Integration of N- and P- elements in sodium alginate aerogels for efficient flame retardant and thermal insulating properties.

In the field of building energy conservation, the development of biodegradable biomass aerogels with excellent mechanical performance, flame retardancy and thermal insulation properties is of particular importance. Here, a directional freeze-drying method was used for fabricating composite sodium alginate (SA) aerogels containing functionalized ammonium polyphosphate (APP) flame retardant. In particular, APP was coated with melamine (MEL) and phytic acid (PA) by a supramolecular assembly process. Through optimizing the flame retardant addition, the SA-20 AMP sample exhibited excellent flame retardant and thermal insulation properties, with the limiting oxygen index of 38.2 % and the UL-94 rating of V-0. Such aerogels with anisotropic morphology demonstrated a low thermal conductivity of 0.0288 (W/m·K) in the radial direction (perpendicular to the lamellar structure). In addition, as-obtained aerogels displayed remarkable water stability and mechanical properties, indicating significant potential for practical applications.

Cellulose-based bi-layer hydrogel evaporator with a low evaporation enthalpy for efficient solar desalination.

Interfacial evaporation through hydrogel-based evaporators is emerging as a sustainable and cost-effective strategy for drinkable water production. Herein, a specially designed bi-layer hydrogel evaporator was fabricated and used for efficient solar water desalination. With cotton linter as cellulose precursor, it was dispersed in a highly concentrated ZnCl2 (65 %) solution, and cross-linked by epichlorohydrin to prepare cellulose composite hydrogel. After removing inorganic salts by salt-leaching, polyaniline (PANi) with broadband and wide-range light absorption was then integrated into the top surface of hydrogel through in situ polymerization to construct a bi-layer evaporator. As a solar evaporator, the water could be evaporated with a low-energy demand, and the heat from the sunlight could be confined at the interface to achieve efficient water evaporation. Therefore, the hydrogel evaporator demonstrates an optimal water evaporation rate of 3.02 kg m-2 h-1 and photothermal conversion efficiency of 89.09 % under 1 sun (1 kW m-2) irradiation. This work provides new possibilities for efficient solar water purification systems with assured water quality.

Copper sulfide integrated functional cellulose hydrogel for efficient solar water purification.

Hydrogels are emerging materials for solar steam generation to alleviate water scarcity. Herein, a semiconductor of copper sulfide (CuS) was integrated into cellulose hydrogel to fabricate a solar steam evaporator. Sustainable and low-cost cotton linter (cellulose) was regenerated by NaOH/urea solvent. Epichlorohydrin was added as a cross-linking agent to enhance the mechanical robustness of the composite hydrogel, and CuS crystals were tightly attached to cellulose fibers and uniformly distributed in the hydrogel matrix. Under simulated solar light, a heating zone was established at the top surface of the composite hydrogel, and CuS can efficiently absorb and convert light into heat. The hydrophilic cellulose network affords an adequate water supply and a low water vaporization enthalpy. By tuning the CuS loadings, the optimized evaporation rate and solar-to-vapor efficiency could reach 2.2 kg/m2/h and 87 %, respectively, under 1 sun irradiation. The evaporation rate remained above 2.1 kg/m2/h after 48 h of irradiation. Moreover, the hydrogels (with a CuS loading of 30 wt%) showed a efficiently photocatalytic degradation of 95 % for methylene blue and 92 % for Rhodamine B. Such functional hydrogel evaporator holds great potential for practical water treatment and solar-driven applications.

Facile fabrication of strong and conductive cellulose hydrogels with wide temperature tolerance for flexible sensors.

