Enhanced water stability and catalytic activity of Fe-based metal-organic frameworks with co-ligands for 2,4-dichlorophenol degradation.

Fe-based metal-organic frameworks (MOFs) have good photocatalytic performance, environmental friendliness, low cost, and abundance. However, their applications are limited by low water stability, particularly in the presence of light irradiation and oxidizing agents. In this study, we present a MIL-53(Fe)-based MOF using 1,4-naphthalene dicarboxylic (1,4-NDC) and 1,4-benzenedicarboxylic (H2BDC) acid co-ligands, denoted MIL-53(Fe)-Nx, where Nx represents the ratio of 1,4-NDC. This MOF exhibits high water stability and good photocatalytic activity because of the hydrophobicity of naphthalene. The removal and mineralization rates for 100 mg/L 2,4-dichlorophenol reached 100% and 22%, respectively, within 60 min. After three cycles of use, the Fe leached into the solution from the catalysts was significantly lower than the maximum permissible limit indicated in the European Union standard. Of note, 1,4-NDC can be used to make a rigid MOF, thereby improving the crystallinity, porosity, and hydrophobicity of the resultant materials. It also significantly reduced the bandgap energy and improved the charge separation efficiency of the catalysts. This study provides a route to enhance the water stability of Fe-based MOFs via a mixed-ligand strategy to expand their applications in pollutant control.

Disulfidptosis-related signatures for prognostic and immunotherapy reactivity evaluation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and a nonnegligible health concern on a worldwide scale. Disulfidptosis is a novel mode of cell death, which is mainly caused by the collapse of the actin skeleton. Although many studies have demonstrated that various types of cell death are associated with cancer treatment, the relationship between disulfidptosis and HCC has not been elucidated. METHODS: Here, we mainly applied bioinformatics methods to construct a disulfidptosis related risk model in HCC patients. Specifically, transcriptome data and clinical information were downloaded from the Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) database. A total of 45 co-expressed genes were extracted between the disulfidptosis-related genes (DRGs) and the differential expression genes (DEGs) of liver hepatocellular carcinoma (LIHC) in the TCGA database. The LIHC cohort was divided into two subgroups with different prognosis by k-mean consensus clustering and functional enrichment analysis was performed. Subsequently, three hub genes (CDCA8, SPP2 and RDH16) were screened by Cox regression and LASSO regression analysis. In addition, a risk signature was constructed and the HCC cohort was divided into high risk score and low risk score subgroups to compare the prognosis, clinical features and immune landscape between the two subgroups. Finally, the prognostic model of independent risk factors was constructed and verified. CONCLUSIONS: High DRGs-related risk score in HCC individuals predict poor prognosis and are associated with poor immunotherapy response, which indicates that risk score assessment model can be utilized to guide clinical treatment strategy.

Aging population and digital inclusive finance, a natural experiment from china.

This paper studies the role played by the digitization level of inclusive finance for the aging population. We leverage an unexpected Chinese national strategy that promotes mobile internet and other internet related integration in China to identify the impact of changes in state policies on the digitization level for inclusive finance in a regression discontinuity design. Although aging population is negatively correlated with the digitization level of inclusive finance, our empirical analysis reveals that the policy shock significantly increased the digitization level of inclusive finance among the aging population. We also find two opposite mechanisms: the income effect and the caring effect. Finally, our study suggests that the economic and social outcomes of the digitization level among aging population are bifurcated: happiness decreased but real estate investment increased.

Catalytic Conversion of Carbohydrates into 5-Hydroxymethylfurfural by Phosphotungstic Acid Encapsulated in MIL-101 (Cr, Sn) Catalyst in Deep Eutectic Solvents.

