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Glucose metabolism and innate immunity evolved side-by-side. It is unclear if and how the two systems interact with each other during hepatitis B virus (HBV) infections and, if so, which mechanisms are involved. Here, we report that HBV activates glycolysis to impede retinoic acid-inducible gene I (RIG-I)-induced interferon production. We demonstrate that HBV sequesters MAVS from RIG-I by forming a ternary complex including hexokinase (HK). Using a series of pharmacological and genetic approaches, we provide in vitro and in vivo evidence indicating that HBV suppresses RLR signaling via lactate dehydrogenase-A-dependent lactate production. Lactate directly binds MAVS preventing its aggregation and mitochondrial localization during HBV infection. Therefore, we show that HK2 and glycolysis-derived lactate have important functions in the immune escape of HBV and that energy metabolism regulates innate immunity during HBV infection. RIG-I is a cytosolic antiviral nucleic acid sensor that signals via MAVS to produce type 1 interferons. Here the authors show that hepatits B virus can repress this pathway by activating glycolysis and lactate production, enabling accumulated lactate to bind MAVS and prevent its mitochondrial localization.

Mental health is a significant concern for teenagers. Given that about 80% of Chinese high school students spend the majority of their time indoors on campus, school environments present opportunities not just for learning but also for reducing students’ stress and promoting their well‐being. Previous research has shown that direct interactions with natural elements such as green plants have restorative effects, but limited attention has been given to indirect interactions with nature. We investigated the impact of three design forms—nonbiophilic, curved, and biomimicry—within school corridors and classrooms on Chinese high school students’ stress and cognitive functions. We employed a combination of subjective assessments and objective measurements to examine the protective and restorative impacts of these three design forms and utilized virtual 3D models in order to control confounding environmental variables during a visual experience. Through virtual reality simulations involving 96 participants, we collected physiological responses, including skin conductance level, heart rate, indicators of heart rate variability, and cognitive responses, including creativity and attention test scores, to evaluate participants’ changes in stress levels and cognitive performance. Our results indicated that indirect exposure to nature, particularly curved forms, facilitates greater cognitive improvement and stress reduction, whereas nonbiophilic forms offer enhanced stress protection benefits. Therefore, learning environments with nonbiophilic design may be more suitable for tasks that induce stress, such as classes and examinations. Learning environments that feature curved biophilic forms may be better suited for promoting relaxation, creativity, and attention.

In complex backgrounds and under severe occlusions, the accuracy of vision-based robotic grasping pose estimation decreases significantly, further making objects difficult to manipulate and grasp. This paper proposes an iterative closed-loop optimization framework that deeply couples SAM with FoundationPose. The framework breaks through the open-loop logic bottleneck of “segmentation first, then estimation” found in traditional vision algorithms and constructs a mask correction mechanism based on rendered projection. By performing 3D rendering of the initially estimated 6D pose, a geometric prior mask of the object is generated and then fed back into SAM’s prompt encoder, thereby guiding the model to achieve pixel-level refinement of the target’s boundary in the next perception cycle. Meanwhile, to overcome the blind spots of a single metric, the framework designs a multi-dimensional confidence assessment module that integrates both the 2D image domain and the 3D geometric domain to comprehensively evaluate the reliability of the current pose. The SAM prior, the closed-loop iterative mechanism, and the multi-dimensional confidence assessment module work in synergy to form a complete optimization loop. In robustness experiments on pose estimation under cluttered and stacked scenes, the proposed method achieves an overall ADD-S recall rate of 91.7%, with the average translation and rotation errors reduced to as low as 3.5 mm and 2.1°. In 200 real-world robotic grasping verification trials, the overall grasping success rate reaches 96.5%. These experimental results demonstrate the effectiveness and enhanced robustness of the proposed closed-loop optimization framework in the tested unstructured environments.

