding temperature and pressure.

A computer-generated moiré profilometry based on algebraic addition instead of algebraic multiplication is proposed. Firstly, the two AC components of the captured fringe patterns on the reference plane with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pi /2$$\end{document}π/2 phase difference are retrieved and saved in advance. While measuring, two sinusoidal gratings with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pi$$\end{document}π phase difference are projected onto the measured object alternatively, and the corresponding deformed patterns are captured. Then the AC component of the captured deformed pattern can be separated exactly. When the positive and negative AC component of the captured deformed pattern are added to the two prestored AC components respectively, two moiré fringes only reflect sine and cosine of the object’s phase information can be successfully generated via a series of data processing procedures. Finally, the phase distribution of the measured object can be extracted by arctangent of the ratio of these two moiré fringes. Compared with computer-generated moiré profilometry based on algebraic multiplication, this proposed method can reduce the effect of high frequency noise and residual DC component on measurement and improve the measurement accuracy. While compared with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pi$$\end{document}π phase shifting FTP, this method can measure more complex objects with better measurement capability. Experimental results verify the feasibility and validity of the proposed method.

Owing to the potential to manipulate simultaneously amplitude and phase of electromagnetic wave, complex-amplitude holographic metasurfaces (CAHMs) can achieve improved image-reconstruction quality compared with amplitude-only and phase-only ones. However, prevailing design methods based on Huygens–Fresnel theory for CAHMs, e.g., Rayleigh–Sommerfeld diffraction theory (RSDT), restrict acquisition of high-precision reconstruction in a large field of view (FOV), especially in the small numerical aperture (NA) scenario. To this end, a CAHM consisting of Sine-shaped meta-atoms is proposed in a microwave region, enabled by a novel complex amplitude retrieval method, to realize large FOV holograms while breaking the large NA limitation. Calculations and full-wave simulations demonstrate that the proposed method can achieve superior-quality holograms, even for nonparaxial holograms in a relatively small NA scenario, thus improving FOV and aperture utilization efficiency of CAHMs. The reconstruction comparison of a complex multi-intensity field distribution between CAHM prototypes designed by our method and by RSDT further confirms this point. We also compare both theoretically and experimentally the CAHM by our method with the phase-only metasurface by weighted Gerchberg–Saxton algorithm. Superior-quality holograms with suppressed background noise and relieved deformation, promised by the extra amplitude manipulation freedom, is witnessed. Finally, due to its wavelength irrelevance, the proposed method is applicable to the entire spectrum, spanning from microwave to optics.

The magnetomechanical effect describes a phenomenon for magnetic materials, and most studies focus on ferromagnetic materials. To further study the mechanism of the magnetomechanical effect, the characteristics of the magnetomechanical effect of aluminum alloy 2A12 are experimental studied in this paper. The experimental magnetic hysteresis losses of the aluminum alloy under different stresses and plastic deformations are calculated, and its quantitative correlations with stress and plastic deformation are compared. It is found that (1) in the elastic deformation stage, the magnetic hysteresis loss increases approximately linearly with the increase of stress; (2) in the plastic deformation stage, the magnetic hysteresis loss decreases approximately linearly with the increase of plastic deformation. This study not only has engineering application value to quantitative evaluation stress and plastic deformation of aluminum alloy 2A12 but also has significance and reference value to further study the mechanism of the magnetomechanical effect.

Five flavonoids with similar polarity were obtained from Caragana korshinskii Kom. by preparative high speed counter-current chromatography. Due to their similar polarity, it is difficult to select a suitable solvent system for one-step separation. Three fractions including one pure compound were only obtained with a relatively suitable solvent system of ethyl acetate: n-butanol:water (0.5% glacial acetic acid) (4:6:10, v:v:v). In order to improve the separation efficiency, recycling and heart cut modes were introduced. As a result, two flavonoids with separation factor value at 1.13 and the other two with separation factor value at 1.20 were successfully separated. Finally, five flavonoids with purity higher than 98% were obtained. Fortunately, a new compound named myricetin 3'-methyl ether 3-O-glucoside-7-O-rhamnoside was obtained. The results indicated that the recycling combined with heart-cut mode could be effective for the preparation of natural compounds with similar polarity.

