Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy. However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients. Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation. Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome. This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.

[1] The global ionospheric map (GIM) is used to observe variations in the total electron content (TEC) of the global positioning system (GPS) associated with 35 M ! 6.0 earthquakes that occurred in China during the 10-year period of 1 May 1998 to 30 April 2008. The statistical result indicates that the GPS TEC above the epicenter often pronouncedly decreases on day 3-5 before 17 M ! 6.3 earthquakes. The GPS TEC of the GIM and electron density profiles probed by six microsatellites of FORMOSAT3/ COSMIC (F3/C) are further employed to simultaneously observe seismoionospheric anomalies during an M w 7.9 earthquake near Wenchuan, China, on 12 May 2008. It is found that GPS TEC above the forthcoming epicenter anomalously decreases in the afternoon period of day 6-4 and in the late evening period of day 3 before the earthquake, but enhances in the afternoon of day 3 before the earthquake. The spatial distributions of the anomalous and extreme reductions and enhancements indicate that the earthquake preparation area is about 1650 km and 2850 km from the epicenter in the latitudinal and longitudinal directions, respectively. The F3/C results further show that the ionospheric F 2 peak electron density, N m F 2 , and height, h m F 2 , significantly decreases approximately 40% and descends about 50-80 km, respectively, when the GPS TEC anomalously reduces.

[1] An earthquake of magnitude 9.0 occurred near the east coast of Honshu (Tohoku area), Japan, producing overwhelming Earth surface motions and inducing devastating tsunamis, which then traveled into the ionosphere and significantly disturbed the electron density within it (hereafter referred to as seismotraveling ionospheric disturbances (STIDs)). The total electron content (TEC) derived from nationwide GPS receiving networks in Japan and Taiwan is employed to monitor STIDs triggered by seismic and tsunami waves of the Tohoku earthquake. The STIDs first appear as a disk-shaped TEC increase about 7 min after the earthquake occurrence centered at about 200 km east of the epicenter, near the west edge of the Japan Trench. Fast propagating disturbances related to Rayleigh waves quickly travel away from the epicenter along the main island of Japan with a speed of 2.3-3.3 km/s, accompanied by sequences of concentric circular TEC wavefronts and followed by circular ripples (close to a tsunami speed of about 720-800 km/h) that travel away from the STID center. These are the most remarkable STIDs ever observed where signatures of Rayleigh waves, tsunami waves, etc., simultaneously appear in the ionosphere.

We present a simple microfluidics-based technique to fabricate Janus particles using double-emulsion droplets as templates. Since each half of the particles is templated from a different immiscible fluid, this method enables the formation of particles from two materials with vastly different properties. The use of microfluidics affords excellent control over the size, morphology, and monodispersity of the particles.

wileyonlinelibrary.comhydrogels exhibit slow macroscale response with a magnitude of minutes to hours. [10][11][12][13] Meanwhile, they are typically mechanically weak or brittle, [ 14,15 ] resulting in unstable performance after cycles of stimulation. In addition, most of these hydrogels possess isotropic porous structures, showing size changes evenly, making desirable locomotion (e.g., bending, twisting, and folding) diffi cult to achieve. [ 16,17 ] Modulation of pores size and their distributions is essential for manipulating hydrogels properties. Several strategies including gas foaming, [ 18 ] fi ber bonding, [ 19 ] and porogen leaching [ 20 ] were developed to fabricate homo geneous macropore sized hydrogels for rapid responses. However, the orientation responses of such materials were limited, causing diffi culties in anisotropic locomotion. Moreover, mechanical strength of these hydrogels was relatively weak due to the fragile macrosized pore structures. On the other hand, electrophoresis-assisted porogen leaching and hydrogel layering methods [21][22][23][24] have been developed to produce responsive hydrogels with stepwisedistributed pore structures to enable their anisotropic responsive capabilities. However, these hydrogels have some adverse properties including less pore interconnectivity, decelerated mass transport, and being prone to delamination, causing their slow response to stimuli and poor mechanical properties. To date, synthesis of hydrogels with simultaneously rapid thermal response kinetics, robust mechanical strength, and desirable anisotropic locomotion remains an unsolved challenge.In this study, we presented a heterobifunctional crosslinker enabled hydrothermal process, forming hydrogels with gradient porous structure to address these issues. The hydrothermal synthesis is performed in closed systems of relatively high temperatures and pressures, in which only water is used as the reactive medium. At elevated temperatures, hydrothermal process can prompt a variety of chemical reactions such as vinyl polymerizations and intermolecular dehydration. [25][26][27] N -isopropylacrylamide (NIPAM), a well-known thermo-responsive material bearing two highly reactive double bonds, [ 28,29 ] was used as monomer. 4-hydroxybutyl acrylate (4HBA), an acrylic ester possessing a reactive double bond and a less reactive hydroxyl group at either end of the molecule, was innovatively applied Programmable locomotion of responsive hydrogels has gained increasing attention for potential applications in soft robotics, microfl uidic components, actuators, and artifi cial muscle. Modulation of hydrogel pore structures is essential for tailoring their mechanical strength, response speeds, and motion behaviors. Conventional methods forming hydrogels with homogeneous or stepwise-distributed pore structures are limited by the required compromise to simultaneously optimize these aspects. Here, a heterobifunctional crosslinker enabled hydrothermal process is introduced to synthesize responsive hydrogels with well-defi...