Design, synthesis, and antitumor activity evaluation of 1,2,3-triazole derivatives as potent PD-1/PD-L1 inhibitors.

A series of 1,2,3-triazole derivatives targeting the PD-1/PD-L1 pathway were designed, synthesized, and evaluated both in vitro and in vivo. Among them, compound III-4 demonstrated exceptional inhibitory activity against the interaction of PD-1/PD-L1 and showed great binding affinity with hPD-L1, with an IC50 value of 2.9 nM and a KD value of 3.33 nM. In the co-culture of Hep3B/OS-8/hPD-L1 cells and CD3+ T cells assay, III-4 relieved the inhibition of PD-L1 on PD-1 and promoted the expression of IFN-γ, which shared a comparable effect to that of the PD-1 monoclonal antibody Pembrolizumab (5 µg/mL). Moreover, compound III-5, an ester prodrug derived from III-4, demonstrated significant antitumor effects in the hPD-L1-MC38 C57BL/6 mouse model (TGI: 49.6 %) by oral administration. These findings suggest that compound III-5 holds promise as an inhibitor of the PD-1/PD-L1 interaction for cancer immunotherapy.

Mechanism of balloon burst during transcatheter aortic valve replacement pre-dilatation: Image observation and validation by finite element analysis.

BACKGROUND: Balloon burst during transcatheter aortic valve replacement (TAVR) is serious complication. This study pioneers a novel approach by combining image observation and computer simulation validation to unravel the mechanism of balloon burst in a patient with bicuspid aortic valve (BAV) stenosis. METHOD: A new computational model for balloon pre-dilatation was developed by incorporating the element failure criteria according to the Law of Laplace. The effects of calcification and aortic tissue material parameters, friction coefficients, balloon types and aortic anatomy classification were performed to validate and compare the expansion behavior and rupture mode of actual balloon. RESULTS: Balloon burst was dissected into three distinct stages based on observable morphological changes. The mechanism leading to the complete transverse burst of the non-compliant balloon initiated at the folding edges, where contacted with heavily calcified masses at the right coronary sinus, resulting in high maximum principal stress. Local sharp spiked calcifications facilitated rapid crack propagation. The elastic moduli of calcification significantly influenced balloon expansion behavior and crack morphology. The simulation case of the calcific elastic modulus was set at 12.6 MPa could closely mirror clinical appearance of expansion behavior and crack pattern. Furthermore, the case of semi-compliant balloons introduced an alternative rupture mechanism as pinhole rupture, driven by local sharp spiked calcifications. CONCLUSIONS: The computational model of virtual balloons could effectively simulate balloon dilation behavior and burst mode during TAVR pre-dilation. Further research with a larger cohort is needed to investigate the balloon morphology during pre-dilation by using this method to guide prosthesis sizing for potential favorable outcomes.

Application of time-domain gating technique in water content measurement of gas-liquid two-phase flow.

This paper introduces an application of the time-domain gating technique in water content measurement of gas-liquid two-phase flow. According to the principle that water and gas have different absorption effects on microwaves, a sensor with transmitting and receiving antennas is designed. Combined with the back propagation neural network, the water content of two-phase fluids can be obtained from the complex transmission coefficient (S21) of antennas. In order to reduce the influence of the sensor structure on antenna measurement, the time-domain gating technique can be used to filter out the interference components in S21 so that the water content can be more easily predicted. Built on the above, an automatic test system is established. In the range of 0%-78%, the absolute test error of the water content is lower than 3%.

Anomalous interaction of Airy beams in the fractional nonlinear Schrödinger equation.

We investigate the mutual interaction of two spatially-separated Airy beams in the nonlinear Schrödinger equation with the fractional Laplacian. Depending on the beam separation (d), relative phase and Lévy index (α), we observed an anomalous attraction or repulsion between the Airy beams. Anomalous attraction leads to a single breather soliton with a period that grows exponentially as α increases. In this region of the parameter space, we identify a crossover between two asymmetric regimes: as the Lévy index exceeds a critical value α c, the period of breather soliton for d>0 is orders of magnitude larger than for d<0, while the opposite occurs as α<α c. Our results reveal a novel scenario for Airy beams interaction in the framework of fractional nonlinear Schrödinger equation and provide an alternative mechanism to control breather soliton generation.

XYZLMS interim connection space for spectral image compression and reproduction.

To improve the spectral image representation and reproduction accuracy, an interim connection space (ICS) was proposed. Three offset functions were defined to make up the wave regions uncovered by the CIEXYZ color matching functions. The XYZLMS ICS was determined based on the CIEXYZ and defined offset functions. The spectral and colorimetric representation accuracy of the proposed ICS was compared to LabPQR and LabRGB with various spectral datasets as testing samples. The results indicated that the proposed ICS outperformed the other two ICS as a whole.