Carboxymethyl Cellulose Gel Electrolyte Based on Hydrolyzed Keratin Modified for Dendrite-Free Zinc-Ion Batteries.

In order to alleviate the dendrite problem of zinc-ion batteries, a gel electrolyte is prepared by Maillard reactions occurring between hydrolyzed wool keratin and carboxymethyl cellulose under heating conditions. The prepared gel electrolyte with the addition of hydrolyzed wool keratin possesses good mechanical properties, and its maximum breaking strength, Young's modulus, and elastic modulus are 58.7, 10.77 MPa, and 157.73 MJ m2, respectively, which are far superior to those of the pure carboxymethyl cellulose gel electrolyte. Because hydrolyzed wool keratin includes amino acids and polypeptides, the ionic conductivity of the prepared gel electrolyte is improved. More importantly, amino and carboxyl groups introduced by hydrolyzed wool keratin contribute to uniform deposition of zinc ions and ease dendrite growth. The assembled symmetric battery was stable for 600 h at a current density of 0.5 mA cm-2 with a capacity of 0.5 mAh cm-2. Combined with a NH4V4O10 cathode, a full battery provides a cycling stability of over 2000 h with a Coulomb efficiency of 98.02%.

PDCD4 deficiency in hepatocytes exacerbates nonalcoholic steatohepatitis through enhanced MHC class II transactivator expression.

Nonalcoholic steatohepatitis (NASH) is a primary cause of liver cirrhosis and hepatocellular carcinoma, presenting a significant and unmet medical challenge. The necessity to investigate the molecular mechanisms underlying NASH is highlighted by the observed decrease in programmed cell death 4 (PDCD4) expression in NASH patients, suggesting that PDCD4 may play a protective role in maintaining liver health. In this study, we identify PDCD4 as a natural inhibitor of NASH development in mice. The absence of PDCD4 leads to the spontaneous progression of NASH. Notably, PDCD4-deficient hepatocytes display elevated major histocompatibility complex class II (MHCII) expression due to CIITA activation, indicating that PCDC4 prevents the abnormal transformation of hepatocytes into antigen-presenting cells (APCs). Cell co-culture experiments reveal that hepatocytes lacking PDCD4, which resemble APCs, can directly activate CD4+ T cells by presenting multiple peptides, resulting in the release of inflammatory factors. Additionally, both cellular and animal studies show that CIITA promotes lipid accumulation in hepatocytes and exacerbates NASH progression. In summary, our findings reveal a novel role of PDCD4 in regulating CIITA and MHCII expression during NASH development, offering new therapeutic approaches for NASH treatment.

Identification of Oxidative Stress-Related Biomarkers for Pain-Depression Comorbidity Based on Bioinformatics.

Oxidative stress has been identified as a major factor in the development and progression of pain and psychiatric disorders, but the underlying biomarkers and molecular signaling pathways remain unclear. This study aims to identify oxidative stress-related biomarkers and signaling pathways in pain-depression comorbidity. Integrated bioinformatics analyses were applied to identify key genes by comparing pain-depression comorbidity-related genes and oxidative stress-related genes. A total of 580 differentially expressed genes and 35 differentially expressed oxidative stress-related genes (DEOSGs) were identified. By using a weighted gene co-expression network analysis and a protein-protein interaction network, 43 key genes and 5 hub genes were screened out, respectively. DEOSGs were enriched in biological processes and signaling pathways related to oxidative stress and inflammation. The five hub genes, RNF24, MGAM, FOS, and TKT, were deemed potential diagnostic and prognostic markers for patients with pain-depression comorbidity. These genes may serve as valuable targets for further research and may aid in the development of early diagnosis, prevention strategies, and pharmacotherapy tools for this particular patient population.

Nitrogen-Mediated Promotion of Cobalt-Based Oxygen Evolution Catalyst for Practical Anion-Exchange Membrane Electrolysis.

Scarce and expensive iridium oxide is still the cornerstone catalyst of polymer-electrolyte membrane electrolyzers for green hydrogen production because of its exceptional stability under industrially relevant oxygen evolution reaction (OER) conditions. Earth-abundant transition metal oxides used for this task, however, show poor long-term stability. We demonstrate here the use of nitrogen-doped cobalt oxide as an effective iridium substitute. The catalyst exhibits a low overpotential of 240 mV at 10 mA cm-2 and negligible activity decay after 1000 h of operation in an alkaline electrolyte. Incorporation of nitrogen dopants not only triggers the OER mechanism switched from the traditional adsorbate evolution route to the lattice oxygen oxidation route but also achieves oxygen nonbonding (ONB) states as electron donors, thereby preventing structural destabilization. In a practical anion-exchange membrane water electrolyzer, this catalyst at anode delivers a current density of 1000 mA cm-2 at 1.78 V and an electrical efficiency of 47.8 kW-hours per kilogram hydrogen.