Herein, we report the synthesis of bimetal-organic frameworks (BMOFs) with both Brønsted and Lewis acidities, in which phosphotungstic acid (PTA) was encapsulated in BMOFs. It is efficient in converting starch to 5-hydroxymethyl-furfural (HMF) in deep eutectic solvents (DESs) such as choline chloride and formic acid. The highest yield of HMF (37.94%) was obtained using P0.5/BMOFs1.0 to catalyze starch in a mixed solvent system comprising DESs and ethyl acetate (EAC) (v/v; 2:3) at 180 °C and a reaction time of 10 min. Employing a DES as a cocatalyst and solvent reduced the use of organic solvents. The catalyst showed adequate reusability, and the HMF yield only decreased by 2.88% after six cycles of reuse compared with that of the initial catalyst. This study demonstrates the application potential of BMOFs in the conversion of biomass to useful molecules with commercial and/or research value.

Effects of Acid Modulators on the Microwave-Assisted Synthesis of Cr/Sn Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) have attracted remarkable attention for their distinguished structural designability. Precisely controlling the particle size and improving the structural stability of MOF nanoparticles influence their catalytic activity significantly. In this study, six acids (nitric, hydrochloric, formic, acetic, succinic, and citric acids) were used as modulators to prepare bimetallic MIL-101 (Cr, Sn) (MIL stands for Materials of Institut Lavoisier) via a microwave-assisted hydrothermal method. Changes in volumetric, structural, stability, and catalytic properties, size, and shape of MIL-101 (Cr, Sn) were examined using scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, and N2 adsorption-desorption measurements. All modulators altered the MOF properties. Compared with other samples, acetic acid as a modulator mildly altered the MOF morphology by narrowing their particle size distribution, enhancing the specific surface area, and significantly improving their water and thermal stabilities. The addition of acetic acid was suitable for the catalytic conversion of glucose to 5-hydroxymethylfurfural (5-HMF), achieving a 43.1% 5-HMF yield with 91.4% glucose conversion in a mixed solution of γ-valerolactone and saturated salt water at 150 °C after 30 min.

Platelet-To-Lymphocyte and Neutrophil-To-Lymphocyte Ratios Predict Intestinal Injury in Male Heroin Addicts.

Objective: To explore the potential link between gut damage and proinflammatory cytokines in heroin-dependent patients. Methods: We retrospectively analyzed and compared partial blood counts and biomarkers of intestinal injury and their potential correlations in 38 male heroin abuse patients and 29 healthy male participants. In addition, we compared and assessed proinflammatory cytokines and immune cells in 10 heroin abuse patients and 10 healthy participants. Results: Neutrophil counts, platelets/lymphocytes (PLR), neutrophils/lymphocytes (NLR), gut injury biomarkers, and proinflammatory cytokines, CD19+B in patients compared with healthy subjects' cells increased significantly. The number of lymphocytes, CD3 CD4 T cells, and CD3 CD8 T cells decreased in patients compared to healthy individuals. When distinguishing between heroin addicts and healthy people, ROC/AUC analysis showed that a cutoff of 142.42 for PLR and 2.18 for NLR yielded a sensitivity of 65% and 85% and a specificity of 96.5% and 89.7%, respectively (p = 0.001, p < 0.001). For predicting intestinal injury, ROC/AUC analysis showed that a cutoff of 135.7 for PLR and 0.15 for NLR yielded a sensitivity of 52% and 60% and a specificity of 82% and 86.4%, respectively (p = 0.003, p = 0.009). Male heroin addicts are subject to intestinal injury and present with increased proinflammatory cytokine levels. Conclusion: NLR and PLR are possible indirect biomarkers for heroin dependence based on intestinal injury.

Fast visual monitoring of the freshness of beef using a smart fluorescent sensor.

