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Cantharidin (CTD), an effective ingredient derived from poisonous traditional Chinese medicine Mylabris, shows unique efficacy against hepatocellular carcinoma (HCC), but severe toxicity hinders its clinical application. Liposomes (LPs) are considered to be a platform for the effective delivery of chemotherapeutic agents. Nevertheless, the application of cholesterol, which is usually used to stabilize the structure of LPs, has been compromised due to various drawbacks. Glycyrrhizic acid (GA) has the ability to improve the properties of the phospholipid bilayer in addition to its targeting and hepatoprotective effects. Here, we develop a GA LP loaded with CTD (CTD–GA–LP) utilizing GA as a cholesterol replacement to effectively overcome the obstacles faced by common LPs and to enhance the efficacy of CTD and reduce its toxicity. In the study, CTD–GA–LP was prepared by the ethanol injection method and comprised a homogeneous spherical shape with an evenly distributed particle size, showing a particle size and polydispersity index of 76.12 ± 4.01 nm and 0.18 ± 0.02, respectively. CTD–GA–LP exhibited a better drug loading capacity and stability than CTD–C–LP. An in vitro study showed that CTD–GA–LP can selectively target tumor cells and significantly improve cellular absorption by the GA-receptor-mediated endocytosis pathway to achieve active targeted delivery of drugs. Compared with CTD–C–LP, CTD–GA–LP exhibited notably higher toxicity to the growth of HepG2 cells and low toxicity to L-02 hepatocytes. Using a H22 tumor-bearing mice model, CTD–GA–LP was proved to be able to promote the accumulation of CTD in the tumor tissue and possessed the most pronounced tumor inhibitory rate. Also, CTD–GA–LP reduced the accumulation of CTD in normal organs and prolonged the survival time of tumor-bearing mice. In conclusion, CTD–GA–LP provides an attractive and potential strategy for the treatment of HCC and is very useful for improving the effectiveness and safety of CTD. [ABSTRACT FROM AUTHOR]

The rotational barriers about the N3-(2-pyridyl) bond in 2- iso -propyl-3-(pyridin-2-yl)quinazolin-4-one and the thione analogue were evaluated though VT-NMR measurement of a diastereotopic iso -propyl group followed by a line-shape simulation. In 3-(pyridin-2-yl)quinazoline-4-thione bearing a chiral center as the C2 substituent, the formation of dynamic diastereomers was detected by NMR. The rotational pathway about the N3-(2-pyridyl) bond and the stereochemistries of dynamic diastereomers were revealed through a computational study.

The selective adsorption of target acid gas molecules from binary gas mixtures by porous aromatic frameworks (PAFs) with two identical functional groups per aromatic ring (PAF-R 2 ) was computationally investigated using grand canonical Monte Carlo simulations. PAF-R 2 adsorption was considered for three binary mixtures of small molecular concentrations of acid gas and abundant nitrogen gas (CO 2 /N 2 , SO 2 /N 2 , and H 2 S/N 2 ). The results indicate that additional functional groups enhance acid gas loadings and selectivity, compared with pristine PAF and single-functionalized PAFs. Low pressures yield linearly increasing gas loadings and constant selectivity, while high pressures yield much higher adsorption and selectivity. In particular, SO 2 loading and selectivity under high pressures are heavily influenced by the PAF's maximum adsorption limit, which can be linked back to the functional groups and their configuration. In summary, PAF-(3,5)-(COOH) 2 (nomenclature of PAFs is provided in the Appendix in the Supporting Information) and many other PAF with the same two electron-withdrawing groups are predicted to have great acid gas adsorption and selectivity from gas mixtures, while PAF-(3,5)-(OH) 2 (one of PAFs with two identical electron-donating groups) is predicted to have good adsorption and selectivity, especially under elevated pressures. The results of this work can provide insights into various types of PAFs with great selective adsorption ability and their corresponding conditions. The simulation procedures and results may inspire the exploration and screening of other types of PAFs or porous materials, for acid gas absorption.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is an extracellular enzyme responsible for hydrolyzing cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), the endogenous agonist for the stimulator of interferon genes (STING) pathway. Inhibition of ENPP1 can trigger STING and promote antitumor immunity, offering an attractive therapeutic target for cancer immunotherapy. Despite progress in the discovery of ENPP1 inhibitors, the diversity in chemical structures and the efficacy of the agents are far from desirable, emphasizing the demand for novel inhibitors. Herein, we describe the design, synthesis, and biological evaluation of a series of ENPP1 inhibitors based on the pyrido[2,3- d ]pyrimidin-7-one scaffold. Optimization efforts led to compound 31 with significant potency in both ENPP1 inhibition and STING pathway stimulation in vitro. Notably, 31 demonstrated in vivo efficacy in a syngeneic 4T1 mouse triple negative breast cancer model. These findings provide a promising lead compound with a novel scaffold for further drug development in cancer immunotherapy.