Repetitive Transcranial Magnetic Stimulation-Mediated Neuroprotection in the 5xFAD Mouse Model of Alzheimer's Disease Through GABRG2 and SNAP25 Modulation.

Alzheimer's disease (AD) is a leading neurodegenerative disorder with substantial impacts on cognition and behavior. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, has been used to treat various neuropsychiatric disorders, but its efficacy in AD has not been thoroughly investigated. This study examines the neuroprotective effects of rTMS in the 5xFAD mouse model of AD, with a particular focus on its modulation of GABAergic neuronal activity via the GABRG2 and SNAP25 proteins. Transcriptomic sequencing of rTMS-treated 5xFAD mice revealed 32 genes influenced by the treatment, among which GABRG2 was identified as a critical modulatory target. Electrophysiological assessments, including whole-cell patch clamp recordings from frontal cortex neurons, demonstrated significant alterations in inhibitory synaptic currents following rTMS. Subsequent experiments involved sh-GABRG2 transduction combined with rTMS treatment (20Hz, 14 days), examining behavioral responses, GABAergic neuron functionality, cortical GABA expression, cerebrospinal fluid GABA concentrations, ß-amyloid accumulation, and pro-inflammatory cytokine levels. The results indicated notable improvements in behavioral performance, enhanced functionality of GABAergic neurons, and reductions in ß-amyloid deposition and neuroinflammation after rTMS treatment. Further analysis revealed that SNAP25 overexpression could counteract the negative effects of GABRG2 silencing, highlighting the crucial role of SNAP25 downstream of GABRG2 in mediating rTMS's therapeutic effects in AD. This research highlights rTMS's potential to modulate synaptic and vesicular transport mechanisms, offering a promising avenue for ameliorating symptoms of AD through neuroprotective pathways.

LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction-associated steatotic liver disease progression.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the foremost cause of chronic liver disease, yet its underlying mechanisms remain elusive. Our group previously discovered a novel long non-coding RNA (lncRNA) in rats, termed lncHC and its human counterpart, LNCHC. This study aimed to explore the role of LNCHC in the progression of MASLD. METHODS: RNA-binding proteins bound to LNCHC were searched by mass spectrometry. The target genes of LNCHC and Y-Box binding protein 1 (YBX1) were identified by RNA-seq. MASLD animal models were utilised to examine the roles of LNCHC, YBX1 and patatin-like phospholipase domain containing 3 (PNPLA3) in MASLD progression. RESULTS: Here, we identified LNCHC as a native restrainer during MASLD development. Notably, LNCHC directly binds YBX1 and prevents protein ubiquitination. Up-regulation of YBX1 then stabilises PNPLA3 mRNA to alleviate lipid accumulation in hepatocytes. Furthermore, both cell and animal studies demonstrate that LNCHC, YBX1 and PNPLA3 function to improve hepatocyte lipid accumulation and exacerbate metabolic dysfunction-associated steatohepatitis development. CONCLUSIONS: In summary, our findings unveil a novel LNCHC functionality in regulating YBX1 and PNPLA3 mRNA stability during MASLD development, providing new avenues in MASLD treatment.

Testosterone deficiency worsens mitochondrial dysfunction in APP/PS1 mice.

