Spatially resolved transcriptomics enable comprehensive measurement of gene expression at subcellular resolution while preserving the spatial context of the tissue microenvironment. While deep learning has shown promise in analyzing SCST datasets, most efforts have focused on sequence data and spatial localization, with limited emphasis on leveraging rich histopathological insights from staining images. We introduce GIST, a deep learning-enabled gene expression and histology integration for spatial cellular profiling. GIST employs histopathology foundation models pretrained on millions of histology images to enhance feature extraction and a hybrid graph transformer model to integrate them with transcriptome features. Validated with datasets from human lung, breast, and colorectal cancers, GIST effectively reveals spatial domains and substantially improves the accuracy of segmenting the microenvironment after denoising transcriptomics data. This enhancement enables more accurate gene expression analysis and aids in identifying prognostic marker genes, outperforming state-of-the-art deep learning methods with a total improvement of up to 49.72%. GIST provides a generalizable framework for integrating histology with spatial transcriptome analysis, revealing novel insights into spatial organization and functional dynamics.

Protein phosphatase 2A (PP2A) is one of the most abundant serine/threonine phosphatases and plays critical roles in regulating cell fate and function. We previously showed that PP2A regulates the differentiation of CD4⁺ T cells and the development of thymocytes. Nevertheless, its role in CD8⁺ T cells remains elusive. By ablating the catalytic subunit α (Cα) of PP2A in CD8⁺ T cells, we revealed the essential role of PP2A in promoting the effector functions of CD8⁺ T cells. Notably, PP2A Cα-deficient CD8⁺ T cells exhibit reduced proliferation and decreased cytokine production upon stimulation in vitro. In vivo, mice lacking PP2A Cα in T cells displayed defective immune responses against lymphocytic choriomeningitis virus infection, associated with reduced CD8⁺ T cell expansion and decreased cytokine production. Consistently, the ablation of the PP2A Cα subunit in CD8⁺ T cells results in attenuated antitumor activity in mice. There is a notable decrease in the infiltration of PP2A Cα-deficient CD8⁺ T cells within the tumor microenvironment, and the cells that do infiltrate exhibit diminished effector functions. Mechanistically, PP2A Cα deficiency impedes CD28-induced AKT Ser⁴⁷³ phosphorylation, thus impairing CD8⁺ T cell costimulation signal. Collectively, our findings underscore the critical role of phosphatase PP2A as a propeller for CD28-mediated costimulation signaling in CD8⁺ T cell effector function by fine-tuning T cell activation.

Solar-driven CO₂ photoreduction holds promise for sustainable fuel and chemical productions, but the complex proton-coupled multi-electron transfer processes and sluggish oxidation half-reaction kinetics substantially hinder its efficiency. Here, we devised a rational catalyst design to address these challenges by fabricating ferrocene carboxylic acid-functionalized Cs₃Sb₂Br₉ nanocrystals (CSB-Fc NCs), which facilitate simultaneous benzyl alcohol oxidation and CO₂ reduction reactions under visible-light irradiation. The synchronized proton-coupled electron transfer processes between the reduction and oxidation half-reactions on CSB-Fc NCs resulted in a 5-fold increase in the CO₂ reduction rate (45.56 μmol g⁻¹ h⁻¹, 97.9% CO selectivity) and a 5.8-fold enhancement in benzyl alcohol conversion (97.7% selectivity for benzaldehyde) compared to the CSB. In situ Raman and ultraviolet-visible diffuse reflectance spectra revealed that the dynamic Fe²⁺/Fe³⁺ redox loop within the Fc unit serves as the actual active site, facilitating the activation of substrate molecules. More importantly, in situ attenuated total reflection Fourier transform infrared spectroscopy and gas chromatography–mass spectrometry spectroscopy, with isotope labeling of Deuteron-benzyl alcohol and ¹³CO₂, confirmed that proton transfer from the hydroxyl group generates reactive protons at the Fe²⁺/Fe³⁺ site, enabling efficient CO₂ photoreduction through subsequent protonation steps. This work offers a cost-effective and efficient approach for synergetic CO₂ photoreduction driven by organic synthesis, advancing solar energy utilization.

Numerous diseases have been connected to protein arginine methylations mediated by protein arginine methyltransferase 5 (PRMT5). Clinical investigations of the PRMT5-specific inhibitor GSK3326595 are currently being conducted, and the results are promising for preventing cancers. However, the detailed mechanism of PRMT5 promoting colorectal cancer (CRC) malignant progression remains unclear. Here, we found that PRMT5 directly catalyzes AlkB homologue 5 (ALKBH5) symmetric dimethylation at the R316 residue (meR316-ALKBH5), which enhances TRIM28-mediated ALKBH5 ubiquitination degradation. Then, an ALKBH5 decrease attenuates ALKBH5-mediated m6A demethylation on the CD276 transcript 3′ untranslated region, which increases CD276 messenger RNA stability and its expression in CRC cells. Furthermore, a CD276 expression increase facilitates CRC immune evasion by inhibiting cytotoxic T-cell functions. Moreover, we revealed that PRMT5-mediated meR316-ALKBH5 activates CD276 transcription by increasing its messenger RNA m6A modification to increase CRC immune evasion in vitro and in vivo. Furthermore, we consistently showed a strong association between meR316-ALKBH5 and poor outcomes in patients with CRC. Finally, we demonstrated that combining an anti-PD1 antibody with the PRMT5 inhibitor GSK3326595 markedly halts the progression of CRC. Our findings could serve as a basis for the development of a PRMT5–meR316-ALKBH5–CD276 axis-targeting treatment approach for CRC.

Edge contact is essential for achieving the ultimate device pitch scaling of stacked nanosheet transistors with monolayer 2-dimensional (2D) channels. However, due to large edge-contact resistance between 2D channels and contact metal, there is currently a lack of high-performance edge-contact device technology for 2D material channels. Here, we report high-performance edge-contact monolayer molybdenum disulfide (MoS₂) field-effect transistors (FETs) utilizing well-controlled plasma etching techniques. Plasma etching with pure argon improves the edge dangling bonds and thus improves the edge-contact quality. Edge-contact monolayer MoS₂ FET shows good ohmic contact even at cryogenic temperatures (20 K), achieving a record-low contact resistance (R _c) of 1.25 kΩ·μm among all edge-contact MoS₂ devices. The record-high on-state current of 436 μA/μm and transconductance of 123 μS/μm at V _ds = 1 V are achieved on an edge-contact monolayer MoS₂ FET with L _ch = 120 nm. This work highlights the great potential of edge contacts for high-performance monolayer transition metal dichalcogenide (TMD) material electronics.

Gut microbiota is crucial for protecting the homeostasis of immune locally and systemically, and its dysbiosis is essentially correlated to tumorigenesis, cancer progression, and refractoriness to cancer treatments, including the novel immunotherapy. Increasing evidence unravel the intricate role of gut microbiota in reshaping tumor microenvironment and affecting the efficacy and toxicities of immunotherapy, which shed more light on the future applications of gut microbiota in efficacious biomarker and combination treatment of immunotherapy. To better grasp the underlying crosstalk between gut microbiota and immunotherapy, more experimental and clinical trials are indispensable for the customized gut microbiota-based treatments in cancer patients undergoing immunotherapy.

Immune recognition and activation by the peptide-laden major histocompatibility complex–T cell receptor (TCR)–CD3 complex is essential for anti-tumor immunity. Tumors may escape immune surveillance by dissembling the complex. Here, we report that transferrin, which is overexpressed in patients with liver metastasis, disassociates TCR from the CD3 signaling apparatus by targeting the constant domain (CD) of T cell receptor α (TCRα), consequently suppresses T cell activation, and inhibits anti-metastatic and anti-tumor immunity. In mouse models of melanoma and lymphoma, transferrin overexpression exacerbates liver metastasis, while its knockdown, antibody, designed peptides, and CD mutation interfering with transferrin–TCRα interaction inhibit metastasis. This work reveals a novel strategy of tumor evasion of immune surveillance by blocking the coupling between TCRs and the CD3 signaling apparatus to suppress TCR activation. Given the conservation of CD and transferrin up-regulation in metastatic tumors, the strategy might be a common metastatic mechanism. Targeting transferrin–TCRα holds promise for anti-metastatic treatment.

The electrocatalytic carbon dioxide reduction reaction (CO₂RR) at industrial-level current densities provides a sustainable approach to converting CO₂ into value-added fuels and feedstocks using renewable electricity. However, the CO₂RR conducted typically in alkaline and neutral electrolytes encounters some challenges due to the inevitable reaction between CO₂ and OH⁻ ions, which undermines CO₂ utilization and leads to poor operational stability. Acidic media present a viable alternative by reducing (bi)carbonate production, thereby enhancing the carbon efficiency and stability in CO₂RR. The objective of this paper is to provide a concise account of the recent advancements and challenges in the field of acidic CO₂RR, with an emphasis on future developments and opportunities.

The presence of Hg²⁺ causes substantial stress to plants, adversely affecting growth and health by disrupting cell cycle divisions, photosynthesis, and ionic homeostasis. Accurate visualization of the spatiotemporal distribution of Hg²⁺ in plant tissues is crucial for the management of Hg pollution; however, the related research is still at its early stage. Herein, a small-molecule amphiphilic fluorescent probe (termed LJTP2) was developed for the specific detection of Hg²⁺ with a high sensitivity (~16 nM). Fluorescent imaging applications with LJTP2 not only detected the dynamic distribution of Hg²⁺ within plant cells at the subcellular level but also enabled the understanding of cell membrane health under Hg²⁺ stress. This study introduces a valuable imaging tool for elucidating the molecular mechanism of Hg²⁺ stress in plants, demonstrating the potential of the application of small-molecule fluorescent probes in plant science.

Autonomous vehicles with self-evolution capabilities are expected to improve their performance through learning algorithms, to automatically adapt to the external environment. However, due to the infinity, complexity, and variability of the actual traffic environment, it is necessary to develop quantitative representation indicators of scenario difficulty and generate targeted scenarios to ensure the evolution gradually, so as to quickly approach the performance limit of the algorithm. Therefore, this paper proposes a data-driven quantitative representation method of scenario difficulty. Specifically, the concept of environment agent is proposed, and a reinforcement learning method combined with mechanism knowledge is constructed for policy search to obtain an agent with an adversarial behavior. The model parameters of the environment agent at different stages in the training process are extracted to construct a policy group, and then agents with different adversarial intensities are obtained, which are used to realize data generation in different difficulty scenarios through the simulation environment. Finally, a data-driven scenario difficulty quantitative representation model is constructed, which is used to output the environment agent policy under different difficulties. Experimental results show the effectiveness of the proposed method. The result analysis shows that the proposed algorithm can generate reasonable and interpretable scenarios with high discrimination and can provide quantifiable difficulty representation without any expert logic rule design. Compared with the rule-based discrete scenario difficulty representation method, the proposed algorithm can achieve continuous difficulty representation. The video link is https://www.youtube.com/watch?v=GceGdqAm9Ys.