Zeolites, silica-supported amines, and metal-organic frameworks (MOFs) have been demonstrated as promising adsorbents for direct air CO 2 capture (DAC), but the shaping and structuring of these materials into sorbent modules for practical processes have been inadequately investigated compared to the extensive research on powder materials. Furthermore, there have been relatively few studies reporting the DAC performance of sorbent contactors under cold, subambient conditions (temperatures below 20 °C). In this work, we demonstrate the successful fabrication of adsorbent monoliths composed of cellulose acetate (CA) and adsorbent particles such as zeolite 13X and MOF MIL-101(Cr) by a 3D printing technique: solution-based additive manufacturing (SBAM). These monoliths feature interpenetrated macroporous polymeric frameworks in which microcrystals of zeolite 13X or MIL-101(Cr) are evenly distributed, highlighting the versatility of SBAM in fabricating monoliths containing sorbents with different particle sizes and density. Branched poly(ethylenimine) (PEI) is successfully loaded into the CA/MIL-101(Cr) monoliths to impart CO 2 uptakes of 1.05 mmol g monolith -1 at -20 °C and 400 ppm of CO 2 . Kinetic analysis shows that the CO 2 sorption kinetics of PEI-loaded MIL-101(Cr) sorbents are not compromised in the monoliths compared to the powder sorbents. Importantly, these monoliths exhibit promising working capacities (0.95 mmol g monolith -1 ) over 14 temperature swing cycles with a moderate regeneration temperature of 60 °C. Dynamic breakthrough experiments at 25 °C under dry conditions reveal a CO 2 uptake capacity of 0.60 mmol g monolith -1 , which further increases to 1.05 and 1.43 mmol g monolith -1 at -20 °C under dry and humid (70% relative humidity) conditions, respectively. Our work showcases the successful implementation of SBAM in making DAC sorbent monoliths with notable CO 2 capture performance over a wide range of sorption temperatures, suggesting that SBAM can enable the preparation of efficient sorbent contactors in various form factors for other important chemical separations.

Exclusive capture of carbon dioxide (CO 2 ) from hydrocarbons via adsorptive separation is an important technology in the petrochemical industry, especially for acetylene (C 2 H 2 ) production. However, the physicochemical similarities between CO 2 and C 2 H 2 hamper the development of CO 2 -preferential sorbents, and CO 2 is mainly discerned via C recognition with low efficiency. Here, we report that the ultramicroporous material Al(HCOO) 3 , ALF, can exclusively capture CO 2 from hydrocarbon mixtures, including those containing C 2 H 2 and CH 4 . ALF shows a remarkable CO 2 capacity of 86.2 cm 3 g -1 and record-high CO 2 /C 2 H 2 and CO 2 /CH 4 uptake ratios. The inverse CO 2 /C 2 H 2 separation and exclusive CO 2 capture performance from hydrocarbons are validated via adsorption isotherms and dynamic breakthrough experiments. Notably, the hydrogen-confined pore cavities with appropriate dimensional size provide an ideal pore chemistry to specifically match CO 2 via a hydrogen bonding mechanism, with all hydrocarbons rejected. This molecular recognition mechanism is unveiled by in situ Fourier-transform infrared spectroscopy, X-ray diffraction studies, and molecular simulations.

