Thiolation of Terminal Alkynes with Thiuram Disulfide Reagents Using Water as the Hydrogen Source: Stereoselective Synthesis of (Z)-Vinyl Sulfides.

A stereoselective and environmentally friendly thiolation of terminal alkynes was reported. Thiuram disulfide reagents (tetramethylthiuram disulfide and tetraethylthiuram disulfide) that reacted with alkynes in dimethyl sulfoxide (DMSO)/H2O could give (Z)-vinyl sulfides in good yields (up to 88%). This protocol features broad substrate scope, good stereoselectivity, high atom economy, good yields, and is transition metal-free. Mechanistic studies revealed that water and DMSO served as hydrogen sources, which greatly highlighted the unique reactivity of this special reaction involving two H-atom donors.

Excellent Dark/Light Dual-Mode Photoresponsive Activities Based on g-C3N4/CMCh/PVA Nanocomposite Hydrogel Using Electron Beam Radiation Method.

Photocatalytic technology for inactivating bacteria in water has received much attention. In this study, we reported a dark-light dual-mode sterilized g-C3N4/chitosan/poly (vinyl alcohol) hydrogel (g-CP) prepared through freeze-thaw cycling and an in situ electron-beam radiation method. The structures and morphologies of g-CP were confirmed using Fourier infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), solid ultraviolet diffuse reflectance spectroscopy (UV-vis DRS), and Brunauer-Emmett-Teller (BET). Photocatalytic degradation experiments demonstrated that 1 wt% g-CP degraded rhodamine B (RhB) up to 65.92% in 60 min. At the same time, g-CP had good antimicrobial abilities for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) within 4 h. The shapes of g-CP were adjustable (such as bar, cylinder, and cube) and had good mechanical properties and biocompatibility. The tensile and compressive modulus of 2 wt% g-CP were 0.093 MPa and 1.61 MPa, respectively. The Cell Counting Kit-8 (CCK-8) test and Hoechst33342/PI double staining were used to prove that g-CP had good biocompatibility. It is expected to be applied to environmental sewage treatment and wound dressing in the future.

Self-Healing and Shape Memory Hypercrosslinked Metal-Organic Polyhedra Polymers via Coordination Post-Assembly.

Coordination-driven crosslinking networks with reversible and dynamic characteristics are gaining increasing interest in diverse application fields. Herein, we use a coordination crosslinking approach using metal-organic polyhedra (MOPs) as high-connectivity building blocks to post-assemble a class of coordination hypercrosslinked MOP (CHMOP) polymers. The introduction of 12-connected MOP nodes to the polymeric networks is critical to producing membranes that overcome the trade-off between mechanical properties and dynamic healing, and meanwhile possess multifunctionalities including shape memory, solution processability, and 3D printing. The CHMOPs can also be used for anticorrosion coating and achieve function couplings, e.g., shape memory-assisted self-healing (SMASH), which have not been achieved in the MOP-based hybrid materials yet. This work not only offers a feasible strategy to construct new multifunctional materials but also greatly expands the application scopes of MOPs.

Cs2CO3-Promoted Hydrothiolation of Alkynes with Aryl Thioureas: Stereoselective Synthesis of (Z)-Vinyl Sulfides.

A metal-free Cs2CO3-promoted hydrothiolation of alkynes with aryl thioureas for stereoselective synthesis of (Z)-vinyl sulfides has been reported. Vinyl thioethers were obtained without a metal catalyst in good yields via anti-Markovnikov and cis addition. The protocol features a broad substrate scope of the starting materials, high atom economy, good yields, and exclusive stereoselectivity, showing potential synthetic value for the synthesis of a diversity of (Z)-vinyl thioethers.

Oxidation Control of Bottlebrush Molecular Conformation for Producing Libraries of Photonic Structures.

Self-assembly is important for creating photonic structures and structural color is typically tunable by varying the size of building blocks, which are themselves obtained after time-consuming chemical syntheses. The molecular conformation of bottlebrush block copolymers (BBCPs) in solution can be manipulated to create libraries of photonic structures. Amphiphilic BBCPs bearing oxidation-responsive ferrocene groups on the hydrophilic block are used to fabricate porous particles via evaporation-induced self-assembly of water-in-oil-in-water (W/O/W) double emulsions stabilized by the BBCP surfactant. In situ oxidation of the ferrocene groups by hydrogen peroxide at the W/O interface leads to enhanced hydrophilicity, more hydration, and chain extension of the hydrophilic block. Consequently, larger internal water droplets are spontaneously formed, yielding larger pores within the microparticles. The pore diameter is readily tunable from 144 to 301 nm with a single BBCP, thereby generating full-spectrum structural colors. This work provides a straightforward method for fabrication of libraries of photonic pigments in an easy and scalable manner.

