Measurement of carbon emissions and responsibility sharing for the industrial sector in Zhejiang, China.

Carbon reduction is imperative for achieving carbon peaking and neutrality. Accordingly, it is important to determine which industrial sectors have more responsibility in this matter. Based on data from Zhejiang's input-output tables, this study applies the Input-Output method to measure and compare the carbon emissions of 42 industrial sectors in Zhejiang Province from 2002 to 2017, and then assesses the carbon emission attributes of each industrial sector, and ultimately determines the responsibility for carbon emission reduction from the perspectives of the producers and consumers. The results of the study show that direct carbon emissions and whole-process carbon emissions in Zhejiang increased continuously from 2002 to 2017, with carbon emission intensity first decreasing and then increasing. However, carbon emission intensity was much lower in 2017 than in 2002. Over time, the attributes of carbon emissions by sector changed little. Particularly, high-carbon sectors covered most of the energy supply sectors, low-carbon sectors were mostly tertiary-related, and pseudo-low-carbon sectors were mainly found in the productive services sector. In terms of carbon emission reduction responsibilities, there are large differences in emission reduction responsibilities between sectors, with the electricity and heat sectors bearing the largest responsibilities based on their production, consumption and total carbon emission reductions. The conclusions of this study can provide some data support for the further development of carbon peak and carbon neutral plans.

[Arsenic speciation and valence].

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.

[Varieties systematization and standards status analysis of fermented Chinese medicine].

Fermented Chinese medicine has long been used. Amid the advance for preservation of experience, the connotation of fermented Chinese medicine has been enriched and improved. However, fermented Chinese medicine prescriptions generally contain a lot of medicinals. The fermentation process is complicated and the conventional fermentation conditions fail to be strictly controlled. In addition, the judgment of the fermentation end point is highly subjective. As a result, quality of fermented Chinese medicine is of great difference among regions and unstable. At the moment, the quality standards of fermented Chinese medicine are generally outdated and different among regions, with simple quality control methods and lacking objective safe fermentation-specific evaluation indictors. It is difficult to comprehensively evaluate and control the quality of fermented medicine. These problems have aroused concern in the industry and also affected the clinical application of fermented Chinese medicine. This article summarized and analyzed the application, quality standards, and the modernization of fermentation technology and quality control methods of fermented Chinese medicine and proposed suggestions for improving the quality standards of the medicine, with a view to improving the overall quality of it.

Study on the Absorption of Arsenic Species in Realgar Based on the Form and Valence.

At present, several experiments have been carried out to study the changes in total arsenic content of realgar and its prescription, but few researches on its form and valence. We evaluated the change in arsenic species concentration in realgar from the perspective of absorption by using an in vitro dissolution study, an in vivo unidirectional intestinal perfusion study, transmembrane transport in Caco-2 cells, and a pharmacokinetic study in rats. In the gastrointestinal tract, arsenic species are mainly present inorganic forms of AsIII and AsV. The cumulative dissolution rates of soluble arsenic in 4 h artificial gastric fluid and 8 h artificial intestinal fluid were 21.99% and 59.20%, respectively. The P app values of soluble arsenic in realgar in the duodenum, jejunum, and ileum of rats were 5.4 × 10-3, 6.1 × 10-3 and 5.8 × 10-3 cm/min, respectively. In the process of small intestine perfusion, the AsIII of realgar was partially converted into AsV in the duodenum and jejunum. As the transport time increased, the transmembrane transport rate and P app value of soluble arsenic in realgar were increased in Caco-2 cells, and it also suggested that arsenic species may be passively transported across the Caco-2 cell monolayer. The C max and AUC (0-24) of AsIII, AsV, and DMA in plasma of realgar were 41.26 ng L-1/343.977 ng h mL-1, 21.626 ng L-1/47.310 ng h mL-1, and 2.372 ng L-1/30.429 ng h mL-1, respectively. T max and MRT (0-∞) of AsIII, AsV, and DMA were 2.571 h/9.649 h, 0.393 h/2.790 h, and 3.143 h/23.145 h, respectively. It is hoped to provide a basis for clarifying the arsenic species in realgar.

Construction of a Multifunctional Nano-Scale Metal-Organic Framework-Based Drug Delivery System for Targeted Cancer Therapy.

The antitumor activity of triptolide (TP) has received widespread attention, although its toxicity severely limits its clinical application. Therefore, the design of a targeted drug delivery system (TDDS) has important application prospects in tumor treatment. Metal-organic frameworks (MOFs), with high drug-carrying capacity and good biocompatibility, have aroused widespread interest for drug delivery systems. Herein, folic acid (FA) and 5-carboxylic acid fluorescein (5-FAM) were used to modify Fe-MIL-101 to construct a functionalized nano-platform (5-FAM/FA/TP@Fe-MIL-101) for the targeted delivery of the anti-tumor drug triptolide and realize in vivo fluorescence imaging. Compared with Fe-MIL-101, functionalized nanoparticles not only showed better targeted therapy efficiency, but also reduced the systemic toxicity of triptolide. In addition, the modification of 5-FAM facilitated fluorescence imaging of the tumor site and realized the construction of an integrated nano-platform for fluorescence imaging and treatment. Both in vitro and in vivo studies of functionalized nanoparticles have demonstrated excellent fluorescence imaging and synergistic targeting anticancer activity with negligible systemic toxicity. The development of functional nano-platform provides new ideas for the design of MOF-based multifunctional nano-drug delivery system, which can be used for precise treatment of tumor.

