Discovery of highly efficient CRBN-recruiting HPK1-PROTAC as a potential chemical tool for investigation of scaffolding roles in TCR signaling.

Hematopoietic progenitor kinase 1 (HPK1, MAP4K1) is a promising target for immune-oncology therapy. It has been recently demonstrated that loss of HPK1 kinase activity can enhance T cell receptor (TCR) signaling. However, many essential functions mediated by the HPK1 scaffolding role are still beyond the reach of any kinase inhibitor. Proteolysis targeting chimera (PROTAC) has emerged as a promising strategy for pathogenic proteins degradation with the characteristics of rapid, reversible, and low-cost versus RNA interference or DNA knock-out technology. Herein we first disclosed the design, synthesis, and evaluation of a series of thalidomide-based PROTAC molecules and identified B1 as a highly efficient HPK1 degrader with DC50 value of 1.8 nM. Further mechanism investigation demonstrated that compound B1 inhibits phosphorylation of the SLP76 protein with IC50 value of 496.1 nM, and confirmed that B1 is a bona fide HPK1-PROTAC degrader. Thus, this study provides a basis for HPK1 degraders development and the candidate could be used as a potential chemical tool for further investigation of the kinase-independent signaling of HPK1 in TCR.

Co-axial electrospun polystyrene/polyurethane fibres for oil collection from water surface.

The pollution arising from oil spills is a matter of great concern due to its damaging impacts on the ecological environment, which has created a tremendous need to find more efficient materials for oil spill cleanup. In this work, we reported a sorbent for oil soak-up from a water surface with a high sorption capacity, good selectivity, and excellent reusability based on the hydrophobic-oleophilic fibrous mats that were fabricated via co-axial electrospinning polystyrene (PS) solution as the shell solution and polyurethane (PU) solution as the core solution. The fine structures of as-prepared fibers were regulated by manipulating the spinning voltages, core solution concentrations, and solvent compositions in shell solutions, which were also characterized by field emission scanning electron microscopy, transmission electron microscopy, nitrogen adsorption method, and synchrotron radiation small-angle X-ray scattering. The effects of inter-fiber voids and intra-fiber porosity on oil sorption capacities were well studied. A comparison of oil sorption capacity for the single fiber with different porous structures was also investigated with the help of scanning transmission X-ray microscopy. The results showed that the sorption capacities of the as-prepared sorbent with regards to motor oil and sunflower seed oil can be 64.40 and 47.48 g g(-1), respectively, approximately 2-3 times that of conventional polypropylene (PP) fibers for these two same oils. Even after five sorption cycles, a comparable oil sorption capacity with PP fibers was still maintained, exhibiting an excellent reusability. We believe that the composite PS-PU fibrous mats have a great potential application in wastewater treatment, oil accident remediation and environmental protection.

An in situ polymerization approach for the synthesis of superhydrophobic and superoleophilic nanofibrous membranes for oil-water separation.

Superhydrophobic and superoleophilic nanofibrous membranes exhibiting robust oil-water separation performance were prepared by a facile combination of electrospun cellulose acetate (CA) nanofibers and a novel in situ polymerized fluorinated polybenzoxazine (F-PBZ) functional layer that incorporated silica nanoparticles (SiO(2) NPs). By employing the F-PBZ/SiO(2) NPs modification, the pristine hydrophilic CA nanofibrous membranes were endowed with a superhydrophobicity with the water contact angle of 161° and a superoleophilicity with the oil contact angle of 3°. Surface morphological studies have indicated that the wettability of resultant membranes could be manipulated by tuning the surface composition as well as the hierarchical structures. The quantitative hierarchical roughness analysis using the N(2) adsorption method has confirmed the major contribution of SiO(2) NPs on enhancing the porous structure, and a detailed correlation between roughness and solid-liquid interface pinning is proposed. Furthermore, the as-prepared membranes exhibited fast and efficient separation for oil-water mixtures and excellent stability over a wide range of pH conditions, which would make them a good candidate in industrial oil-polluted water treatments and oil spill cleanup, and also provided a new insight into the design and development of functional nanofibrous membranes through F-PBZ modification.

Synthesis of superhydrophobic silica nanofibrous membranes with robust thermal stability and flexibility via in situ polymerization.

Superhydrophobic silica nanofibrous membranes exhibiting robust thermal stability and flexibility were prepared by a facile combination of electrospun silica nanofibers and a novel in situ polymerized fluorinated polybenzoxazine (F-PBZ) functional layer that incorporated SiO(2) nanoparticles (SiO(2) NPs). By using F-PBZ/SiO(2) NP modification, the pristine hydrophilic silica nanofibrous membranes were endowed with superhydrophobicity with a water contact angle (WCA) of up to 161°. Surface morphological studies have revealed that the wettability of resultant membranes could be manipulated by tuning the surface composition as well as the hierarchical structures. Quantitative fractal dimension analysis using the N(2) adsorption method has confirmed the correlation between hierarchical roughness and WCA for the modified membranes. Furthermore, the as-prepared membranes exhibited high thermal stability (450 °C), good flexibility (0.0127 gf cm), and comparable tensile strength (2.58 MPa), suggesting their use as promising materials for a variety of potential applications in high-temperature filtration, self-cleaning coatings, catalyst carriers, etc., and also provided new insight into the design and development of functional nanofibrous membranes through F-PBZ modification.

Facile control of intra-fiber porosity and inter-fiber voids in electrospun fibers for selective adsorption.

We report a facile method to control intra-fiber porosity via varying the relative humidity and inter-fiber voids through the blending of two different polymeric fibers via multi-nozzles spinning of electrospun fibers for selective adsorption of oil from water.

Nanoporous polystyrene fibers for oil spill cleanup.

The development of oil sorbents with high sorption capacity, low cost, scalable fabrication, and high selectivity is of great significance for water environmental protection, especially for oil spillage on seawater. In this work, we report nanoporous polystyrene (PS) fibers prepared via a one-step electrospinning process used as oil sorbents for oil spill cleanup. The oleophilic-hydrophobic PS oil sorbent with highly porous structures shows a motor oil sorption capacity of 113.87 g/g, approximately 3-4 times that of natural sorbents and nonwoven polypropylene fibrous mats. Additionally, the sorbents also exhibit a relatively high sorption capacity for edible oils, such as bean oil (111.80 g/g) and sunflower seed oil (96.89 g/g). The oil sorption mechanism of the PS sorbent and the sorption kinetics were investigated. Our nanoporous material has great potential for use in wastewater treatment, oil accident remediation and environmental protection.