Background: Recent studies show testosterone (T) deficiency worsens cognitive impairment in Alzheimer's disease (AD) patients. Mitochondrial dysfunction, as an early event of AD, is becoming critical hallmark of AD pathogenesis. However, currently, whether T deficiency exacerbates mitochondrial dysfunction of men with AD remains unclear. Objective: The purpose of this study is to explore the effects of T deficiency on mitochondrial dysfunction of male AD mouse models and its potential mechanisms. Methods: Alzheimer's disease animal model with T deficiency was performed by castration to 3-month-old male APP/PS1 mice. Hippocampal mitochondrial function of mice was analyzed by spectrophotometry and flow cytometry. The gene expression levels related to mitochondrial biogenesis and mitochondrial dynamics were determined through quantitative real-time PCR (qPCR) and western blot analysis. SH-SY5Y cells treated with flutamide, T and/or H2O2 were processed for analyzing the potential mechanisms of T on mitochondrial dysfunction. Results: Testosterone deficiency significantly aggravated the cognitive deficits and hippocampal pathologic damage of male APP/PS1 mice. These effects were consistent with exacerbated mitochondrial dysfunction by gonadectomy to male APP/PS1 mice, reflected by further increase in oxidative damage and decrease in mitochondrial membrane potential, complex IV activity and ATP levels. More importantly, T deficiency induced the exacerbation of compromised mitochondrial homeostasis in male APP/PS1 mice by exerting detrimental effects on mitochondrial biogenesis and mitochondrial dynamics at mRNA and protein level, leading to more defective mitochondria accumulated in the hippocampus. In vitro studies using SH-SY5Y cells validated T's protective effects on the H2O2-induced mitochondrial dysfunction, mitochondrial biogenesis impairment, and mitochondrial dynamics imbalance. Administering androgen receptor (AR) antagonist flutamide weakened the beneficial effects of T pretreatment on H2O2-treated SH-SY5Y cells, demonstrating a critical role of classical AR pathway in maintaining mitochondrial function. Conclusion: Testosterone deficiency exacerbates hippocampal mitochondrial dysfunction of male APP/PS1 mice by accumulating more defective mitochondria. Thus, appropriate T levels in the early stage of AD might be beneficial in delaying AD pathology by improving mitochondrial biogenesis and mitochondrial dynamics.

Edaravone Dexborneol ameliorates the cognitive deficits of APP/PS1 mice by inhibiting TLR4/MAPK signaling pathway via upregulating TREM2.

Currently, there are no effective therapeutic agents available to treat Alzheimer's disease (AD). However, edaravone dexborneol (EDB), a novel composite agent used to treat acute ischemic stroke, has recently been shown to exert efficacious neuroprotective effects. However, whether EDB can ameliorate cognitive deficits in AD currently remains unclear. To this end, we explored the effects of EDB on AD and its potential mechanisms using an AD animal model (male APP/PS1 mice) treated with EDB for 10 weeks starting at 6 months of age. Subsequent analyses revealed that EDB-treated APP/PS1 mice exhibited improved cognitive abilities compared to untreated APP/PS1 mice. Administration of EDB in APP/PS1 mice further alleviated neuropathological alterations of the hippocampus, including Aß deposition, pyramidal cell karyopyknosis, and oxidative damage, and significantly decreased the levels of inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and COX-2 in the hippocampus of APP/PS1 mice. Transcriptome sequencing analysis demonstrated the critical role of the inflammatory reaction in EDB treatment in APP/PS1 mice, indicating that the alleviation of the inflammatory reaction by EDB in the hippocampus of APP/PS1 mice was linked to the action of the TREM2/TLR4/MAPK signaling pathway. Further in vitro investigations showed that EDB suppressed neuroinflammation in LPS-stimulated BV2 cells by inhibiting the TLR4/MAPK signaling pathway and upregulating TREM2 expression. Thus, the findings of the present study demonstrate that EDB is a promising therapeutic agent for AD-related cognitive dysfunction.

SASAN: Spectrum-Axial Spatial Approach Networks for Medical Image Segmentation.

Ophthalmic diseases such as central serous chorioretinopathy (CSC) significantly impair the vision of millions of people globally. Precise segmentation of choroid and macular edema is critical for diagnosing and treating these conditions. However, existing 3D medical image segmentation methods often fall short due to the heterogeneous nature and blurry features of these conditions, compounded by medical image clarity issues and noise interference arising from equipment and environmental limitations. To address these challenges, we propose the Spectrum Analysis Synergy Axial-Spatial Network (SASAN), an approach that innovatively integrates spectrum features using the Fast Fourier Transform (FFT). SASAN incorporates two key modules: the Frequency Integrated Neural Enhancer (FINE), which mitigates noise interference, and the Axial-Spatial Elementum Multiplier (ASEM), which enhances feature extraction. Additionally, we introduce the Self-Adaptive Multi-Aspect Loss ( LSM ), which balances image regions, distribution, and boundaries, adaptively updating weights during training. We compiled and meticulously annotated the Choroid and Macular Edema OCT Mega Dataset (CMED-18k), currently the world's largest dataset of its kind. Comparative analysis against 13 baselines shows our method surpasses these benchmarks, achieving the highest Dice scores and lowest HD95 in the CMED and OIMHS datasets. Our code is publicly available at https://github.com/IMOP-lab/SASAN-Pytorch.

Recent Progress in Improving Rate Performance of Cellulose-Derived Carbon Materials for Sodium-Ion Batteries.

Cellulose-derived carbon is regarded as one of the most promising candidates for high-performance anode materials in sodium-ion batteries; however, its poor rate performance at higher current density remains a challenge to achieve high power density sodium-ion batteries. The present review comprehensively elucidates the structural characteristics of cellulose-based materials and cellulose-derived carbon materials, explores the limitations in enhancing rate performance arising from ion diffusion and electronic transfer at the level of cellulose-derived carbon materials, and proposes corresponding strategies to improve rate performance targeted at various precursors of cellulose-based materials. This review also presents an update on recent progress in cellulose-based materials and cellulose-derived carbon materials, with particular focuses on their molecular, crystalline, and aggregation structures. Furthermore, the relationship between storage sodium and rate performance the carbon materials is elucidated through theoretical calculations and characterization analyses. Finally, future perspectives regarding challenges and opportunities in the research field of cellulose-derived carbon anodes are briefly highlighted.

Woven fabric-based separators with low tortuosity for sodium-ion batteries.

In order to achieve high-performance and stable sodium-ion batteries, numerous attempts have been made to construct continuous ion transport pathways, in which a separator is one of the key components that affects the battery performance. In this study, a novel low-tortuosity woven fabric separator is fabricated by combining a weaving technique with a cellulose-solution method, followed by an infusion of a TEMPO-oxidized bacterial cellulose slurry into woven fabric substrates. The macropores in the fabric combine with the micropores in the oxidized bacterial cellulose to form a separator with a suitable pore structure and low tortuosity, forming a continuous sodium ion transport channel within the sodium-ion battery and effectively enhancing ion transport dynamics. The results show that, compared with a commercial polypropylene separator, the TEMPO-oxidized bacterial cellulose-woven fabric separator has a special weaving structure and lower tortuosity (0.77), as well as significant advantages in tensile strength (3.07 MPa), ionic conductivity (1.15 mS c), ionic transfer number (0.75), thermal stability, and electrochemical stability. This novel and simple preparation method provides new possibilities for achieving high-performance separators of sodium-ion batteries through rational structural design by textile technology.

Segmentation of Low-Light Optical Coherence Tomography Angiography Images under the Constraints of Vascular Network Topology.

Optical coherence tomography angiography (OCTA) offers critical insights into the retinal vascular system, yet its full potential is hindered by challenges in precise image segmentation. Current methodologies struggle with imaging artifacts and clarity issues, particularly under low-light conditions and when using various high-speed CMOS sensors. These challenges are particularly pronounced when diagnosing and classifying diseases such as branch vein occlusion (BVO). To address these issues, we have developed a novel network based on topological structure generation, which transitions from superficial to deep retinal layers to enhance OCTA segmentation accuracy. Our approach not only demonstrates improved performance through qualitative visual comparisons and quantitative metric analyses but also effectively mitigates artifacts caused by low-light OCTA, resulting in reduced noise and enhanced clarity of the images. Furthermore, our system introduces a structured methodology for classifying BVO diseases, bridging a critical gap in this field. The primary aim of these advancements is to elevate the quality of OCTA images and bolster the reliability of their segmentation. Initial evaluations suggest that our method holds promise for establishing robust, fine-grained standards in OCTA vascular segmentation and analysis.

Low-input lipidomics reveals lipid metabolism remodelling during early mammalian embryo development.

Lipids are indispensable for energy storage, membrane structure and cell signalling. However, dynamic changes in various categories of endogenous lipids in mammalian early embryonic development have not been systematically characterized. Here we comprehensively investigated the dynamic lipid landscape during mouse and human early embryo development. Lipid signatures of different developmental stages are distinct, particularly for the phospholipid classes. We highlight that the high degree of phospholipid unsaturation is a conserved feature as embryos develop to the blastocyst stage. Moreover, we show that lipid desaturases such as SCD1 are required for in vitro blastocyst development and blastocyst implantation. One of the mechanisms is through the regulation of unsaturated fatty-acid-mediated fluidity of the plasma membrane and apical proteins and the establishment of apical-basal polarity during development of the eight-cell embryo to the blastocyst. Overall, our study provides an invaluable resource about the remodelling of the endogenous lipidome in mammalian preimplantation embryo development and mechanistic insights into the regulation of embryogenesis and implantation by lipid unsaturation.

