Significant Association of Serum Albumin With the Severity of Coronary Microvascular Dysfunction Using Dynamic CZT-SPECT.

OBJECTIVE: Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. METHODS: We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. RESULTS: The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. CONCLUSION: Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.

The death domain-associated protein suppresses porcine epidemic diarrhea virus replication by interacting with signal transducer and activator of transcription 1 and inducing downstream ISG15 expression.

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute enteric disease in piglets and severely threatens the pig industry all over the world. Death domain-associated protein (DAXX) is a classical chaperone protein involved in multiple biological processes, such as cell apoptosis, transcriptional regulation, DNA damage repair, and host innate immunity. However, whether DAXX functions in the anti-PEDV innate immune responses remains unclear. In this study, we found that PEDV infection upregulated DAXX expression and induced its nucleocytoplasmic translocation in IPEC-J2 cells. Furthermore, we found that DAXX overexpression was inhibitory to PEDV replication, while downregulation of DAXX by RNA interference facilitated PEDV replication. The antiviral activity of DAXX was due to its positive effect on IFN-λ3-STAT1 signaling, as DAXX positively regulated STAT1 activation through their interaction in cytoplasm and enhancing the downstream ISG15 expression. Mutation of tryptophan at 621 to alanine in DAXX increased its abundance in the cytoplasm, leading to the upregulation of STAT1 phosphorylation and ISG15 expression. It indicated that cytoplasmic fraction of DAXX was advantageous for the STAT1-ISG15 signaling axis and PEDV inhibition. In summary, these results show that DAXX inhibits PEDV infection by increasing IFN-λ3-induced STAT1 phosphorylation and the downstream ISG15 expression.

Appendicitis Hospitalization Care Costs Among Patients With Delayed Diagnosis of Appendicitis.

Importance: Delayed appendicitis diagnosis is associated with worse outcomes. Appendicitis hospital care costs associated with delayed diagnosis are unknown. Objective: To determine whether delayed appendicitis diagnosis was associated with increased appendicitis hospital care costs. Design, Setting, and Participants: This cohort study used data from patients receiving an appendectomy aged 18 to 64 years in 5 states (Florida, Maryland, Massachusetts, New York, Wisconsin) that were captured in the Healthcare Cost and Utilization Project State Inpatient and Emergency Department databases for the years 2016 and 2017 with no additional follow-up. Data were analyzed January through April 2023. Exposures: Delayed diagnosis was defined as a previous emergency department or inpatient hospital encounter with an abdominal diagnosis other than appendicitis, and no intervention 7 days prior to appendectomy encounter. Main Outcomes and Measures: The main outcome was appendicitis hospital care costs. This was calculated from aggregated charges of encounters 7 days prior to appendectomy, the appendectomy encounter, and 30 days postoperatively. Cost-to-charge ratios were applied to charges to obtain costs, which were then adjusted for wage index, inflation to 2022 US dollar, and with extreme outliers winsorized. A multivariable Poisson regression estimated appendicitis hospital care costs associated with a delayed diagnosis while controlling for age, sex, race and ethnicity, insurance status, care discontinuity, income quartile, hospital size, teaching status, medical school affiliation, percentage of Black and Hispanic patient discharges, core-based statistical area, and state. Results: There were 76 183 patients (38 939 female [51.1%]; 2192 Asian or Pacific Islander [2.9%], 14 132 Hispanic [18.5%], 8195 non-Hispanic Black [10.8%], 46 949 non-Hispanic White [61.6%]) underwent appendectomy, and 2045 (2.7%) had a delayed diagnosis. Delayed diagnosis patients had median (IQR) unadjusted cost of $11 099 ($6752-$17 740) compared with $9177 ($5575-$14 481) for nondelayed (P < .001). Patients with delayed diagnosis had 1.23 times (95% CI, 1.16-1.28 times) adjusted increased appendicitis hospital care costs. The mean marginal cost of delayed diagnosis was $2712 (95% CI, $2083-$3342). Even controlling for delayed diagnosis, non-Hispanic Black patients had 1.22 times (95% CI, 1.17-1.28 times) the adjusted increased appendicitis hospital care costs compared with non-Hispanic White patients. Conclusions and Relevance: In this cohort study, delayed diagnosis of appendicitis was associated with increased hospital care costs.

