Since its initial identification in 2019, lactylation has emerged as a critical posttranslation modification, attracting substantial research interest due to its diverse roles in biological processes. Lysine lactylation represents a recently characterized posttranslational modification wherein lactate moieties are covalently attached to protein lysine residues through both enzymatic and nonenzymatic pathways. Lactate, a primary glycolytic product, suggests a link between cell metabolism and protein function regulation. In neoplastic tissues, the Warburg effect induces preferential glucose-to-lactate metabolism in cancer cells, establishing hypoxic conditions and elevated lactate concentrations as defining characteristics of the tumor microenvironment. Extensive research has demonstrated lactate’s pivotal role in tumor metastasis and patient outcomes, particularly through its influence on tumor immune microenvironment remodeling, although the precise molecular mechanisms remain under investigation. The characterization of lysine lactylation provides a novel framework for understanding these mechanisms and presents innovative opportunities for therapeutic intervention. This review examines the influence of lactylation on the tumor microenvironment and its effect in various malignancies and explores emerging therapeutic strategies, including genetic manipulation, small-molecule inhibitors, clinical pharmaceuticals, and nanoparticle-based approaches, offering new perspectives in cancer treatment.

Large language models (LLMs) have showcased remarkable capabilities in the realm of AI for Science, and chemistry has greatly benefited from the advancement of AI tools. With a strong capacity for learning sequential data like natural language, LLMs offer immense potential. Despite this promise, the application of LLMs in chemistry remains limited, with few models specifically designed for chemical data and tasks. Hence, we propose leveraging LLMs to comprehensively model both chemical sequences and natural language sequences, aiming to tackle diverse chemical tasks. We introduce BatGPT-Chem, a general foundation large-scale model with 15 billion parameters tailored for chemical engineering. Built on a corpus of over 100 million chemical instances, BatGPT-Chem specializes in 5 core tasks: retrosynthesis prediction, molecule design, molecule description, product inference, and yield prediction. BatGPT-Chem comprehensively models the information flow between chemical language and natural language, enabling full-spectrum prediction across chemical tasks. It is one of the largest bilingual chemistry-specific LLMs, supporting both English and Chinese for input and output. BatGPT-Chem is also the first automated retrosynthesis tool capable of explicitly predicting reaction conditions, a critical but often overlooked aspect in previous models. Through rigorous zero-shot evaluations, BatGPT-Chem demonstrates state-of-the-art performance, surpassing both existing chemical LLMs and general-purpose models in accuracy and validity across a diverse range of tasks. Notably, it demonstrates superior ability in predicting both reactants and reaction conditions, as well as strong generalization in low-data settings. These results suggest that BatGPT-Chem is among the most advanced and practical chemical LLMs, with strong potential to support real-world applications in synthesis planning, drug discovery, and materials design.

Ischemic stroke (IS), a common neurological disease, lacks satisfactory treatments worldwide. Neural stem cell (NSC) therapy is a promising strategy for stroke, while microenvironmental disturbance, including but not limited to acidosis, oxidative stress, and excessive neuroinflammation, restricts the therapeutic potential of endogenous and exogenous NSC post-IS. The present study introduces the effect of common disturbance on NSC and the underlying mechanism to screen out feasible methods aiming to potentiate the reparative capacity of NSC following IS.

Microcarriers have demonstrated substantial potential in therapeutic delivery for rheumatoid arthritis (RA) treatment. Herein, we propose a novel spatiotemporal ultrasound-responsive microcapsule carrier to reinforce curcumin-based sonodynamic therapy in treating RA. Based on microfluidic technology, microcapsules with a hydrogel shell loaded with curcumin and a perfluorocarbon core enriched with oxygen (CUR/O₂-MCs) can be obtained. Ascribed to the liquid-to-gas transition property of perfluorocarbon and the sonosensitivity of curcumin, ultrasound stimulation can realize controlled oxygen release followed by sonodynamic reactive oxygen species production. We have demonstrated that the ultrasound-activated CUR/O₂-MCs can elevate reactive oxygen species amounts in overproliferating fibroblast-like synoviocytes, subsequently inducing fibroblast-like synoviocyte apoptosis. In addition, the released curcumin and oxygen can bring about macrophage repolarization, antiangiogenesis, and hypoxia alleviation, which are also important in blocking RA progression. Thus, in collagen-induced arthritis rats, our spatiotemporal sonodynamic microcapsules can attenuate symptoms and reduce joint damage. These results indicate that our ultrasound-responsive multifunctional microcapsule is an ideal candidate for sonodynamic therapy enhancement and RA treatment.

In the field of 4-dimensional (4D) printing, magnetically responsive smart materials have attracted much attention due to their advantages such as large deformation rate, fast dynamic response, and remote controllability. Focusing on this field, this review systematically reviews the research progress of magnetically responsive 4D printing technology from 3 dimensions: printing process, material design, and interdisciplinary applications. Firstly, it elaborates on the core principles and key technologies of 4D printing and conducts an in-depth analysis of the design principles, response mechanisms, and performance optimization strategies of magnetic shape memory materials, providing a clear framework for understanding the fundamental principles of this technology. On this basis, it explores the innovative applications of magnetically responsive 4D printing in the fields of biomedical tissue engineering, intelligent robotics, and functional devices, highlighting its substantial advantages in non-contact manipulation, high-precision response, and biocompatibility, and demonstrating the practical application value of the technology. Finally, it proposes a collaborative design framework of “material–process–application” in order to promote the application of magnetically responsive materials in interdisciplinary fields.