Separating oxygen from air to create oxygen-enriched gas streams is a process that is significant in both industrial and medical fields. However, the prominent technologies for creating oxygen-enriched gas streams are both energy and infrastructure intensive as they use cryogenic temperatures or materials that adsorb N 2 from air. The latter method is less efficient than the methods that adsorb O 2 directly. Herein, we show, via a combination of gas adsorption isotherms, gas breakthrough experiments, neutron and synchrotron X-ray powder diffraction, Raman spectroscopy, and computational studies, that the metal-organic framework, Al(HCOO) 3 (ALF), which is easily prepared at low cost from commodity chemicals, exhibits substantial O 2 adsorption and excellent time-dependent O 2 /N 2 selectivity in a range of 50-125 near dry ice/solvent (≈190 K) temperatures. The effective O 2 adsorption with ALF at ≈190 K and ≈0.21 bar (the partial pressure of O 2 in air) is ≈1.7 mmol/g, and at ice/salt temperatures (≈250 K), it is ≈0.3 mmol/g. Though the kinetics for full adsorption of O 2 near 190 K are slower than at temperatures nearer 250 K, the kinetics for initial O 2 adsorption are fast, suggesting that O 2 separation using ALF with rapid temperature swings at ambient pressures is a potentially viable choice for low-cost air separation applications. We also present synthetic strategies for improving the kinetics of this family of compounds, namely, via Al/Fe solid solutions. To the best of our knowledge, ALF has the highest O 2 /N 2 sorption selectivity among MOF adsorbents without open metal sites as verified by co-adsorption experiments..

A variety of amine-impregnated porous solid sorbents for direct air capture (DAC) of CO 2 have been developed, yet the effect of amine-solid support interactions on the CO 2 adsorption behavior is still poorly understood. When tetraethylenepentamine (TEPA) is impregnated on two different supports, commercial γ-Al 2 O 3 and MIL-101(Cr), they show different trends in CO 2 sorption when the temperature (-20 to 25 °C) and humidity (0-70% RH) of the simulated air stream are varied. In situ IR spectroscopy is used to probe the mechanism of CO 2 sorption on the two supported amine materials, with weak chemisorption (formation of carbamic acid) being the dominant pathway over MIL-101(Cr)-supported TEPA and strong chemisorption (formation of carbamate) occurring over γ-Al 2 O 3 -supported TEPA. Formation of both carbamic acid and carbamate species is enhanced over the supported TEPA materials under humid conditions, with the most significant enhancement observed at -20 °C. However, while equilibrium H 2 O sorption is high at cold temperatures (e.g., -20 °C), the effect of humidity on a practical cyclic DAC process is expected to be minimal due to slow H 2 O uptake kinetics. This work suggests that the CO 2 capture mechanisms of impregnated amines can be controlled by adjusting the degree of amine-solid support interaction and that H 2 O adsorption behavior is strongly affected by the properties of the support materials. Thus, proper selection of solid support materials for amine impregnation will be important for achieving optimized DAC performance under varied deployment conditions, such as cold (e.g., -20 °C) or ambient temperature (e.g., 25 °C) operations.

Accurate, fast, and flexible approaches for contact angle estimation in molecular dynamics simulations are of great importance for characterization of surface wettability, especially for machine learning approaches which would usually require thousands of computational contact angle evaluations for training and prediction purposes. However, evaluation of the contact angle from molecular simulations is typically a human-intensive process, which hinders the required fast throughput. To address this challenge, here a flexible and automated contact angle estimation tool, ContactAngleCalculator, is developed to meet these new requirements. In contrast to the current widely used computational approaches that are laborious and human intensive, this code is based on the concepts of the coarse-graining technique and equivalent contact area and volume of the droplet. Once the parameters are determined for a target liquid, it can automatically estimate the contact angle of different time points of one case or multiple cases by only one click. This tool is targeted for integration with machine learning methods, in which it can substantially streamline and reduce human labor and time in a computational contact angle estimation.