Spoiled meat contains many pathogenic bacteria; hence, the intake of spoiled food can lead to various illnesses. To screen the freshness of food, in this study, we devised a ratiometric fluorescence sensor dicyanovinyl coumarin (CMDC) for the determination of cadaverine, an important biomarker for the spoilage of meat. CMDC underwent aza-Michael addition with cadaverine, exhibiting high sensitivity, fast response (50 s), and distinct fluorescence color transition. Test strips fabricated using CMDC showed a noticeable color change from red to green when exposed to cadaverine vapor. The test strips were successfully used to visually monitor the spoilage of beef based on the fluorescence color change. Furthermore, the as-developed test strip coupled with a smartphone provides a simple tool for consumers and suppliers to obtain information about meat quality.

Phase Ia/Ib Study of the Selective MET Inhibitor, Savolitinib, in Patients with Advanced Solid Tumors: Safety, Efficacy, and Biomarkers.

BACKGROUND: Savolitinib has shown good tolerability and preliminary efficacy, but efficacy biomarkers require investigation. The main purpose of this study was to confirm in Chinese patients the recommended phase II dose (RP2D) of savolitinib and to explore overall benefit in tumors bearing c-Met aberration. METHODS: This was an open-label, multi-center, 2-part phase I study. A starting dose of 600 mg QD was initiated in the escalation phase, utilizing a 3+3 design with repeated QD and BID dosing. In the dose expansion phase, we enrolled patients with gastric cancer and non-small cell lung cancer (NSCLC) with documented c-met aberration into 5 cohorts to further explore biomarkers. c-Met overexpression and amplification were assessed by immunohistochemistry and FISH, respectively. RESULTS: The safety analysis set included 85 patients. Only one dose-limiting toxicity (grade 3 fatigue) was reported in the 600 mg BID dosing group. The most frequent treatment-related adverse events were nausea (29.4%), vomiting (27.1%), and peripheral edema (21.2%). Notably, in gastric cancer, response was only observed in patients with MET amplification (copy number 9.7-18.4), with an objective response rate of 35.7% and a disease control rate of 64.3%. For patients with NSCLC bearing a MET exon 14 skipping mutation, obvious target lesion shrinkage was observed in 2 of 4 patients, although PR was not achieved. CONCLUSION: The RP2D of savolitinib was established as 600 mg QD or 500 mg BID in Chinese patients. The promising response observed in patients with gastric cancer with c-met amplification and NSCLC with MET exon 14 skipping mutation warrants further investigation. CLINICALTRIALS.GOV IDENTIFIER: NCT0198555.

Mechanistic insights into acid-affected hydrogenolysis of glycerol to 1,3-propanediol over an Ir-Re/SiO2 catalyst.

Glycerol hydrogenolysis to 1,3-propanediol is identified to follow the dehydration-hydrogenation pathway with the rate-determining step (RDS) of H* + OH* → H2O* over an IrRe catalyst. The positive effects of solid acids are elucidated to originate from the reduced energy barrier of the RDS by H protons, while the negative ones of liquid acids are from excessively strong adsorption of anions.

A single-arm, multicenter, open-label phase 2 trial of surufatinib in patients with unresectable or metastatic biliary tract cancer.

BACKGROUND: Several clinical studies of vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) therapy as a second-line treatment for biliary tract cancer (BTC) have shown modest efficacy. In this study, surufatinib was evaluated as a second-line VEGFR therapy in patients with BTC. METHODS: This was a single-arm, multicenter, open-label phase 2 study conducted in China. The study enrolled eligible patients with BTC, who had received surufatinib monotherapy as second-line treatment, at a dose of 300 mg, once daily, in 28-day cycles. Tumor assessments were performed every 8 weeks (±7 days) according to the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: As of November 30, 2018, 39 patients with BTC, including 29 (74.4%) with intrahepatic cholangiocarcinoma, 5 (12.8%) with extrahepatic cholangiocarcinoma, and 5 (12.8%) with gallbladder cancer, were enrolled and treated with surufatinib. The 16-week progression-free survival rate was 46.33% (95% CI, 24.38-65.73), with median progression-free survival of 3.7 months and median overall survival of 6.9 months. In addition, results from subgroup and post hoc analyses revealed that patients with the proper tumor locations or appropriate levels of serum biomarkers might receive greater clinical benefits. The top 3 treatment-related adverse events with severity of grade ≥3 included blood bilirubin increased (20.5%), hypertension (17.9%), and proteinuria (12.8%). CONCLUSIONS: When applied in the treatment of patients with BTC, surufatinib monotherapy has offered moderate clinical efficacy and shown expected tolerability and safety profiles.

