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The existing available antipsychotics have failed to manage the cognitive impairment of schizophrenia and induced a number of seriously undesirable effects. Trace amine-associated receptor 1 (TAAR1) has emerged as an ideal target for the design of antischizophrenia drugs, with the ability to mediate multiple psychological functions by sensing endogenous amine-containing metabolites without the side effects of catalepsy. In this work, a series of novel TAAR1 agonists were designed based on the structural analysis of the TAAR1 activation pocket. Among them, 6edisplayed a potent TAAR1-Gs/Gqdual-pathway activation property, being different from that of the clinical drug candidate SEP-363856 with only TAAR1-Gspathway activation. In rodent models, 6esignificantly alleviated MK-801-induced schizophrenia-like cognitive phenotypes without inducing catalepsy. Furthermore, 6e·HClexhibited favorable pharmacokinetic (T1/2= 2.31 h, F= 39%) and safety properties. All these demonstrated that 6e·HClmay be used as a novel drug candidate for schizophrenia treatment.

Biomimetic aggregates have flourished in various fields, particularly in small-molecule catalysis, but their application in polymer synthesis remains understudied. Herein, we propose a strategy for constructing aggregate catalysts based on aggregation-regulating cooperativity to enhance the copolymerization of CO2/propylene oxide (PO). The key design strategy involves constructing polymeric aluminum porphyrin catalysts (PAPCs) with varied stacking modes induced by substituents’ electronic effects, enabling effective modulation of metal synergism. PAPCs with –Cl and –Br substitution exhibit H-aggregates of porphyrin units, leading to a strong metal synergy effect and stability at high temperatures. The H-aggregate catalysts show high activity (TOF > 10,000 h–1) and high selectivity (>98%). Meanwhile, the activity was maintained at a very low catalyst loading ([Al]/PO = 1/100,000), with the number-average molecular weight of the resulting copolymer over 480 kg/mol. Contrarily, −CH3- and −CH2CH3-substituted PAPCs display J-aggregates with a weak metal synergy effect (unstable at a high temperature). The J-aggregate catalysts show low activity (TOF < 2500 h–1) and polymer selectivity (<90%). The present strategy of designing aggregate catalysts provides a new perspective to regulate metal cooperativity, suitable not only for CO2/epoxide or anhydride/epoxide copolymerization but also for lactone ring-opening polymerizations.

In vitro 3D models are advanced biological tools that have been established to overcome the shortcomings of oversimplified 2D cultures and mouse models. Various in vitro 3D immuno-oncology models have been developed to mimic and recapitulate the cancer–immunity cycle, evaluate immunotherapy regimens, and explore options for optimizing current immunotherapies, including for individual patient tumours. Here, we review recent developments in this field. We focus, first, on the limitations of existing immunotherapies for solid tumours, secondly, on how in vitro 3D immuno-oncology models are established using various technologies — including scaffolds, organoids, microfluidics and 3D bioprinting — and thirdly, on the applications of these 3D models for comprehending the cancer–immunity cycle as well as for assessing and improving immunotherapies for solid tumours.

Ship speed extraction (SSE) in busy water based on an automatic identification system (AIS) has received widespread attention due to its high efficiency. However, this method is usually degraded by data delay and loss. In this article, we propose a novel SSE method based on machine vision and unmanned aerial vehicle (UAV) video to measure ship speed and repair AIS data in busy water. Our framework integrates YOLO v4 into simple online and real-time tracking with a deep association metric (Deep SORT) to detect and track ship targets. Specifically, we design a tracking buffer to promote the insensitivity of the tracker under uncertain environmental changes and filter the tracker for measuring speed. Furthermore, a motion vector computation term is proposed based on sparse optical flow and a box diagram. After using camera calibration to convert the motion vector to displacement in the real world, the SSE results are obtained. Exhaustive experiments are conducted on various scenarios, i.e., illumination and ship distribution, from our ship’s remote dataset. The results verify that the proposed framework performs excellently, with an average speed measurement accuracy above 95% in complex waters, and the AIS data repair effect is remarkable. Moreover, it is also proven that machine vision technology can assist AIS information in supervising complex waters and ensuring navigation safety, which paves the way for extracting ship traffic flow information.

Filling the cyan gap is the key element in achieving full-spectrum illumination using violet chip to excite red, green and blue phosphors. However, designing cyan phosphors suitable for violet light excitation with excellent performance remains challenging. Herein, a novel cyan phosphor Ba9Lu2-x-nSi6O24:xCe (n-BLS:Ce) with multiple crystal sites of Ba2+and Lu3+for Ce3+ions was designed and prepared via crystal-site engineering. The Ce3+ions at Ba2+sites emit ultraviolet light at 385 nm under 325 nm ultraviolet light excitation, and the Ce3+ions at Lu3+sites emit cyan light at 485 nm under 395 nm violet light excitation. The favorable occupation of Ce3+ions at Lu3+sites could be realized by introducing Lu vacancies. Significantly, the cyan light emission intensity of Ba9Lu1.4Si6O24:0.3Ce (n0.3-BLS:Ce) with Lu vacancies is effectively improved by 47 % compared to Ba9Lu1.7Si6O24:0.3Ce (n0-BLS:Ce) without Lu vacancies. And the emission intensity at 150 °C retains 96 % of that at room temperature. The color rendering index increases from 87.9 to 94.5 after supplementing Ba9Lu2-x-nSi6O24:xCe cyan phosphor in w-LEDs devices combining commercial red, green, and blue phosphors with a violet chip, indicating its potential practical application in full-spectrum lighting. This work also provides new ideas for the design and development of new and efficient high-quality light-emitting materials.

A series of (CexGd1–x)3Ga2Al3O12(x= 0–0.8%) (Ce/GGAG) crystals were grown by the optical floating zone (OFZ) method. Ce/GGAG single crystals with good crystallinity were successfully obtained by introducing oxygen atmosphere (100%) and auxiliary pressure (0.3 MPa) to suppress Ga2O3volatilization in a container-free environment. The photoluminescence (PL) and scintillation properties of those Ce/GGAG crystals with different Ce3+doping concentrations were investigated. In the 0.2–0.8 at. % Ce concentration range, the integral PL intensities were found to vary according to the approximate Gaussian distribution with Ce concentration, and the 0.6 at. % Ce/GGAG crystal has the highest integral PL intensity. Gd3+emission was observed under X-ray excitation, which was rarely reported before. The maximum light yield reaches to 38,848 pho/MeV in the 0.6 at. % Ce/GGAG crystal. More importantly, fast decay and high ratio of the fast component (71 ns 66%) were successfully obtained in Ce/GGAG crystals with a Ga/Al = 2/3 ratio, which might be attributed to the suppression of composition deviation by introducing O2(100%) atmosphere during crystal growth. It indicates that the optical floating zone method is effective in the composition engineering study of Ce/GGAG crystals to optimize the scintillation performance.

Mixed crystal strategy is an effective approach of improving the luminescence properties of optical materials and has been adopted widely in many systems. In this paper, the La-mixed Gd2Si2O7:Ce polycrystalline samples were successfully synthesized by a sol-gel method. The crystal structure and luminescence properties were confirmed and discussed by XRD, UV-Vis luminescence spectra, and XEL, respectively. The vacuum ultraviolet excitation spectra and thermoluminescence glow curves were also systematically investigated and discussed at varied temperature. A combination of the first-principles calculations and optical characterization experiments was employed to study the electronic band structure of host material, revealing that the band gap is narrowed and the 5d1level of Ce3+shifts to higher energy as the La content increases. The luminescence thermo-stability and activation energy were also measured and calculated. It indicates that thermo-stability is strongly dependent on the La concentration. An effective approach is developed to tune the electronic band structure, luminescence properties and thermostability of (Gd1–xLax)2Si2O7:Ce scintillator by adjusting La/Gd ratio.

Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult, greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.

We melted, annealed, and recrystallized ultrathin films of oriented polyethylene (PE) molecules prepared by melt-drawing. A large number of randomly oriented asymmetric leaf-shaped crystalline structures consisting of preferentially oriented lamellae were formed simultaneously, as observed by optical and atomic force microscopies. The structural arrangement within these leaf-shaped crystalline structures was identified by grazing incidence X-ray diffraction. These structures consisted of two distinct sections, both differing strongly from circular spherulites obtained by crystalizing an isotropic melt. Besides, regions containing groups of stacks of slightly inclined but well-aligned flat-on lamellae and regions of less orderly arranged edge-on lamellae were found. When increasing the annealing temperature and/or annealing time, a change in morphology from the leaf-shaped crystalline structures to spherulites with two symmetric “eyes” was observed. Intriguingly, the annealing times required for such a change in crystalline morphology were about four orders of magnitude longer than the longest bulk relaxation time (reptation time). Because the appearance of spherulites indicates that films became equilibrated and reached a state of an isotropic melt before recrystallization, we may conclude that oriented PE chains in ultrathin films possessed a long-term memory of the preparation-induced chain stretching. Considering that the morphology and relaxation kinetics of PE films depended appreciably on the substrate properties and film thickness, we conclude that the formation of asymmetric leaf-shaped crystalline structures was also affected by the interaction of PE chains with the substrate and spatial confinement. The present results may shed new light on slow relaxation and reorganization processes encountered when long-chain polymers became oriented during sample processing.

Anti‐Tumor Drug Screening In article 2200863by Huayu Yang, Yuan Pang, and co‐workers, a polydimethylsiloxane (PDMS)‐based oxygen‐permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets of the microwell device provide high flux oxygen and function like in vivo neighboring hepatic sinusoids in terms of oxygen supply. The generated spheroids can be used as a favorable model mimicking early‐stage avascular HCCs for high‐throughput drug screening.

For high‐throughput anti‐cancer drug screening, microwell arrays may serve as an effective tool to generate uniform and scalable tumor spheroids. However, microwell arrays are commonly anchored in non‐oxygen‐permeable culture plates, leading to limited oxygen supply for avascular spheroids. Herein, a polydimethylsiloxane (PDMS)‐based oxygen‐permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets at the bottom of the microwell device provide a high flux of oxygen like in vivo neighboring hepatic sinusoids. Owing to the better oxygen supply, the generated HepG2 spheroids are larger in size and exhibit higher viability and proliferation with less cell apoptosis and necrosis. These spheroids also exhibit lower levels of anaerobic cellular respiration and express higher levels of liver‐related functions. In anti‐cancer drug testing, spheroids cultured in PDMS plates show a significantly stronger resistance against doxorubicin because of the stronger stem‐cell and multidrug resistance phenotype. Moreover, higher expression of vascular endothelial growth factor‐A produces a stronger angiogenesis capability of the spheroids. Overall, compared to the spheroids cultured in conventional non‐oxygen‐permeable plates, these spheroids can be used as a more favorable model for early‐stage HCCs and be applied in high‐throughput anti‐cancer drug screening. A polydimethylsiloxane (PDMS)‐based oxygen‐permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets of the microwell device provide high flux oxygen and function like in vivo neighboring hepatic sinusoids in terms of oxygen supply. The generated spheroids can be used as a favorable model mimicking early‐stage avascular HCCs for high‐throughput drug screening.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent an indispensable part of anti-HIV-1 therapy. To discover novel HIV-1 NNRTIs with increased drug resistance profiles and improved pharmacokinetic (PK) properties, a series of novel diarylpyrimidine derivatives were generated via the cocrystal structure-based drug design strategy. Among them, 36aexhibited outstanding antiviral activity against HIV-1 IIIB and a panel of mutant strains (L100I, K103N, Y181C, Y188L, E138K, F227L + V106A, and RES056), with EC50ranging from 2.22 to 53.3 nM. Besides, 36awas identified with higher binding affinity (KD= 2.50 μM) and inhibitory activity (IC50= 0.03 μM) to HIV-1 RT. Molecular docking and molecular dynamics simulation were performed to rationalize the design and the improved drug resistance of these novel inhibitors. Additionally, 36a·HClexhibited favorable PK (T1/2= 5.12 h, F= 12.1%) and safety properties (LD50> 2000 mg/kg). All these suggested that 36a·HClmay serve as a novel drug candidate anti-HIV-1 therapy.