Implementation of micelle-enabled C(sp2)-C(sp3) cross-electrophile coupling in pharmaceutical synthesis.

A sustainable C(sp2)-C(sp3) cross-electrophile coupling was developed between readily available 5-bromophthalide and 1-benzyl-4-iodopiperidine under micellar conditions, leading to a key intermediate of one of our development compounds. Copper was found to play a crucial role as a co-catalyst in this dual catalysis system. The chemistry and process were successfully demonstrated in a kilo scale to deliver sufficient drug substance to the clinical campaigns. This is the first reported scale-up of such a challenging cross-electrophilic coupling that uses an aqueous medium, and not undesirable reprotoxic polar aprotic solvents (e.g. DMF, DMAc, and NMP).

Prevention and Control of Coal and Gas Outburst by Directional Hydraulic Fracturing through Seams and Its Application.

The regionalized pressure relief, permeability enhancement, and outburst prevention of "three high and one low" coal seams with high gas, high ground stress, high outburst risk, and low permeability have become important problems to be solved urgently in realizing the sustainable development of coal mines. In this study, a combination of theoretical research, RFPA2D-Flow numerical simulation, and field test was used to study the initiation mechanism and propagation law of directional hydraulic fracturing fractures through the seam. The results show that fracture initiation depends on the axial and radial horizontal stress of the fracture hole, the physical and mechanical properties of coal and rock, and the inside of the weakest layer. Single-hole hydraulic fracturing can achieve a pressure relief radius of 7-8 m, but there is a stress concentration zone outside, which is not conducive to regional pressure relief and permeability enhancement. Directional hydraulic fracturing with multiple holes produces an approximate cylindrical compression and crushing ring and a penetrating fracture surface along the center line of the pressure crack hole and the directional hole, which better eliminates the phenomenon of stress concentration in nondirectional hydraulic fracturing. The technology was applied to the 2238 auxiliary roadway of Chengzhuang Mine of Jinmei Group, and the field implementation results showed that field implementation results showed that directional hydraulic fracturing through the seam reduced the gas content in the coal seam to a great extent, and the coal seam gas content was reduced by about 42.3%, indicating that the technology can effectively reduce the risk of coal and gas outbursts.

Triphase contrast-enhanced CT to evaluate indications for autologous liver transplantation in patients with end-stage hepatic alveolar echinococcosis.

Autologous liver transplantation (ALT) to cure end-stage hepatic alveolar echinococcosis (HAE) requires that hepatobiliary surgeons understand the invasion of intrahepatic structure and adjacent tissues or organs. Triphase contrast-enhanced CT of the liver has been widely used for diagnosis and preoperative evaluation of HAE. Three-dimensional (3D) reconstruction allows for accurate measurement of remnant liver volume (RLV). The objective of the study was to evaluate value of triphase contrast-enhanced CT together with 3D reconstruction in preoperative evaluation of indications for ALT in patients with end-stage HAE. This cohort include twenty-one consecutive patients with end-stage HAE, who preoperatively underwent triphase enhanced CT together with 3D reconstruction for ALT. To depict the indications, the 2D image data were reviewed statistically focusing on porta hepatis invasion, retrohepatic vena cava (RHVC) involvement and degrees of intrahepatic vessel invasion, and the 3D reconstruction was performed to obtain ratio of RLV to standard liver volume (SLV). The results showed that 95.24% patients (20/21) had porta hepatis invasion. When lesions located in right liver lobe, porta hepatis invasion occurred most commonly in the second and third porta hepatis (7/10), whereas the first, second and third porta hepatis were most commonly invaded by lesions in the right and caudate / left medial liver lobes (7/11) (P < 0.05). The mean value of longitudinal invasion of RHVC was 8.0 cm, and 95.2% (20/21) of patients had RHVC invasion with ≥ 180° circumferential invasion. As for the important vascular events, moderate and severe invasion occurred most commonly in the right hepatic vein, right branch of portal vein and RHVC each in 95.2% (20/21) patients (P < 0.05). We also found that preoperative CT had a good agreement with intraoperative findings in assessing intrahepatic vascular involvement by HAE (kappa index = 0.77). The estimated average ratio of RLV to SLV was 0.95 (range, 0.43-1.62). In conclusion, the 2D contrast-enhanced CT could well depict anatomic location and size of HAE, and invasion of porta hepatis and vascular by this disease, and involvement of other adjacent organs and tissues. Above all, 3D reconstruction could accurately measure RLV in patients with end-stage HAE for ALT.

Dynamic Evolution of Nanoscale Pores of Different Rank Coals Under Solvent Extraction.