A Mild Synthesis of 2-Substituted Benzothiazoles via Nickel-Catalyzed Intramolecular Oxidative C-H Functionalization.

A highly efficient synthetic method for the preparation of 2-aminobenzothiazoles starting from arylthioureas has been reported. By using a nickel catalyst, arylthioureas undergo intramolecular oxidative C-H bond functionalization, giving the desired 2-aminobenzothiazoles in good to excellent yields. This protocol features an inexpensive catalyst, low catalyst loading, mild reaction conditions, a short reaction time, and good to excellent yields, and it can be scaled up easily to a gram scale with almost no yields decreasing.

Zebrafish B Cell Development without a Pre-B Cell Stage, Revealed by CD79 Fluorescence Reporter Transgenes.

CD79a and CD79b proteins associate with Ig receptors as integral signaling components of the B cell Ag receptor complex. To study B cell development in zebrafish, we isolated orthologs of these genes and performed in situ hybridization, finding that their expression colocalized with IgH-µ in the kidney, which is the site of B cell development. CD79 transgenic lines were made by linking the promoter and upstream regulatory segments of CD79a and CD79b to enhanced GFP to identify B cells, as demonstrated by PCR analysis of IgH-µ expression in sorted cells. We crossed these CD79-GFP lines to a recombination activating gene (Rag)2:mCherry transgenic line to identify B cell development stages in kidney marrow. Initiation of CD79:GFP expression in Rag2:mCherry+ cells and the timing of Ig H and L chain expression revealed simultaneous expression of both IgH-µ- and IgL-κ-chains, without progressing through the stage of IgH-µ-chain alone. Rag2:mCherry+ cells without CD79:GFP showed the highest Rag1 and Rag2 mRNAs compared with CD79a and CD79b:GFP+ B cells, which showed strongly reduced Rag mRNAs. Thus, B cell development in zebrafish does not go through a Raghi CD79+IgH-µ+ pre-B cell stage, different from mammals. After the generation of CD79:GFP+ B cells, decreased CD79 expression occurred upon differentiation to Ig secretion, as detected by alteration from membrane to secreted IgH-µ exon usage, similar to in mammals. This confirmed a conserved role for CD79 in B cell development and differentiation, without the requirement of a pre-B cell stage in zebrafish.

One-Step Access to Sequence-Controlled Block Copolymers by Self-Switchable Organocatalytic Multicomponent Polymerization.

A one-step procedure for the self-switchable block copolymerization of monomer mixtures of epoxides, cyclic anhydrides, and lactide (LA) was developed by using simple organocatalysts without an external stimulus. This multicomponent polymerization bridges two catalytic cycles involving ring-opening alternating copolymerization of epoxides with anhydrides and ring-opening polymerization (ROP) of LA, in which the presence/absence of anhydrides in mixed feedstocks switched the ROP of LA off/on. The self-switchable terpolymerization showed distinct noncoordinating and living nature, as well as perfect chemoselectivity. Different combinations of epoxides, anhydrides, and initiators enabled the generation of a variety of new block polyester polyols.

Lack of global epigenetic methylation defects in CBS deficient mice.

Cystathionine ß-synthase (CBS) deficiency is a recessive inborn error of metabolism in which patients have extremely elevated plasma total homocysteine and have clinical manifestations in the vascular, visual, skeletal, and nervous systems. Homocysteine is an intermediary metabolite produced from the hydrolysis of S-adenosylhomocysteine (SAH), which is a by-product of methylation reactions involving the methyl-donor S-adenosylmethionine (SAM). Here, we have measured SAM, SAH, DNA and histone methylation status in an inducible mouse model of CBS deficiency to test the hypothesis that homocysteine-related phenotypes are caused by inhibition of methylation due to elevated SAH and reduced SAM/SAH ratio. We found that mice lacking CBS have elevated cellular SAH and reduced SAM/SAH ratios in both liver and kidney, but this was not associated with alterations in the level of 5-methylcytosine or various histone modifications. Using methylated DNA immunoprecipitation in combination with microarray, we found that of the 241 most differentially methylated promoter probes, 89 % were actually hypermethylated in CBS deficient mice. In addition, we did not find that changes in DNA methylation correlated well with changes in RNA expression in the livers of induced and uninduced CBS mice. Our data indicates that reduction in the SAM/SAH ratio, due to loss of CBS activity, does not result in overall hypomethylation of either DNA or histones.