Fe3O4 hollow nanospheres on graphene oxide as an efficient heterogeneous photo-Fenton catalyst for the advanced treatment of biotreated papermaking effluent.

This study focused on the feasibility of using Fe3O4/graphene oxide (FGO) nanocomposites as heterogeneous catalysts for the advanced treatment of real industrial wastewater. FGO nanocomposites with different graphene oxide (GO) ratios were synthesized by coprecipitating iron salts onto GO sheets in basic solution. The characterization of the resulting material structures and functionalities was performed using a range of analytical techniques. A low GO loading afforded a good Fe3O4 nanoparticle dispersibility and resulted in a higher Brunauer-Emmett-Teller surface area and pore volume. The FGO nanocomposites and pure Fe3O4 were used to treat papermaking wastewater in a heterogeneous photo-Fenton process. The results suggested that the nanocomposite designated FGO1 (GO loading of 25 mg) exhibits a higher photocatalytic efficiency than other FGO nanocomposites and pure Fe3O4. A maximum chemical oxygen demand degradation efficiency of 89.6% was achieved in 80 min with 1.5 g L-1 FGO1 at pH 3. The degradation of different pollutants present in wastewater was evaluated with the aid of gas chromatography-mass spectrometry and 3D excitation-emission-matrix analysis. Inductively coupled plasma atomic emission spectroscopy and magnetic measurements confirmed that the FGO1 nanocomposites possess a low iron leachability and a high reusability. Thus, a comprehensive advanced treatment of real industrial wastewater using a magnetic FGO catalyst is demonstrated.

Application Value of Real-Time Shear Wave Elastography in Diagnosing the Depth of Infiltrating Muscular Layer of Endometrial Cancer.

OBJECTIVE: To explore the clinical value of real-time shear wave ultrasonic elastography in diagnosing the depth of infiltrating muscularis of endometrial cancer. METHODS: Seventy-one patients with stage I endometrial cancer infiltrating the myometrium and 37 patients with normal physical examination were enrolled and divided into three groups: endometrial cancer superficial muscle infiltration group, endometrial cancer deep muscle infiltration group, and normal control group. After completing 2-dimensional ultrasound examination, each patient switched to the real-time shear wave elastography mode to measure the elasticity values Emax, Emean, and Esd. RESULTS: For control group, comparison of elastic modulus values between superficial muscular layer near the intimal surface and the deep muscular layer near the serosa surface showed no difference (P > 0.05). For endometrial cancer superficial muscular infiltration group, significant difference was found regarding the elastic modulus values of infiltrated muscular layer and uninfiltrated muscular layer (Emax and Emean) without difference for Esd (P > 0.05). A significant difference of elastic modulus was observed between control group and deep myometrial infiltration group (P < 0.05) without difference of Emean or Emax but with difference of Esd. The accuracy in diagnosing muscular layer infiltration was 78.9% for Emax cutoff and 82.5% for Emean cutoff. The rate of using Emax ≥32.22 kPa or Emean ≥27.54 kPa as the ultrasound standard for diagnosing myometrium infiltration was 92.9%. The accuracy for the diagnosis of muscular layer infiltration was 96.1% for Emax cutoff, 94.1% for Emean cutoff and 86.3% for Esd cutoff. CONCLUSION: Real-time shear wave elastography is helpful to determine the depth of infiltrating myometrium of endometrial cancer.

Adsorption characteristics and mechanism of norfloxacin in water by γ-Fe2O3@BC.

Using waste pomelo peel as raw material, pomelo peel-based biochar (BC) was prepared by pyrolysis at 400 °C, and the pomelo peel-based biochar was prepared by loading γ-Fe2O3 onto the surface of the pomelo peel-based biochar by unlimited oxygen chemical precipitation. The results showed that the pomelo peel biochar loaded with γ-Fe2O3 had higher specific surface area and larger pore volume. The load of γ-Fe2O3 gives γ-Fe2O3@BC excellent magnetic separation ability, and its magnetic saturation intensity is as high as 30.60 emu/g. BC and γ-Fe2O3@BC were applied to remove norfloxacin (NOR) from a water body. It was found that the adsorption of NOR by both of them followed the pseudo-second-order kinetic model. The adsorption isotherm mainly conforms to the Sips model, and the adsorption process of NOR is a spontaneous endothermic reaction. The pH and ionic strength have a great influence on the adsorption of NOR by BC and γ-Fe2O3@BC, and they play a role mainly by influencing the morphology of NOR in water. The adsorption mechanism showed that cation exchange and hydrogen bonding were the main forces for BC to adsorb NOR. Moreover, the γ-Fe2O3 particles enhanced the hydrophobicity of the pomelo peel-based biochar, making the hydrophobicity become the main force for the adsorption of NOR by the γ-Fe2O3@BC. The adsorption-desorption experiment showed that after four cycles of recycling, the adsorption capacity of γ-Fe2O3@BC for NOR was still up to 61.43% of the initial adsorption capacity, and it had a good recycling property.

Surufatinib in Chinese Patients with Locally Advanced or Metastatic Differentiated Thyroid Cancer and Medullary Thyroid Cancer: A Multicenter, Open-Label, Phase II Trial.

Background: Thyroid cancer is the most common endocrine tumor with an increasing incidence. Limited treatment options are available for patients with advanced or recurrent metastatic disease, resulting in a poor prognosis. Surufatinib targets multiple kinases (vascular endothelial growth factor receptors, fibroblast growth factor receptor-1, and colony-stimulating factor-1 receptor) involved in tumor angiogenesis and tumor immune evasion. Surufatinib has demonstrated promising antitumor activity in various advanced solid tumors. This study aimed to determine the objective response rate (ORR) of surufatinib in patients with locally advanced or distant metastatic differentiated thyroid cancer (DTC) or medullary thyroid cancer (MTC). Methods: This Phase II open-label study by Simon's two-stage design was conducted at 10 sites across China. Patients with radioiodine (RAI)-refractory DTC with locally advanced disease or distant metastasis (DTC1 group); patients who received limited initial surgery and then developed locally advanced unresectable recurrences and were not considered candidates for RAI therapy due to residual normal thyroid tissue (DTC2 group); or patients with MTC with locally advanced disease or distant metastasis (MTC group) were enrolled. A total of 59 patients were enrolled (26 in DTC1, 6 in DTC2, and 27 in MTC) and received 300 mg surufatinib daily in 28-day cycles. The primary endpoint was ORR as determined by the investigators. Results: Overall ORR was 23.2% [95% confidence interval, CI 12.98-36.42]: 21.7% in the DTC1 cohort, 33.3% in the DTC2 cohort, and 22.2% in the MTC cohort. Forty-nine patients achieved disease control (87.5% [CI 75.93-94.82]): 87.0% in the DTC1 cohort, 83.3% in the DTC2 cohort, and 88.9% in the MTC cohort. Median time to response was 59.0 days, and 59.0, 85.5, and 59.0 days in the DTC1, DTC2, and MTC cohorts. Overall median progression-free survival was 11.1 months [CI 5.98-16.69]; 11.1 months in DTC1 and MTC cohorts, while the DTC2 cohort had not reached the median at the data cutoff. The most common treatment-emergent adverse events grade ≥3 were hypertension (20.3%), proteinuria (11.9%), and then elevated blood pressure, hypertriglyceridemia, and pulmonary inflammation (5.1% each). Conclusions: Surufatinib demonstrated promising efficacy with a tolerable and manageable safety profile for patients with locally advanced or metastatic MTC, RAI-refractory DTC, or locally advanced unresectable recurrences unable to receive RAI.