AMPK, a master regulator of metabolic homeostasis, is activated by both AMP-dependent and AMP-independent mechanisms. The conditions under which these different mechanisms operate, and their biological implications are unclear. Here, we show that, depending on the degree of elevation of cellular AMP, distinct compartmentalized pools of AMPK are activated, phosphorylating different sets of targets. Low glucose activates AMPK exclusively through the AMP-independent, AXIN-based pathway in lysosomes to phosphorylate targets such as ACC1 and SREBP1c, exerting early anti-anabolic and pro-catabolic roles. Moderate increases in AMP expand this to activate cytosolic AMPK also in an AXIN-dependent manner. In contrast, high concentrations of AMP, arising from severe nutrient stress, activate all pools of AMPK independently of AXIN. Surprisingly, mitochondrion-localized AMPK is activated to phosphorylate ACC2 and mitochondrial fission factor (MFF) only during severe nutrient stress. Our findings reveal a spatiotemporal basis for hierarchical activation of different pools of AMPK during differing degrees of stress severity.

Graph-enhanced Retrieval-Augmented Generation (RAG) frameworks, such as GraphRAG, improve large language model (LLM)-based question answering (QA) by constructing and leveraging structured, knowledge-condensed graph information. However, they still face challenges in complex multi-hop reasoning tasks and often incur substantial time and resource costs, resulting in low efficiency. To address these limitations, we propose DualGraphRAG, a dual-view graph-enhanced RAG framework designed to achieve both high QA performance and computational efficiency for complex reasoning over open-domain corpora. Specifically, DualGraphRAG constructs a knowledge graph (KG) by automatically extracting triples from unstructured text using LLMs, and embeds KG nodes with unified text embeddings. For each query, multiple types of KG nodes are generated through a dedicated query enhancement module. Based on these nodes, DualGraphRAG employs a dual-view retrieval strategy to retrieve both one-hop triples that capture local context and shortest paths that compress global connectivity information, thereby facilitating answer generation. Experimental results show that, compared with NaiveRAG, GraphRAG, and LightRAG, DualGraphRAG achieves the best or competitive performance on benchmark datasets and significantly improves efficiency. Overall, DualGraphRAG organizes and exploits KG information in a dual-view manner, leveraging triples and shortest paths to offer a reliable and efficient framework for open-domain QA with complex multi-hop reasoning.

Using the near-space platform to conduct radiometric calibrations of ocean color sensors is a promising method for refining calibration precision, but there is knowledge gap about the radiance contributions above near-space over the open ocean. We used the radiative transfer (RT) model (PCOART) to assess the contributions (LR) of the upwelling radiance received at the near-space balloons to the total radiance (Lt) measured at the top of the atmosphere (TOA). The results indicated that the LR displayed distinct geometric dependencies with exceeding 2% across most observation geometries. Moreover, the LR increased with wavelengths under the various solar zenith angles, and the LR values fell below 1% only for the two near-infrared bands. Additionally, the influences of variations in oceanic constituents on LR were negligible across various azimuth angles and spectral bands, except in nonalgal particle (NAP)-dominated waters. Furthermore, the influences of aerosol optical thicknesses (AOTs) and atmospheric vertical distributions on LR were examined. Outside glint-contaminated areas, the atmosphere-associated LR variations could exceed 2% but declined substantially as AOTs increased under most observation geometries. The mean height of the vertically inhomogeneous layer (hm) significantly influenced LR, and the differences in Lt could exceed 5% when comparing atmospheric vertical distributions following homogeneous versus Gaussian-like distributions. Finally, the transformability from near-space radiance to Lt was examined based on a multiple layer perceptron (MLP) model, which exhibited high agreement with the RT simulations. The MAPD averaged 0.420% across the eight bands, ranging from 0.218% to 0.497%. Overall, the radiometric calibration utilizing near-space represents a significant innovation method for satellite-borne ocean color sensors.