Cellulose-based ionic conductive hydrogels (ICHs) have found extensive applications in flexible electronics and multifunctional sensors. However, simultaneous realization of sufficient conductivity, superior mechanical property and extreme environment tolerance for ICHs remains to be a huge challenge. In this work, a facile one-pot approach was developed to fabricate ICHs by directly dissolving cotton linter cellulose and polyvinyl alcohol (PVA) in a concentrated ZnCl2 solution. By regulating the content of PVA in ICHs, the optimal hydrogel (Gel-5) exhibits a tensile strength of 0.30 MPa, a compressive strength of 2.05 MPa and a conductivity of 8.16 S m-1. Moreover, the resulting dual-network ICHs present high transparency, good thermal reversibility and desirable ionic conductivity. Due to the high concentration of inorganic salts in the porous dual-network structure, the ICH presents good anti-drying and anti-freezing (as low as -90 °C) properties. Such hydrogel can be assembled into multi-functional sensors for human motion and temperature monitoring, and they demonstrate durable sensitivity, cycling stability in a wide operating temperature. This work will shed light on the design of cellulose-based hydrogels with good ionic conductivity and mechanical performance under extreme conditions.

Highly conductive and anti-freezing cellulose hydrogel for flexible sensors.

Ionic conducting hydrogels (ICHs) are emerging materials for multi-functional sensors in the fields of healthcare monitoring and flexible electronics. However, there is a long-standing dilemma between ionic conductivity and mechanical properties of the ICHs. In this work, ionic conductive, flexible, transparent, and anti-freezing hydrogels are fabricated by dissolving cotton linter pulp in ZnCl2/CaCl2 solution and cross-linking with epichlorohydrin (ECH). The presence of inorganic salt imparts the hydrogel with high ionic conductivity and low-temperature tolerance. While the introduction of ECH as the second network gives the hydrogel with desirable mechanical performance. By tailoring the ECH addition, the tensile strength, compressive strength, elongation at break, and conductivity of the hydrogel could reach 0.82 MPa, 2.80 MPa, 260 %, and 5.48 S m-1, respectively. The prepared ICHs are fabricated into sensors for detecting full-range human body motions, and they demonstrate fast response and durable sensitivity to both tensile strain and compressive deformation. Moreover, flexible sensors can work at subzero temperatures. This work provides a new idea for the preparation of cellulose-based hydrogels with good ionic conductivity and mechanical properties under extreme conditions.

A Transmission Efficiency Evaluation Method of Adaptive Coding Modulation for Ka-Band Data-Transmission of LEO EO Satellites.

Nowadays low Earth orbit (LEO) Earth observation (EO) satellites commonly use constant coding modulation (CCM) or variable coding modulation (VCM) schemes for data transmission to ground stations (G/S). Compared with CCM and VCM, the adaptive coding modulation (ACM) could further improve the data throughput of the link by making full use of link resource and the time-varying characteristics of atmospheric attenuation. In order to comprehensively study the data transmission performance, one new index which could be utilized as a quantitative index for the satellite-to-ground data transmission scheme selection, the transmission efficiency factor (TEF) of LEO satellites is proposed and defined as "the product of the link availability and the average useful data rate". Then, the transmission efficiency of CCM, VCM and ACM at typical G/S with different weather characteristics at Ka-band is compared and analyzed. The results show that ACM is more suitable for the G/S with moderate and abundant rainfall. Compared with the CCM of MCS 28, for Beijing G/S and Sanya G/S, ACM not only improves the transmission efficiency with the TEF increased by 3.62% and 24.51%, respectively, but also improves the link availability with the outage period reduced by 82.47% and 75.18%, respectively.

Hierarchical Network Enabled Flexible Textile Pressure Sensor with Ultrabroad Response Range and High-Temperature Resistance.

Thin, lightweight, and flexible textile pressure sensors with the ability to detect the full range of faint pressure (<100 Pa), low pressure (≈KPa) and high pressure (≈MPa) are in significant demand to meet the requirements for applications in daily activities and more meaningfully in some harsh environments, such as high temperature and high pressure. However, it is still a significant challenge to fulfill these requirements simultaneously in a single pressure sensor. Herein, a high-performance pressure sensor enabled by polyimide fiber fabric with functionalized carbon-nanotube (PI/FCNT) is obtained via a facile electrophoretic deposition (EPD) approach. High-density FCNT is evenly wrapped and chemically bonded to the fiber surface during the EPD process, forming a conductive hierarchical fiber/FCNT matrix. Benefiting from the large compressible region of PI fiber fabric, abundant yet firm contacting points and high elastic modulus of both PI and CNT, the proposed pressure sensor can be customized and modulated to achieve both an ultra-broad sensing range, long-term stability and high-temperature resistance. Thanks to these merits, the proposed pressure sensor could monitor the human physiological information, detect tiny and extremely high pressure, can be integrated into an intelligent mechanical hand to detect the contact force under high-temperature.