Sustainable habitation systems are critical to enabling deep-space exploration on Mars, where challenges such as low gravity, extreme thermal fluctuations, and resource constraints demand advanced structural innovations. This study introduces Zhuque Base, a habitat concept inspired by terrestrial cave-dwelling principles, optimized through finite element analysis via COMSOL Multiphysics. Three arch-based configurations—the eggshell, catenary, and 2-centered arch—were systematically evaluated by parameterizing geometric variables. The study demonstrated that eggshell arches significantly outperformed 2-centered and catenary arches in mechanical properties, reducing vertical displacement of critical points such as sidewalls by 53% and 44%, respectively. In terms of thermal efficiency, the optimal catenary arch showed 5.5% and 6.7% lower heat loss than eggshell and 2-centered arches. Furthermore, the implementation of optimal parameters (span: 3.2 m, height: 1.25 or 1.45 m) limits the peak compressive stress to 195.72 to 203.38 kPa, while the cross-sectional area can be increased by 14% to maximize the available internal space. These findings establish a parameter-driven framework for in situ Mars habitat optimization, emphasizing the trade-off between mechanical robustness and thermal efficiency in extraterrestrial structural design.

O-glycopeptides are highly expressed in various human cancers and play a key role in cancer progression and metastasis, making them promising biomarkers for early diagnostics. However, the inherent complexity and heterogeneity of glycans pose a major challenge for the simultaneous and precise analysis of multiple glycopeptides. Here, we developed a low-temperature nanopore technique capable of simultaneously discriminating 4 truncated O-glycopeptides with varied glycoforms. This method enables the direct identification and relative quantification of O-glycopeptides from a mixture, achieving a discrimination accuracy of 92.9%. This general strategy holds promise for the label-free analysis of glycopeptide biomarkers, with potential applications in cancer diagnostics.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by a high propensity for metastasis, poor prognosis, and limited treatment options. Research has demonstrated a substantial correlation between the expression of protein arginine N-methyltransferase 1 (PRMT1) and enhanced proliferation, metastasis, and poor outcomes in TNBC. However, the specific role of PRMT1 in lung metastasis and chemoresistance remains unclear. Single-cell RNA sequencing coupled with bioinformatics analysis was employed to identify pertinent genes within metastatic TNBC samples. Functional assays, including cell cycle, apoptosis, wound healing, Transwell migration, colony formation, and Cell Counting Kit-8 Assay (CCK-8), were conducted to evaluate the role of PRMT1. The interaction between PRMT1 and PARP1 was validated by mass spectrometry (MS) and immunoprecipitation. Downstream signaling pathways were explored, with a focus on P65 activation. Enzyme-linked immunosorbent assay was used to quantify the effect of PRMT1 on interleukin-1β secretion. Our study identified a significant association between elevated PRMT1 expression and both lung metastasis and chemoresistance in TNBC. PRMT1 boosts TNBC cell growth, invasion, and lung metastasis. Additionally, high PRMT1 expression contributed to increased resistance to docetaxel in TNBC. Mechanistically, PRMT1 methylates PARP1. On the one hand, this methylation promotes the DNA damage repair ability of PAPA1. On the other hand, it in turn modulates the NF-κB signaling pathway. This modulation enhances the stemness of tumor cells and induces immune suppression within the tumor microenvironment, thereby exacerbating chemoresistance in TNBC. PRMT1 drives lung metastasis and chemoresistance in TNBC through PARP1 methylation and P65 activation. These findings position PRMT1 as a promising biomarker and therapeutic target to overcome resistance and limit metastatic progression in TNBC.

Retinal degenerative disorders pose critical challenges for vision restoration, with traditional prosthetics limited by spectral sensitivity and invasive surgeries. In recent work published in Science, revolutionary tellurium nanowire networks converted broadband visible to near-infrared-II (up to 1,550 nm) light into electrical signals without external bias, restoring functional vision in blind animal models.

The inhibition of dependent glutamine metabolism is an effective treatment for triple-negative breast cancer (TNBC) starvation, but it is limited by compensatory glycolysis and inadequate delivery efficiency. Herein, we construct a pH-responsive size/charge-reprogrammed micelle with hierarchical delivery characteristics for TNBC suppression with glutamine depletion and vessel blockade. It consists of a positively charged prodrug micelle chemically grafted with the glutamine transport inhibitor V9302 as the inner core layer, the neovascular disruptor CA4P adsorbed in the middle layer, and a pH-responsive peelable polymer as the outer shell. The nanosystem PPD/PPQV@C could effectively reduce size and reverse charge in response to the tumor acidic microenvironment by removing the outer polymer PPD, as accompanying the release of CA4P. Furthermore, the remaining PPQV could responsively release V9302 in the cytoplasm of tumor cells, improving the bioavailability of cargoes and overcoming permeability barrier through precise hierarchical release strategy. Importantly, V9302 and CA4P localized in the tumor intracellular and extracellular matrix could effectively block TNBC-dependent glutamine metabolism and inhibit compensatory nutrient by blocking angiogenesis, achieving the desired tumor suppression with prolonged survival time. This work exhibits a smart nanoplatform for efficient TNBC treatment via dual blockade of the dependent glutamine metabolism and angiogenesis.

Collecting duct carcinoma (CDC) is a rare but aggressive form of renal cell carcinoma (RCC) that has limited understanding and an undefined systemic therapeutic regimen. Herein, we conducted a comprehensive proteogenomic analysis of CDC tumors and normal adjacent tissues to elucidate the biology of the disease. CDC exhibited high heterogeneity in tumor mutational burden, and enhanced ribosome biogenesis was the most striking malignant feature of CDC, even compared with other common kidney carcinomas. Genomic data indicated that UTP6 and HN1 amplification on chromosome 17q were associated with the activations of ribosome biogenesis and cell migration, respectively, which were relevant to tumor proliferation and metastasis. Proteomic-based classification identified 3 clusters, among which, tumors overexpressing ribosome biogenesis signaling (GP1) clustered into the most aggressive subtype, while tumors with increased energy metabolism (GP3) exhibited significant sensitivity to anti-vascular endothelial growth factor agents. Immune subtyping revealed a complex immune landscape of CDC. Additionally, increased RPF2, contributing to ribosome production, was validated to be associated with malignant phenotypes, and targeting RPF2 could exert an anti-oncogenic role by disrupting ribosome biogenesis and perturbing the MDM2–p53 interaction.