Plant growth and development are adversely affected by various environmental stresses. In this study, we investigated the possible function of glycinebetaine (GB) in improving abiotic stress tolerance in maize plants by exogenous application. Results indicated that GB application could effectively improve maize germination percentages, biomass weights and grain yield per plant under abiotic stresses. Moreover, GB-treated plants showed higher reactive oxygen species (ROS)-scavenging capacities, therefore less oxidative destruction than control plants under stresses. In addition, abscisic acid (ABA) levels were increased in GB-treated plants compared to control plants. The comparison of transcriptome profile was performed to analyze the possible mechanism underlying the enhanced tolerance mediated by GB. Many differentially expressed genes (DEGs) between GB-treated and control plants were found to be involved in responses to oxidative stress, abiotic stress and ABA. Taken together, these results indicated that GB might enhance abiotic stress tolerance in maize by regulating ROS-scavenging capacities and ABA-mediated stress-responsive pathways.

A series of N-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives with NF-κB inducing kinase (NIK) inhibitory activity were obtained through structure-based drug design and synthetic chemistry. A...

In this paper, we consider the k-sink location problem in a path network with the goal of optimizing a combinational function of the maximum completion time and the total completion time. Let $$P=\left( V,E\right) $$ be an undirected path network with n vertices. Each vertex has a positive weight, indicating the initial amount of supplies, and each edge has a positive length and a uniform capacity, which is the maximum amount of supplies that can enter the edge per unit time. Our goal is to identify k sink locations on the path P so that all supplies will be successfully evacuated and the given objective function is optimized. This paper presents two efficient polynomial time algorithms, which achieve $$O\left( n \right) $$ for $$k=1$$ and $$O\left( n^6 \right) $$ for general k, respectively.

Clopidol is one of the most widely used anti-coccidiosis drugs. Its residues in poultry products and the environment pose a serious threat to human health. In this work, microwave-assisted synthesis of magnetic ionic liquid/gold nanoparticles (MIL-Au NPs) as the SERS substrates were first designed for sensitive and reliable determination of clopidol residue in egg samples. The experiment shows that MIL(1-methyl-3-hexyl imidazole ferric tetrachloride ([C6mim]FeCl4)) and microwave play a key role in the dispersion and morphology of Au NPs. Under the optimal conditions, the as-prepared MIL-Au NPs were applied to the SERS detection of clopidol in methanol and egg solution and its detection limits can be as low as to 0.5 μg/kg (equal to 0.5 ppb) in both solutions. The standard curves with regression coefficients of 0.9298 and 0.93496 were constructed in the linear range of 100–1000 ppb and 0.5–50 ppb for clopidol in egg solutions. Moreover, satisfactory recoveries (97.5–103.2%) were obtained for egg samples. The developed SERS method provides a way for quantitation of clopidol and can be applied for the convenient, reliable, and highly sensitive detection of antibiotic residues in food and environment, which has great potential in food safety and biological monitoring.

Laser welding of TC4 Titanium (Ti) alloy to 304 stainless steel (SS) has been applied using Ag73-Cu16-Zn11 alloy as filler metal. A new welding process for SS-Ti alloy joint was introduced on the basis of the controlling the formation of Ti-Fe intermetallics in the joint. One pass welding involving creation of a joint with one fusion weld and one diffusion weld separated by remaining unmelted SS. When laser beam on the SS side was 1.5 mm, SS would not be completely melted in joint. Through heat conduction of unmelted SS, the atomic diffusion occurred at the SS-Ti alloy interface. A diffusion weld was formed at the SS-Ti alloy interface with the main microstructure of γ-Fe + Fe3Zn2, AgZn3 + Cu5Zn8 and α-Ti + Ti2Cu. The joint fractured at the diffusion weld with the maximum tensile strength of 129 MPa. Keywords: TC4 Ti alloy, 304 stainless steel, Laser welding, Diffusion welding, Microstructure, Filler metal