Synthesis of Petal-Like MnO2 Nanosheets on Hollow Fe3O4 Nanospheres for Heterogeneous Photocatalysis of Biotreated Papermaking Effluent.

Owing to the implementation of increasingly stringent water conservation policies and regulations, the pulp and paper mill industry must make increased efforts to meet the limits for pollutant emissions. The primary pretreatment and secondary biochemical treatment methods used currently generally fail to meet the country-specific environmental regulations, and the wastewater must be processed further even after being subjected to secondary biochemical treatments. In this work, we synthesized Fe3O4/MnO2 nanocomposites (FMNs) with a flower-like structure for use in the heterogeneous photocatalytic treatment of biotreated papermaking wastewater. FMNs1.25, which were formed using a KMnO4/Fe3O4 molar ratio of 1.25, could be separated readily using an external magnetic field and exhibited higher photocatalytic activity than those of the other samples as well as MnO2 and Fe3O4. The effects of various experimental parameters on the photocatalytic activity of FMNs1.25, including the initial pH of the wastewater and the catalyst dosage, were determined. The common chemical oxygen demand (CODCr) reduction rate in the case of this sample reached 56.58% within 120 min at a pH of 3, the CODCr of effluent after treatment was 52.10 mg/L. Further, even under neutral conditions, the CODCr of the treated effluent was below the current limit for discharge in China. Moreover, the nanocomposites exhibited good recyclability, and their catalytic activity did not decrease significantly even after five usage cycles. This study should serve as a platform for the fabrication of effective photocatalysts for the advanced treatment of biotreated papermaking effluent and refractory organic wastewater.

[Purification and biochemical function of Astragalus membtanaceus pathogenesis-related protein 10].

Astragalus membranaceus pathogenesis-related protein 10 (AmPR-10) is largely expressed in case of environmental pressure and pathogen invasion. This study aims to explore the biochemical functions of AmPR-10. The dried root of Astragalus membranaceus was mechanically homogenized and extracted by Tris-HCl buffer to obtain its crude extract, which was then purified by anion exchange chromatography and gel filtration chromatography to obtain electrophoretically pure AmPR-10. The nuclease activity of AmPR-10 was tested with different RNAs by detecting the absorption value at 260 nm. The results demonstrated potent nuclease activity toward yeast tRNA, yeast RNA, Poly (A) and Poly (C). The optimum reaction temperature was 50 °C and pH was 7-8. EDTA showed no effect on its activity, while Mg²âº exhibited potent activation effect on the activity, and Co²âº, Ca²âº and Zn²âº manifested moderately inhibition of the activity. Since AmPR-10 had no sequence homology with other known nucleases, AmPR-10 was probably a novel nuclease. The inhibition kinetic data against papain was analyzed by Lineweaver-Burk plots, and the results showed that the inhibition of papain followed noncompetitive-type kinetics. AmPR-10 played an important role in Astragalus membranaceus defense mechanism against environmental pressure and pathogen invasion, which may be achieved by inhibiting cycteine enzymes activity.

Boosting Size-Selective Hydrogen Combustion in the Presence of Propene Using Controllable Metal Clusters Encapsulated in Zeolite.

A strategy is presented for making metal clusters encapsulated inside microporous solids selectively accessible to reactant molecules by manipulating molecular sieve size and affinity for adsorbed molecules. This expands the catalytic capabilities of these materials to reactions demanding high selectivity and stability. Selective hydrogen combustion was achieved over Pt clusters encapsulated in LTA zeolite (KA, NaA, CaA) in a propene-rich mixture obtained from propane dehydrogenation, showing pore-size dependent selectivity and coking rate. Propene tended to adsorb at channels or external surfaces of zeolite, interfering the diffusion of hydrogen and oxygen. Tailoring the surface of LTA zeolite with additional alkali or alkaline earth oxides contributed to narrowing zeolite pore size and their affinity for propene. The thus-modified Pt@KA catalyst displayed excellent hydrogen combustion selectivity (98.5 %) with high activity and superior anti-coking and anti-sintering properties.