Deep eutectic solvent with bifunctional Brønsted-Lewis acids for highly efficient lignocellulose fractionation.

Green and low cost deep eutectic solvents (DESs) are promising to replace the solid acids and ionic liquids in biomass fractionation process. To enhance the lignocellulose pretreatment efficiency, an acidic DES that composed of Brønsted acid (ZnCl2) as hydrogen bond acceptor and Lewis acid (lactic acid) as hydrogen bond donator was designed. This bifunctional DES was used for the extraction of lignin from poplar sawdust. Under the optimal pretreatment condition, the ZnCl2-lactic acid DES could recover 95.2 wt% of lignin with a purity of 92.1%. The recovered lignin demonstrated a low polydispersity of 1.67 and small amount of ß-aryl-ethers. Moreover, the acidic DES had a good recyclability and reusability. Such performance was attributed to the presence of bifunctional acid sites, which help selectively cleave lignin-carbohydrate complex linkages. The acidity and polarity of Brønsted acid can be modulated by the Lewis acid, thus synergistically promote the lignin extraction and production.

Structure reorganization of cellulose hydrogel by green solvent exchange for potential plastic replacement.

Petroleum-based plastics have raised great environmental concerns from the beginning of their production to the end-of-life cycle. It is urgently needed to develop sustainable and green materials with certain plastic properties. Herein, biobased cellulose films are fabricated from low quality cotton cellulose by manipulating its hydrogen bonding network with green solvents. The cellulose is dispersed in inorganic salts (ZnCl2/CaCl2) to form ionic hydrogels, and then transformed into tough and flexible films through ethanol exchange and air drying. Without extra hot-pressing treatment, the aggregate structure of cellulose is re-organized with the disruption and re-construction of hydrogen bonds. Benefiting from the densely packed structure and highly in-plane orientation, the cellulose film presents outstanding optical, thermal and mechanical properties. Such cellulose materials hold a potential for plastic replacement in the field of biodegradable packing.

In situ growth of amino-functionalized ZIF-8 on bacterial cellulose foams for enhanced CO2 adsorption.

Zeolitic imidazolate frameworks (ZIFs) hold great potential for carbon capture, while a major challenge for the practical application of ZIFs is the development of convenient three-dimensional bulk materials. Here, sustainable and biodegradable bacterial cellulose (BC) was used as the substrate for ZIF growth. Amino-functionalized ZIF-8 (ZIF-8-NH2) was prepared within BC substrate via an in situ growth approach. ZIF crystals were wrapped uniformly over cellulose fibers and the chelating effect between metal (zinc) ions and hydroxyl groups makes the composites have high interface affinity and compatibility. The resulting foams presented a high CO2 adsorption capacity of 1.63 mmol/g (25 °C, 1 bar). Moreover, ZIF-8-NH2@BC foams are facile to be regenerated by heating at 80 °C. This work provides a new avenue to construct ZIF/cellulose composites for gas treatment applications.

Highly Sensitive and Wide Linear-Response Pressure Sensors Featuring Zero Standby Power Consumption under Bending Conditions.

