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Stimuli-responsive biomaterials that contain logic gates hold great potential for detecting and responding to pathological markers as part of clinical therapies. However, a major barrier is the lack of a generalized system that can be used to easily assemble different ligand-responsive units to form programmable nanodevices for advanced biocomputation. Here we develop a programmable polymer library by including responsive units in building blocks with similar structure and reactivity. Using these polymers, we have developed a series of smart nanocarriers with hierarchical structures containing logic gates linked to self-immolative motifs. Designed with disease biomarkers as inputs, our logic devices showed site-specific release of multiple therapeutics (including kinase inhibitors, drugs and short interfering RNA) in vitro and in vivo. We expect that this ‘plug and play’ platform will be expanded towards smart biomaterial engineering for therapeutic delivery, precision medicine, tissue engineering and stem cell therapy.A programmable polymer library that responds to external and internal stimuli has been developed and used to fabricate a series of nanocarriers for drug release. The carriers respond to disease biomarkers, triggering self-immolative motifs and leading to the site-specific release of therapeutics both in vitro and in vivo.

Understanding the heterogeneity of epigenetic modifications within single cells is pivotal for unraveling the nature of the complexity of gene expression and cellular function. In this study, we have developed a strategy based on multichrome encoding and “AND” Boolean logic recognition for multiplexed, spatially resolved imaging of single-cell RNA epigenetic modifications, termed as PRoximity Exchange-assisted Encoding of Multichrome (PREEM). Through the implementation of this strategy, we can now map the expression and nuclear distribution of multiple site-specific RNA N6-methyladenosine (m 6 A) modifications at the single-molecule resolution level in single-cells, and reveal the previously unknown heterogeneity. Notably, we demonstrate how these patterns change after treatment with various drugs. Moreover, cyclic imaging with tailed DNA self-assembly further suggest the scalability and adaptability of PREEM’s design. As an innovative epigenetic modification imaging tool, PREEM not only broadens the horizons of single-cell epigenetics research, enabling joint analysis of multiple targets beyond the limitations of imaging channels, but also reveals cell-to-cell variability, thereby enhancing our capacity to explore cellular functions. Understanding the heterogeneity of epigenetic modifications is pivotal for unraveling cellular functions. Here, the authors developed a strategy based on multichrome encoding and “AND” Boolean logic recognition, termed as PREEM, for multiplexed imaging of m6A modifications of single-cell RNA.

Northeast China, situated in the eastern Central Asian Orogenic Belt (CAOB), marks the terminal closure zone of the Paleo-Asian Ocean (PAO) (eastern segment). At present, due to extensive Quaternary cover, the structural deformation characteristics and deep structure of the Solonker Suture Zone in the east of the Nenjiang–Balihan fault remain poorly constrained, which limits our understanding of the tectonic evolution of the PAO. This study integrates deep seismic reflection (DSR) and magnetotelluric (MT) sounding profiles to investigate the crustal structural, sedimentary framework, and tectonic evolution of the oceanic and continental crusts along the western slope of the Songliao Basin. Two regional detachment surfaces (D1 and D2) were identified. The D2 interface demarcates the upper crust’s basal boundary, overlain by multiple high-amplitude monoclinic reflections. The area below the D2 interface exhibits a network structure of arcuate and variably oriented reflections, indicating a dual-layered orogenic structure. The upper crust exhibits distinct structural domains defined by strongly contrasting monoclinal reflections: north-dipping, low-resistivity zones in the southern sector and south-dipping, high-resistivity zones in the northern sector. These oppositely oriented reflections have been interpreted as marking an Early Paleozoic accretionary wedge and oceanic island arc, respectively. Interposed between these opposing structural domains, the Paleozoic to Early Mesozoic forearc basin sequences are preserved, with a pre-Middle Permian oceanic basin identified north of the study area. By integrating characteristics of seismic reflection sequences with regional geological data, this paper clarifies the processes of closure and collision at the northern margin of the PAO (Eastern Segment).

Therapeutic strategies for peritoneal metastasis in solid tumors are urgently needed. Programming chimeric antigen receptor macrophages (CAR-Ms) in situ offers opportunities for an unmet demand. However, potential intracellular domains (ICDs) for CAR design and their antitumor mechanisms for macrophage empowerment remain to be explored systematically. By developing a macrophage-targeted mRNA lipid nanoparticle (mRNA-LNP) system, we evaluate 36 CAR formats in CAR-Ms. Tailored CAR-Ms with CD3ζ TLR4 ICDs elicit robust adaptive immune activation and significantly synergize with PD-1/L1 therapy. Single-cell RNA sequencing (scRNA-seq) reveals that CAR-Ms reshape the immunosuppressive tumor microenvironment (TME) and boost the TCF1 + PD-1 + progenitor-exhausted CD8 + T cells (Tpex) population. Mechanistically, CAR-Ms maintain a proinflammatory phenotype and simultaneously upregulate MHC-I and PD-L1 by perturbing NF-κB pathways. Collectively, this approach enables intraperitoneal programming of tailored CAR-Ms and broadens understanding of both regulatory and feedback mechanisms for CAR-M therapies against solid tumors. Peritoneal metastasis remains a major clinical challenge due to the lack of effective therapeutic options. In this study, the authors present intraperitoneal programming of tailored chimeric antigen receptor macrophages (CAR-Ms) as a strategy against peritoneal metastasis.