Empowering Real-World Image Super-Resolution With Flexible Interactive Modulation.

Interactive image restoration aims to construct an interactive pathway between users and restoration networks, which empowers users to modulate the restoration results according to their own demands. However, existing methods are primarily limited to training their networks with predefined and simplistic synthetic degradations. Consequently, these methods often encounter significant performance degradation when confronted with real-world degradations that deviate from their assumptions. Furthermore, existing interactive image restoration approaches solely support global modulation, wherein a single modulation factor governs the reconstruction process for the entire image. In this paper, we propose a novel method to perform real-world and intricate image super-resolution in an interactive manner. Specifically, we propose a metric-learning-based degradation estimation strategy to estimate not only the overall degradation level of the entire image but also the finer-grained, pixel- wise degradation within real-world scenarios. This enables local control over the restoration results by selectively modulating the corresponding regions based on the densely-estimated degradation map. Additionally, a new metric-argumented loss is proposed to further enhance the performance of real-world image super-resolution. Through extensive experimentation, we demonstrate the efficacy of our method in achieving exceptional modulation and restoration performance in real-world image super-resolution tasks, all while maintaining an appealing model complexity.

NeRF-Texture: Synthesizing Neural Radiance Field Textures.

Texture synthesis is a fundamental problem in computer graphics that would benefit various applications. Existing methods are effective in handling 2D image textures. In contrast, many real-world textures contain meso-structure in the 3D geometry space, such as grass, leaves, and fabrics, which cannot be effectively modeled using only 2D image textures. We propose a novel texture synthesis method with Neural Radiance Fields (NeRF) to capture and synthesize textures from given multi-view images. In the proposed NeRF texture representation, a scene with fine geometric details is disentangled into the meso-structure textures and the underlying base shape. This allows textures with meso-structure to be effectively learned as latent features situated on the base shape, which are fed into a NeRF decoder trained simultaneously to represent the rich view-dependent appearance. Using this implicit representation, we can synthesize NeRF-based textures through patch matching of latent features. However, inconsistencies between the metrics of the reconstructed content space and the latent feature space may compromise the synthesis quality. To enhance matching performance, we further regularize the distribution of latent features by incorporating a clustering constraint. In addition to generating NeRF textures over a planar domain, our method can also synthesize NeRF textures over curved surfaces, which are practically useful. Experimental results and evaluations demonstrate the effectiveness of our approach.

COVID-19 increases extracorporeal coagulation during hemodialysis associated with upregulation of vWF/FBLN5 signaling in patients with severe/critical symptoms.

BACKGROUND: COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis. METHODS: A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA. RESULTS: Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated. CONCLUSIONS: Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation.

INPP5E Regulates the Distribution of Phospholipids on Cilia in RPE1 Cells.

BACKGROUND: Primary cilia are static microtubule-based structures protruding from the cell surface and present on most vertebrate cells. The appropriate localization of phospholipids is essential for cilia formation and stability. INPP5E is a cilia-localized inositol 5-phosphatase; its deletion alters the phosphoinositide composition in the ciliary membrane, disrupting ciliary function. METHODS: The EGFP-2xP4MSidM, PHPLCδ1-EGFP, and SMO-tRFP plasmids were constructed by the Gateway system to establish a stable RPE1 cell line. The INPP5E KO RPE1 cell line was constructed with the CRISPR/Cas9 system. The localization of INPP5E and the distribution of PI(4,5)P2 and PI4P were examined by immunofluorescence microscopy. The fluorescence intensity co-localized with cilia was quantified by ImageJ. RESULTS: In RPE1 cells, PI4P is localized at the ciliary membrane, whereas PI(4,5)P2 is localized at the base of cilia. Knocking down or knocking out INPP5E alters this distribution, resulting in the distribution of PI(4,5)P2 along the ciliary membrane and the disappearance of PI4P from the cilia. Meanwhile, PI(4,5)P2 is located in the ciliary membrane labeled by SMO-tRFP. CONCLUSIONS: INPP5E regulates the distribution of phosphoinositide on cilia. PI(4,5)P2 localizes at the ciliary membrane labeled with SMO-tRFP, indicating that ciliary pocket membrane contains PI(4,5)P2, and phosphoinositide composition in early membrane structures may differ from that in mature ciliary membrane.

