Molecular activatable probes with near‐infrared (NIR) fluorescence play a critical role in in vivo imaging of biomarkers for drug screening and disease diagnosis. With structural diversity and high fluorescence quantum yields, hemicyanine dyes have emerged as a versatile scaffold for the construction of activatable optical probes. This Review presents a survey of hemicyanine‐based NIR activatable probes (HNAPs) for in vivo imaging and early diagnosis of diseases. The molecular design principles of HNAPs towards activatable optical signaling against various biomarkers are discussed with a focus on their broad applications in the detection of diseases including inflammation, acute organ failure, skin diseases, intestinal diseases, and cancer. This progress not only proves the unique value of HNAPs in preclinical research but also highlights their high translational potential in clinical diagnosis.

Tumor microenvironment (TME) plays a crucial role in the initiation and progression of lung adenocarcinoma (LUAD); however, there is still a challenge in understanding the dynamic modulation of the immune and stromal components in TME. In the presented study, we applied CIBERSORT and ESTIMATE computational methods to calculate the proportion of tumor-infiltrating immune cell (TIC) and the amount of immune and stromal components in 551 LUAD cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were analyzed by COX regression analysis and protein-protein interaction (PPI) network construction. Then, Bruton tyrosine kinase (BTK) was determined as a predictive factor by the intersection analysis of univariate COX and PPI. Further analysis revealed that BTK expression was negatively correlated with the clinical pathologic characteristics (clinical stage, distant metastasis) and positively correlated with the survival of LUAD patients. Gene Set Enrichment Analysis (GSEA) showed that the genes in the high-expression BTK group were mainly enriched in immune-related activities. In the low-expression BTK group, the genes were enriched in metabolic pathways. CIBERSORT analysis for the proportion of TICs revealed that B-cell memory and CD8+ T cells were positively correlated with BTK expression, suggesting that BTK might be responsible for the preservation of immune-dominant status for TME. Thus, the levels of BTK might be useful for outlining the prognosis of LUAD patients and especially be a clue that the status of TME transition from immune-dominant to metabolic activity, which offered an extra insight for therapeutics of LUAD.

Activatable phototheranostics holds promise for precision cancer treatment owing to the "turn-on" signals and therapeutic effects. However, most activatable phototheranostic probes only possess photodynamic therapy (PDT) or photothermal therapy (PTT), which suffer from poor therapeutic efficacy due to deficient cellular oxygen and complex tumor microenvironment. We herein report a dual-locked activatable phototheranostic probe that activates near-infrared fluorescence (NIRF) signals in tumor, triggers PDT in response to a tumor-periphery biomarker, and switches from PDT to PTT upon detecting a tumor-core-hypoxia biomarker. This PDT-PTT auto-regulated probe exhibits complete tumor ablation under the photoirradiation of a single laser source by producing cytotoxic singlet oxygen at the tumor periphery and generating hyperthermia at tumorcore where is too hypoxic for PDT. This dual-locked probe represents a promising molecular design approach toward precise cancer phototheranostics.

CuInS 2 quantum dots (QDs) are promising alternatives for user-and environment-friendly light-emitting diode (LED) applications, but the capping of electrically insulating ligands on QDs limits the device charge injection efficiency and results in poor LED performance. To solve the problem, in this work, we demonstrate the facile synthesis of Cu−In−S/ZnS (CIS/ZnS) core/shell QDs employing 1dodecanethiol (DT) as the single ligand. The capping of QDs solely by DT not only enhances the colloidal stability of the QD ink by avoiding proton transfer between different kinds of ligands but also improves the electrical property of the QD films. By controlling the molar feed ratio of cations, the photoluminescence emission peak of the CIS/ZnS QDs is tunable from 530 to 710 nm. Because the QD surface chemistry is optimized, it becomes facile to perform QD surface modification for LED application. A QD LED prototype is fabricated using CIS/ZnS QDs as the emissive layer, which exhibits a maximum luminance of 4490 cd m −2 and a peak external quantum efficiency of 7.8%, boosting the best performance of CIS QD-based LEDs.

Small cell lung cancer (SCLC) is the most aggressive histologic subtype of lung cancer, with a strong predilection for early brain metastases. Despite efforts and advances in new therapeutics for SCLC, the prognosis of patients with SCLC with brain metastases is consistently poor. Therefore, a better understanding of the mechanisms of SCLC brain metastasis is important in improving current treatments. In this study, elevated S100A16 levels were associated with SCLC brain metastases, which was a possible secondary event arising from the brain metastatic microenvironment. Using an in vitro cell coculture system, we found that the coculturing of SCLC cells with human brain microvascular endothelial cells (HBMECs) led to an increased expression of S100A16 in SCLC cells. Conversely, treatment of HBMECs with GW4869, an inhibitor of exosome release, significantly blocked this effect in the cocultured SCLC cells. Alternatively, the results from Western blot analyses and immunofluorescence indicated that the HBMEC exosomes purified by ultracentrifugation also induced the elevation and translocation from the cytoplasm to the nucleus of S100A16 in the recipient SCLC cells. The inhibition experiments demonstrated that elevated S100A16 contributed a benefit of HBMEC exosomes for the survival of the recipient SCLC cells under stress. Moreover, the elevation of S100A16 in SCLC cells prevented the loss of mitochondrial membrane potential (Δψm) and enhanced resistance to apoptosis under stressful conditions, which were determined by Annexin V/propidium iodide and JC-1 assay. Further results showed that the S100A16-mediated protective effect was caused by the presence of an important element in Δψm, prohibitin (PHB)-1, a protein in the mitochondrial inner membrane. Conversely, the delivery of PHB-1 siRNAs into S100A16 overexpressing SCLC cells weakened these protective effects. Our findings suggest that elevated S100A16 plays an active role in facilitating the survival of SCLC cells through modulating the mitochondrial function, identifying S100A16 as an important potential target in SCLC brain metastasis.-Xu, Z.-H., Miao, Z.-W., Jiang, Q.-Z., Gan, D.-X., Wei, X.-G., Xue, X.-Z., Li, J.-Q., Zheng, F., Qin, X.-X., Fang, W.-G., Chen, Y.-H., Li. B. Brain microvascular endothelial cell exosome-mediated S100A16 up-regulation confers small cell lung cancer cell survival in brain.

A feasible strategy for the in situ growth of two-dimensional (2D) [Ni3(OH)2(1,4-BDC)2-(H2O)4]·2H2O (Ni-BDC; 1,4-BDC = 1,4-benzenedicarboxylate) and the subsequent partial sulfurization treatment for the decoration of nickle sulfide (NiS) is developed. The fabricated hierarchically structured Ni-BDC@NiS as a synergistic electrocatalyst shows extremely high activity toward the oxygen evolution reaction (OER). The optimal Ni-BDC@NiS catalyst acquires a current density of 20 mA cm–2 at a lower overpotential of 330 mV and low Tafel slope of 62 mV dec–1, outperforming most previously reported Ni-based sulfide catalysts. Clearly, the combination of the NiS and Ni-BDC array contributed to the improvement of electron transfer, promotion of water adsorption, and increase of rich active species. In addition, the in situ created hierarchical structure not only affords feasible access for mass transport but also strengthens structural integrity, contributing to efficient and stable OER performance. This general and effective strategy anchoring conductive active species on a porous metal–organic framework (MOF) thus provides an efficient way to fabricate synergistic electrocatalysts for the OER.

Cancer immunotherapy has shown tremendous potential to train the intrinsic immune system against malignancy in the clinic. However, the extracellular matrix (ECM) in tumor microenvironment is a formidable barrier that not only restricts the penetration of therapeutic drugs but also prevents the infiltration of antitumor immune cells. We herein report a semiconducting polymer-based ECM nanoremodeler (SPNcb) to combine photodynamic antitumor activity with cancer-specific inhibition of collagen-crosslinking enzymes (lysyl oxidase (LOX) family) for activatable cancer photo-immunotherapy. SPNcb is self-assembled from an amphiphilic semiconducting polymer conjugated with a LOX inhibitor (β-aminopropionitrile, BAPN) via a cancer biomarker (cathepsin B, CatB)cleavable segment. BAPN can be exclusively activated to inhibit LOX activity in the presence of the tumoroverexpressed CatB, thus blocking collagen crosslinking and decreasing ECM stiffness. Such an ECM nanoremodeler synergizes immunogenic phototherapy and checkpoint blockade immunotherapy to improve the tumor infiltration of cytotoxic T cells, inhibiting tumor growth and metastasis.

The electrochemical N2 reduction reaction (eNRR) represents a carbon-free alternative to the Haber–Bosch process for a sustainable NH3 synthesis powered by renewable energy under ambient conditions. Despite significant efforts to develop catalyst activity and selectivity toward eNRR, an appropriate electrochemical system to obstruct the drawback of low N2 solubility remains broadly unexplored. Here, we demonstrate an electrocatalytic system combining a ruthenium/carbon black gas diffusion electrode (Ru/CB GDE) with a three-compartment flow cell, enabling solid–liquid–gas catalytic interfaces for the highly efficient Ru-catalyzed eNRR. The electrolyte optimization and the Ru/CB GDE development through the hydrophobicity, the Ru/CB loading, and the post-treatment have revealed the crucial contribution of interfacial N2 transportation and local pH environment. The optimized hydrophobic Ru/CB GDE generated excellent eNRR performance, achieving a high NH3 yield rate of 9.9 × 10–10 mol/cm2 s at −0.1 V vs RHE, corresponding to the highest faradaic efficiency of 64.8% and a specific energy efficiency of 40.7%, exceeding the most reported system. This work highlights the critical role of design and optimization of the GDE-flow cell combination and provides a valuable practicable solution to enhance the electrochemical reaction involving gas-phase reactants with low solubility.