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PROteolysis-TArgeting Chimeras (PROTACs) have emerged as an innovative drug development platform. However, most PROTACs have been generated empirically because many determinants of PROTAC specificity and activity remain elusive. Through computational modelling of the entire NEDD8-VHL Cullin RING E3 ubiquitin ligase (CRLVHL)/PROTAC/BCL-xL/UbcH5B(E2)-Ub/RBX1 complex, we find that this complex can only ubiquitinate the lysines in a defined band region on BCL-xL. Using this approach to guide our development of a series of ABT263-derived and VHL-recruiting PROTACs, we generate a potent BCL-xL and BCL-2 (BCL-xL/2) dual degrader with significantly improved antitumor activity against BCL-xL/2-dependent leukemia cells. Our results provide experimental evidence that the accessibility of lysines on a target protein plays an important role in determining the selectivity and potency of a PROTAC in inducing protein degradation, which may serve as a conceptual framework to guide the future development of PROTACs.

Rhamnogalacturonan-I-enriched pectin (WRP) was recovered from citrus segment membrane. WRP can stimulate the growth of beneficial microbiome. In addition, the effect was enhanced by free-radical depolymerizing of WRP into DWRP.

Poly(ether ether ketone) (PEEK) hollow fiber membrane modules were scaled up from 2 inch diameter and 16 inch long to 4 inch diameter and 58 inch long (a factor of 90 increase in membrane area) for CO 2 capture from flue gases using a membrane contactor process, which combines advantageous features of both absorption and membrane processes. Field tests of a 4-inch-diameter module with activated methyldiethanolamine (aMDEA) solvent demonstrated greater than 90% CO 2 removal. The mass transfer coefficient in the absorption step was 1.2 (sec)-1 , which is over an order of magnitude greater than that of conventional column contactors. The membrane module was further scaled up from 4 inch to 8 inch diameter (a factor of 3 increase in membrane area). Singlegas permeation measurements indicated that 8-inch modules have an intrinsic CO 2 permeance as high as 2,150-2,670 GPU. One 8-inch-diameter module was tested in membrane contactor mode for CO 2 capture using a simulated flue gas. Carbon dioxide removal rate of 91.3% was achieved with a mass transfer coefficient of 1.5 (sec)-1. Parametric tests indicated CO 2 flux and capture rate increased with increasing feed pressure, solvent flow velocity and solvent temperature. PEEK hollow fiber membrane contactor is effective in capturing CO 2 from low CO 2-concentration feeds, showing its high potential for natural gas flue gas CO 2 capture.

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SiO2, TiO2, γ-Al2O3, and HY zeolite supported phosphide catalysts were prepared by the hydrogen temperature-programmed reduction method from phosphate precursors. The physicochemical properties of the catalysts were characterized by means of N2 adsorption−desorption, hydrogen temperature-programmed reduction, X-ray diffraction, X-ray photoelectron spectroscopy, hydrogen temperature-programmed desorption, inductively coupled plasma atomic emission spectroscopy, energy-dispersion X-ray spectroscopy, and thermal gravimetric analysis. The catalyst performance in the hydrodechlorination of chlorobenzene was evaluated in a fixed-bed reactor at atmospheric pressure. It has been found that the support property remarkably affects the formation of nickel phosphides. With the same Ni/P molar ratio (about 0.7) in the precursors, Ni2P is prepared on SiO2 and TiO2; however, Ni and Ni3P form on γ-Al2O3 and Ni and Ni12P5 form on HY. This phenomenon is attributed to some phosphorus reacting with γ-Al2O3 and HY to form AlPO4, and the phosphorus reacting with nickel is scarce. Under identical reaction conditions, the hydrodechlorination performance of the catalysts decrease in the order of SiO2-supported N2P, γ-Al2O3-supported Ni−Ni3P, TiO2-supported N2P, and HY-supported Ni−Ni12P5. The catalyst performance is closely related to the properties of active phases and hydrogen species. Nickel phosphides have better performance than metallic nickel due to the electron deficiency of nickel, and the spilt-over hydrogen species also contribute to the hydrogenolysis of C−Cl bond. The chlorobenzene conversion exceeds 99% over SiO2-supported Ni2P during 130 h at 573 K. The excellent performance is ascribed to the strong poison resistance of Ni2P to chlorine and the abundant hydrogen species. TiO2-supported N2P and HY-supported Ni−Ni12P5 have good initial activities; however, their deactivation is remarkable, especially HY-supported Ni−Ni12P5. Their deactivation is mainly owing to the carbonous deposition.

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