The development of combination immunotherapy based on the mediation of regulatory mechanisms of the tumor immune microenvironment (TIME) is promising. However, a deep understanding of tumor immunology must involve the systemic tumor immune environment (STIE) which was merely illustrated previously. Here, we aim to review recent advances in single-cell transcriptomics and spatial transcriptomics for the studies of STIE, TIME, and their interactions, which may reveal heterogeneity in immunotherapy responses as well as the dynamic changes essential for the treatment effect. We review the evidence from preclinical and clinical studies related to TIME, STIE, and their significance on overall survival, through different immunomodulatory pathways, such as metabolic and neuro-immunological pathways. We also evaluate the significance of the STIE, TIME, and their interactions as well as changes after local radiotherapy and systemic immunotherapy or combined immunotherapy. We focus our review on the evidence of lung cancer, hepatocellular carcinoma, and nasopharyngeal carcinoma, aiming to reshape STIE and TIME to enhance immunotherapy efficacy.

A 36-mer guanine (G)-rich DNA aptamer (OBA36) is able to distinguish one atomic difference between ochratoxin analogues A (OTA) and B (OTB), showing prominent recognition specificity and affinity among hundreds of aptamers for small molecules. Why OBA36 has >100-fold higher binding affinity to OTA than OTB remains a long-standing question due to the lack of high-resolution structure. Here we report the solution NMR structure of the aptamer–OTA complex. It was found that OTA binding induces the aptamer to fold into a well-defined unique duplex–quadruplex structural scaffold stabilized by Mg2+ and Na+ ions. OTA does not directly interact with the G-quadruplex, but specifically binds at the junction between the double helix and G-quadruplex through π–π stacking, halogen bonding (X-bond), and hydrophobic interaction. OTB has the same binding site as OTA but lacks the X-bond. The strong X-bond formed between the chlorine atom of OTA and the aromatic ring of C5 is the key to discriminating the strong binding toward OTA. The present research contributes to a deeper insight of aptamer molecular recognition, reveals structural basis of the high-affinity binding of aptamers, and provides a foundation for further aptamer engineering and applications.

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Rapid sensitive detection of targets is desired in broad fields, such as environmental monitoring, food safety, and molecular diagnosis. We demonstrated an innovative strategy of constructing aptamer thermal switch for target detection, which affords a large difference in heating-induced conformation changes between the bound and the unbound states. This aptamer thermal switch is obtained by rational engineering aptamer sequence and modulating aptamer conformation stability under heating. We further introduced a conformation-sensitive fluorophore into the aptamers, converting heating-induced conformation changes to heating-induced fluorescence changes. The bound and unbound aptamers showed a large difference in heating-induced fluorescence change. Using these aptamers in microscale thermophoresis (MST), which is a powerful tool for quickly measuring fluorescence responses to heating with precise ratiometric analysis, we achieved detection of a variety of targets (e.g., cadmium ions (Cd 2+ ), small molecule aflatoxin B1, and protein biomarker immunoglobulin E) within seconds with pronounced sensitivity. We envision that this strategy will have wide applications to detection of targets of interest in broad research fields, and it will also be helpful for affinity binding study.

Cathode materials are critical for Na-ion batteries while facing challenges due to the instability of the structure and interfaces. In this work, we propose a strategy to achieve an in situ plastic-crystal Na3–3x Al x PO4 coating and bulk Al doping for an O3-NaNi0.4Fe0.2Mn0.4O2 cathode through a simple one-step method. Na3–3x Al x PO4 exhibits high ion transport performance due to its unique “paddle-wheel” mechanism. The in situ formed Na3–3x Al x PO4 could consume the residual alkali compounds and induce the formation of a Na-deficient phase, thus leading to enhanced Na+ transport kinetics. Furthermore, strong Al–O bonds formed in the bulk further enhance the crystal structure stability. In a full cell, the capacity retention rate reached 70% after 500 cycles, making its commercial operation possible. Altogether, these results suggest that the in situ plastic-crystal-coating strategy can significantly improve the surface and bulk structure stability of NaNi0.4Fe0.2Mn0.4O2, thus leading to improved electrochemical performance.

Global Fishing Watch (GFW) provides global open-source data collected via automated monitoring of vessels to help with sustainable management of fisheries. Limited previous global fishing effort analyses, based on Automatic Identification System (AIS) data (2017–2020), suggest economic and environmental factors have less influence on fisheries than cultural and political events, such as holidays and closures, respectively. As such, restrictions from COVID-19 during 2020 provided an unprecedented opportunity to explore added impacts from COVID-19 restrictions on fishing effort. We analyzed global fishing effort and fishing gear changes (2017–2019) for policy and cultural impacts, and then compared impacts of COVID-19 lockdowns across several countries (i.e., China, Spain, the US, and Japan) in 2020. Our findings showed global fishing effort increased from 2017 to 2019 but decreased by 5.2% in 2020. We found policy had a greater impact on monthly global fishing effort than culture, with Chinese longlines decreasing annually. During the lockdown in 2020, trawling activities dropped sharply, particularly in the coastal areas of China and Spain. Although Japan did not implement an official lockdown, its fishing effort in the coastal areas also decreased sharply. In contrast, fishing in the Gulf of Mexico, not subject to lockdown, reduced its scope of fishing activities, but fishing effort was higher. Our study demonstrates, by including the dimensions of policy and culture in fisheries, that large data may materially assist decision-makers to understand factors influencing fisheries’ efforts, and encourage further marine interdisciplinary research. We recommend the lack of data for small-scale Southeast Asian fisheries be addressed to enable future studies of fishing drivers and impacts in this region.

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Microscale thermophoresis (MST) technology has emerged as a powerful growing method in a molecular interaction study by measuring fluorescence responses of molecules inside a capillary to infrared (IR) laser heating with the benefits of rapid ratiometric measurement, separation-free, no immobilization, and low sample consumption. Combining the advantages of RNA-cleaving DNAzymes in target recognition and enzymatic catalysis and the strength of MST technology for fluorescence signaling, here, we reported a DNAzyme-based MST method for sensitive target detection. We introduced a fluorescein terminal label at the RNA-cleaving DNAzyme, and the substrate was linked to DNAzyme together with a poly-T sequence in a unimolecular design or not conjugated with DNAzyme in a bimolecular design. The presence of the cofactor activated DNAzyme to catalytically cleave the substrate, causing molecular structure alteration and significant changes in MST signals. This DNAzyme MST sensor enabled sensitively detecting activator targets Pb2+ and l-histidine, with a detection limit of 49 pM Pb2+ and 3.9 μM l-histidine. This biosensing strategy is universal and promising for wide applications.