Stochastic computing (SC) has a substantial amount of study on application-specific integrated circuit (ASIC) design for artificial intelligence (AI) edge computing, especially the convolutional neural network (CNN) algorithm. However, SC has little to no optimization on field-programmable gate array (FPGA). Scaling up the ASIC logic without FPGA-oriented designs is inefficient, while aggregating thousands of bitstreams is still challenging in the conventional SC. This research has reinvented several FPGA-efficient 8-bit SC CNN computing architectures, i.e., SC multiplexer multiply-accumulate, multiply-accumulate function generator, and binary rectified linear unit, and successfully scaled and implemented a fully parallel CNN model on Kintex7 FPGA. The proposed SC hardware only compromises 0.14% accuracy compared to binary computing on the handwriting Modified National Institute of Standards and Technology classification task and achieved at least 99.72% energy saving per image feedforward and 31× more data throughput than modern hardware. Unique to SC, early decision termination pushed the performance baseline exponentially with minimum accuracy loss, making SC CNN extremely lucrative for AI edge computing but limited to classification tasks. The SC's inherent noise heavily penalizes CNN regression performance, rendering SC unsuitable for regression tasks.

Fut2-mediated α1,2-fucosylation is important for gut homeostasis, including the intestinal stem cell (ISC). The stemness of ISC declines with age, and aging-associated ISC dysfunction is closely related to many age-related intestinal diseases. We previously found intestinal epithelial dysfunction in some aged Fut2 knockout mice. However, how Fut2-mediated α1,2-fucosylation affects ISC aging is still unknown. On this basis, the herein study aims to investigate the role of Fut2-mediated α1,2-fucosylation in ISC aging. Aging models in ISC-specific Fut2 knockout mice were established. ISCs were isolated for proteomics and N-glycoproteomics analysis. ISC functions and mitochondrial functions were examined in mice and organoids. Ulex europaeus agglutinin I chromatography and site-directed mutagenesis were used to validate the key target fucosylated proteins of Fut2. As a result, Fut2 knockout impaired ISC stemness and promoted aging marker expression in aged mice. Proteomics analysis indicated mitochondrial dysfunction in Fut2 knockout ISC. More injured mitochondria, elevated levels of reactive oxygen species, and decreased levels of adenosine 5′-triphosphate (ATP) in Fut2 knockout ISC were found. Moreover, respiratory chain complex impairment and mitophagy dysfunction in Fut2 knockout ISC were further noted. Finally, Fut2 was demonstrated to regulate mitochondrial functions mainly by regulating the α1,2-fucosylation of N-acyl sphingosine amidohydrolase 2 (Asah2) and Niemann–Pick type C intracellular cholesterol transporter 1 (Npc1). In conclusion, this study demonstrated the substantial role of Fut2 in regulating ISC functions during aging by affecting mitochondrial function. These findings provide novel insights into the molecular mechanisms of ISC aging and therapeutic strategies for age-related intestinal diseases.

Pixel-level structure segmentations have attracted considerable attention, playing a crucial role in autonomous driving within the metaverse and enhancing comprehension in light field-based machine vision. However, current light field modeling methods fail to integrate appearance and geometric structural information into a coherent semantic space, thereby limiting the capability of light field transmission for visual knowledge. In this paper, we propose a general light field modeling method for pixel-level structure segmentation, comprising a generative light field prompting encoder (LF-GPE) and a prompt-based masked light field pretraining (LF-PMP) network. Our LF-GPE, serving as a light field backbone, can extract both appearance and geometric structural cues simultaneously. It aligns these features into a unified visual space, facilitating semantic interaction. Meanwhile, our LF-PMP, during the pretraining phase, integrates a mixed light field and a multi-view light field reconstruction. It prioritizes considering the geometric structural properties of the light field, enabling the light field backbone to accumulate a wealth of prior knowledge. We evaluate our pretrained LF-GPE on two downstream tasks: light field salient object detection and semantic segmentation. Experimental results demonstrate that LF-GPE can effectively learn high-quality light field features and achieve highly competitive performance in pixel-level segmentation tasks.