Health-education package to prevent worm infections in Chinese schoolchildren.

BACKGROUND: Soil-transmitted helminths are among the most prevalent sources of human infections globally. We determined the effect of an educational package at rural schools in Linxiang City District, Hunan province, China, where these worms are prevalent. The intervention aimed to increase knowledge about soil-transmitted helminths, induce behavioral change, and reduce the rate of infection. METHODS: We conducted a single-blind, unmatched, cluster-randomized intervention trial involving 1718 children, 9 to 10 years of age, in 38 schools over the course of 1 school year. Schools were randomly assigned to the health-education package, which included a cartoon video, or to a control package, which involved only the display of a health-education poster. Infection rates, knowledge about soil-transmitted helminths (as assessed with the use of a questionnaire), and hand-washing behavior were assessed before and after the intervention. Albendazole was administered in all the participants at baseline and in all the children who were found to be positive for infection with soil-transmitted helminths at the follow-up assessment at the end of the school year. RESULTS: At the follow-up assessment, the mean score for the knowledge of helminths, calculated as a percentage of a total of 43 points on a questionnaire, was 90% higher in the intervention group than in the control group (63.3 vs. 33.4, P<0.001), the percentage of children who washed their hands after using the toilet was nearly twice as high in the intervention group (98.9%, vs. 54.2% in the control group; P<0.001), and the incidence of infection with soil-transmitted helminths was 50% lower in the intervention group than in the control group (4.1% vs. 8.4%, P<0.001). No adverse events were observed immediately (within 15 minutes) after albendazole treatment. CONCLUSIONS: The health-education package increased students' knowledge about soil-transmitted helminths and led to a change in behavior and a reduced incidence of infection within 1 school year. (Funded by UBS Optimus Foundation, Zurich, Switzerland; Australian New Zealand Clinical Trials Registry number, ACTRN12610000048088.).

[Rapid Measurement of Carbon Dioxide with Laser-Induced Breakdown Spectroscopy Based on Atomic and Molecular Spectrum].

With the rapid development of economy and industrialization, global warming is becoming the most serious sensitive global climate issues, which causes the rising of sea level and many other negative effects. The cause of global warming is the emission of greenhouse gases and carbon dioxide is the main component of greenhouse gases. The control of CO2 emssion is beneficial to addressing gobal climate change and environmental degradation. Therefore, it's important to develop a rapid detection of CO2 for accurate control. There are amounts of methods to detect CO2 at present, including titration, electrochemical method, gas chromatography, infrared absorption spectroscopy and so on, however, t they still have the deficiency for online monitoring in industrial field. laser induced breakdown spectroscopy (LIBS), which is developing rapidly in recent few decades, is a detecting technology with characteristics of time-saving and synchronous measuring of multicomponent. What's more, there is no need for sample pretreating. To develop the online monitoring technique of CO2 emission in the industrial field, LIBS was employed to measure CO2 in this study. The mass flow controller was used to adjust the flow of high purity CO2 and N2 to obtain mixed gas with different CO2 concentrations. The mixed gas was firstly mixed in an air mixing chamber for thorough mixing and then sent to the sample cell for LIBS measurement. The evolution of C atomic spectral line and CN molecular band with different delay times were being studied, which demonstrated parts of CO2 react with air ambient to form CN molecular during the plasma generation, the CN molecular band should be taken into consideration for quantitative analysis, and the parameters were optimized for synchronous measurement of C line and CN band: 800 ns was the optimal delay time. During the plasma generation, many factors in the plasma may interact with others, the analysis index had close relationship wih serval measuring parameters. With the consideration of the effect of C, CN and the self-absorption in high concentration, multivariate calibration method was employed to establish calibration models of CO2. The results showed that the correlation coefficients R2 and the slope were 0.978 and 0.981, respectively. Compared with calibrated with single factor, the multivariate method improved the reliability of the model. What's more, the feasibility of the application of LIBS to measure CO2 rapidly was proved.

[Investigation of exogenous stimulus effect on the interaction of CdSe/ZnS quantum dots/TiO2 nanocomposites with human serum albumin by resonance light scattering].