Accurate quantitative determination of affinity and binding kinetics for tight binding inhibition of xanthine oxidase.

The accurate quantitative determination of affinity and binding kinetics (BK) for tight binding inhibition is extraordinary important from both the continuous optimization of compounds, particularly in developing structure-activity relationships (SAR), and the prediction of in vivo target occupancy (TO). Due to the unique properties for tight binding inhibition that the inhibitors are characterized by the ultrahigh-affinity, relatively fast association to the target enzyme combined with extremely slow dissociation of the inhibitor-enzyme binary complex, the classical steady state equilibrium methods are no longer valid. Here, we made several recommendations of how to design the optimal experiments and apply special mathematical calculation approaches to quantitatively evaluate the accurate affinity and BK as the examples of two tight binding inhibitors against the xanthine oxidase (XO), as well as compared the differences in the results calculated from the different data analytical methods and analyzed the influence of these differences on the XO engagement in human. Analysis of the results displayed that the accurate apparent dissociation constant (Ki*,app) was 0.2 ± 0.06 nM for topiroxotstat and was 0.45 ± 0.2 nM for febuxostat; that on-rate (kon) was (4.3 ± 1.1) × 106 M-1s-1 for topiroxotstat and was(133.3 ± 3.5) × 106 M-1s-1 for febuxostat, and off-rate (koff) was (1.0±0.2) × 10-5 s-1 for topiroxotstat and was ≤ 0.16 × 10-5 s-1for febuxostat. Moreover, there were significant differences in the Ki*,app and koff values estimated using the appropriate specialized methods for tight binding inhibition versus classical steady state equilibrium methods, with the substantial differences of 14-fold and 32-fold reduction for topiroxostat, respectively, and of 9.6-fold and ≥ 213-fold reduction for febuxostat, while the kon values remain the moderate differences for the two inhibitors. The obvious greater AUC of XO engagement time courses and longer durations of above 70% engagement by the appropriate specialized methods for tight binding inhibition were observed that the results display the differences of 70.1% and 88%, respectively for topiroxostat and of 38.1% and 35.0%, respectively for febuxostat in human liver cell than by classical steady state equilibrium methods. Again, our studies provide several valuable recommendations of the optimal experiment protocols and appropriate analytical approaches for accurately quantitatively assessing the affinity and BK parameters as well as demonstrate the ability of our recommended methods to generate reliable data for tight binding inhibitors against XO.

Construction of flexible enzymatic electrode based on gradient hollow fiber membrane and multi-wall carbon tubes meshes.

In this study, we developed a convenient way to construct a flexible enzymatic electrode with excellent stability and electrochemical performance for implanted glucose monitoring. The electrode was constructed through the co-immobilization of the glucose oxidase micro-particles (GOD MPs) and multi-wall carbon nanotubes (CNT) on the inner surface of a gradient-structured hollow fiber membrane (GHM), where CNT improved the electron transport efficiency and GHM controlled the transfer of substances and interferences. GOD MPs showed higher stability under various operation conditions than the free enzymes due to the MnCO3 template method, which enabled the biosensor to remain relative sensitivity at >86% over 9 days. The GOD MPs biosensor also showed high selectivity, reproducibility, and linear sensing range from 0 mM to 24 mM (R2 = 0.9993) with a current sensitivity of 25 nA/mM. The combination of porous-structured membrane and the flexible CNT meshes ensures the electrical connections and sensing accuracy of the biosensor under the deformation status. In-vivo experiments showed reliable current responses to variations in blood glucose concentrations that were consistent with tail blood test results. This co-immobilization of enzyme micro-particles in the 3D porous structure method developed a bio-composite platform technology towards the applications in flexible sensing and implantable medical devices.

Prediction of the pharmacokinetics and pharmacodynamics of topiroxostat in humans by integrating the physiologically based pharmacokinetic model with the drug-target residence time model.

Topiroxostat is a selective xanthine oxidoreductase (XOR) inhibitor for the management of hyperuricemia in patients with or without gout. In this work, we aim to employ the physiologically based pharmacokinetic (PBPK) model with the drug-target residence time model to predict and characterize both the pharmacokinetics (PK) and pharmacodynamics (PD) of topiroxostat in humans. The plasma concentration-time profile of topiroxostat was simulated based on drug properties and human physiology parameters. The predictive power of this PBPK model was then demonstrated by comparison of stimulated to observed pharmacokinetic parameters. The utility of the model was further demonstrated through predicting the oral absorption and disposition characteristics of topiroxostat in humans. Finally, by combining the PBPK model and the drug-target residence time model, we successfully predicted the target occupancy and built the relationship between PK and PD using in vitro, in vivo and in silico information. The results showed that topiroxostat exhibited significant in vivo pharmacological activity even after the complete clearance of this drug from the liver (target site), which may be due to the long residence time of the binary topiroxostat-XOR complex. This work may be helpful to guide future investigations of topiroxostat and also provides a novel strategy for PK/PD studies.

Ginsenoside Rb1 Ameliorates Autophagy of Hypoxia Cardiomyocytes from Neonatal Rats via AMP-Activated Protein Kinase Pathway.

OBJECTIVE: To investigate whether ginsenoside-Rb1 (Gs-Rb1) improves the CoCl-induced autophagy of cardiomyocytes via upregulation of adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway. METHODS: Ventricles from 1- to 3-day-old Wistar rats were sequentially digested, separated and incubated in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum for 3 days followed by synchronization. Neonatal rat cardiomyocytes were randomly divided into 7 groups: control group (normal level oxygen), hypoxia group (500 µmol/L CoCl2), Gs-Rb1 group (200 µmol/L Gs-Rb1 + 500 µmol/L CoCl2), Ara A group (500 µmol/L Ara A + 500 µmol/L CoCl2), Ara A+ Gs-Rb1 group (500 µmol/L Ara A + 200 µmol/L Gs-Rb1 + 500 µmol/L CoCl2), AICAR group [1 mmol/L 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) + 500 µmol/L CoCl2], and AICAR+Gs-Rb1 group (1 mmol/L AICAR + 200 µmol/L Gs-Rb1 + 500 µmol/L CoCl2). Cells were treated for 12 h and cell viability was determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cardiac troponin I (cTnI) levels were detected by enzyme-linked immunosorbent assay (ELISA). AMPK activity was assessed by 2',7'-dichlorofluorescein diacetate (DCFH-DA) ELISA assay. The protein expressions of Atg4B, Atg5, Atg6, Atg7, microtubule-associated protein 1A/1B-light chain 3 (LC3), P62, and active-cathepsin B were measured by Western blot. RESULTS: Gs-Rb1 significantly improved the cell viability of hypoxia cardiomyocytes (P<0.01). However, the viability of hypoxia-treated cardiomyocytes was significantly inhibited by Ara A (P<0.01). Gs-Rb1 increased the AMPK activity of hypoxia-treated cardiomyocytes. The AMPK activity of hypoxia-treated cadiomyocytes was inhibited by Ara A (P<0.01) and was not affected by AICAR =0.983). Gs-Rb1 up-regulated Atg4B, Atg5, Beclin-1, Atg7, LC3B II, the LC3B II/I ratio and cathepsin B activity of hypoxia cardiomyocytes (P<0.05), each of these protein levels was significantly enhanced by Ara A (all P<0.01), but was not affected by AICAR (all P>0.05). Gs-Rb1 significantly down-regulated P62 levels of hypoxic cardiomyocytes (P<0.05). The P62 levels of hypoxic cardiomyocytes were inhibited by Ara A (P<0.05) and were not affected by AICAR (P=0.871). CONCLUSION: Gs-Rb1 may improve the viability of hypoxia cardiomyocytes by ameliorating cell autophagy via the upregulation of AMPK pathway.

The effects of ginsenoside Rb1 on fatty acid ß-oxidation, mediated by AMPK, in the failing heart.

OBJECTIVES: This study intended to investigate the effects of Ginsenoside-Rbl (Gs-Rbl) on fatty acid ß-oxidation (FAO) in rat failing heart and to identify potential mechanisms of Gs-Rbl improving heart failure (HF) by FAO pathway dependent on AMP-activated protein kinase (AMPK). MATERIALS AND METHODS: Rats with chronic HF, induced by adriamycin (Adr), were randomly grouped into 7 groups. Gs-Rb1, adenine 9-ß-D-arabinofuranoside (Ara A, specific AMPK inhibitor), and 5'-aminoimidazole-4-carboxamide riboside (Aicar, specific AMPK activator) were administered to rats with HF, singly and/or combinedly. Myocardial high-energy phosphate (such as phosphocreatine, ADP, and ATP), free L-Carnitine, malonyl-CoA, and the activity of FAO-related enzymes in left ventricle from different groups were measured by using the corresponding molecular biological techniques. RESULTS: Gs-Rb1 improved HF significantly, accompanied by a significant increase in phosphocreatine (PCr), ADP, ATP, PCr/ATP ratio, free carnitine, malonyl-CoA, mRNA, activity of carnitine palmitoyltransferase (Cpt), medium-chain Acyl-CoA Dehydrogenase (MCAD) and long-chain acyl-CoA Synthetase (ACSL) and a significant decrease of the ADP/ATP ratio in the left ventricular myocardium. However, all those effects were almost abolished by Ara A and were not further improved by Aicar. CONCLUSION: Taken together, it suggests that Gs-Rb1 may modulate cardiac metabolic remodeling by improving myocardial fatty acid ß-oxidation in failing heart. In addition, the effects of Gs-Rb1 may be mediated via activating AMPK.