Association of daytime napping with incidence of chronic kidney disease and end-stage kidney disease: A prospective observational study.

BACKGROUND AND AIMS: Few studies have examined the relationship between daytime napping and risk of kidney diseases. We aimed to investigate the association of daytime napping with the incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). We also examined whether sleep duration modified the association of nap with CKD or ESKD. METHODS: We recruited 460,571 European middle- to older-aged adults without prior CKD or ESKD between March 13, 2006, and October 1, 2010, in the UK Biobank. Sleep behavior data were obtained through questionnaires administered during recruitment. The analysis of the relationship between napping and the occurrence of CKD and ESKD utilized Cox proportional hazards regression models. The modification role of sleep duration on the effect of nap on CKD and ESKD was also examined. RESULTS: After a mean follow-up of 11.1 (standard deviation 2.2) years, we observed 28,330 incident CKD cases and 927 ESKD cases. The daytime napping was associated with incident CKD (P for trend = .004). After fully adjusted, when compared with participants who did not take nap, those in sometimes and usually nap groups had higher risk of CKD. Nevertheless, the available evidence did not support a link between daytime napping and ESKD (P for trend = .06). Simultaneously, there was insufficient evidence suggesting that sleeping duration modified the association of daytime napping with incident CKD or ESKD. CONCLUSION: Daytime napping was associated with an increased risk of CKD. However, the absence of conclusive evidence did not indicate a connection between daytime napping and ESKD.

Chinese Title Generation for Short Videos: Dataset, Metric and Algorithm.

Previous work for video captioning aims to objectively describe the video content but the captions lack human interest and attractiveness, limiting its practical application scenarios. The intention of video title generation (video titling) is to produce attractive titles, but there is a lack of benchmarks. This work offers CREATE, the first large-scale Chinese shoRt vidEo retrievAl and Title gEneration dataset, to assist research and applications in video titling, video captioning, and video retrieval in Chinese. CREATE comprises a high-quality labeled 210K dataset and two web-scale 3M and 10M pre-training datasets, covering 51 categories, 50K+ tags, 537K+ manually annotated titles and captions, and 10M+ short videos with original video information. This work presents ACTEr, a unique Attractiveness-Consensus-based Title Evaluation, to objectively evaluate the quality of video title generation. This metric measures the semantic correlation between the candidate (model-generated title) and references (manual-labeled titles) and introduces attractive consensus weights to assess the attractiveness and relevance of the video title. Accordingly, this work proposes a novel multi-modal ALignment WIth Generation model, ALWIG, as one strong baseline to aid future model development. With the help of a tag-driven video-text alignment module and a GPT-based generation module, this model achieves video titling, captioning, and retrieval simultaneously. We believe that the release of the CREATE dataset, ACTEr metric, and ALWIG model will encourage in-depth research on the analysis and creation of Chinese short videos. Project webpage: https://createbenchmark.github.io/.

Make-Your-Video: Customized Video Generation Using Textual and Structural Guidance.