Intervertebral disc degeneration (IVDD) is a prevalent chronic spinal condition characterized by the deterioration of the intervertebral discs (IVD), leading to structural damage and associated pain. This degenerative process is closely linked to oxidative stress injury, which plays a pivotal role in its onset and progression. Oxidative stress in IVDD results from the excessive production of reactive oxygen species (ROS) and impaired ROS clearance mechanisms, disrupting the redox balance within the intervertebral disc. Consequently, oxidative stress contributes to the degradation of the extracellular matrix (ECM), promotes cell apoptosis, and exacerbates disc tissue damage. Current treatment options for IVDD face significant challenges in effectively alleviating the oxidative stress-induced damage and facilitating disc tissue repair. However, recent advancements in biomaterials have opened new avenues of hope for IVDD treatment by addressing oxidative stress. In this review, we first provide an overview of the pathophysiological process of IVDD and explore the mechanisms and pathways associated with oxidative stress injury. Then, we delve into the current research on antioxidant biomaterials employed in the treatment of IVDD, and outline the advantages and limitations of hydrogel, nanomaterials, polyphenol and inorganic materials. Finally, we propose the future research direction of antioxidant biomaterials in IVDD treatment. The main idea of this review is shown in Scheme 1. [Display omitted] •The mechanisms of oxidative stress damage in intervertebral disc degeneration are discussed.•The pathophysiological changes that occur during the process of the intervertebral disc degeneration are discussed.•Recent findings on antioxidant biomaterials for the treatment of intervertebral disc degeneration are summarized.•The future applications of antioxidant biomaterials in the intervertebral disc degeneration are prospected.

Active magnetic bearings (AMBs) are widely used in high-speed turbines, precision machining, and energy storage systems due to their non-contact operation, high rotational speeds, and low maintenance. The 8-pole radial magnetic bearing (RMB), commonly adopted in AMB systems, faces limitations in load-carrying capacity and space utilization under heavy loads. To address this, a 12-pole RMB with E-type magnetic poles is proposed, enhancing stator space utilization and electromagnetic force generation. However, optimizing the 12-pole RMB is challenging due to the trade-off between maximizing electromagnetic force and minimizing stator volume, with limited research on its multi-objective optimization. This study fills this gap by systematically investigating the structural design and optimization of the 12-pole RMB. A mathematical model using an equivalent magnetic circuit is developed, validated by Finite Element Method (FEM) simulations, showing strong agreement. FEM further assesses magnetic flux density, dynamic performance, and structural parameter effects. Using the NSGA-II algorithm, a multi-objective optimization framework optimizes the conflicting objectives, selecting six key variables based on their Pareto effect. A prototype of the optimized 12-pole RMB is fabricated and tested, demonstrating stable levitation and confirming the design’s effectiveness. This study offers a systematic approach for designing 12-pole RMBs, providing valuable insights for industrial applications.

Zinc (Zn) is an essential trace element that plays important roles in growth, digestion, antioxidant defense, immunity, and inflammation regulation in fish. This study investigated the effects of graded dietary Zn levels on growth performance, serum biochemistry, digestive enzyme activity, zinc transporter expression, antioxidant capacity, immune responses, and inflammatory regulation in juvenile black carp (Mylopharyngodon piceus). Six isonitrogenous and isoenergetic diets were formulated to contain 27.95, 34.38, 44.90, 66.52, 116.14, and 199.56 mg/kg Zn by supplementing ZnSO4·7H2O. Juvenile fish with an initial weight of 2.88 ± 0.12 g were fed the experimental diets for 60 days in triplicate tanks. Growth performance increased with dietary Zn and then plateaued at 44.90–199.56 mg/kg; broken-line regression estimated the optimal dietary Zn requirement at 44.6 mg/kg. Adequate Zn supplementation also reduced whole-body lipid content, increased digestive enzyme activities, improved serum HDL-C and ALP levels, and decreased AST and ALT activities. In addition, adequate dietary Zn (44.90 mg/kg) significantly modulated the expression of zinc transporter genes in the liver and intestine. Adequate dietary Zn supplementation enhanced antioxidant capacity by activating the Nrf2/Keap1 signaling pathway, improved intestinal immunity, and strengthened barrier function by increasing the expression of tight junction proteins and mucins. Moreover, adequate dietary Zn could alleviate inflammatory responses by upregulating anti-inflammatory factors and downregulating pro-inflammatory cytokines via the MAPK14 signaling pathway. These findings suggest that dietary zinc at 44.60 mg/kg is sufficient to promote growth, antioxidant status, immune function, and intestinal health in juvenile black carp.