Transient and Persistent Room-Temperature Mechanoluminescence from a White-Light-Emitting AIEgen with Tricolor Emission Switching Triggered by Light.

Persistent luminescence from purely organic materials is basically triggered by light and electricity, which largely confines its practical applications. A purely organic AIEgen exhibits not only persistent photoluminescence, but also transient and persistent room-temperature mechanoluminescence. By simply turning on and off a UV lamp, tricolor emission switching between blue, white, and yellow was achieved. The data from single-crystal structure analysis and theoretical calculation suggest that mechanism of the observed persistent mechanoluminescence (pML) is correlated with the strong spin-orbit coupling of the bromine atom, as well as the formation of H-aggregates and restriction of intramolecular motions in noncentrosymmetric crystal structure. These results outline a fundamental principle for the development of new pML materials, providing an important step forward in expanding the application scope of persistent luminescence.

Evaluating Sustainability of Regional Water Resources Based on Improved Generalized Entropy Method.

The sustainability of regional water resources has important supporting data needed for establishing policies on the sustainable development of the social economy. The purpose of this paper is to propose an assessment method to accurately reflect the sustainability of regional water resources in various areas. The method is based on the relative entropy of the information entropy theory. The steps are as follows. Firstly, the pretreatment of the evaluation sample data is required, before the relative entropy of each standard evaluation sample and evaluation grade (SEG) is calculated to obtain the entropy weight of each evaluation index. After this, the entropy weighted comprehensive index (WCI) of the standard evaluation grade sample is obtained. The function relation between WCI and SEG can be fitted by the cubic polynomial to construct the evaluation function. Using the above steps, a generalized entropy method (GEM) for the sustainable assessment of regional water resources is established and it is used to evaluate the sustainability of water resources in the Pingba and Huai River areas in China. The results show that the proposed GEM model can accurately reflect the sustainable water resources in the two regions. Compared with the other evaluation models, such as the Shepherd method, Artificial Neural Network and Fuzzy comprehensive evaluation, the GEM model has larger differences in its evaluation results, which are more reasonable. Thus, the proposed GEM model can provide scientific data support for coordinating the relationship between the sustainable development and utilization of regional water resources in order to improve the development of regional population, society and economy.

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy.

VEGF/VEGFR signal axis has been proven to be an important target for development of novel cancer therapies. One challenging aspect in small molecular VEGFR inhibitors is to achieve sustained target inhibition at tolerable doses previously seen only with the long-acting biologics. It would require high potency (low effective drug concentrations) and sufficient drug exposures at tolerated doses so that the drug concentration can be maintained above effective drug concentration for target inhibition within the dosing period. Fruquintinib (HMPL-013) is a small molecule inhibitor with strong potency and high selectivity against VEGFR family currently in Phase II clinical studies. Analysis of Phase I pharmacokinetic data revealed that at the maximum tolerated dose of once daily oral administration fruquintinib achieved complete VEGFR2 suppression (drug concentrations were maintained above that required to produce >85% inhibition of VEGFR2 phosphorylation in mouse) for 24 hours/day. In this article, the preclinical data for fruquintinib will be described, including kinase enzyme activity and selectivity, cellular VEGFR inhibition and VEGFR-driven functional activity, in vivo VEGFR phosphorylation inhibition in the lung tissue in mouse and tumor growth inhibition in a panel of tumor xenograft and patient derive xenograft models in mouse. Pharmacokinetic and target inhibition data are also presented to provide a correlation between target inhibition and tumor growth inhibition.