Creating a vivid video from the event or scenario in our imagination is a truly fascinating experience. Recent advancements in text-to-video synthesis have unveiled the potential to achieve this with prompts only. While text is convenient in conveying the overall scene context, it may be insufficient to control precisely. In this paper, we explore customized video generation by utilizing text as context description and motion structure (e.g. frame- wise depth) as concrete guidance. Our method, dubbed Make-Your-Video, involves joint-conditional video generation using a Latent Diffusion Model that is pre-trained for still image synthesis and then promoted for video generation with the introduction of temporal modules. This two-stage learning scheme not only reduces the computing resources required, but also improves the performance by transferring the rich concepts available in image datasets solely into video generation. Moreover, we use a simple yet effective causal attention mask strategy to enable longer video synthesis, which mitigates the potential quality degradation effectively. Experimental results show the superiority of our method over existing baselines, particularly in terms of temporal coherence and fidelity to users' guidance. In addition, our model enables several intriguing applications that demonstrate potential for practical usage. The code, model weights, and videos are publicly available at our project page: https://doubiiu.github.io/projects/Make-Your-Video/.

Degradative autophagy regulates the homeostasis of miRnas to control cancer development.

Macroautophagy/autophagy acts as an anti-tumor mechanism in early cancer stages but promotes growth in established tumors. Similarly, miRNAs function as tumor suppressors or oncogenes, depending on their target genes. This reciprocal relationship between autophagy and miRNAs is a well-studied area, primarily focused on how miRNAs regulate autophagy-related genes. Our research provides innovative insights into how autophagy selectively controls miRNAs. For instance, MIR224 is preferentially degraded within autophagosomes, leading to the upregulation of SMAD4 and suppressing hepatocellular carcinoma (HCC) tumorigenesis. Conversely, autophagy positively regulates MIR449A by degrading EP300/p300 to activate FOXO1 and facilitate MIR449A transcription in colorectal cancer (CRC). In conclusion, our findings reveal the role of autophagy in maintaining the cellular balance of two miRNAs to mitigate tumorigenic stresses and highlight that autophagy-regulated miRNA profiles may serve as diagnostic and therapeutic markers for cancer development.

Association between periodontal diseases and chronic obstructive pulmonary disease: Evidence from sequential cross-sectional and prospective cohort studies based on UK Biobank.

AIM: To investigate the association between periodontal diseases, airflow limitation and incident chronic obstructive pulmonary disease (COPD) in a large-scale prospective UK Biobank cohort. MATERIALS AND METHODS: Our approach comprised a cross-sectional study and a prospective cohort. Periodontal diseases were determined based on the participants' self-reported dental symptoms, including painful gums, bleeding gums and loose teeth. Logistic regression and Cox proportional hazards models were used to evaluate the association of periodontal diseases with airflow limitation and incident COPD in the cross-sectional study and the prospective cohort, respectively. RESULTS: The cross-sectional study involved 495,610 participants. Multivariable analysis found that periodontal diseases were significantly associated with airflow limitation (odds ratio = 1.036, 95% confidence interval [CI]: 1.015-1.059). The cohort study included 379,266 participants with a median follow-up period of 12.68 years. An elevated risk of incident COPD was associated with the presence of periodontal diseases (hazard ratio: 1.248, 95% CI: 1.174-1.326). The effect was consistent among subgroups, including baseline age (≤65 or >65 years), sex, smoking status and diabetes mellitus. CONCLUSIONS: Periodontal diseases are associated with airflow limitation and elevated COPD incidence. Maintaining good periodontal health in patients with chronic bronchitis and emphysema may help prevent the onset of COPD.

Kidney Function Measures and Mortality: A Mendelian Randomization Study.