Successful restoration of blood supply still follows with serious secondary brain injury in cerebral ischemia reperfusion injury (CIRI). However, conventional management after CIRI exhibits numerous limitations.Transcranial low-intensity ultrasound stimulation (TLUS) has been extensively utilized in the field of neuromodulation owing to its characteristics of zero potential side effects, noninvasiveness, deep tissue penetration, and precise spatial targeting capability. Here, we develop a smart multifunctional ultrasound-responsive delivery system to regulate CIRI. Briefly, curcumin, a well-documented safe neuroprotective monomer derived from traditional Chinese medicine, is encapsulated into self-assembled liposomal nanocarriers (RRP@Lipo-Cur). These nanocarriers are modified with reactive oxygen species- and ultrasound-responsive functional elements, as well as neuron-targeting peptides, enabling targeted accumulation in ischemic penumbra and stimuli-responsive drug release. In the mouse model of middle cerebral artery occlusion/reperfusion (MCAO/r), the synergistic treatment of RRP@Lipo-Cur and TLUS significantly facilitated the polarization of microglia from the M1 to the M2 phenotype via the intracellular mitogen-activated protein kinase (MAPK) and nuclear factor κB signaling (NF-κB) pathways, which effectively promoted the establishment of an anti-inflammatory microenvironment in the ischemic penumbra, thereby providing neuroprotection for the damaged neurons. Furthermore, in comparison to single nanomaterial or TLUS interventions, synergistic treatment can optimally modulate neuroinflammation, safeguard injured neurons, and enhance the recovery of neurological function.

Abnormal brain oscillatory activity is a well-established hallmark of bradykinesia and motor impairment in Parkinson’s disease (PD), yet its molecular underpinnings remain unclear. To address this gap, we analyzed over 100,000 single-cell RNA transcriptomes from fresh dorsolateral prefrontal cortex tissue of individuals with PD and non-PD controls, undergoing deep brain stimulation—2 cohorts, which open up an unprecedent window to the characterization of human cortical brain tissue, aiming to uncover the molecular mechanisms of abnormal brain oscillatory activity in PD. Fresh brain tissue samples offer a unique opportunity to precisely elucidate the molecular underpinnings of known, clinically relevant electrophysiological hallmarks of neurodegeneration, which can be used to inform targeted therapeutic strategies. We depicted in microglia and astrocytes enrichment of mitochondrial electron transport and oxidative phosphorylation pathways, which were directly linked to the increase of pathological brain activity and the decrease of prokinetic brain activity. Additionally, the abnormal phase–amplitude coupling of beta–gamma brain activity was related to the dysfunction of oligodendrocyte precursor cells and inflammasome activation mediated by lymphocyte-driven adaptive immunity. We identified a distinct set of dysregulated genes from the mitogen-activated protein kinase phosphorylation pathways, mitochondrial electron transport at the intersection of neuroinflammation and neurodegeneration, suggesting pivotal roles in PD pathology. This unique dataset provides unprecedented insights into the immune and metabolic dysregulation underlying PD, offering a mechanistic framework for understanding invasive transcriptomic biomarkers related to prokinetic and pathologic brain activity in PD.

Ulcerative colitis is a chronic nonspecific intestinal inflammatory disease, which usually occurs in the rectal and colonic mucosa and submucosa. Ligustilide, a major component derived from Angelica sinensis (Oliv.) Diels, exerts anti-inflammation effect. However, its impact and molecular mechanism on colitis remain obscure. In this study, in vivo and in vitro experiments verified that ligustilide protected against colitis by suppressing macrophage-mediated inflammation and repairing intestinal barrier. Of note, we utilized a thermal proteome profiling strategy to preliminarily find early growth response factor 1 (EGR1) as a target of ligustilide. Cellular thermal shift assay, drug affinity responsive target stability, and surface plasmon resonance analysis revealed that ligustilide directly targeted His386 to bind to EGR1. Furthermore, RNA-sequencing, dual luciferase reporter gene assay, and rescue experiments illustrated that ligustilide disturbed the nuclear translocation of EGR1 and broke its combination with a disintegrin and metalloproteinase 17 (ADAM17) promoter, thereby inhibiting ADAM17 transcription and downstream tumor necrosis factor-α (TNF-α) production, as well as expression of inflammatory proteins cyclooxygenase 2 and inducible nitric oxide synthase. Finally, the in vivo experiment with EGR1 overexpression proved that EGR1 was essential for the protective effects of ligustilide on colitis mice. Taken together, our study demonstrates that ligustilide targets EGR1 to inhibit the EGR1-ADAM17-TNFα pathway, thus alleviating macrophage-mediated intestinal inflammation and restoring gut barrier.

Dynamic chromatin 3-dimensional (3D) conformation is a key mechanism regulating gene expression and cellular function during development and disease. Elucidating the structure, functional dynamics, and spatiotemporal organization of the 3D genome requires integrating multiple experimental approaches, including chromatin conformation capture techniques, precise genome manipulation tools, and advanced imaging technologies. Notably, CRISPR/Cas systems have emerged as a revolutionary genome-editing platform, offering unprecedented opportunities for manipulating 3D genome organization and investigating disease mechanisms. This review systematically examines recent advances in CRISPR-based mammalian 3D genome engineering and explores the therapeutic potential of 3D genome engineering strategies in disease intervention.

Aging is characterized by a gradual decline in the functionality of all the organs and tissues, leading to various diseases. As the global population ages, the urgency to develop effective anti-aging strategies becomes increasingly critical due to the growing severity of associated health problems. Immunotherapy offers novel and promising approaches to combat aging by utilizing approaches including vaccines, antibodies, and cytokines to target specific aging-related molecules and pathways. In this review, we summarize the recent advancements of immunotherapies to eliminate senescence cells and senescence-associated secretory phenotypes (SASPs). Next, we describe immunotherapies against age-related diseases containing neurodegenerative diseases, vascular pathologies, type 2 diabetes (T2D), arthritis, osteoporosis, chronic obstructive pulmonary disease (COPD), fibrosis, skin aging, and cancer, detailing the targets, corresponding manipulations, and clinical trials. Related problems including immunosenescence, serious adverse effects, the duality of function of senescent cells and SASPs, and inherent problems of immunotherapy are also discussed, suggesting directions for improvement. In addition to recent development and challenges in the field, we describe a blueprint of personalized aging immunotherapy by multi-omics, Big Data, artificial intelligence (AI), and nanobots in the future, aiming to inspire the development of novel strategies for healthy aging.