The interaction between CdSe/ZnS(quantum dots)/TiO2 nanocomposites and human serum albumin(HSA) was investigated by resonance light scattering (RLS) spectroscopic methods under approximate physiological conditions. Much important information of the interaction between CdSe/ZnS(Quantum Dots)/TiO2 nanocomposites and HSA was obtained by studying comprehensively the Exogenous influence factors of nanocomposites concentration, pH, NaCl concentration, reaction temperature, detection time, coexisting ions, surfactants, sequence of adding to the sample etc. It was showed that the new formation of complex system is likely to enhance the protein hydrophobic cavity and tend to focus the hydrophobic interface in aqueous solution, resulting in strengthening the intensity of resonance light scattering; Also it is very sensitive to the changes in the pH value in the system; The sensitivity of I(RLS) in system can be increased by the appropriate NaCl concentration; The value of IRLS in system would be changed with the change in the concentration of coexisting ions; The value of I(RLS) in system is basically stable when the reaction time reaches 5 min; The value of I(RLS) in system is not exactly the same with a surfactant, and strong electrostatic interaction has occurred between oppositely charged surfactant and nano composites; It is obvious that the value of I(RLS) in complex system is affected by the sequence of adding to sample; It has the incomplete monotonically increasing trend with the changes in temperature. The information is useful for providing theoretical supporting for the mechanism of interaction between nanomaterials and bio-macromolecule, and for understanding the biocompatibility and safety of nano-materials.

Artificial nonenzymatic antioxidant Prussian blue/KGM-BSA nanocomposite hydrogel dressing as ROS scavenging for diabetic wound healing.

The process of diabetic wound healing was influenced by the excessive proliferation of reactive oxygen species (ROS). Therefore, in the process of healing diabetic wounds, it was crucial to removing ROS. This study designed composited nanoparticles: KBP, consisted by Konjac glucomannan, bovine serum albumin, and Prussian blue. Then they were embedded in Konjac glucomannan and hydroxypropyl trimethylammonium chloride chitosan composite hydrogel (KH), The KBP@KH hydrogel finally achieved excellent efficacy in diabetic wound healing. The in vitro and in vivo experiments demonstrated that KPB nanoparticles exhibited favorable ROS scavenging capability and biosafety. The KBP@KH hydrogel not only effectively eliminated ROS from diabetic wounds, but also exhibited excellent wound adaptability. The KBP@KH hydrogel facilitated angiogenesis and suppressed the production of inflammatory factors. Overall, the KBP@KH hydrogel dressing was characterized by its user-friendly nature, safety, and high efficiency.

Changes in Arabidopsis thaliana gene expression in response to silver nanoparticles and silver ions.

The release of silver nanoparticles (AgNPs) in the environment has raised concerns about their effects on living organisms, including plants. In this study, changes in gene expression in Arabidopsis thaliana exposed to polyvinylpyrrolidone-coated AgNPs and silver ions (Ag(+)) were analyzed using Affymetrix expression microarrays. Exposure to 5 mg/L AgNPs (20 nm) for 10 days resulted in upregulation of 286 genes and downregulation of 81 genes by reference to nonexposed plants. Exposure to 5 mg/L Ag(+) for 10 days resulted in upregulation of 84 genes and downregulation of 53 genes by reference to nonexposed plants. Many genes differentially expressed by AgNPs and Ag(+) were found to be involved in the response of plants to various stresses: upregulated genes were primarily associated with the response to metals and oxidative stress (e.g., vacuolar cation/proton exchanger, superoxide dismutase, cytochrome P450-dependent oxidase, and peroxidase), while downregulated genes were more associated with response to pathogens and hormonal stimuli [e.g., auxin-regulated gene involved in organ size (ARGOS), ethylene signaling pathway, and systemic acquired resistance (SAR) against fungi and bacteria]. A significant overlap was observed between genes differentially expressed in response to AgNPs and Ag(+) (13 and 21% of total up- and downregulated genes, respectively), suggesting that AgNP-induced stress originates partly from silver toxicity and partly from nanoparticle-specific effects. Three highly upregulated genes in the presence of AgNPs, but not Ag(+), belong to the thalianol biosynthetic pathway, which is thought to be involved in the plant defense system. Results from this study provide insights into the molecular mechanisms of the response of plants to AgNPs and Ag(+).

[Influence factors of Schistosoma japonicum infection among fishermen in eastern Dongting Lake Region].

