Background: Hepatic ischemia-reperfusion injury (HIRI) stands as an unavoidable complication arising from liver surgery, profoundly intertwined with its prognosis. The role of lysine methyltransferase SET domain bifurcated 1 (SETDB1) in HIRI remains elusive, despite its confirmation as a potential therapeutic target for diverse diseases. Here, we investigated the mechanism by which SETDB1 regulated HIRI. Methods: RNA sequencing data were used to identify the expression and potential targets of SETDB1 through bioinformatics analysis. To elucidate the impact of SETDB1 on HIRI, both an in vivo model of HIRI in mice and an in vitro model of hepatocyte hypoxia/reoxygenation were established. Biochemical and histological analyses were used to investigate the influence of SETDB1 on liver damage mediated by HIRI. Chromatin immunoprecipitation and coimmunoprecipitation were implemented to explore the in-depth mechanism of SETDB1 regulating HIRI. Results: We confirmed that hepatocellular SETDB1 was up-regulated during HIRI and had a close correlation with HIRI-related inflammation and apoptosis. Moreover, inhibition of SETDB1 could mitigate HIRI-induced liver damage, inflammation, and apoptosis. Through our comprehensive mechanistic investigation, we revealed that SETDB1 interacts with apoptosis-signal-regulating kinase 1 (ASK1) and facilitates the methylation of its lysine residues. Inhibition of SETDB1 resulted in reduced phosphorylation of ASK1, leading to a marked suppression of downstream c-Jun N-terminal kinase (JNK)/p38 signaling pathway activation. The therapeutic effect on inflammation and apoptosis achieved through SETDB1 inhibition was nullified by the restoration of JNK/p38 signaling activation through ASK1 overexpression. Conclusions: The findings from our study indicate that SETDB1 mediates lysine methylation of ASK1 and modulates the activation of the ASK1–JNK/p38 pathway, thus involved in HIRI-induced inflammation and apoptosis. These results suggest that SETDB1 holds promise as a potential therapeutic target for mitigating HIRI.

Electrochemiluminescence (ECL) has established itself as an excellent transduction technique in biosensing and light-emitting device, while conventional ECL mechanism depending on spontaneous emission of luminophores lacks reversibility and tunable emission characters, limiting the universality of ECL technique in the fields of fundamental research and clinical applications. Here, we report the first observation of stimulated emission route in ECL and thus establish a reversible tuning ECL microscopy for single-cell imaging. This microscopy uses a focused red-shifted beam to transfer spontaneous ECL into stimulated ECL, which enables selective and reversible tuning of ECL emission from homogeneous solution, single particles, and single cells. After excluding other possible competitive routes, the stimulated ECL emission route is confirmed by a dual-objective system in which the suppressed spontaneous ECL is accompanied by the enhanced stimulated ECL. By incorporating a commercial donut-shaped beam, the sharpness of single-cell matrix adhesion is improved 2 to 3 times compared with the counterpart in confocal ECL mode. The successful establishment of this stimulated emission ECL will greatly advance the development of light-emitting device and super-resolution ECL microscopy.

Proteins secreted by Gram-negative bacteria are tightly linked to the virulence and adaptability of these microbes to environmental changes. Accurate identification of such secreted proteins can facilitate the investigations of infections and diseases caused by these bacterial pathogens. However, current bioinformatic methods for predicting bacterial secreted substrate proteins have limited computational efficiency and application scope on a genome-wide scale. Here, we propose a novel deep-learning-based framework—DeepSecE—for the simultaneous inference of multiple distinct groups of secreted proteins produced by Gram-negative bacteria. DeepSecE remarkably improves their classification from nonsecreted proteins using a pretrained protein language model and transformer, achieving a macro-average accuracy of 0.883 on 5-fold cross-validation. Performance benchmarking suggests that DeepSecE achieves competitive performance with the state-of-the-art binary predictors specialized for individual types of secreted substrates. The attention mechanism corroborates salient patterns and motifs at the N or C termini of the protein sequences. Using this pipeline, we further investigate the genome-wide prediction of novel secreted proteins and their taxonomic distribution across ~1,000 Gram-negative bacterial genomes. The present analysis demonstrates that DeepSecE has major potential for the discovery of disease-associated secreted proteins in a diverse range of Gram-negative bacteria. An online web server of DeepSecE is also publicly available to predict and explore various secreted substrate proteins via the input of bacterial genome sequences.