Antibiotic cocktails (ABX) serve as potent therapeutic interventions for refractory ulcerative colitis (UC), yet invariably induce gut dysbiosis. This study demonstrates that pectin oligosaccharides synergistically enhance ABX efficacy by restoring gut microbiota balance and selectively enriched antibiotic-resistant Parabacteroides goldsteinii in a colitis mouse model. Our results further indicate that the gavage administration of P. goldsteinii AM58-2XD markedly alleviated colitis via enhancing the branched-chain amino acid metabolic pathway, particularly by facilitating valine metabolism. Notably, these anticolitis effects were partially attenuated in P. goldsteinii^ΔilvE mutants, which are defective in valine-derived isobutyrate (IBN) biosynthesis. We further demonstrated that exogenous IBN supplementation effectively alleviated colitis symptoms in mice and enhanced gut barrier function via activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway. Conditional knockout of PPARγ in Caco-2 intestinal epithelial cells markedly abrogated the IBN-induced enhancement of tight junctions, thereby substantiating the critical role of the IBN-PPARγ pathway in metabolite-mediated mucosal repair. Collectively, we delineate a prebiotic/probiotic–metabolite axis wherein P. goldsteinii facilitates mucosal repair via IBN/PPARγ-dependent epithelial metabolic reprogramming. This insight redefines antibiotic-resistant commensals as precise biotherapeutics for microbiota restoration in refractory UC management.

The elevated dielectric properties of carbonized cotton fibers with refined conductive networks result in substantial impedance mismatch, severely compromising their electromagnetic wave (EMW) absorption performance. Using cotton fibers and [Zn(pz)₂]_n complexes as easily prepared and low-cost raw materials, nano-hierarchically porous MnFeCuCe@C composites were constructed efficiently through optimization of the dynamic balance of element content and carbonization temperature. The results show that MnFeCuCe@C-20% exhibited a minimum reflection loss (RL_min) of −81.44 dB with a thickness of only 1.52 mm at an ultralow loading of 20 wt%, and the effective absorption bandwidth of MnFeCuCe@C-900 °C was also remarkably enlarged to 5.13 GHz at a thickness of 1.6 mm. Modifying only the metal content of the precursor and carbonization temperature can effectively reinforce the magnetic–dielectric synergy and impedance matching. The augmented EMW attenuation primarily stems from the inherent hierarchical porous structure of the MnFeCuCe@C nanocomposite and the rapid electron migration within its high-entropy metal particles. Furthermore, its excellent dissipation capability in practical application scenarios was demonstrated further through radar cross-section simulations. This work comprehensively delineates the optimization strategies for material dielectric properties as well as the convenient and environmental synthesis method.

U-structure has become a foundational approach in medical image segmentation, consistently demonstrating strong performance across various segmentation tasks. Most current models are based on this framework, customizing encoder–decoder components to achieve higher accuracy across various segmentation challenges. However, this often comes at the cost of increased parameter counts, which inevitably limit their practicality in real-world applications. In this study, we provide an E-shaped segmentation framework that discards the traditional step-by-step resolution recovery decoding process, instead directly aggregating multi-scale features extracted by the encoder at each stage for deep cross-level integration. Additionally, we propose an innovative multi-scale large-kernel convolution (MLKConv) module, designed to enhance high-level feature representation by effectively capturing both local and global contextual information. Compared to U-structure, the proposed E-structured approach substantially reduces parameters while delivering superior performance, especially in complex segmentation tasks. Based on this structure, we develop 2 segmentation networks specifically for 2-dimensional (2D) and 3D medical images. 2D E-SegNet is evaluated on four 2D segmentation benchmark datasets (Synapse multi-organ, ACDC, Kvasir-Seg, and BUSI), while 3D E-SegNet is assessed on four 3D segmentation benchmark datasets (Synapse, ACDC, NIH Pancreas, and Lung). Experimental results demonstrate that our approach outperforms the current leading U-shaped models across multiple datasets, achieving new state-of-the-art (SOTA) performance with fewer parameters. In summary, our research introduces a novel approach to medical image segmentation, offering potential improvements and contributing to ongoing advancements in the field. Our code is publicly available on https://github.com/zhaoqi106/E-SegNet.

Real-time wearable sleep monitors process diverse biological signals while operating under tight energy and computation budgets. The existing algorithms are facing problems of high energy consumption due to separate hardware storage and computation units. In this work, textile-integrated in-memory neuromorphic computing electronics based on MoS₂ quantum dot fiber memristors was proposed for physical reservoir computing for the first time. Textile electronics convert raw electroencephalogram (EEG)and snoring audio directly into rich, high-dimensional state vectors based on intrinsic nonlinear dynamics. Leveraging 16 pulse-programmable conductance levels, the reservoir realizes an accuracy of 94.8%, 95.4%, and 93.5% in snoring events, sleep stages, and multimodal fusion, respectively. To enhance the robustness of feature extraction and improve classification performance under noisy conditions, the linear readout layer was replaced with a lightweight convolutional neural network. The hybrid neural network is 6 times faster than traditional deep-learning methods in 24-h segment EEG analysis. The memristors switch at ±1 V and sub-nanoampere currents, providing picowatt energy consumption suited to continuous on-body use. The results establish fiber memristor reservoir computing as an energy-efficient path to in-fabric, multimodal intelligence for next-generation home sleep analysis and wearable health care.