The ability of a flexible pressure sensor to possess zero power consumption in standby mode, high sensitivity, and wide linear-response range is critical in real flexible matrix-based scenes. However, when the conventional flexible pressure sensors are attached on a curved surface, a pseudosignal response is generated because of the normal stress, resulting in a short linear-response range. Here, a flexible piezoresistive pressure sensor with high performance, zero standby power consumption is demonstrated. The flexible pressure sensor is fabricated from polydimethylsiloxane (PDMS)/carbon black (CB), patterned polyimide (PI) spacer layer, and laser-induced graphene (LIG) interdigital electrodes. Benefiting from the hierarchical structure and sufficient roughness of PDMS/CB and LIG interdigital electrodes, the proposed pressure sensors (PDMS/CB/PI/LIG) exhibit high sensitivity (43 kPa-1), large linear-response range (0.4-13.6 kPa), fast response (<40 ms), and long-term cycle stability (>1800 cycles). The resulting pressure sensor also features zero standby power consumption merit under certain bending conditions (bending angle: 0-5o). Furthermore, the effect of the hole diameter of the PI spacer layer on the performance of the pressure sensors is experimentally and theoretically investigated. As a proof of concept, a bioinspired artificial haptic neuron system has been successfully equipped to modulate the number of lit LED lights. The proposed high-performance pressure sensor has promising potential to be used in flexible and wearable electronics, especially for the applications in actual flexible matrix-based scenes.

Highly transparent graphene oxide/cellulose composite film bearing ultraviolet shielding property.

This work investigates the ultraviolet (UV) shielding property of composite films synthesized with graphene oxide (GO) nanosheets and regenerated cellulose. Regenerated cellulose was prepared from ZnCl2/CaCl2/GO solution. The GO sheets presented a homogenous dispersion in the film matrix. The incorporation of GO endows the cellulose films with improved UV shielding capacity. When GO loading reaches 2%, the UVA and UVB blocking percentages are 66.7% and 54.2%, respectively. Moreover, the composite films had excellent visible light transmittance. The resulting films possess promising applications as protective and packing materials.

Structure-Based Design and Identification of FT-2102 (Olutasidenib), a Potent Mutant-Selective IDH1 Inhibitor.

Inhibition of mutant IDH1 is being evaluated clinically as a treatment option for oncology. Here we describe the structure-based design and optimization of quinoline lead compounds to identify FT-2102, a potent, orally bioavailable, brain penetrant, and selective mIDH1 inhibitor. FT-2102 has excellent ADME/PK properties and reduces 2-hydroxyglutarate levels in an mIDH1 xenograft tumor model. This compound has been selected as a candidate for clinical development in hematologic malignancies, solid tumors, and gliomas with mIDH1.

Metal nanoparticle-embedded bacterial cellulose aerogels via swelling-induced adsorption for nitrophenol reduction.

Bacterial cellulose aerogels were chosen as the substrate for supporting and dispersing metal nanoparticles (Cu and Ni). During the catalyst preparation, we found that the swelling-induced adsorption process could control the metal size and dispersion simultaneously. Cu and Ni nanoparticles were confined into the bacterial cellulose network and SEM results demonstrated that Cu particles had a smaller size compared to Ni particles. The metal-loaded catalysts exhibited good catalytic performance in the 4-nitrophenol reduction reaction. The optimal sample (BC-Cu-0.5) prepared with 0.5 wt% CuSO4 solution could complete the reduction process within 8 min. Besides, the BC-Cu-0.5 catalyst showed excellent stability and reusability. This study sheds light on the deposition of metal particles and provides a wider application for bacterial cellulose.

Discovery of novel biaryl sulfonamide based Mcl-1 inhibitors.

Mcl-1 is an anti-apoptotic protein overexpressed in hematological malignancies and several human solid tumors. Small molecule inhibition of Mcl-1 would offer an effective therapy to Mcl-1 mediated resistance. Subsequently, it has been the target of extensive research in the pharmaceutical industry. The discovery of a novel class of Mcl-1 small molecule inhibitors is described beginning with a simple biaryl sulfonamide hit derived from a high through put screen. A medicinal chemistry effort aided by SBDD generated compounds capable of disrupting the Mcl-1/Bid protein-protein interaction in vitro. The crystal structure of the Mcl-1 bound ligand represents a unique binding mode to the BH3 binding pocket where binding affinity is achieved, in part, through a sulfonamide oxygen/Arg263 interaction. The work highlights the some of the key challenges in designing effective protein-protein inhibitors for the Bcl-2 class of proteins.