Pulsed laser welding of TC4 Titanium alloy to SUS301 L stainless steel with V sheet as interlayer was applied. V does not form any intermetallic compound with Ti and Fe. V is used as an interlayer for joining Titanium alloy and stainless steel that the laser successively focused near the Titanium alloy-V and V-stainless steel interfaces. In this way, only two weld zones and unmelted V interlayer can be produced, but also by microstructure of residual solid V interlayer situated between two separately formed weld zones. The unmelted V interlayer acted as a barrier to mixing of the two base materials. The unmelted part of V interlayer also acted as a diffusion barrier between Ti and Fe to avoid the Ti-Fe intermetallics. The tensile strength of joint was 587 MPa accordingly. Keywords: TC4 Titanium alloy, SUS301L stainless steel, V Interlayer, Welding, Weld zone, Microstructure

Background Fipronil is an effective phenylpyrazole insecticide commonly used in agriculture for pest control. In creature, fipronil could be metabolized to several more toxic metabolites. These compounds can contaminate or migrate into foodstuffs and potentially pose danger to human health. Scope and approach This review aims to provide a comprehensive review on the determination methods used for fipronil and its metabolites, including gas chromatography-electron capture detector (GC-ECD), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-ultraviolet detector (LC-UV), liquid chromatography-mass spectrometry (LC-MS) and other fast screening techniques. Detailed information regarding sample preparation, separation and detection condition, and methodological result is provided. Key findings GC-ECD is quite fit for these fluorine-rich analytes, GC-MS method has good selectivity and sensitivity, but they take long time for separation. LC based methods have advantage in fast separation, but LC-UV method isn't satisfactory for low sensitivity, LC-MS is the most preferred technique at the expense of expensive instrument. At last, new directions and perspectives are discussed.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, which is demanding powerful diagnosis tools. Although the traditionally used serological biomarker alpha-fetoprotein (AFP) cannot meet the requirement of accurate diagnosis, its isoform alpha-fetoprotein L3 (AFP-L3) ratio in total AFP is emerging as a highly specific alternative. The routine electrophoretic blotting methods for analyzing AFP-L3 isoform ratio are reliable but often lack speediness, sensitivity, or accuracy. Herein, an elemental mass spectrometric strategy was established to simultaneously detect total AFP and AFP-L3 for the accurate HCC diagnosis. The metal isotopes inside colloidal gold nanoparticle (AuNP) and colloidal silver nanoparticle (AgNP) reporters were used to sensitively detect total AFP and AFP-L3, respectively. AFP-L3 and total AFP were accurately and simultaneously detected with the limits of detection (LODs) of 0.1 ng mL

A novel, Gram-stain-negative, motile, flagellated, aerobic, rod-shaped (0.5–0.7 µm wide and 1.0–1.2 µm long) and faint-yellow strain, designated ALS 84T, was isolated from marine sediment sampled at Ailian bay, Rongcheng, PR China. Growth occurred in the presence of 1–3 % (w/v) NaCl (optimum, 2 % NaCl), at pH 4.0–8.0 (pH 6.0–7.0) and at 8–30 °C (28 °C). The genome size was 4.37 Mbp. The G+C content of the genomic DNA was 33.6 mol%. The results of phylogenetic analysis based on 16S rRNA gene sequences suggested that strain ALS 84T belongs to the genus Flavicella within the family Flavobacteriaceae , and is most closely related to Flavicella marina (95.6 % similarity). The major fatty acids (>10 %) were iso-C15 : 0 3-OH (22.9 %), iso-C15 : 0 (14.0 %) and C16 : 0 (10.9 %). The major polar lipids were phosphatidylethanolamine and three unidentified lipids. Menaquinone-6 (MK-6) was identified as the respiratory quinone. On the basis of the phenotypic, phylogenetic and chemotaxonomic data obtained in the study, strain ALS 84T is considered to represent a novel species of the genus Flavicella , for which the name Flavicella sediminum sp. nov. is proposed. The type strain of the novel species is strain ALS 84T (=KCTC 62398T=MCCC 1K03480T).