Most human viral pandemics are caused by animal-originated viruses with human adaptation. It is challenging to infer adaptation from viral genes or their coded protein sequences, particularly when the data labels for modeling are inadequate or the input sequence to be predicted is incomplete. Here, we developed a semi-supervised General Intelligence framework to predict Virus Adaptation based on Language-model-embedded protein sequences (GIVAL) for blind input of virus sequences. The language model in GIVAL, named virus Bidirectional Encoder Representations from Transformers (vBERT), was pretrained for embedding using hidden Markov model-contextualized tokens of viral protein sequences. vBERT outperformed prevalent pretrained models like DNABERT-2, proteinBERT, ESM-2, Transformer, and Word2Vec on distinguishing viral proteins with various-grained labels, such as serotypes and single phenotype-altering mutation. The semi-supervised GIVAL obtained higher accuracy in virus adaptation prediction and better fault tolerance on raw labels in the training dataset, overcoming the obstacle of modeling with insufficient labels and predicting blind input. GIVAL was applicable to the adaptation prediction of diverse viruses. For influenza A viruses (IAVs), higher human adaptation was predicted for equine-origin H3N8 IAVs and bovine H5N1 IAVs with simulated mutations. For coronaviruses, GIVAL predicted an adaptation shift of receptor binding from Middle East respiratory syndrome–related coronavirus (MERS-CoV) receptor to severe acute respiratory syndrome coronavirus receptor of 2 recently reported MERS-CoV-like virus variants. For monkeypox viruses, GIVAL quantified an incremental adaptation shift of viral variants, matching the rise in human monkeypox cases. Summarily, GIVAL provides a generally intelligent framework for predicting virus adaptation based on its genotype, with the potential to extend to more genotype-to-phenotype prediction scenarios.

Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disease with no effective therapeutic intervention. Vascular smooth muscle cell (VSMC) phenotypic switching and elevated matrix metalloproteinase (MMP) levels are key pathogeneses of AAA, although the underlying regulatory mechanisms remain to be fully elucidated. In our study, single-cell RNA-sequencing data analysis demonstrated a substantial elevation in modulated VSMCs in patients with aortic aneurysm, accompanied by Dickkopf 3 (DKK3) up-regulation. Both systemic DKK3 knockout and VSMC-specific DKK3 knockdown led to a marked decrease in both the incidence and mortality of AAA in mice. Reintroduction of DKK3 in Dkk3^−/−Apoe^−/− mice via adeno-associated virus (AAV) exacerbated AAA development. DKK3 deficiency maintained the contractile phenotype of VSMC and inhibited MMP production. Given the critical role of TGF-β signaling in VSMC phenotypic switching and the progression of AAA, its regulatory mechanisms exhibit spatiotemporal heterogeneity, and the precise underlying mechanisms require further investigation. Next, we aim to investigate the regulators of this pathway. Mechanistically, DKK3 deficiency activates the TGFβ3–Smad2/3 signaling pathway by down-regulating ATF6, thereby inhibiting VSMC phenotype switching. In summary, these findings indicate that DKK3 drives the phenotypic transition of VSMCs to a synthetic phenotype through the ATF6–TGFβ3–Smad2/3 signaling pathway during the development of AAA, which represents a potential target for therapeutic intervention to maintain VSMC homeostasis in AAA.

With the rapid advancement of communication technologies, issues of electromagnetic pollution and electromagnetic compatibility have become increasingly severe, heightening the demand for high-performance electromagnetic wave absorption materials. Metal-organic frameworks (MOFs) have flourished in this field owing to their chemical tunability, high porosity, tailored topological structures, and functionality. MOF-derived composites exhibit diverse loss mechanisms and heterogeneous structures, achieving lightweight, broadband, and highly efficient absorption. Notably, recent developments in conductive MOFs (cMOFs) have positioned pristine MOFs as promising intrinsic absorbers. Accordingly, this review comprehensively classifies and summarizes recent progresses in MOF derivatives and cMOF-based absorbers, with a focus on 3 critical aspects: design strategies (compositional and structural engineering), absorption performance (reflection loss and bandwidth), and loss mechanisms (dielectric and magnetic loss). Finally, perspectives on future development directions for MOF-based absorption materials are proposed. This review provides methodological guidelines for constructing high-performance MOF-based absorption materials in the future, while highlighting persisting challenges in their development. Ultimately, it charts a course toward designing and fabricating lightweight, broadband, and high-efficiency MOF absorption materials with structural–functional integration.

Dysfunction of motor behavior during spaceflight is linked to alterations in neuronal activities. However, the longitudinal functional changes in the motor cortex triggered by simulated weightlessness remain ambiguous. In this study, we utilized a miniaturized 2-photon microscope to examine the dynamic shifts in neuronal activities within the hindlimb motor cortex during simulated weightlessness and its subsequent recovery period at the single-cell level. Our results demonstrated that simulated weightlessness led to a progressive decline in motor behavior during open-field and rotarod tasks, which was fully reversed after a 2-week recovery period. Single-cell analysis revealed that hindlimb motor neurons could be classified as activated, inhibited, or unchanged. During active locomotion in the open field, the activity of locomotion-activated neurons increased, while the activity of locomotion-inhibited neurons decreased, despite their numbers remaining constant. Conversely, during passive rotation on the rotarod test, the number of rotation-activated neurons decreased, while their activity increased, and the number of rotation-inhibited neurons increased along with their activity. These changes were largely restored after reloading. These findings elucidate motor dysfunction under simulated weightlessness and the heterogeneous changes in neuronal activities within the hindlimb motor cortex, offering valuable insights into understanding behavioral changes regulated by the motor cortex during spaceflight.

Plasma wakefield acceleration in the nonlinear blowout regime has achieved marked milestones in electron beam acceleration, demonstrating high acceleration gradients and energy efficiency while preserving excellent beam quality. However, this regime is deemed unsuitable for achieving positron acceleration of comparable results, which is vital for future compact electron–positron colliders. In this article, we find that an intense positron beam loaded at the back of beam-driven blowout cavity can self-consistently induce the focusing field and flatten the longitudinal wakefield, leading to stable, high-efficiency, and high-quality positron acceleration. This is achieved through the formation of an on-axis electron filament induced by positron beam load, which shapes the plasma wakefield in a distinct way compared to electron beam load in the blowout regime. Via a nonlinear analytic model and numerical simulations, we explain the novel beam loading effects of the interaction between the on-axis filament and the blowout cavity. High-fidelity simulations show that a high-charge positron beam can be accelerated with >20% energy transfer efficiency, ~1% energy spread, and ~1 mm·mrad normalized emittance, while considerably depleting the energy of the drive beam. The concept can also be extended to simultaneous acceleration of electron and positron beams and high transformer ratio positron acceleration as well. This development offers a new route for the application of plasma wakefield acceleration into particle physics.