During the coalification process, coalbed methane (CBM) is formed and mainly adsorbed in the pores of coal. Pore structure evolution is critical to CBM adsorption/desorption and extraction. This paper puts forward two parameters, namely the variety degree x and variety gene σ, for characterizing pore structure through mercury injection tests. Then, under extraction with different solvents, the dynamic evolution characteristics of nanoscale pores are addressed and quantified by taking four different rank coals (lignite, medium-volatile bituminous coal, low-rank anthracite and mediumrank anthracite) from different coal mines of China as the study object. The results indicate that the content of meso- and macropores after solvent extraction is much larger, but that there is no obvious law with the content of transition pores and micropores in the size range of 50-7.2 nm, according to the basic data sets of specific surface area (SSA) and pore volume (PV) of all coal samples. This phenomenon can be explained by the pore increase and expansion effects in nanoscale pores during solvent extraction. Generally, with the increasing of the solvent extraction degree, the difference in variety degree x with respect to the total PV and total SSA of different coals shows a significant decreasing trend, which expresses a homogeneous development in the change in pore structure. In regard to different solvents, benzene mainly causes pore expansion in meso- and macropores, and CS2 has a great effect on micropores. Whereas acetone plays an important role in mesopores and transition pores with pore expansion, THF has various effects on different size pores. Further study with higher variety gene σ values shows that the total PV mainly depends on the change in the absolute content of meso- and macropores. While the change in the absolute content of transition pores and micropores (less than 50 nm) has a great influence on the total SSA. As the extraction degree increases, the influence of the transition pores and micropores on the total PV is increased, and then, the content of meso- and macropores also plays an important role on the total SSA. However, this effect is highly different for raw coals of different ranks.

Effects of cold storage and 1-methylcyclopropene treatments on ripening and cell wall degrading in rabbiteye blueberry (Vaccinium ashei) fruit.

The effect of postharvest 1-methylcyclopropene and/or cold storage application on texture quality parameters during storage was determined. The changes in fruit quality (including weight loss, firmness, total soluble solids content, and ethylene production), cell wall material (including water-soluble fraction, ethylenediaminetetraacetic acid-soluble fraction, Na2CO3-soluble fraction, 4% KOH-soluble fraction, and 14% KOH-soluble fraction), and cell wall hydrolase activities (including polygalacturonase, endo-1,4-beta-D-glucanase, pectinesterase, alpha-L-arabinofuranosidase, and beta-galactosidase) were periodically measured up to 25 days after postharvest treatments. The application of cold storage reduced weight loss, ethylene production, and delayed ripening of blueberry fruit. The inhibition of senescence was associated with suppressed increase in cell wall hydrolase activities and retarded solubilization of pectins and hemicelluloses. Furthermore, no obvious differences in firmness, weight loss, ethylene production, and cell wall hydrolase activities between fruits with or without 1-methylcyclopropene application were observed, while significant lower levels of the detected parameters were found in cold storage fruit compared with fruit stored in room temperature. Thus, cold storage can be viewed as an effective means to extend the shelf life of blueberry fruit.

Characterization of poly(ethylene glycol)-modified bovine hemoglobin by capillary zone electrophoresis.

In this study capillary zone electrophoresis (CZE) was used to analyze the poly(ethylene glycol)-modified bovine hemoglobin(PEG-bHb). The results show that CZE separated the subunit of bovine hemoglobin based on the number of PEG conjugating to the protein surface, which makes it possible to evaluate the degree of modification of hemoglobin subunit; meanwhile, it also reflected the stability of PEG attaching to hemoglobin after incubating with hydroxylamine, which makes it successful to detect the distribution of attachment site and evaluate the stability of PEG on the surface of hemoglobin. As a simple, fast and accurate method, CZE is suitable to monitor the production procedures and quality control of the final products of the PEG-bHb.

Determination of the molecular weight distribution of the PEGylated bovine hemoglobin (PEG-bHb).

The method to determine the average molecular weight and distribution of molecular weight of the PEGylated hemoglobin (PEG-bHb) and their molecular weight of polypeptides in PEG-bHb with UV absorbance (UV), light scattering (LS) and refractive index (RI) detectors is described in this paper. The results indicate that when molar ratio of PEG to hemoglobin is 7:1, the average molecular weight of PEG-bHb (M(CP) is 95 kDa, the average molecular weigh of protein moiety in PEG-bHb (M(P)) is 68 kDa, and their distribution is from 48-157 kDa and 44-121 kDa, respectively; when the molar ratio is 10:1, the M(CP) is 106 kDa, the M(P) is 70kDa, and their distribution is from 56-216kDa, 49-135kDa, respectively; when the molar ratio is 13:1, the M(CP) is 73kDa, and their distribution is from 81-272 kDa and 41-144 kDa, respectively. It has been proved that this method is a simple and reliable way for the determination of average molecular weight and distribution of molecular weight of PEGlyted hemoglobin. This experiment also suggests that there exists not only aggregation in the frontal of elution peak of PEG-bHb, but dissociation of tetramer of hemoglobin into dimmer in the tail of elution peak, and the degree of aggregation is depended on the molar ratio of PEG to hemoglobin due to the present of diol PEG and the dissociation is dependant on the concentration of hemoglobin.