Discovery and Optimization of Quinolinone Derivatives as Potent, Selective, and Orally Bioavailable Mutant Isocitrate Dehydrogenase 1 (mIDH1) Inhibitors.

Mutations at the arginine residue (R132) in isocitrate dehydrogenase 1 (IDH1) are frequently identified in various human cancers. Inhibition of mutant IDH1 (mIDH1) with small molecules has been clinically validated as a promising therapeutic treatment for acute myeloid leukemia and multiple solid tumors. Herein, we report the discovery and optimization of a series of quinolinones to provide potent and orally bioavailable mIDH1 inhibitors with selectivity over wild-type IDH1. The X-ray structure of an early lead 24 in complex with mIDH1-R132H shows that the inhibitor unexpectedly binds to an allosteric site. Efforts to improve the in vitro and in vivo absorption, distribution, metabolism, and excretion (ADME) properties of 24 yielded a preclinical candidate 63. The detailed preclinical ADME and pharmacology studies of 63 support further development of quinolinone-based mIDH1 inhibitors as therapeutic agents in human trials.

Inorganic Salts Induce Thermally Reversible and Anti-Freezing Cellulose Hydrogels.

Inspired by the anti-freezing mechanisms found in nature, ionic compounds (ZnCl2 /CaCl2 ) are integrated into cellulose hydrogel networks to enhance the freezing resistance. In this work, cotton cellulose is dissolved by a specially designed ZnCl2 /CaCl2 system, which endows the cellulose hydrogels specific properties such as excellent freeze-tolerance, good ion conductivity, and superior thermal reversibility. Interestingly, the rate of cellulose coagulation could be promoted by the addition of extra water or glycerol. This new type of cellulose-based hydrogel may be suitable for the construction of flexible devices used at temperature as low as -70 °C.

Discovery and optimization of novel piperazines as potent inhibitors of fatty acid synthase (FASN).

The discovery, structure-activity relationships, and optimization of a novel class of fatty acid synthase (FASN) inhibitors is reported. High throughput screening identified a series of substituted piperazines with structural features that enable interactions with many of the potency-driving regions of the FASN KR domain binding site. Derived from this series was FT113, a compound with potent biochemical and cellular activity, which translated into excellent activity in in vivo models.

Identification of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with no evidence of CYP3A4 time-dependent inhibition and improved aqueous solubility.

Herein we report the optimization efforts to ameliorate the potent CYP3A4 time-dependent inhibition (TDI) and low aqueous solubility exhibited by a previously identified lead compound from our NAMPT inhibitor program (1, GNE-617). Metabolite identification studies pinpointed the imidazopyridine moiety present in 1 as the likely source of the TDI signal, and replacement with other bicyclic systems was found to reduce or eliminate the TDI finding. A strategy of reducing the number of aromatic rings and/or lowering cLogD7.4 was then employed to significantly improve aqueous solubility. These efforts culminated in the discovery of 42, a compound with no evidence of TDI, improved aqueous solubility, and robust efficacy in tumor xenograft studies.

Discovery of potent and efficacious cyanoguanidine-containing nicotinamide phosphoribosyltransferase (Nampt) inhibitors.

A co-crystal structure of amide-containing compound (4) in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein and molecular modeling were utilized to design and discover a potent novel cyanoguanidine-containing inhibitor bearing a sulfone moiety (5, Nampt Biochemical IC50=2.5nM, A2780 cell proliferation IC50=9.7nM). Further SAR exploration identified several additional cyanoguanidine-containing compounds with high potency and good microsomal stability. Among these, compound 15 was selected for in vivo profiling and demonstrated good oral exposure in mice. It also exhibited excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model. The co-crystal structure of this compound in complex with the NAMPT protein was also determined.