With the fast development of society and industry, atmospheric levels of carbon dioxide (CO2) have increased seriously, becoming a threat to the world’s climate. Electrochemical transformation of CO2 into fuels and chemicals using copper (Cu)-based materials has attracted enormous attention. However, the competitive hydrogen evolution reaction (HER) heavily influences their efficiency. Thus, it is urgent to promote the CO2 reduction reaction (CO2RR) and suppress the competitive HER. In this work, enhanced CO2RR with suppressed HER was achieved on polytetrafluoroethylene (PTFE) coated Cu nanoneedles (CuNNs). The concentration of surface adsorbed CO2 could be enhanced via the field-induced reagent concentration (FIRC) effect through the CuNN structures. The hydrophobic PTFE can prevent the supply of protons to CuNNs and thus suppress the HER. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray absorption spectroscopy (XAS) revealed that the PTFE coated CuNNs maintained the nanoneedle structures and metallic Cu state during the catalytic reaction process. As a result, highly suppressed HER coupled with high C2 selectivity can be achieved on these PTFE coated CuNNs with a Faraday efficiency (FE) of 47% toward C2 products and an ultralow FE of 5.9% toward H2 at −1.49 V vs. RHE (without IR correction). This work provides an effective strategy to promote the CO2RR and suppress the competitive HER.

Laser welding-brazing of TC4 Titanium (Ti) alloy to 304 stainless steel (SS) has been applied using 38Zn-61Cu alloy as filler metal. Microstructures of the joints were studied using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and X-ray diffraction (XRD). Mechanical properties of the joints were evaluated by performing tensile tests. The temperature field and stress field distributed in laser welding based on SS-Ti alloy joint were dynamically simulated using the ANSYS in this study. A new welding process for SS-Ti alloy joint was introduced on the basis of the controlling the formation of Ti-Fe intermetallics in the joint. One process was one pass welding involving creation of a joint with one fusion weld and one brazed weld separated by remaining unmelted SS. When laser beam on the SS side was 1.5 mm, SS would not be completely melted in joint. Through heat conduction, the filler metal melted occurred at the SS-Ti alloy interface. A brazed weld was formed at the SS-Ti alloy interface with the main microstructure of (Fe, Zn)+Fe3Zn7, β-CuZn and β-CuZn + Ti2Zn3. The joint fractured at the brazed weld with the maximum tensile strength of 210 MPa. By comparing the simulation results with the corresponding experimental findings, the validity of the numerical model is confirmed. Keywords: TC4 Ti alloy, 304 stainless steel, Laser welding-brazing, Microstructure, Filler metal, Numerical simulation

In this paper, we theoretically investigated stress-induced magnetic anisotropy and presented a model based on a unidirectional tensile stress experiment. Firstly, the theoretical model was simulated based on the work of Jiles. Secondly, experiments were conducted, and data under unidirectional tensile stress were collected and analyzed. Finally, the model was developed by correlating the experimental data and theoretical model. Our model provides a good description of stress-induced magnetic anisotropy under unidirectional tensile stresses and lays down a foundation for the quantitative testing and evaluation of stress of ferromagnetic materials through the magnetic method.

The vegetation temperature condition index (VTCI) has been shown to perform well for drought monitoring using multiyear advanced very high-resolution radiometer (AVHRR) and moderate resolution imaging spectroradiometer (MODIS) data. Compared to single-year VTCI, the VTCI calculated by multiyear data can quantitatively reflect the degree of drought and precipitation in a region. Sentinel-3 is a recently launched remote sensing satellite with high temporal resolution and is similar to the satellites carrying AVHRR and MODIS sensors. One year of Sentinel-3 data is available for calculating the VTCI, and given the need for developing quantitatively drought monitoring capabilities, the aim of this study is to investigate the methods used to calculate the potential multiyear Sentinel-3 VTCI for quantitative drought monitoring. This is based on a comparison with multiyear Terra MODIS VTCI and a correlation analysis with cumulative precipitation data. The analysis results indicate that the potential multiyear Sentinel-3 VTCI can be accurately calculated from the single-year Sentinel-3 VTCI based on the linear correlation between the single-year VTCI and multiyear VTCI derived from Terra MODIS, which do not exhibit obvious systematic deviations from the multiyear Terra MODIS VTCI (the absolute value of the average bias 2 = 0.731, P