Cancer persists as one of the most formidable global public health crises and socioeconomic burdens of our era, compelling the scientific community to develop innovative and diversified therapeutic modalities to revolutionize clinical management and enhance patient outcomes. The recent seminal discovery by Swamynathan et al. has unveiled menadione, a vitamin K precursor, as a potent inducer of triaptosis—a novel regulated cell death pathway mediated through the oxidative modulation of phosphatidylinositol 3-kinase PIK3C3/VPS34. This mechanistically distinct cell death paradigm, characterized by its intimate association with endosomal dysfunction and oxidative stress-induced cellular catastrophe, has demonstrated remarkable therapeutic efficacy in preclinical prostate cancer models, outperforming conventional therapeutic regimens and emerging as a potential paradigm-shifting strategy in oncology. This comprehensive review provides a critical synthesis of the triaptosis discovery landscape, elucidating its molecular intricacies and pathophysiological implications. We systematically examine the multifaceted roles of endosomal biology in oncogenesis and tumor progression, while offering a nuanced perspective on redox homeostasis in malignant cells and the therapeutic potential of oxidative stress modulation. Furthermore, we address the inherent dichotomy of oxidative stress induction in cancer therapy, balancing its therapeutic promise against potential adverse effects. Looking toward the horizon of cancer research, we explore transformative therapeutic strategies leveraging triaptosis induction and its potential applications beyond oncology, aiming to catalyze a new era of precision medicine that ultimately enhances patient survival and quality of life.

Visual bionic systems are of crucial importance in the development of artificial intelligence for environmental perception. However, the traditional artificial vision system has problems such as complex system and high energy consumption due to the physical separation of image perception, storage, and processing unit. In this work, we designed an ITO/ZTO/ZnO/ITO/Mica structure optoelectronic synaptic device, which is capable of integrating optical sensing, information storage, and logic computation. Utilizing its excellent light response characteristics, the PPF, learning-experience behavior, and Pavlov experiment were successfully simulated. In a 3 × 5 array, the “F” hidden in “E” was identified by using 2 different lighting conditions, successfully simulating color recognition. Furthermore, a further design of an automatic meeting vehicle system based on the embedded platform was carried out, and the meeting vehicle behavior was successfully achieved by utilizing the light response of the ZTO device. This discovery demonstrates the potential of ZTO devices in simulating the behavior of biological synapses, providing new avenue for neuroscience research and the development of bioelectronic devices.

Accumulating evidence demonstrates crosstalk involving the intestine and the brain, with the gut microbiota serving as a critical mediator of this interaction. The gut microbiota, along with its derived metabolites and bioactive compounds, modulates the immune microenvironment of brain tumors via the gut–brain axis, thereby influencing tumor initiation, progression, invasion, and metastasis. This review systematically summarizes the pathophysiological mechanisms underlying gut–brain axis modulation of brain tumors and examines emerging therapeutic approaches, including advances in immunotherapy and targeted therapy, that hold promise for future brain tumor treatment strategies.

Aging has important impacts on both the function and structure of the brain, yet the interplay between these changes remains unclear. Here, we present a unified framework including both single-modal and multimodal age predictions using a large UK Biobank dataset (27,793 healthy subjects, 49 to 76 years) to identify and validate brain functional network connectivity (FNC) and gray matter volume (GMV) changes associated with aging, then propose a novel analysis method to reveal various joint aging patterns, and finally investigate the association between joint function–structure changes and cognitive declines. Multimodality outperforms single modality in the age prediction, underscoring the significance of multimodal aging-related changes. Aging primarily induces synergistic changes, with both FNC and GMV decreased in the cerebellum, frontal pole, paracingulate gyrus, and precuneus cortex, indicating consistent degeneration in motor control, sensory processing, and emotional regulation, and contradictory changes with increased FNC magnitude but decreased GMV in the occipital pole, lateral occipital cortex, and frontal pole, acting as a compensatory mechanism as one ages to preserve visual acuity, cognitive ability, and behavioral modulation. Particularly, joint changes, with both FNC and GMV decreased in the crus I cerebellum and the paracingulate gyrus, show a strong Pearson correlation with the reaction time. In summary, our study unveils diverse joint function–structure changes, providing strong evidence for understanding distinct cognitive deteriorations during aging.

Solar-driven interfacial evaporators represent a promising technique to address the energy crisis and freshwater scarcity issues. However, simultaneously achieving both high evaporation efficiency and long-term stability in a single evaporator system under multifactorial environmental conditions remains challenging. Herein, inspired by the anisotropic channel structure of wood, a novel evaporator featuring a vertical channel structure and excellent photothermal conversion performance for evaporation is developed through the covalent-bond bridging of MXene–polydopamine–cellulose nanocrystals. Polydopamine-modified MXene acts as a photothermal material, exhibiting excellent photothermal conversion efficiency. The vertical channels endow the evaporator with efficient thermal management and rapid mass transfer capabilities to dynamically balance the feedwater supply and photothermic energy input. Thereby, the evaporator exhibits an enhanced evaporation rate of 2.29 kg m⁻² h⁻¹, accompanied by a remarkable 97.34% evaporation efficiency under 1-sun illumination. Additionally, the evaporator possesses a mechanical strength as high as 0.454 MPa, which ensures its long-term stability. Over 14 d of testing, stable evaporation rates of 2.27 kg m⁻² h⁻¹ were maintained over 8-h cycles with no salt crystallization. This work introduces a novel evaporator design with a strong evaporation capability, which has potential applications in addressing the energy crisis and water scarcity challenges.

Slice-based additive manufacturing has been intensively investigated due to its potential in complex 3-dimensional (3D) structure construction across various fields. Current researches focus on curing surface and resin formation regulation to realize continuous printing. However, multi-material construction necessitates vat switching, compromising construction continuity. Achieving simultaneous multi-material construction within a single layer and enabling continuous multi-material construction continue to pose substantial challenges. Here, we present a continuous multi-material additive manufacturing (CMAM) approach by integrating extruding multi-liquid phases into droplet-based 3D printing system. The multi-droplet-based multi-liquid reservoir enables both 2D patterning of multi-liquid materials and their real-time curing, along with continuous resin replenishment to achieve continuous multi-material 3D construction. Additionally, extrusion parameters (extrusion number, spatial distribution, and extrusion flow rates) are controllable layer by layer, leading to controllable muti-material 3D distribution. Interfacial fusion can be controlled by adjusting printing speed and resin viscosity, leading to enhanced mechanical adhesions of 2 materials without influencing interfacial boundary precision. Increasing extrusion number can realize multi-material 3D structure construction with controlled material distribution, which can be extended to 3D structure-based anti-counterfeiting and soft robotics, guaranteeing a highly efficient and sustainable approach to multi-material 3D fabrication.

Introduction: Topographical cues of biomaterial scaffolds directly guide cell behaviors by determining integrin ligation and subsequent mechanotransducive pathways, but their influence on organelle (e.g., mitochondrion) behaviors remains unclear. Objectives: Considering the high sensitivity of mitochondria in cardiomyocytes to topographical signals, this study focused on investigating the impact of oriented micro/nano-wrinkled surfaces with varying wavelengths (0.5 to 25.0 μm) and amplitudes (0.05 to 4.30 μm) on the mitochondrial functions of rat embryonic myocardial cell line H9c2. Methods and Results: The results uncover a nonlinear response of cardiomyocyte behavior and mitochondrial homeostasis to these surface features. Notably, surfaces with a 3-μm wavelength and 0.7-μm amplitude (W3) promoted substantial cell elongation and orientation, whereas surfaces with a 0.5-μm wavelength and 0.05-μm amplitude (W0.5) triggered pronounced mitochondrial division. Remarkably, W0.5 topography facilitated mitochondrial division via cytoskeletal remodeling, involving vinculin and tubulin, which disrupted mitochondrial energy metabolism, enhanced reactive oxygen species (ROS)-mediated oxidative stress, and perturbed mitochondrial homeostasis by stimulating the adenosine 5′-monophosphate-activated protein kinase (AMPK) pathway. The transcriptomic analysis identifies the pivotal involvement of the p53, FoxO, mTOR, HIF-1, and AMPK signaling pathways in regulating mitochondrial dynamics in myocardial cells induced by W0.5, confirming the essential role of the polyadenylation signal (AATAAA) in modulating transcript splicing processes. Conclusion: Overall, this study offers important insights into the regulatory mechanisms by which aligned micro/nano topographical stimuli impact mitochondrial responses in cardiomyocytes, which hold potential for the development of novel biomaterial-focused approaches for diagnosing and treating cardiovascular diseases.

As a key component of perovskite-based tandem photovoltaic devices, wide-bandgap (WBG) perovskite solar cells (PSCs) have been extensively explored recently. For WBG perovskite with mixed Cs/formamidinium (FA) cations and I/Br anions, it is challenging to control ordered crystal growth due to component complexity, and defect-mediated halogen migration causes severe phase separation, leading to poor film quality and inferior device performance. In this work, CsPb₂Br₅ has been developed to serve as a heteronucleation agent to regulate the crystal growth of Cs_0.2FA_0.8Pb(I_0.6Br_0.4)₃ perovskite for producing high-quality film. Theoretical and experimental results show that CsPb₂Br₅ reduces the energy barrier of nucleation and increases the defect formation energy, which not only promotes the homogeneous nucleation and guides the vertical growth of perovskite, which is beneficial for charge transport, but also reduces the defect density and releases the residual strains that suppress phase separation in the film. Therefore, optimized 1.80-eV PSCs yield a champion power conversion efficiency of 20.14% and a record-high fill factor of 85.39% with enhanced device stability. Notably, the constructed 4-terminal tandem devices yield promising power conversion efficiencies of 31.13% (perovskite/silicon) and 28.39% (all-perovskite). This work adds critical building blocks for efficient and stable WBG PSCs by rational crystallization control.

Background: Cardiac surgery patients frequently experience perioperative neurocognitive disorder. Cognitive reserve (CR) is known to mitigate such deficits. Here, we investigate whether global left frontal cortex (gLFC) connectivity, a neural proxy of CR, modulates the relationship between postoperative inflammation and cognitive recovery. Methods: Twenty-five patients scheduled for heart valve replacement surgery were compared to healthy controls using neuropsychological assessments, magnetic resonance imaging, and cytokine levels measured at 3 intervals (before surgery and 7 and 30 days after surgery). Linear regression analysis was used to examine the relationship between the increase in inflammation markers on postoperative day 7 (ΔInflammatory factor_{[7d-baseline]}) and changes in cognition from postoperative day 7 to 30 (ΔNeuropsychological assessment_[30d-7d]). Moderation analysis combined with Johnson–Neyman threshold testing was performed to assess how gLFC connectivity across 3 time points moderated the relationship between ΔIL-6_{[7d-baseline]} and cognitive change. Results: Patients exhibited significant cognitive decline, particularly in executive and memory function, as well as decreased gLFC connectivity on postoperative day 7, compared to controls. This decline was followed by recovery on postoperative day 30. In patients, ΔIL-6_{[7d-baseline]} was negatively correlated with ΔCorsi block test_(30d-7d): β = −0.62, P < 0.001 and ΔDigit symbol test_(30d-7d): β = −0.47, P = 0.017. The interactions of gLFC connectivity at 3 time points × ΔIL-6_{[7d-baseline]} were separately significant on postoperative cognitive recovery. Johnson–Neyman analysis revealed that the effect of ΔIL-6_{[7d-baseline]} was significant when gLFC connectivity was within a specific range. Conclusion: These findings suggest that gLFC connectivity, reflecting CR, may serve as a target for interventions to enhance cognitive resilience in cardiac surgery patients.

The diversity of neutrophils’ subtypes and functions in the tumor microenvironmentunderlies their contributions to both pro- and anti-tumorigenic activities. How to elucidate the antitumor mechanisms of neutrophil and effectively utilize it still needs to be studied. In this study, neutrophil stimulus reaction index (NSRI) was established for high selectivity of neutrophils. Sufficient and highly selective exogenous neutrophils were used to infuse into tumor-bearing mice. Navigation technique was used to make neutrophils rapidly infiltrate into the tumor tissue, which played a key role in inhibiting tumor growth. We found that tumor cells were efficiently killed in direct coculture with sufficient neutrophils by promoting a multimodal death primarily dominated by apoptosis. Interestingly, colon cancer organoid diameters were decreased markedly cocultured with neutrophils, and were more remarkable in the application of organoid microinjection of neutrophils. Consistent with the 3D-printed model, in vivo model indicated that neutrophils meaningfully inhibited the tumor growth by formation of neutrophil extracellular traps (NETs) with neutrophil elastase (NE) payload. This study not only unveils the crucial anticancer effects of neutrophils but also sets out an innovative strategy of aggressive dose exogenous neutrophils with precise navigation, which provided the basis for advancements in neutrophil-based immunotherapy for colon cancer treatment.

T lymphocyte dysfunction represents a pivotal determinant of immunosuppression in sepsis. Our previous studies demonstrated that nuclear fragile X mental retardation-interacting protein 1 (NUFIP1)-mediated ribophagy conferred cytoprotection against apoptosis in CD4⁺ T lymphocytes during sepsis, thereby preserving host immunocompetence. Despite growing evidence linking PANoptosis to the pathogenesis of various diseases, the potential role of ribophagy in modulating CD4⁺ T lymphocytes’ PANoptosis in sepsis remains largely unclear. In the present study, we employed both lipopolysaccharide-stimulated Jurkat T cells and cecal ligation and puncture (CLP)-induced sepsis models to demonstrate marked exacerbation of CD4⁺ T lymphocyte PANoptosis following NUFIP1 knockdown (KD), associated with impaired immune function, as evidenced by diminished cytokine production and T cell proliferation. Tandem mass tagging (TMT) proteomic analysis identified Z-nucleic acid binding protein 1 (ZBP1)-mediated PANoptosome formation and the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway as critical nodes in ribophagy-dependent cytoprotection. Mechanistically, sepsis-induced ribosome collision activated the cGAS-STING signaling axis, which in turn recruited NUFIP1 to STING protein complexes. Clinical analysis of septic patients revealed enhanced ribophagy and PANoptosis in peripheral blood CD4⁺ T cells, consistent with the experimental findings. These results suggest that NUFIP1-mediated ribophagy alleviates CD4⁺ T lymphocyte PANoptosis in sepsis via the cGAS-STING pathway, highlighting the therapeutic potential of targeting ribophagy and PANoptosis pathways to mitigate immune paralysis and improve the outcomes following septic insults.

Histidine phosphorylation, the neglected but vital phosphoproteome, is a reversible posttranslational modification catalyzed by histidine kinases and erased by phosphohistidine (pHis) phosphatases (e.g., LHPP). Traditional types of phosphorylation have been implicated with the deadliest adult ocular tumor uveal melanoma (UM), which is lipid metabolism dysfunction related. However, the role of histidine phosphorylation in UM remains unknown. Here, up-regulated histidine phosphorylation is associated with poor UM prognosis. Reversal of histidine phosphorylation by LHPP exerts therapeutic effects. Mechanistically, we identified LHPP as metabolically related protein with mitochondrial targeting sequence. LHPP interacts and reduces excessive histidine phosphorylation of mitochondrial aconitase ACO2 at H73 site, thus restoring ACO2 enzymatic activity and mitochondrial citrate transit in TCA cycle. Reduction of citrate accumulation attenuates overloaded lipid synthesis. Besides, genetic ablation of LHPP in mouse eye exhibits abnormal lipid metabolism. These findings illustrate the antagonistic roles of oncogenic histidine phosphorylation and therapeutic mitochondrial LHPP and provide metabolic insight of pHis modification in ocular diseases.

Background: The hypersensitive state of the central nervous system, commonly known as central sensitization, presumably drives allergic rhinitis (AR) pathogenesis. However, the involvement of central sensitization in AR and its related mechanisms have rarely been studied. Methods: An AR mouse model was induced via ovalbumin treatment. Activation of trigeminal nucleus caudalis (TNC) neurons was assessed by electrophysiological recordings and immunofluorescence staining. The role of TNC neurons in AR was investigated by selectively manipulating them through chemogenetics. The contribution of microglial neuroinflammation to central sensitization and AR was assessed by pharmacologically inhibiting microglial activation. The mechanism of central sensitization in AR was further determined using a microglia–neuron co-culture system. The role of interleukin (IL)-4 in neuroinflammation in AR was explored using in vivo and in vitro methods. Results: The intrinsic neuronal excitability and molecular markers of central sensitization were increased within the TNC of AR mice. Chemogenetic inhibition of TNC neurons ameliorated nasal symptoms, histological changes, autonomic dysfunction, and immune imbalance in AR mice. Moreover, AR mice exhibited an increased number of pro-inflammatory microglia, activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, and enhanced IL-1β production in the TNC. Pharmacological inhibition of microglial activation reduced central sensitization in AR mice and was accompanied by remission of AR. Transcriptomics analysis revealed the inflammatory-prone characteristics of IL-4-treated microglia. IL-4 exposure enhanced lipopolysaccharide-stimulated NLRP3 inflammasome activation in microglia. Intracerebral injection of IL-4 neutralizing antibodies ameliorates neuroinflammation and central sensitization in AR mice and was accompanied by remission of AR. Conclusions: This research uncovers a previously unidentified mechanism wherein microglial neuroinflammation-induced central sensitization in the TNC contributes to AR, providing a new promising approach for the treatment of AR. IL-4 induces noncanonical pro-inflammatory-prone microglia and participates in microglial NLRP3 inflammasome activation in AR.