Two-dimensional covalent organic frameworks (2D COFs) have been widely viewed as rigid porous materials with smooth and reversible gas sorption isotherms. In the present study, we report an unusual hysteresis step in the CO 2 adsorption isotherm of a 2D COF, TAPB-OMeTA. In situ powder X-ray diffraction (PXRD) measurements, computational modeling, and Pawley refinement indicate that TAPB-OMeTA experiences slight interlayer shifting during the CO 2 adsorption process, resulting in a new structure that is similar but not identical to the AA stacking structure, namely, a quasi-AA stacking structure. This interlayer shifting is responsible for the step in its CO 2 adsorption isotherm. We attribute the interlayer shifting to the interactions between COF and CO 2 , which weaken the attraction strength between adjacent COF layers. Notably, the repulsion force between the methoxy groups on the backbone of TAPB-OMeTA is essential in facilitating the interlayer shifting process. After further increasing the size of side groups by grafting poly(N-isopropylacrylamide) oligomers to the TAPB-OMeTA backbone via surface-initiated atom transfer radical polymerization (SI-ATRP), we observed a second interlayer shifting and two adsorption steps in the CO 2 adsorption isotherm, suggesting tunability of the interlayer shifting process. Density functional theory (DFT) calculations confirm that the quasi-AA stacking structure is energetically preferred over AA stacking under a CO 2 atmosphere. These findings demonstrate that 2D COFs can be "soft" porous materials when interacting with gases, providing new opportunities for 2D COFs in gas storage and separation.

Phase-gradient metasurfaces (PGMs) constitute an efficient platform for deflection of a beam in a desired direction. According to the generalized Snell's law, the direction of the reflected/refracted wave can be tuned by the spatial phase function provided by the PGMs. However, most studies on PGM focus only on a single diffraction order, that is, the incident wave can be reflected or refracted to a single target direction. Even in the case of multiple beams pointing in different directions, the beams are still in the same order mode, and the energy carried by different beams cannot be controlled. In addition, the energy ratio of multiple beams is generally uncontrollable. Here, we propose a general method to perfectly control diffraction patterns based on a multi-beam PGM. An analytical solution for arbitrarily controlling diffraction beams is derived through which the generation and energy distribution in high-order diffraction beams can be achieved. Three metasurfaces with different diffraction orders and energy ratios are designed and fabricated to demonstrate the proposed method. The efficiencies of diffraction for the desired channels are close to 100%. The simulated and measured far-field patterns are in good agreement with theoretical predictions, validating the proposed method that provides a new way to design multi-beam antennas and that has significance in wireless communication applications.

Covalent organic frameworks (COFs) have found wide applications due to their crystalline structures. However, it is still challenging to quantify crystalline phases in a COF sample. This is because COFs, especially 2D ones, are usually obtained as mixtures of polycrystalline powders. Therefore, the understanding of the aggregated structures of 2D COFs is of significant importance for their efficient utilization. Here we report the study of the aggregated structures of 2D COFs using 13 C solid-state nuclear magnetic resonance ( 13 C SSNMR). We find that 13 C SSNMR can distinguish different aggregated structures in a 2D COF because COF layer stacking creates confined spaces that enable intimate interactions between atoms/groups from adjacent layers. Subsequently, the chemical environments of these atoms/groups are changed compared with those of the nonstacking structures. Such a change in the chemical environment is significant enough to be captured by 13 C SSNMR. After analyzing four 2D COFs, we find it particularly useful for 13 C SSNMR to quantitatively distinguish the AA stacking structure from other aggregated structures. Additionally, 13 C SSNMR data suggest the existence of offset stacking structures in 2D COFs. These offset stacking structures are not long-range-ordered and are eluded from X-ray-based detections, and thus they have not been reported before. In addition to the dried state, the aggregated structures of solvated 2D COFs are also studied by 13 C SSNMR, showing that 2D COFs have different aggregated structures in dried versus solvated states. These results represent the first quantitative study on the aggregated structures of 2D COFs, deepen our understanding of the structures of 2D COFs, and further their applications.

The use of cellulose has considerable promise in a wide range of industrial applications but is hampered by degradation in mechanical properties due to ambient moisture uptake. Existing models of equilibrium moisture content can predict the impact of these effects, but at present, the dynamical, atomic-scale picture of water ingress into cellulose is lacking. The present work reports nonequilibrium molecular simulations of the interface between cellulose and water aimed at capturing the initial stages of two simultaneous dynamical processes, water ingress into cellulose and cellulose dissolution into water. These simulations demonstrate that the process depends on the temperature and chain length in the amorphous region, where high temperatures can induce more mass exchange and short chains can easily detach from amorphous cellulose. A cooperative mechanism that involves both chemical and physical aspects, namely, hydrogen bonding and chain intertwining, respectively, is proposed to interpret the incipient dual ingress/dissolution process. Outcomes of this work will provide a foundation for cellulose functionalization strategies to impede moisture uptake and preserve the mechanical properties of nanocellulose in applications.