The presence of endotoxemia is strongly linked to the development of endothelial dysfunction and disruption of myocardial microvascular reactivity. These factors play a crucial role in the progression of endotoxemic cardiomyopathy. Sepsis-related multiorgan damage involves the participation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). However, whether DNA-PKcs contributes to endothelial dysfunction and myocardial microvascular dysfunction during endotoxemia remains unclear. Hence, we conducted experiments in mice subjected to lipopolysaccharide (LPS)-induced endotoxemic cardiomyopathy, as well as assays in primary mouse cardiac microvascular endothelial cells. Results showed that endothelial-cell-specific DNA-PKcs ablation markedly attenuated DNA damage, sustained microvessel perfusion, improved endothelial barrier function, inhibited capillary inflammation, restored endothelium-dependent vasodilation, and improved heart function under endotoxemic conditions. Furthermore, we show that upon LPS stress, DNA-PKcs recognizes a TQ motif in cofilin2 and consequently induces its phosphorylation at Thr²⁵. Phosphorylated cofilin2 shows increased affinity for F-actin and promotes F-actin depolymerization, resulting into disruption of the endothelial barrier integrity, microvascular inflammation, and defective eNOS-dependent vasodilation. Accordingly, cofilin2-knockin mice expressing a phospho-defective (T25A) cofilin2 mutant protein showed improved endothelial integrity and myocardial microvascular function upon induction of endotoxemic cardiomyopathy. These findings highlight a novel mechanism whereby DNA-PKcs mediates cofilin2^Thr25 phosphorylation and subsequent F-actin depolymerization to contribute to endotoxemia-related cardiac microvascular dysfunction.

Early detection and treatment of congenital heart disease (CHD) can significantly improve the prognosis of children. However, inexperienced sonographers often face difficulties in recognizing CHD through transthoracic echocardiogram (TTE) images. In this study, 2-dimensional (2D) and Doppler TTEs of children collected from 2 clinical groups from Beijing Children's Hospital between 2018 and 2022 were analyzed, including views of apical 4 chamber, subxiphoid long-axis view of 2 atria, parasternal long-axis view of the left ventricle, parasternal short-axis view of aorta, and suprasternal long-axis view. A deep learning (DL) framework was developed to identify cardiac views, integrate information from various views and modalities, visualize the high-risk region, and predict the probability of the subject being normal or having an atrial septal defect (ASD) or a ventricular septaldefect (VSD). A total of 1,932 children (1,255 healthy controls, 292 ASDs, and 385 VSDs) were collected from 2 clinical groups. For view classification, the DL model reached a mean [SD] accuracy of 0.989 [0.001]. For CHD screening, the model using both 2D and Doppler TTEs with 5 views achieved a mean [SD] area under the receiver operating characteristic curve (AUC) of 0.996 [0.000] and an accuracy of 0.994 [0.002] for within-center evaluation while reaching a mean [SD] AUC of 0.990 [0.003] and an accuracy of 0.993 [0.001] for cross-center test set. For the classification of healthy, ASD, and VSD, the model reached the mean [SD] accuracy of 0.991 [0.002] and 0.986 [0.001] for within- and cross-center evaluation, respectively. The DL models aggregating TTEs with more modalities and scanning views attained superior performance to approximate that of experienced sonographers. The incorporation of multiple views and modalities of TTEs in the model enables accurate identification of children with CHD in a noninvasive manner, suggesting the potential to enhance CHD detection performance and simplify the screening process.

Catheters navigating through complex vessels, such as sharp turns or multiple U-turns, remain challenging for vascular embolization. Here, we propose a novel multistage vascular embolization strategy for hard-to-reach vessels that releases untethered swimming shape-memory magnetic microrobots (SMMs) from the prior catheter to the vessel bifurcation. SMMs, made of organo-gel with magnetic particles, ensure biocompatibility, radiopacity, thrombosis, and fast thermal and magnetic responses. An SMM is initially a linear shape with a 0.5-mm diameter at 20 °C inserted in a catheter. It transforms into a predetermined helix within 2 s at 38 °C blood temperature after being pushed out of the catheter into the blood. SMMs enable agile swimming in confined and tortuous vessels and can swim upstream using helical propulsion with rotating magnetic fields. Moreover, we validated this multistage vascular embolization in living rabbits, completing 100-cm travel and renal artery embolization in 2 min. After 4 weeks, the SMMs maintained the embolic position, and the kidney volume decreased by 36%.

Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications in intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that a novel circATXN1 highly accumulates in aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, and inhibits mitochondrial respiration. Mechanistically, circATXN1, regulated by heterogeneous nuclear ribonucleoprotein A2B1-mediated splicing circularization, promotes progerin translocation from the cell nucleus to the cytoplasm and inhibits the expression of insulin-like growth factor 1 receptor (IGF-1R). To demonstrate the therapeutic potential of circATXN1, siRNA targeting the backsplice junction of circATNX1 was screened and delivered by tetrahedral framework nucleic acids (tFNAs) due to their unique compositional and tetrahedral structural features. Our siRNA delivery system demonstrates superior abilities to transfect aging cells, clear intracellular ROS, and enhanced biological safety. Using siRNA–tFNAs to silence circATXN1, aging NPCs exhibit reduced mislocalization of progerin in the cytoplasm and up-regulation of IGF-1R, thereby demonstrating a rejuvenated cellular phenotype and improved mitochondrial function. In vivo, administering an aging cell-adapted siRNA nucleic acid framework delivery system to progerin pathologically expressed premature aging mice (zmpste24^−/−) can ameliorate the cellular matrix in the nucleus pulposus tissue, effectively delaying IVDD. This study not only identified circATXN1 functioning as a cell senescence promoter in IVDD for the first time, but also successfully demonstrated its therapeutic potential via a tFNA-based siRNA delivery strategy.