RATIONALE & OBJECTIVE: Individuals with a low estimated glomerular filtration rate (eGFR) are at a high risk of death. However, the causes underpinning this association are largely uncertain. This study aimed to assess the causal relationship of low eGFR with all-cause and cause-specific mortality. STUDY DESIGN: Retrospective cohort study incorporating Mendelian randomization (MR). SETTING & PARTICIPANTS: Individual-level data from 436,214 White participants (54.3% female; aged 56.8±8.0 years) included in the UK Biobank. EXPOSURES: eGFR estimated using cystatin C (eGFRcyst). OUTCOMES: The outcomes of interest included all-cause mortality, cardiovascular mortality, cancer mortality, infection mortality, and other-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards analysis for the conventional observational analyses; linear and nonlinear MR analyses implemented using genetic allele scores as instrumental variables representing kidney function to estimate the effect of kidney function on the survival outcomes. RESULTS: During a median follow-up of 12.1 years, there were 30,489 deaths, 6,098 of which were attributed to cardiovascular events, 15,538 to cancer, 1,516 to infection, and 7,227 to other events. In the conventional observational analysis, eGFRcyst exhibited a nonlinear association with all the outcomes. MR analysis suggested that a genetically predicted lower eGFRcyst was linearly associated with a higher rate of cardiovascular mortality (HR, 1.43; 95% CI, 1.18-1.75) across the entire measurement range (every 10-mL/min/1.73m2 decrement). Nonetheless, no causal associations between eGFRcyst and all-cause mortality (HR, 1.07; 95% CI, 0.98-1.17) or any types of noncardiovascular mortality were detected. LIMITATIONS: Potential misclassification of the actual cause of death, a nonrepresentative sample, and potential error in the interpretation of the magnitude of associations generated in MR analyses. CONCLUSIONS: These findings suggest a potential causal association between low eGFR and cardiovascular mortality in the general population, but no causal relationship with all-cause mortality or noncardiovascular mortality was observed. Further studies in other populations are warranted to confirm these findings. PLAIN-LANGUAGE SUMMARY: This study investigated the existence of a causal relationship between lower kidney function and death of different causes. Using data from 436,214 people in the United Kingdom, we applied conventional statistical analyses and those incorporating genetic data to implement Mendelian randomization, an approach that estimates causal associations. The observational analysis showed a nonlinear association between kidney function and various types of mortality outcomes. However, Mendelian randomization analysis suggested a linear increase in the risk of cardiovascular mortality with lower kidney function, but no causal link between the level of kidney function and all-cause or noncardiovascular mortality was identified. Managing kidney health may help reduce cardiovascular mortality, but caution is needed in interpreting the magnitudes of these results. Further validation in other populations and in those with advanced kidney failure is needed.

Factors influencing the development of executive function in adolescents / 中国学校卫生

Abstract@#Executive function is an advanced cognitive process aimed at the flexible coordination, optimization, and control of the cognitive processes of task solving in order to accomplish a specific task, ensuring that the individual produces effective behaviors, including inhibitory control, working memory, and cognitive flexibility. Given the sensitivities and specificities that characterize an individual s physical and mental development during adolescence, this period is critical for the development of executive function in adolescents. In the paper, the influencing factors of adolescents executive function development are systematically described from three dimensions, namely, biology, environment and lifestyle; by analyzing the mechanisms and differences in the effects of different influencing factors, this editorial provides a scientific basis for adolescents executive function improvement and intervention.

Intervention effects of moderate and high intensities of classroom physical activity on cardiorespiratory fitness and executive function among junior grade one students in Tibetan / 中国学校卫生