OBJECTIVE: To investigate schistosome infection among the professional fishermen in Yueyang County, East Dongting Lake Region and its influence factors. METHODS: A total of 275 fishermen from two fisherman villages in Yueyang County were selected in 2009. They were investigated by fecal examination and questionnairing. The stool-egg positive individuals were detected by B ultrasound. The multivariate unconditional Logistic regression analysis was used to explore the related factors of schistosome infection and liver in fishermen. RESULTS: The total infection rate in fishermen was 40.4% (111/275), and the geometric mean of EPG was 17.4 +/- 4.4. B ultrasound data showed among 111 egg positive individuals, 39 (35.1%) cases manifested as hepatomegaly, 22 (19.8%) had splenomegaly, 11 (9.9%) had portal vein expansion and 65 (58.6%) had hepatic fibrosis. Multivariate unconditional Logistic regression analysis showed that age groups (OR = 0.630), fishing working years (OR = 2.470), chemotherapy frequency (OR = 0.425) and chemotherapy in 2008 (OR = 0.290) were the influence factors on schistosome infection (P < 0.01). CONCLUSION: Schistosome infection rate is high, Schistosoma japonicum-induced liver and spleen injuries are still severe in fisherman of Eastern Dongting Lake Region.

Transcriptomes of Injured Lamprey Axon Tips: Single-Cell RNA-Seq Suggests Differential Involvement of MAPK Signaling Pathways in Axon Retraction and Regeneration after Spinal Cord Injury.

Axotomy in the CNS activates retrograde signals that can trigger regeneration or cell death. Whether these outcomes use different injury signals is not known. Local protein synthesis in axon tips plays an important role in axon retraction and regeneration. Microarray and RNA-seq studies on cultured mammalian embryonic or early postnatal peripheral neurons showed that axon growth cones contain hundreds to thousands of mRNAs. In the lamprey, identified reticulospinal neurons vary in the probability that their axons will regenerate after axotomy. The bad regenerators undergo early severe axon retraction and very delayed apoptosis. We micro-aspirated axoplasms from 10 growing, 9 static and 5 retracting axon tips of spinal cord transected lampreys and performed single-cell RNA-seq, analyzing the results bioinformatically. Genes were identified that were upregulated selectively in growing (n = 38), static (20) or retracting tips (18). Among them, map3k2, csnk1e and gtf2h were expressed in growing tips, mapk8(1) was expressed in static tips and prkcq was expressed in retracting tips. Venn diagrams revealed more than 40 components of MAPK signaling pathways, including jnk and p38 isoforms, which were differentially distributed in growing, static and/or retracting tips. Real-time q-PCR and immunohistochemistry verified the colocalization of map3k2 and csnk1e in growing axon tips. Thus, differentially regulated MAPK and circadian rhythm signaling pathways may be involved in activating either programs for axon regeneration or axon retraction and apoptosis.

Controlled preparation of a MCC-g-AM/EDA/PA loaded Fe(iii) adsorbent by the pre-radiation grafting method and its application for the adsorption removal of phosphate.

A new spherical cellulose-based adsorbent and high phosphate removal rate microcrystalline cellulose-g-acrylamide/ethylenediamine/phthalic anhydride (MCC-g-AM/EDA/PA) loaded Fe(iii) adsorbent was prepared by a pre-radiation grafting and chemical modification method. Fe(iii) was successfully introduced into the modified grafted chains of the MCC-g-AM/EDA/PA resin, and characterized by FTIR, TG, XRD, SEM and XPS. The optimized conditions for the grafting reaction of acrylamide (AM) onto MCC were 20% AM emulsion at an absorbed dose of 30 kGy, and a grafting rate as high as 247%. In addition, the adsorption performance of the adsorbent was tested by static adsorption experiments with phosphate. The adsorbent resin showed excellent adsorption performance under alkaline conditions, contributions to the synergetic effect of precipitation, and inner-sphere surface complex reactions. The adsorption efficiency can reach 89.7% at low concentration. In summary, the neotype spherical cellulose-based adsorbent has the advantages of being separation-free in bulk materials, avoiding secondary pollution, and being easy to recycle, and it could be employed as an environmentally friendly adsorbent for phosphate removal in eutrophic water.

Comparison of two approaches for measuring household wealth via an asset-based index in rural and peri-urban settings of Hunan province, China.