Mitochondria, known as the powerhouses of cells, are considered a key source of reactive oxygen species (ROS) production in various cell types. In the context of neuropathic and inflammatory pain, both mitochondrial dysfunction and hyperfunction can lead to aberrant production of mitochondrial reactive oxygen species (mtROS), which has been implicated in the development and persistence of pain hyperalgesia. This comprehensive review delves into the compelling correlation between mitochondrial functional activity and diverse pain conditions, with a special emphasis on inflammatory pain and chemotherapy-induced peripheral neuropathy (CIPN). Furthermore, it explores the therapeutic potential of targeting mitochondrial protection and mtROS scavenging to maintain mitochondrial redox homeostasis, offering a novel approach for pain management. The findings presented here provide valuable insights into the multifaceted role of mitochondria in pain modulation, laying a solid foundation for future research and the development of innovative analgesic strategies.

Dosage of key regulators impinge on developmental disorders such as FOXG1 syndrome. Since neither knock-out nor knock-down strategy assures flexible and precise protein abundance control, to study hypomorphic or haploinsufficiency expression remains challenging. We develop a system in human pluripotent stem cells (hPSCs) using CRISPR/Cas9 and SMASh technology, with which we can target endogenous proteins for precise dosage control in hPSCs and at multiple stages of neural differentiation. We also reveal FOXG1 dose-dependently affect the cellular constitution of human brain, with 60% mildly affect GABAergic interneuron development while 30% thresholds the production of MGE derived neurons. Abnormal interneuron differentiation accounts for various neurological defects such as epilepsy or seizures, which stimulates future innovative cures of FOXG1 syndrome. By means of its robustness and easiness, dosage-control of proteins in hPSCs and their derivatives will update the understanding and treatment of additional diseases caused by abnormal protein dosage. Altered dosage of developmental regulators such as transcription factors can result in disorders, such as FOXG1 syndrome. Here, the authors demonstrate the utility of SMASh technology for modulating protein dosage by modeling FOXG1 syndrome using human pluripotent stem cell-derived neurons and neural organoids.

This study investigated the technological properties and volatile flavor profiles of tallow from three anatomical regions of Wagyu cattle, omental fats (OF), perirenal fats (PF), and subcutaneous fats (SF), smelted at temperatures ranging from 100 to 160 °C. The objective was to provide a theoretical basis for the targeted utilization of Wagyu fats. Results showed that smelting temperature significantly affected oil yield, with the highest yield obtained at 160 °C for all regions. PF exhibited the greatest oil yield, followed by OF and SF. Physicochemical analyses indicated that OF had the highest degree of unsaturation, whereas PF demonstrated superior hardness and oxidative stability. Microstructural and spectroscopic analyses, Fourier-transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were employed to characterize the samples, revealed that the compact protein structure of SF residues limited oil release, while the porous structures of OF and PF residues facilitated higher yields. With respect to flavor profiling, headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC-MS) was employed to analyze volatile compounds, identified aldehydes as the dominant flavor contributors in OF and PF, imparting fatty and citrus notes, whereas SF was characterized by a distinct creamy aroma primarily due to γ-butyrolactone. These regional differences were further validated by principal component analysis (PCA). Overall, PF obtained the highest comprehensive quality score. The integrated evaluation underscores the potential for precision-based utilization of Wagyu tallow: PF and OF are recommended for applications demanding high yield and intense flavor, whereas SF, characterized by its distinctive creamy aroma, is more suitable for specialized or niche products.

Though the charge transfer efficiency of a liquid-liquid (L-L) nanogenerator is much higher than that of the solid-liquid and solid-solid counterparts, there is still much room for improving the level of interfacial charge transfer. In this study, a power generation system was designed using an ionic liquid (IL)-based immiscible L-L interface via the contact/separation mode. The maximum output electric current reaches as high as about 8.12 μA by contacting a saturated NaCl droplet with an immiscible IL droplet. The magnitude of the generated electric current signals increases with an increase in the ionic concentration of the NaCl solution, the droplet contact area, and the liquid volume of IL. Moreover, the magnitude of the signals varies slightly when the pH value is under 12 and increases sharply in strong alkaline conditions. A maximum instantaneous power output of about 82 nW was obtained with a 100 kΩ resistor in series. The IL-based immiscible L-L interface configuration has been proven to be capable of sensing metal ions at an ultra-low concentration via the contact/separation mode.