Objective@#To explore the intervention effect of different intensity of classroom physical exercise on cardiorespiratory fitness and executive function of Tibetan first grade students at high altitude, so as to provide reference for improving the level of cardiorespiratory fitness and executive function of Tibetan adolescents.@*Methods@#From September to December 2020, 184 Tibetan students from five first grade classes in a middle school in Lhasa, Tibet, were randomly assigned into a control group (81 students in two classes) and an intervention group (103 students in three classes). Both groups followed the same teaching programme, but the intervention group received 36 sessions of moderate to high intensity classroom physical activity, one session per day, Monday,Wednesday and Friday, for 12 weeks. Before and after the intervention, cardiorespiratory fitness and executive function were tested by 20m round trip running and Flanker s experimental paradigm, 2-back s experimental paradigm, and More odd shifting experimental paradigm for inhibitory control, refreshing memory, and switching flexibility, and the results were analysed by analysis of covariance (ANCOVA) to compare the results of the pre and post intervention periods.@*Results@#The maximum oxygen uptake (VO 2max ) of Tibetan first grade students in the intervention group increased by 2.25 mL/(kg〖WW）〗·〖WW(〗min) compared with the control group after the intervention ( t =-3.89, P <0.01); the response time of the inhibitory function was reduced by 4.40 ms, that of the refreshing function by 196.06 ms, and that of the switching function by 92.72 ms in the intervention group compared with the control group ( t =2.98, 4.82 ,3.21, P <0.05).@*Conclusion@#The 12 week moderate to high intensity classroom physical activity intervention has different degrees of improvement effects on cardiorespiratory fitness and executive function in Tibetan adolescents.

Relationship between cardiorespiratory fitness and executive function in adolescents / 中国学校卫生

Objective@#To explore the relationship between cardiorespiratory fitness and executive function in Chinese adolescents, so as to provide a reference for promoting the overall development of Chinese adolescents physical and mental health.@*Methods@#From September to December 2022, a total of 5 018 adolescents aged 13 to 18 years from Shanghai, Suzhou, Taiyuan, Wuyuan, Xingyi, and Urumqi were selected by stratified cluster sampling method to assess cardiorespiratory fitness and executive function. Pearson s correlation and linear hierarchical regression were performed to analyze the relationship between cardiorespiratory fitness and executive functions.@*Results@#Among the sample of adolescents, maximal oxygen consumption (VO 2max ) was negatively correlated with the refreshing(1-back, 2-back) and conversion executive function responses ( r=-0.07, -0.12, -0.12, P <0.01). Linear regression analysis showed that VO 2max was negatively correlated with the reaction times of the refreshing(1-back, 2-back) and conversion functions ( B=-2.99, -6.44, -1.69, P <0.01).@*Conclusions@#Higher cardiorespiratory fitness among adolescents is associated with better performance in executive function. Teenagers should strengthen high intensity cardiopulmonary endurance exercise to promote the improvement of executive function.

Npro of classical swine fever virus enhances HMGB1 acetylation and its degradation by lysosomes to evade from HMGB1-mediated antiviral immunity.

Classical swine fever virus (CSFV) can dampen the host innate immunity by destabilizing IRF3 upon its binding with viral Npro. High mobility group box 1 (HMGB1), a non-histone nuclear protein, has diverse functions, including inflammation, innate immunity, etc., which are closely related to its cellular localization. We investigated potential mutual interactions between CSFV and HMGB1 and their effects on virus replication. We found that HMGB1 at the protein level, but not at mRNA level, was markedly reduced in CSFV-infected or Npro-expressing IPEC-J2 cells. HMGB1 in the nuclear compartment is anti-CSFV by promoting IFN-mediated innate immune response, as evidenced by overexpression of nuclear or cytoplasmic dominant HMGB1 mutant in IPEC-J2 cells stimulated with poly(I:C). However, CSFV Npro upregulates HMGB1 acetylation, a modification that promotes HMGB1 translocation into the cytoplasmic compartment where it is degraded by lysosomes. Ethyl pyruvate could downregulate HMGB1 acetylation and prevent Npro-mediated HMGB1 reduction. Inhibition of deacetylase HDAC1 with MS275 or by RNA silencing could promote Npro-mediated HMGB1 degradation. Taken together, our study elucidates the mechanism with which HMGB1 in the nuclei initiates antiviral innate immune response to suppress CSFV replication and elaborates the pathway by which CSFV uses its Npro to evade from HMGB1-mediated antiviral immunity through upregulating HMGB1 acetylation with subsequent translocation into cytoplasm for lysosomal degradation.