MAGPIE: accurate pathogenic prediction for multiple variant types using machine learning approach.

Identifying pathogenic variants from the vast majority of nucleotide variation remains a challenge. We present a method named Multimodal Annotation Generated Pathogenic Impact Evaluator (MAGPIE) that predicts the pathogenicity of multi-type variants. MAGPIE uses the ClinVar dataset for training and demonstrates superior performance in both the independent test set and multiple orthogonal validation datasets, accurately predicting variant pathogenicity. Notably, MAGPIE performs best in predicting the pathogenicity of rare variants and highly imbalanced datasets. Overall, results underline the robustness of MAGPIE as a valuable tool for predicting pathogenicity in various types of human genome variations. MAGPIE is available at https://github.com/shenlab-genomics/magpie .

Spatiotemporal Modulated Scaffold for Endogenous Bone Regeneration via Harnessing Sequentially Released Guiding Signals.

The design of a scaffold that can regulate the sequential differentiation of bone marrow mesenchymal stromal cells (BMSCs) according to the endochondral ossification (ECO) mechanism is highly desirable for effective bone regeneration. In this study, we successfully fabricated a dual-networked composite hydrogel composed of gelatin and hyaluronic acid (termed GCDH-M), which can sequentially release chondroitin sulfate (CS) and magnesium/silicon (Mg/Si) ions to provide spatiotemporal guidance for chondrogenesis, angiogenesis, and osteogenesis. The fast release of CS is from the GCDH hydrogel, and the sustained releases of Mg/Si ions are from poly(lactide-co-glycolide) microspheres embedded in the hydrogel. There is a difference in the release rates between CS and ions, resulting in the ability for the fast release of CS and sustained release of ions. The dual networks between the modified gelatin and hyaluronic acid via covalent bonding and host-guest interactions render the hydrogel with some dynamic feature to meet the differentiation development of BMSCs laden inside the hydrogel, i.e., transforming into a chondrogenic phenotype, further to a hypertrophic phenotype and eventually to an osteogenic phenotype. As evidenced by the results of in vitro and in vivo evaluations, this GCDH-M composite hydrogel was proved to be able to create an optimal microenvironment for embedded BMSCs responding to the sequential guiding signals, which aligns with the rhythm of the ECO process and ultimately boosts bone regeneration. The promising outcome achieved with this innovative hydrogel system sheds light on novel scaffold design targeting bone tissue engineering.

De novo identification of expressed cancer somatic mutations from single-cell RNA sequencing data.

Identifying expressed somatic mutations from single-cell RNA sequencing data de novo is challenging but highly valuable. We propose RESA - Recurrently Expressed SNV Analysis, a computational framework to identify expressed somatic mutations from scRNA-seq data. RESA achieves an average precision of 0.77 on three in silico spike-in datasets. In extensive benchmarking against existing methods using 19 datasets, RESA consistently outperforms them. Furthermore, we applied RESA to analyze intratumor mutational heterogeneity in a melanoma drug resistance dataset. By enabling high precision detection of expressed somatic mutations, RESA substantially enhances the reliability of mutational analysis in scRNA-seq. RESA is available at https://github.com/ShenLab-Genomics/RESA .

Assessment of visual function in blind mice and monkeys with subretinally implanted nanowire arrays as artificial photoreceptors.

Retinal prostheses could restore image-forming vision in conditions of photoreceptor degeneration. However, contrast sensitivity and visual acuity are often insufficient. Here we report the performance, in mice and monkeys with induced photoreceptor degeneration, of subretinally implanted gold-nanoparticle-coated titania nanowire arrays providing a spatial resolution of 77.5 µm and a temporal resolution of 3.92 Hz in ex vivo retinas (as determined by patch-clamp recording of retinal ganglion cells). In blind mice, the arrays allowed for the detection of drifting gratings and flashing objects at light-intensity thresholds of 15.70-18.09 µW mm-2, and offered visual acuities of 0.3-0.4 cycles per degree, as determined by recordings of visually evoked potentials and optomotor-response tests. In monkeys, the arrays were stable for 54 weeks, allowed for the detection of a 10-µW mm-2 beam of light (0.5° in beam angle) in visually guided saccade experiments, and induced plastic changes in the primary visual cortex, as indicated by long-term in vivo calcium imaging. Nanomaterials as artificial photoreceptors may ameliorate visual deficits in patients with photoreceptor degeneration.