Molecular luminescent materials with optical waveguide have wide application prospects in light-emitting diodes, sensors, and logic gates. However, the majority of traditional optical waveguide systems are based on brittle molecular crystals, which limited the fabrication, transportation, storage, and adaptation of flexible devices under diverse application situations. To date, the design and synthesis of photofunctional materials with high flexibility, novel optical waveguide, and multi-port color-tunable emission in the same solid-state system remain an open challenge. Here, we have constructed new types of zero-dimensional organic metal halides (Au-4-dimethylaminopyridine [DMAP] and In-DMAP) with a rarely high elasticity and rather low loss coefficients for optical waveguide. Theoretical calculations on the intermolecular interactions showed that the high elasticity of 2 molecular crystalline materials was original from their herringbone structure and slip plane. Based on one-dimensional flexible microrods of 2 crystals and the 2-dimensional microplate of the Mn-DMAP, heterojunctions with multi-color and space-resolved optical waveguides have been fabricated. The formation mechanism of heterojunctions is based on the surface selective growth on account of the low lattice mismatch ratio between contacting crystal planes. Therefore, this work describes the first attempt to the design of metal-halide-based crystal heterojunctions with high flexibility and optical waveguide, expanding the prospects of traditional luminescent materials for smart optical devices, such as logic gates and multiplexers.

Non-Hermitian systems associated with exceptional points (EPs) are expected to demonstrate a giant response enhancement for various sensors. The widely investigated enhancement mechanism based on diverging from an EP should destroy the EP and further limits its applications for multiple sensing scenarios in a time sequence. To break the above limit, here, we proposed a new enhanced sensing mechanism based on shifting an EP. Different from the mechanism of diverging from an EP, our scheme is an EP nondemolition and the giant enhancement of response is acquired by a slight shift of the EP along the parameter axis induced by perturbation. The new sensing mechanism can promise the most effective response enhancement for all sensors in the case of multiple sensing in a time sequence. To verify our sensing mechanism, we construct a mass sensor and a gyroscope with concrete physical implementations. Our work will deepen the understanding of EP-based sensing and inspire designing various high-sensitivity sensors in different physical systems.

Great efforts have been devoted to the study of photo-responsive adsorption, but its current methodology largely depends on the well-defined photochromic units and their photo-driven molecular deformation. Here, a methodology to fabricate nondeforming photo-responsive sorbents is successfully exploited. With C₆₀-fullerene doping in metalloporphyrin metal-organic frameworks (PCN-M, M = Fe, Co, or Ni) and intensively interacting with the metalloporphyrin sites, effective charge-transfer can be achieved over the metalloporphyrin-C₆₀ architectures once excited by the light at 350 to 780 nm. The electron density distribution and the resultant adsorption activity are thus changed by excited states, which are also stable enough to meet the timescale of microscopic adsorption equilibrium. The charge-transfer over Co(II)-porphyrin-C₆₀ is proved to be more efficient than the Fe(II)- and Ni(II)-porphyrin-C₆₀ sites, as well as than all the metalloporphyrin sites, so the CO₂ adsorption capacity (CAC; at 0 °C and 1 bar) over the C₆₀-doped PCN-Co can be largely improved from 2.05 mmol g⁻¹ in the darkness to 2.69 mmol g⁻¹ with light, increased by 31%, in contrast to photo-irresponsive CAC over all C₆₀-undoped PCN-M sorbents and only the photo-loss CAC over C₆₀.