Facile fabrication of highly conductive and self-encapsulated graphene electronics is in urgent demand for carbon-based integrated circuits, field effect transistors, optoelectronic devices, and flexible sensors. The current fabrication of these electronic devices is mainly based on layer-by-layer techniques (separate circuit preparation and encapsulation procedures), which show multistep fabrication procedures, complicated renovation/repair procedures, and poor electrical property due to graphene oxidation and exfoliation. Here, we propose a laser-guided interfacial writing (LaserIW) technique based on self-confined, nickel-catalyzed graphitization to directly fabricate highly conductive, embedded graphene electronics inside multilayer structures. The doped nickel is used to induce chain carbonization, which firstly enhances the photothermal effect to increase the confined temperature for initial carbonization, and the generated carbon further increases the light-absorption capacity to fabricate high-quality graphene. Meanwhile, the nickel atoms contribute to the accelerated connection of carbon atoms. This interfacial carbonization inherently avoids the exfoliation and oxidation of the as-formed graphene, resulting in an 8-fold improvement in electrical conductivity (~20,000 S/m at 7,958 W/cm² and 2 mm/s for 20% nickel content). The LaserIW technique shows excellent stability and reproducibility, with ±2.5% variations in the same batch and ±2% variations in different batches. Component-level wireless light sensors and flexible strain sensors exhibit excellent sensitivity (665 kHz/(W/cm²) for passive wireless light sensors) and self-encapsulation (<1% variations in terms of waterproof, antifriction, and antithermal shock). Additionally, the LaserIW technique allows for one-step renovation of in-service electronics and nondestructive repair of damaged circuits without the need to disassemble encapsulation layers. This technique reverses the layer-by-layer processing mode and provides a powerful manufacturing tool for the fabrication, modification, and repair of multilayer, multifunctional embedded electronics, especially demonstrating the immense potential for in-space manufacturing.

Mitochondrial fission promotes glioma progression. The function and regulation mechanisms of lncRNAs in glioma mitochondrial fission are unclear. The expression of LINC00475 and its correlation with clinical parameters in glioma were analyzed using bioinformatics. Then, in vitro and in vivo assays were performed to explore the function of spliced variant LINC00475 (LINC00475-S) in gliomas. To explore the mechanisms, RNA-seq, MeRIP, RIP, pulldown-IP, dCas9-ALKBH5 editing system, LC/MS, and Western blotting were utilized. LINC00475 was confirmed to be overexpressed and with higher frequencies of AS events in gliomas compared to normal brain tissue and was associated with worse prognosis. In vitro and animal tumor formation experiments demonstrated that the effect of LINC00475-S on proliferation, metastasis, autophagy, and mitochondrial fission of glioma cells was significantly stronger than that of LINC00475. Mechanistically, METTL3 induced the generation of LINC00475-S by splicing LINC00475 through m6A modification and subsequently promotes mitochondrial fission in glioma cells by inhibiting the expression of MIF. Pull-down combined LC/MS and RIP assays identified that the m6A recognition protein HNRNPH1 bound to LINC00475 within GYR and GY domains and promoted LINC00475 splicing. METTL3 facilitated HNRNPH1 binding to LINC00475 in an m6A-dependent manner, thereby inducing generation of LINC00475-S. METTL3 facilitated HNRNPH1-mediated AS of LINC00475, which promoted glioma progression by inducing mitochondrial fission. Targeting AS of LINC00475 and m6A editing could serve as a therapeutic strategy against gliomas.

The activation of pro-inflammatory M1-type macrophages by overexpression of reactive oxygen species (ROS) and reactive nitrogen species (RONS) in synovial membranes contributes to osteoarthritis (OA) progression and cartilage matrix degradation. Here, combing Pt and Se with potent catalytic activities, we developed a hybrid Pt–Se nanozymes as ROS and RONS scavengers to exert synergistic effects for OA therapy. As a result, Pt–Se nanozymes exhibited efficient scavenging effect on ROS and RONS levels, leading to repolarization of M1-type macrophages. Furthermore, the polarization of synovial macrophages to the M2 phenotype inhibited the expression of pro-inflammatory factors and salvaged mitochondrial function in arthritic chondrocytes. In vivo results also suggest that Pt–Se nanozymes effectively suppress the early progression of OA with an Osteoarthritis Research International Association score reduction of 68.21% and 82.66% for 4 and 8 weeks, respectively. In conclusion, this study provides a promising strategy to regulate inflammatory responses by macrophage repolarization processes for OA therapeutic.