Beyond radiologist-level liver lesion detection on multi-phase contrast-enhanced CT images by deep learning.

Accurate detection of liver lesions from multi-phase contrast-enhanced CT (CECT) scans is a fundamental step for precise liver diagnosis and treatment. However, the analysis of multi-phase contexts is heavily challenged by the misalignment caused by respiration coupled with the movement of organs. Here, we proposed an AI system for multi-phase liver lesion segmentation (named MULLET) for precise and fully automatic segmentation of real-patient CECT images. MULLET enables effectively embedding the important ROIs of CECT images and exploring multi-phase contexts by introducing a transformer-based attention mechanism. Evaluated on 1,229 CECT scans from 1,197 patients, MULLET demonstrated significant performance gains in terms of Dice, Recall, and F2 score, which are 5.80%, 6.57%, and 5.87% higher than state of the arts, respectively. MULLET has been successfully deployed in real-world settings. The deployed AI web server provides a powerful system to boost clinical workflows of liver lesion diagnosis and could be straightforwardly extended to general CECT analyses.

Hydralazine inhibits neuroinflammation and oxidative stress in APP/PS1 mice via TLR4/NF-κB and Nrf2 pathways.

Alzheimer's disease (AD) is a common chronic progressive neurodegenerative disorder, and curative treatment has not been developed. The objective of this study was to investigate the potential effects of hydralazine (Hyd, a hypertension treatment drug) on the development process of AD and its mechanisms. We treated 6-month-old male APP/PS1 mice with Hyd for 5 weeks, measured changes in behavior and pathological status, and analyzed differences in gene expression by RNA sequencing. The results demonstrated that Hyd improved cognitive deficits and decreased amyloid beta protein deposition in the cortex and hippocampus, while RNA sequencing analysis suggested that the regulation of neuroinflammation and energy metabolism might play pivotal roles for Hyd's beneficial effects. Therefore, we further investigated inflammatory response, redox state, and mitochondrial function, as well as the expression of toll-like receptor 4 (TLR4)/nuclear factor Kappa B (NF-κB)-dependent neuroinflammation gene and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant gene in AD mice. The results showed that Hyd reduced the damage of neuroinflammation and oxidative stress, improved mitochondrial dysfunction, downregulated pro-inflammation gene expression, and upregulated antioxidant gene expression. The results in lipopolysaccharide (LPS)-induced BV2 cell model demonstrated that Hyd suppressed pro-inflammatory response via TLR4/NF-κB signaling pathway. In addition, by silencing the Nrf2 gene expression, it was found that Hyd can reduce LPS-induced reactive oxygen species production by activating the Nrf2 signaling pathway. Therefore, administration of Hyd in the early stage of AD might be beneficial in delaying the pathological development of AD via inhibiting neuroinflammation and oxidative stress.

Temporally integrated transcriptome analysis reveals ASFV pathology and host response dynamics.

African swine fever virus (ASFV) causes a lethal swine hemorrhagic disease and is currently responsible for widespread damage to the pig industry. The pathogenesis of ASFV infection and its interaction with host responses remain poorly understood. In this study, we profiled the temporal viral and host transcriptomes in porcine alveolar macrophages (PAMs) with virulent and attenuated ASFV strains. We identified profound differences in the virus expression programs between SY18 and HuB20, which shed light on the pathogenic functions of several ASFV genes. Through integrated computational analysis and experimental validation, we demonstrated that compared to the virulent SY18 strain, the attenuated HuB20 quickly activates expression of receptors, sensors, regulators, as well as downstream effectors, including cGAS, STAT1/2, IRF9, MX1/2, suggesting rapid induction of a strong antiviral immune response in HuB20. Surprisingly, in addition to the pivotal DNA sensing mechanism mediated by cGAS-STING pathway, infection of the DNA virus ASFV activates genes associated with RNA virus response, with stronger induction by HuB20 infection. Taken together, this study reveals novel insights into the host-virus interaction dynamics, and provides reference for future mechanistic studies of ASFV pathogenicity.