BACKGROUND: There are growing concerns regarding inequities in health, with poverty being an important determinant of health as well as a product of health status. Within the People's Republic of China (P.R. China), disparities in socio-economic position are apparent, with the rural-urban gap of particular concern. Our aim was to compare direct and proxy methods of estimating household wealth in a rural and a peri-urban setting of Hunan province, P.R. China. METHODS: We collected data on ownership of household durable assets, housing characteristics, and utility and sanitation variables in two village-wide surveys in Hunan province. We employed principal components analysis (PCA) and principal axis factoring (PAF) to generate household asset-based proxy wealth indices. Households were grouped into quartiles, from 'most wealthy' to 'most poor'. We compared the estimated household wealth for each approach. Asset-based proxy wealth indices were compared to those based on self-reported average annual income and savings at the household level. RESULTS: Spearman's rank correlation analysis revealed that PCA and PAF yielded similar results, indicating that either approach may be used for estimating household wealth. In both settings investigated, the two indices were significantly associated with self-reported average annual income and combined income and savings, but not with savings alone. However, low correlation coefficients between the proxy and direct measures of wealth indicated that they are not complementary. We found wide disparities in ownership of household durable assets, and utility and sanitation variables, within and between settings. CONCLUSION: PCA and PAF yielded almost identical results and generated robust proxy wealth indices and categories. Pooled data from the rural and peri-urban settings highlighted structural differences in wealth, most likely a result of localized urbanization and modernization. Further research is needed to improve measurements of wealth in low-income and transitional country contexts.

Current Status of Schistosomiasis Control and Prospects for Elimination in the Dongting Lake Region of the People's Republic of China.

Schistosomiasis japonica is an ancient parasitic disease that has severely impacted human health causing a substantial disease burden not only to the Chinese people but also residents of other countries such as the Philippines, Indonesia and, before the 1970s, Japan. Since the founding of the new People's Republic of China (P. R. China), effective control strategies have been implemented with the result that the prevalence of schistosomiasis japonica has decreased markedly in the past 70 years. Historically, the Dongting Lake region in Hunan province is recognised as one of the most highly endemic for schistosomiasis in the P.R. China. The area is characterized by vast marshlands outside the lake embankments and, until recently, the presence of large numbers of domestic animals such as bovines, goats and sheep that can act as reservoir hosts for Schistosoma japonicum. Considerable social, economic and environmental changes have expanded the Oncomelania hupensis hupensis intermediate snail host areas in the Dongting lake region increasing the potential for both the emergence of new hot spots for schistosomiasis transmission, and for its re-emergence in areas where infection is currently under control. In this paper, we review the history, the current endemic status of schistosomiasis and the control strategies in operation in the Dongting Lake region. We also explore epidemiological factors contributing to S. japonicum transmission and highlight key research findings from studies undertaken on schistosomiasis mainly in Hunan but also other endemic Chinese provinces over the past 10 years. We also consider the implications of these research findings on current and future approaches that can lead to the sustainable integrated control and final elimination of schistosomiasis from the P. R. China and other countries in the region where this unyielding disease persists.

Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin-resistant mouse models--association with liver and adipose tissue effects.

Recombinant fibroblast growth factor (FGF)21 has antihyperglycemic, antihyperlipidemic, and antiobesity effects in diabetic rodent and monkey models. Previous studies were confined to measuring steady-state effects of FGF21 following subchronic or chronic administration. The present study focuses on the kinetics of biological actions of FGF21 following a single injection and on the associated physiological and cellular mechanisms underlying FGF21 actions. We show that FGF21 resulted in rapid decline of blood glucose levels and immediate improvement of glucose tolerance and insulin sensitivity in two animal models of insulin resistance (ob/ob and DIO mice). In ob/ob mice, FGF21 led to a 40-60% decrease in blood glucose, insulin, and amylin levels within 1 h after injection, and the maximal effects were sustained for more than 6 h despite the 1- to 2-h half-life of FGF21. In DIO mice, FGF21 reduced fasting blood glucose and insulin levels and improved glucose tolerance and insulin sensitivity within 3 h of treatment. The acute improvement of glucose metabolism was associated with a 30% reduction of hepatic glucose production and an increase in peripheral glucose turnover. FGF21 appeared to have no direct effect on ex vivo pancreatic islet insulin or glucagon secretion. However, it rapidly induced typical FGF signaling in liver and adipose tissues and in several hepatoma-derived cell lines and differentiated adipocytes. FGF21 was able to inhibit glucose release from H4IIE hepatoma cells and stimulate glucose uptake in 3T3-L1 adipocytes. We conclude that the acute glucose-lowering and insulin-sensitizing effects of FGF21 are potentially associated with its metabolic actions in liver and adipose tissues.