Early-life stress can lead to sustained alterations in regional resting-state brain functions, but the underlying molecular mechanism remains unclear. Stress can also induce sustained changes in epigenetic modifications across brain regions, which are not limited to a few genes; rather, they often tend to produce global levels of change. The functional implication of these changes also remains to be elucidated. We hypothesize that global epigenetic changes may partly modulate the resting-state functions of brain regions to influence behavior. To test this hypothesis, we used an adolescent social stress (ASS) model in mice and examined the relationship between epigenetic modifications and regional resting-state brain activity using resting-state functional magnetic resonance imaging (rs-fMRI). The results showed that, compared to the control mice, the stressed mice showed increased anxiety and social avoidance behaviors and greater levels of dimethylation of histone H3 at lysine 9 (H3K9me2) in the medial prefrontal cortex (mPFC). In addition, the resting-state activity represented by the amplitude of low-frequency fluctuation (ALFF) was significantly lower in the mPFC of stressed mice. To verify the relationship of H3K9me2 and ALFF, the specific inhibition of H3Kme2 was performed by using the drug UNC0642, which reversed the anxiety behavior induced by ASS and significantly increase the ALFF value of mPFC in both normal and ASS animals. Our study is the first to report an association between histone modifications and rs-fMRI findings, providing a new perspective for understanding of the significance of regional brain epigenetic changes and a possible molecular explanation for rs-fMRI findings.

Offensive language detection has received important attention and plays a crucial role in promoting healthy communication on social platforms, as well as promoting the safe deployment of large language models. Training data is the basis for developing detectors; however, the available offense-related dataset in Chinese is severely limited in terms of data scale and coverage when compared to English resources. This significantly affects the accuracy of Chinese offensive language detectors in practical applications, especially when dealing with hard cases or out-of-domain samples. To alleviate the limitations posed by available datasets, we introduce AugCOLD (Augmented Chinese Offensive Language Dataset), a large-scale unsupervised dataset containing 1 million samples gathered by data crawling and model generation. Furthermore, we employ a multiteacher distillation framework to enhance detection performance with unsupervised data. That is, we build multiple teachers with publicly accessible datasets and use them to assign soft labels to AugCOLD. The soft labels serve as a bridge for knowledge to be distilled from both AugCOLD and multiteacher to the student network, i.e., the final offensive detector. We conduct experiments on multiple public test sets and our well-designed hard tests, demonstrating that our proposal can effectively improve the generalization and robustness of the offensive language detector.

Acoustically actuated magnetoelectric (ME) antenna based on the efficient oscillation of magnetic dipoles has recently been considered as a promising solution for portable very-low-frequency communications. However, the severe nonlinear dynamic behavior in the case of strong-field excitation results in insufficient radiation capability and poor communication performance for a conventional ME antenna. In this work, we propose to suppress the nonlinearity of an ME antenna by neutralizing the spring-hardening effect in amorphous Metglas and the spring-softening effect in piezoelectric ceramics through an ME multilayered transmitter (ME-MLTx) design. With a driving voltage of 50 V_pp at the resonance frequency of 21.2 kHz, a magnetic flux density as high as 108 fT at a distance of 100 m is produced from a single ME-MLTx. In addition, ME-MLTx performs a decreased mechanical quality factor (Q_m) less than 40.65, and, thus, a broadened bandwidth of 500 Hz is generated. Finally, a communication link transmitting binary American Standard Code for Information Interchange-coded message is built, which allows for an error-free communication with a distance of 18 m and a data rate of 300 bit/s in the presence of heavy environment noise. The communication distance can be further estimated over 100 m when using a femtotesla-class-inductive magnetic field receiver. The obtained results are believed to bring ME antennas one step closer to being applicable in very-low-frequency communications.

Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments. However, great limitations associated with feeble immune responses and serious adverse effects still cannot be neglected due to the complicated multifactorial etiology and pathologic microenvironment in tumors. The rapid development of nanomedical science and material science has facilitated the advanced progress of engineering biomaterials to tackle critical issues. The supramolecular biomaterials with flexible and modular structures have exhibited unparalleled advantages of high cargo-loading efficiency, excellent biocompatibility, and diversiform immunomodulatory activity, thereby providing a powerful weapon for cancer immunotherapy. In past decades, supramolecular biomaterials were extensively explored as versatile delivery platforms for immunotherapeutic agents or designed to interact with the key moleculars in immune system in a precise and controllable manner. In this review, we focused on the crucial role of supramolecular biomaterials in the modulation of pivotal steps during tumor immunotherapy, including antigen delivery and presentation, T lymphocyte activation, tumor-associated macrophage elimination and repolarization, and myeloid-derived suppressor cell depletion. Based on extensive research, we explored the current limitations and development prospects of supramolecular biomaterials in cancer immunotherapy.