Efficient and stable photoelectrodes for water oxidation are highly desirable in the field of photoelectrochemical (PEC) water splitting. However, photoelectrodes with low externally applied bias usually exhibit weak photocurrent and vice versa. Herein, novel and efficient CoOx-TaON/LTON composite photoanodes have been successfully prepared by a microwave assisted method followed with a particle transfer procedure. The obtained photoanode generated an anodic photocurrent of ~7.2 mA cm−2 at 1.2 VRHE and initiated the anodic photourrent at ~0.5 VRHE. The HC-STH of the composite photoelectrode reached 1.0% at 1.2 VRHE. Further, stoichiometric oxygen and hydrogen are stably produced on the photoanode and the counter electrode with a Faraday efficiency of unity for 2 h.

Ruthenium (Ru)-based catalysts, with considerable performance and desirable cost, are becoming highly interesting candidates to replace platinum (Pt) in the alkaline hydrogen evolution reaction (HER). The hydrogen binding at Ru sites (Ru-H) is an important factor limiting the HER activity. Herein, density functional theory (DFT) simulations show that the essence of Ru-H binding energy is the strong interaction between the 4 d z 2 orbital of Ru and the 1s orbital of H. The charge transfer between Ru sites and substrates (Co and Ni) causes the appropriate downward shift of the 4 d z 2 -band center of Ru, which results in a Gibbs free energy of 0.022 eV for H* in the RuCo system, much lower than the 0.133 eV in the pure Ru system. This theoretical prediction has been experimentally confirmed using RuCo alloy-nanosheets (RuCo ANSs). They were prepared via a fast co-precipitation method followed with a mild electrochemical reduction. Structure characterizations reveal that the Ru atoms are embedded into the Co substrate as isolated active sites with a planar symmetric and Z-direction asymmetric coordination structure, obtaining an optimal 4 d z 2 modulated electronic structure. Hydrogen sensor and temperature program desorption (TPD) tests demonstrate the enhanced Ru-H interactions in RuCo ANSs compared to those in pure Ru nanoparticles. As a result, the RuCo ANSs reach an ultra-low overpotential of 10 mV at 10 mA cm-2 and a Tafel slope of 20.6 mV dec-1 in 1 M KOH, outperforming that of the commercial Pt/C. This holistic work provides a new insight to promote alkaline HER by optimizing the metal-H binding energy of active sites.

Electrocatalytic hydrogen evolution reaction (HER) in alkaline media is a promising electrochemical energy conversion strategy. Ruthenium (Ru) is an efficient catalyst with a desirable cost for HER, however, the sluggish H2O dissociation process, due to the low H2O adsorption on its surface, currently hampers the performances of this catalyst in alkaline HER. Herein, we demonstrate that the H2O adsorption improves significantly by the construction of Ru–O–Mo sites. We prepared Ru/MoO2 catalysts with Ru–O–Mo sites through a facile thermal treatment process and assessed the creation of Ru–O–Mo interfaces by transmission electron microscope (TEM) and extended X-ray absorption fine structure (EXAFS). By using Fourier-transform infrared spectroscopy (FTIR) and H2O adsorption tests, we proved Ru–O–Mo sites have tenfold stronger H2O adsorption ability than that of Ru catalyst. The catalysts with Ru–O–Mo sites exhibited a state-of-the-art overpotential of 16 mV at 10 mA cm–2 in 1 M KOH electrolyte, demonstrating a threefold reduction than the previous bests of Ru (59 mV) and commercial Pt (31 mV) catalysts. We proved the stability of these performances over 40 h without decline. These results could open a new path for designing efficient and stable catalysts.

The bromodomain and extra-terminal domain (BET) family of proteins are readers which specifically recognize histone-acetylated lysine residues. Each BET bromodomain protein contains two highly homologous domains: the first bromodomain (BD1) and the second bromodomain (BD2). Pan-BET bromodomain inhibition is a potential therapy for various cancers and immune-inflammatory diseases, but only few reported inhibitors show selectivity within the BET family. Herein, we identified a series of benzo[cd]indol-2(1H)-ones and pyrrolo[4,3,2-de]quinolin-2(1H)-ones with good selectivity for BET BD1. Through structure-based optimization, highly active and selective compounds are ultimately obtained. The representative compounds are the first reported inhibitors with selectivity more than 100-fold for BRD4(1) over BRD4(2). Among them, we further show that 68 (LT052) mediates BRD4/NF-κB/NLRP3 signaling inflammatory pathways with comparable protein expression and significantly improves symptoms of gout arthritis in a rat model. Therefore, selective pharmacological modulation of individual bromodomains could represent a strategy for the treatment of acute gouty arthritis.

Echinococcosis is a serious zoonotic parasitic disease that could be fatal without diagnosis and treatment in a timely manner. Herein, we present a rapid and label-free method for screening of echinococcosis using surface-enhanced Raman spectroscopy (SERS). Three groups of serum SERS spectra based on porous silicon/silver composites are obtained: one group from healthy volunteers (normal, n = 163) and two other groups from patients with pathologically confirmed echinococcosis (cystic echinococcosis (CE), n = 69 and alveolar echinococcosis (AE), n = 38). The derived characteristic spectrum was analyzed to explain differences between echinococcosis and healthy volunteers and a principal component analysis (PCA) was applied for classification. Raman spectra revealed that high sensitivity and specificity for echinococcosis diagnosis were associated with the contents of phenylalanine and tyrosine. In addition, Raman spectroscopy analysis identified two metabolites including phenylalanine and carotenoids that could distinguish three types of serum. Orthogonal partial least squares discriminant analysis (OPLS-DA) was successfully used as a discriminative model to classify echinococcosis with the highest sensitivity and specificity of 100% and 98.6%, respectively. Combination of serum metabolomics with SERS enabled accurate screening of echinococcosis patients. The results indicate that SERS-based serum profile analysis has the potential to be a valuable tool for the early diagnosis and screening of echinococcosis.

The exponential growth of off-shore mariculture worldwide over the last 20 years has had significant impact on coastal sediment biogeochemistry. However, there are no long-term records of the cumulative impacts of mariculture on the benthic bacterial community. Here, total (DNA) and active (RNA) bacterial community compositions were characterized using MiSeq sequencing of 16S rRNA gene in four core sediments of the Ailian Bay, one of the typical intensive mariculture areas in China with more than fifty-year history of kelp and scallop cultivation. The γ-Proteobacteria, δ-Proteobacteria, Acidobacteria and Acitinobacteria were more abundant in the total bacterial communities, while β-Proteobacteria, Anaerolineae, Clostridia, Spirochaetes and Cyanobacteria were enriched in the active bacterial communities. Significant differences were observed between total and active benthic bacterial communities. The influences of different mariculture modes on the total bacterial communities were more significant than those on the active bacterial communities. Only limited groups of the total bacterial communities were significant influenced by the cumulative effects of the long-term mariculture. The bacterial genera with the function in the sulfide cycling and organic consumption were enriched in the total bacterial population of the integrated multi-trophic aquaculture (IMTA) areas. The variations of both total and active bacterial communities were significantly influenced by grain sizes, total organic carbon and nutrients. Both total and active bacterial communities exhibited a slightly stronger response to environmental factors than to spatial (distance) factors. The effects of mutualism might dominate the total and active bacterial networks in the Ailian Bay. The present study demonstrated that the cumulative influences of the long-term and intensive IMTA mariculture on total benthic bacterial communities in the sub-surface sediments of the Ailian Bay were stronger than those on the active benthic bacterial communities, which provided some insights into the potential ecological roles of specific taxa in the sediments of the IMTA ecosystems.

In the past decade, with the signing of the joint declaration by the International Bureau of Weights and Measures (BIPM), the International Organisation of Legal Metrology, the International Laboratory Accreditation Cooperation, and the International Organization for Standardization, and the issuing of new international standards such as ISO/IEC 17025 and ISO 13528, metrological traceability has become more and more important for the mutual recognition of measurement results. It is found that the important factors for ensuring the accuracy of results are not only relevant to calibrants but also to the analysis procedure. This paper focuses on the analysis of key factors that affect measurement results, such as analytical methods, reference materials (RMs), and proficiency testing of mycotoxins. The Capacity Building and Knowledge Transfer Programme for mycotoxins, led by the BIPM, which aims to establish a global measurement system traced to the Système International d’Unités (SI), is well illustrated. Furthermore, this paper suggests to stakeholders that great effort is needed to promote the effective use of certified RM resources that are traced to the SI and globally recognized by the International Committee for Weights and Measures to finally realize “one measurement, global recognition.”

Background: The contamination of food and feed by mycotoxins, Aflatoxin B1 (AfB1) being one of the most prominent examples, is of imminent concern to many countries. Regulatory limits for mycotoxins have been implemented, and these need to be supported by a sound measurement infrastructure for mycotoxin analysis in order to enforce and verify products, protect populations, and avoid technical barriers to trade in food stuffs. Objective: A Capability Building and Knowledge Transfer program on Metrology for Safe Food and Feed in Developing Economies was started at the International Bureau of Weights and Measures to allow National Metrology Institutes or Designated Institutes to work together to strengthen their national mycotoxin metrology infrastructure. Methods: Knowledge transfer to scientists is provided to enable the characterization of selected pure mycotoxin materials and the production of corresponding certified reference material solutions. Results: This higher-order measurement capability can in turn support mycotoxin testing laboratories within their countries through the provision, for example, of standard solutions of critical analytes that are traceable to the International System of Units (SI). Conclusions and Highlights: The purity characterization and value assignment for a high-purity AfB1 material (979.6 ± 2.3 mg/g, k = 2) intended to be used for the gravimetric production of SI traceable calibration solutions for AfB1 is described using an approach combining quantitative NMR and LC–diode array detection–tandem MS for the correction of the mycotoxin-related impurity content.

The microstructure evolution and mechanical properties of laser-welded joints of Ti-24Al-15Nb alloy under different postweld heat treatment (PWHT) conditions were systematically investigated. The results show that the microstructure is very sensitive to PWHT temperatures. The weld zone consists of B2 and O phases after PWHT. With the PWHT temperatures increasing from 850 to 1000 °C, the amount of O phase decreases gradually, while the grains of O precipitates become coarser. After PWHT, there are some thin acicular O precipitates in heat-affected zone (HAZ), and the decomposition of α2-phase caused by niobium diffusion can be observed in the HAZ. The PWHT can significantly increase the microhardness of joints, resulting from O phase precipitation hardening effect. The tensile strength and elongation of joints can be remarkably improved after PWHT, which was closely related to the strengthening effect of O precipitates and slip transmission between O and B2 phases. In addition, the results indicate that the best mechanical properties can be achieved only when the number and size of O phase and B2 phase are the best match.

Direct electrochemical reduction of CO2 to multicarbon products is highly desirable, yet challenging. Here, we present a potentiostatic pulse-electrodeposition of high-aspect-ratio CuxAuy nanowire arrays (NWAs) as high-performance electrocatalysts for the CO2 reduction reaction (CO2RR). The surface electronic structure related to the Cu:Au ratio in the CuxAuy NWAs could be facilely modulated by controlling the electrodeposition potential and the as-fabricated CuxAuy NWAs could be directly used as the catalytic electrode for the CO2RR. The morphology of the high-aspect-ratio nanowire array significantly lowers the onset potential of the alcohol formation due to the diffusion-induced enhancement of the local pH and CO concentration near the nanowire surface. Besides, the properly adjusted surface electronic structure of the CuxAuy NWA enables the adsorption of CO and facilitates the subsequent CO reduction to ethanol via the C-C coupling pathway. Owing to the synergistic effect of morphology and electronic structure, the optimized CuxAuy NWA selectively reduces CO2 to ethanol at low potentials of −0.5–−0.7 V vs. RHE with a highest Faradaic efficiency of 48%. This work demonstrates the feasibility to optimize the activity and selectivity of the Cu-based electrocatalysts toward multicarbon alcohols for the CO2RR via simultaneous adjustment of the electronic structure and morphology of the catalysts.

Metal-organic frameworks (MOFs) are a class of hybrid organic-inorganic materials with porous structure. With the merit of high surface area, uniform nanoscale cavity, good thermal and chemical stability and tailorable chemistry, this class of materials has recently attracted wide attention in sample preparation field. This review mainly focuses on various applications of MOFs as advanced sorbent materials in small organic analytes’ enrichment, including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), volatile organic compounds (VOCs), pharmaceuticals, herbicides, pesticides, toxins, dyes, endocrine-disrupting chemicals (EDCs) and other compounds. Limitations of MOFs as sorbents are presented in detail, and further perspectives are discussed at last.

In this study, Cu was used as an interlayer to restrain the formation of brittle Ti-Fe intermetallics when joining Ti alloy to SS. Microstructures of the joint were analyzed using optical microscopy, scanning electron microscopy and x-ray diffraction. Besides, the tensile strength of the joint was also measured. The melting amount of base materials was controlled by changing thickness of Cu interlayer to control the melting proportion in weld. The melting amount of base materials in weld decreased with the thickness of Cu interlayer. The content of Cu solid solution in weld increased with the thickness of Cu interlayer. Ti-Cu compound layer was formed on the Ti alloy side. The width of the Ti-Cu compound layer increased with the increase in heat input. The tensile strength of joint was largely impacted by Ti-Cu compound layer. The tensile strength of joint first increased and then decreased with the increase in width of the Ti-Cu compound layer.

In the present study, combined chromatographic strategy based on macroporous resin, high-speed counter-current chromatography and preparative high-performance liquid chromatography for systematic separation of antioxidants from crude samples guided by high-performance liquid chromatography with 1,1-diphenyl-2-picrylhydrazyl has been successfully established. Based on this strategy, seven antioxidants including isorugosin A, β -1,2,3,6-tetragalloyl-D-glucose, chebulinic acid, 1,2,3,4,6-penta-O-galloyl-β -D-glucose, chebulagic acid, ethyl gallate, and gallic acid were obtained from the fruit of Terminalia billerica. First, high-performance liquid chromatography with 1,1-diphenyl-2-picrylhydrazyl experiment showed the presence of seven main antioxidants in the crude extract of the fruit of Terminalia billerica. Then, a macroporous resin column chromatography method was developed for the enrichment of these seven antioxidants. Finally, an efficient method based on high-speed counter-current chromatography and preparative high-performance liquid chromatography was developed for the separation of these antioxidants. In the selection of solvent systems, it was found that acetic acid could be a good regulator for modifying the partition coefficient values of tannins. The present study provides a reference for systematic separation of antioxidants from crude samples. Considering the general existence of antioxidants in crude samples, this combined chromatographic strategy might lead to broader application prospects.

Highly efficient water oxidation utilizing visible light is a crucial step in water splitting. Bismuth vanadate (BiVO4) single crystal particles have attracted much attention in water oxidation recently, owing to their outstanding physicochemical properties and exposed active facets. The performance of BiVO4 single crystal particles is generally hindered by their poor conductivity and worse charge separation. Doping BiVO4 single crystal particles with other metal elements has been considered as an efficient way to improve their conductivity, charge separation and performance. However, there are few successful reports, because structure and morphology of BiVO4 single crystal particles are easily changed by addition of impurities. Here, we present that W doped BiVO4 crystal particles were successfully achieved by developing a simple impregnation method following with a high temperature annealing process. The obtained W-BiVO4 single crystal particles exhibited improved conductivity, carrier density and thereby enhanced activity for water oxidation. The solar energy conversion of the W-BiVO4 electrode was doubled compared with the pristine one. Thus, this work opens an avenue for developing efficient single crystal particle photocatalysts.

FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV4-11 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML.