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Metabolic reprogramming within the tumor microenvironment (TME) is a hallmark of cancer and a crucial determinant of tumor progression. Research indicates that various metabolic regulators form a metabolic network in the TME and interact with immune cells, coordinating the tumor immune response. Metabolic dysregulation creates an immunosuppressive TME, impairing the antitumor immune response. In this review, we discuss how metabolic regulators affect the tumor cell and the crosstalk of TME. We also summarize recent clinical trials involving metabolic regulators and the challenges of metabolism-based tumor therapies in clinical translation. In a word, our review distills key regulatory factors and their mechanisms of action from the complex reprogramming of tumor metabolism, identified as tumor metabolic regulators. These regulators provide a theoretical basis and research direction for the development of new strategies and targets in cancer therapy based on tumor metabolic reprogramming. Key points Refining the key regulatory factors and their mechanisms within the complex network of tumor metabolic reprogramming. Depicting the metabolic crosstalk between tumor cells, immune cells, and tumor stromal cells during tumor progression. Emphasizing the unresolved challenges of metabolic therapy in clinical translation and the advantages of personalized treatment. Providing theoretical support and research direction for new strategies for metabolic therapies.

Reservoir computing (RC) offers efficient temporal information processing with low training cost. All-ferroelectric implementation of RC is appealing because it can fully exploit the merits of ferroelectric memristors (e.g., good controllability); however, this has been undemonstrated due to the challenge of developing ferroelectric memristors with distinctly different switching characteristics specific to the reservoir and readout network. Here, we experimentally demonstrate an all-ferroelectric RC system whose reservoir and readout network are implemented with volatile and nonvolatile ferroelectric diodes (FDs), respectively. The volatile and nonvolatile FDs are derived from the same Pt/BiFeO 3 /SrRuO 3 structure via the manipulation of an imprint field ( E imp ). It is shown that the volatile FD with E imp exhibits short-term memory and nonlinearity while the nonvolatile FD with negligible E imp displays long-term potentiation/depression, fulfilling the functional requirements of the reservoir and readout network, respectively. Hence, the all-ferroelectric RC system is competent for handling various temporal tasks. In particular, it achieves an ultralow normalized root mean square error of 0.017 in the Hénon map time-series prediction. Besides, both the volatile and nonvolatile FDs demonstrate long-term stability in ambient air, high endurance, and low power consumption, promising the all-ferroelectric RC system as a reliable and low-power neuromorphic hardware for temporal information processing. While reservoir computing can process temporal information efficiently, its hardware implementation remains a challenge due to the lack of robust and energy efficient hardware. Here, the authors develop an all-ferroelectric reservoir computing system, showing high accuracies and low power consumptions in various tasks like the time-series prediction.

Oxidative carbonylation of methane is an appealing approach to the synthesis of acetic acid but is limited by the demand for additional reagents. Here, we report a direct synthesis of CH 3 COOH solely from CH 4 via photochemical conversion without additional reagents. This is made possible through the construction of the PdO/Pd–WO 3 heterointerface nanocomposite containing active sites for CH 4 activation and C–C coupling. In situ characterizations reveal that CH 4 is dissociated into methyl groups on Pd sites while oxygen from PdO is the responsible for carbonyl formation. The cascade reaction between the methyl and carbonyl groups generates an acetyl precursor which is subsequently converted to CH 3 COOH. Remarkably, a production rate of 1.5 mmol g Pd –1 h –1 and selectivity of 91.6% toward CH 3 COOH is achieved in a photochemical flow reactor. This work provides insights into intermediate control via material design, and opens an avenue to conversion of CH 4 to oxygenates. A light-driven, chemical looping approach to CH 3 COOH synthesis from methane using a Pd/PdO–WO 3 nanocomposite is reported. Methane is converted to methyl and carbonyl intermediates at the Pd and PdO sites, respectively, to produce CH 3 COOH.

Nowadays the development of machine vision is oriented toward real-time applications such as autonomous driving. This demands a hardware solution with low latency, high energy efficiency, and good reliability. Here, we demonstrate a robust and self-powered in-sensor computing paradigm with a ferroelectric photosensor network (FE-PS-NET). The FE-PS-NET, constituted by ferroelectric photosensors (FE-PSs) with tunable photoresponsivities, is capable of simultaneously capturing and processing images. In each FE-PS, self-powered photovoltaic responses, modulated by remanent polarization of an epitaxial ferroelectric Pb(Zr 0.2 Ti 0.8 )O 3 layer, show not only multiple nonvolatile levels but also sign reversibility, enabling the representation of a signed weight in a single device and hence reducing the hardware overhead for network construction. With multiple FE-PSs wired together, the FE-PS-NET acts on its own as an artificial neural network. In situ multiply-accumulate operation between an input image and a stored photoresponsivity matrix is demonstrated in the FE-PS-NET. Moreover, the FE-PS-NET is faultlessly competent for real-time image processing functionalities, including binary classification between ‘X’ and ‘T’ patterns with 100% accuracy and edge detection for an arrow sign with an F-Measure of 1 (under 365 nm ultraviolet light). This study highlights the great potential of ferroelectric photovoltaics as the hardware basis of real-time machine vision. Robust, fast, and low-power hardware platforms are desirable for the implementation of real-time machine vision. Here the authors develop a computing-in-sensor network using ferroelectric photo sensors with remanent-polarization-controlled photo responsivities.

Nonoxidative coupling of methane (NOCM) is a highly important process to simultaneously produce multicarbons and hydrogen. Although oxide-based photocatalysis opens opportunities for NOCM at mild condition, it suffers from unsatisfying selectivity and durability, due to overoxidation of CH 4 with lattice oxygen. Here, we propose a heteroatom engineering strategy for highly active, selective and durable photocatalytic NOCM. Demonstrated by commonly used TiO 2 photocatalyst, construction of Pd–O 4 in surface reduces contribution of O sites to valence band, overcoming the limitations. In contrast to state of the art, 94.3% selectivity is achieved for C 2 H 6 production at 0.91 mmol g –1 h –1 along with stoichiometric H 2 production, approaching the level of thermocatalysis at relatively mild condition. As a benchmark, apparent quantum efficiency reaches 3.05% at 350 nm. Further elemental doping can elevate durability over 24 h by stabilizing lattice oxygen. This work provides new insights for high-performance photocatalytic NOCM by atomic engineering. Photocatalytic nonoxidative coupling of methane (NOCM) emerges as an appealing approach for the production of value-added C2 + hydrocarbons and hydrogen. Here the authors propose a heteroatom engineering strategy to prepare Pd single atoms loaded TiO2 for active and selective photocatalytic NOCM.

The meticulous design of active sites and light absorbers holds the key to the development of high-performance photothermal catalysts for CO 2 hydrogenation. Here, we report a nonmetallic plasmonic catalyst of Mo 2 N/MoO 2 - x nanosheets by integrating a localized surface plasmon resonance effect with two distinct types of active sites for CO 2 hydrogenation. Leveraging the synergism of dual active sites, H 2 and CO 2 molecules can be simultaneously adsorbed and activated on N atom and O vacancy, respectively. Meanwhile, the plasmonic effect of this noble-metal-free catalyst signifies its promising ability to convert photon energy into localized heat. Consequently, Mo 2 N/MoO 2 - x nanosheets exhibit remarkable photothermal catalytic performance in reverse water-gas shift reaction. Under continuous full-spectrum light irradiation (3 W·cm −2 ) for a duration of 168 h, the nanosheets achieve a CO yield rate of 355 mmol·gcat −1 ·h −1 in a flow reactor with a selectivity exceeding 99%. This work offers valuable insights into the precise design of noble-metal-free active sites and the development of plasmonic catalysts for reducing carbon footprints. In this work, the authors design a Mo 2 N/MoO 2 - x nonmetallic plasmonic catalyst by regulating synergy between two specific active sites. Highly efficient, selective, and durable CO 2 hydrogenation under relatively mild reaction conditions is achieved

Fallen trees enter the adjacent stream and are carried away downstream by the current. As the stream joins another one, the complex hydrodynamics near their confluence make the movement of wood hard to predict. These woods may accumulate near the confluence resulting in backwater and subsequent potential flooding. A laboratory study was conducted to investigate the movement and accumulation behavior of individual pieces of wood near the confluence. The characteristics of wood (i.e., the length, diameter, and density) and the hydraulic conditions (i.e., the discharge ratio and the release distance) were varied in this investigation. It was found that the wooden pieces released from the tributary got occasionally trapped in the flow separation zone of the confluence, whereupon they were mainly trapped by a clockwise vortex and continued to stay driven by a reverse cluster of currents within this zone. The accumulation probability of wood was mainly related to its length, the discharge ratio and the release distance. The effect of wood diameter and density within the tested parameters was negligible. The probability increased with an increase in the discharge ratio as well as a decrease in the release distance. The longer pieces had a higher probability of being trapped, whereas for those exceeding some critical value, the probability was nearly the same, or dropped sharply. A generalized model for wood accumulation near the confluence was developed for practical application. These findings carry significant implications for river management, particularly in preventing the risk of flooding caused by wood blockage. Key Points Conducting a laboratory study to investigate the transport, accumulation and trapping mechanism of wood near the confluence Evaluating the wood accumulation probability depending on different wood characteristics and confluence hydrodynamic conditions Wood released from the tributary may be trapped by the clockwise vortex and thus accumulate in the separation zone

BackgroundCentromere protein L (CENPL) is an important member of the centromere protein (CENP) family. However, the correlation between CENPL expression and cancer development and immune infiltration has rarely been studied. Here, we studied the role of CENPL in pan-cancer and further verified the results in lung adenocarcinoma (LUAD) through in vitro experiments.MethodsThe CENPL expression level was studied with TIMER 2.0 and Oncomine databases. The potential value of CENPL as a diagnostic and prognostic biomarker in pan-cancer was evaluated with the TCGA database and GEPIA. The CENPL mutation character was analyzed using the cBioPortal database. The LinkedOmics and CancerSEA databases were used to carry out the function analysis of CENPL. The role of CENPL in immune infiltration was studied using the TIMER and TISIDB websites. Moreover, the expression of CENPL was detected through RT-qPCR and Western blotting. Immunohistochemistry was used to evaluate the infiltration level of CD8+ T cells. Cell proliferation was detected by EdU and CCK8. A flow cytometer was used to analyze the influence of CENPL in cell cycle and apoptosis.ResultsCENPL was increased in most of the cancers. The upregulation and mutation of CENPL were associated with a poorer prognosis in many cancers. The results showed a significant positive correlation between CENPL and myeloid-derived suppressor cell (MDSC) infiltration and a negative correlation between CENPL and T-cell NK infiltration in most of the cancers. CENPL regulated cell proliferation and cell cycle, and was negatively correlated with the inflammation level of LUAD. The in vitro experiments suggested that CENPL was increased in LUAD tissue and cell lines. There was a negative correlation between CENPL expression and CD8+ T-cell infiltration. The knockdown of CENPL significantly suppressed the expression of CDK2 and CCNE2, and induced G0/G1 arrest and apoptosis of LUAD.ConclusionsCENPL may function as a potential biomarker and oncogene in pan-cancer, especially LUAD. Furthermore, CENPL was associated with immune cell infiltration in pan-cancer, providing a potential immune therapy target for tumor treatment.

To better understand how amino acid sequence encodes protein structure, we engineered mutational pathways that connect three common folds (3α, β−grasp, and α/β−plait). The structures of proteins at high sequence-identity intersections in the pathways (nodes) were determined using NMR spectroscopy and analyzed for stability and function. To generate nodes, the amino acid sequence encoding a smaller fold is embedded in the structure of an ~50% larger fold and a new sequence compatible with two sets of native interactions is designed. This generates protein pairs with a 3α or β−grasp fold in the smaller form but an α/β−plait fold in the larger form. Further, embedding smaller antagonistic folds creates critical states in the larger folds such that single amino acid substitutions can switch both their fold and function. The results help explain the underlying ambiguity in the protein folding code and show that new protein structures can evolve via abrupt fold switching. In this work the authors investigate the structure-sequence dependance. The ability to design and characterize proteins at interfaces between three common folds suggests that fold switching is an intrinsic feature of protein folding language and likely important in the evolution of protein structure and function.

Background tRNA-derived fragments (tRFs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of tRFs to colorectal cancer (CRC) remain largely unknown. Methods tRF3008A (a tRFRNA derived from tRNA Val ) was identified by RNA sequencing and validated by quantitative reverse transcription PCR. The role of tRF3008A in CRC progression was assessed both in vitro and in vivo, and its downstream target genes were identified and validated in CRC cells. RNA pull-down with mass spectrometry and AGO-RIP were used to confirm the interaction of tRF3008A and AGO proteins. The clinical implications of tRF3008A were assessed in CRC tissues and blood samples. Results The expression of tRF3008A was reduced in colorectal cancer, and its reduction was significantly correlated with advanced and metastatic disease in CRC. Patients with low tRF3008A expression showed significantly shorter DFS, and multivariate analysis identified tRF3008A as an independent prognostic biomarker in CRC. Functionally, tRF3008A inhibits the proliferation and migration of CRC in vivo and in vitro by repressing endogenous FOXK1, a positive regulator of the Wnt/β-catenin pathway. Mechanistically, tRF3008A binds to AGO proteins as a guide to destabilize oncogenic FOXK1 transcript. Conclusions tRF3008A suppresses the metastasis and progression of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner.