Distinct molecular profiles of skull bone marrow in health and neurological disorders.

The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature. 3D imaging demonstrates the structural and cellular details of human skull-meninges connections (SMCs) compared with veins. Last, using translocator protein positron emission tomography (TSPO-PET) imaging, we show that the skull bone marrow reflects inflammatory brain responses with a disease-specific spatial distribution in patients with various neurological disorders. The unique molecular profile and anatomical and functional connections of the skull show its potential as a site for diagnosing, monitoring, and treating brain diseases.

Cellular and Molecular Probing of Intact Human Organs.

Optical tissue transparency permits scalable cellular and molecular investigation of complex tissues in 3D. Adult human organs are particularly challenging to render transparent because of the accumulation of dense and sturdy molecules in decades-aged tissues. To overcome these challenges, we developed SHANEL, a method based on a new tissue permeabilization approach to clear and label stiff human organs. We used SHANEL to render the intact adult human brain and kidney transparent and perform 3D histology with antibodies and dyes in centimeters-depth. Thereby, we revealed structural details of the intact human eye, human thyroid, human kidney, and transgenic pig pancreas at the cellular resolution. Furthermore, we developed a deep learning pipeline to analyze millions of cells in cleared human brain tissues within hours with standard lab computers. Overall, SHANEL is a robust and unbiased technology to chart the cellular and molecular architecture of large intact mammalian organs.

Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity.

The presence of DNA in the cytoplasm is normally a sign of microbial infections and is quickly detected by cyclic GMP-AMP synthase (cGAS) to elicit anti-infection immune responses. However, chronic activation of cGAS by self-DNA leads to severe autoimmune diseases for which no effective treatment is available yet. Here we report that acetylation inhibits cGAS activation and that the enforced acetylation of cGAS by aspirin robustly suppresses self-DNA-induced autoimmunity. We find that cGAS acetylation on either Lys384, Lys394, or Lys414 contributes to keeping cGAS inactive. cGAS is deacetylated in response to DNA challenges. Importantly, we show that aspirin can directly acetylate cGAS and efficiently inhibit cGAS-mediated immune responses. Finally, we demonstrate that aspirin can effectively suppress self-DNA-induced autoimmunity in Aicardi-Goutières syndrome (AGS) patient cells and in an AGS mouse model. Thus, our study reveals that acetylation contributes to cGAS activity regulation and provides a potential therapy for treating DNA-mediated autoimmune diseases.

G3BP1 promotes DNA binding and activation of cGAS.

Cyclic GMP-AMP synthase (cGAS) is a key sensor responsible for cytosolic DNA detection. Here we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for DNA sensing and efficient activation of cGAS. G3BP1 enhanced DNA binding of cGAS by promoting the formation of large cGAS complexes. G3BP1 deficiency led to inefficient DNA binding by cGAS and inhibited cGAS-dependent interferon (IFN) production. The G3BP1 inhibitor epigallocatechin gallate (EGCG) disrupted existing G3BP1-cGAS complexes and inhibited DNA-triggered cGAS activation, thereby blocking DNA-induced IFN production both in vivo and in vitro. EGCG administration blunted self DNA-induced autoinflammatory responses in an Aicardi-Goutières syndrome (AGS) mouse model and reduced IFN-stimulated gene expression in cells from a patient with AGS. Thus, our study reveals that G3BP1 physically interacts with and primes cGAS for efficient activation. Furthermore, EGCG-mediated inhibition of G3BP1 provides a potential treatment for cGAS-related autoimmune diseases.

Virtual reality-empowered deep-learning analysis of brain cells.

Automated detection of specific cells in three-dimensional datasets such as whole-brain light-sheet image stacks is challenging. Here, we present DELiVR, a virtual reality-trained deep-learning pipeline for detecting c-Fos+ cells as markers for neuronal activity in cleared mouse brains. Virtual reality annotation substantially accelerated training data generation, enabling DELiVR to outperform state-of-the-art cell-segmenting approaches. Our pipeline is available in a user-friendly Docker container that runs with a standalone Fiji plugin. DELiVR features a comprehensive toolkit for data visualization and can be customized to other cell types of interest, as we did here for microglia somata, using Fiji for dataset-specific training. We applied DELiVR to investigate cancer-related brain activity, unveiling an activation pattern that distinguishes weight-stable cancer from cancers associated with weight loss. Overall, DELiVR is a robust deep-learning tool that does not require advanced coding skills to analyze whole-brain imaging data in health and disease.

A chromosome-scale genome of Rhus chinensis Mill. provides new insights into plant-insect interaction and gallotannins biosynthesis.

Rhus chinensis Mill., an economically valuable Anacardiaceae species, is parasitized by the galling aphid Schlechtendalia chinensis, resulting in the formation of the Chinese gallnut (CG). Here, we report a chromosomal-level genome assembly of R. chinensis, with a total size of 389.40 Mb and scaffold N50 of 23.02 Mb. Comparative genomic and transcriptome analysis revealed that the enhanced structure of CG and nutritional metabolism contribute to improving the adaptability of R. chinensis to S. chinensis by supporting CG and galling aphid growth. CG was observed to be abundant in hydrolysable tannins (HT), particularly gallotannin and its isomers. Tandem repeat clusters of dehydroquinate dehydratase/shikimate dehydrogenase (DQD/SDH) and serine carboxypeptidase-like (SCPL) and their homologs involved in HT production were determined as specific to HT-rich species. The functional differentiation of DQD/SDH tandem duplicate genes and the significant contraction in the phenylalanine ammonia-lyase (PAL) gene family contributed to the accumulation of gallic acid and HT while minimizing the production of shikimic acid, flavonoids, and condensed tannins in CG. Furthermore, we identified one UDP glucosyltransferase (UGT84A), three carboxylesterase (CXE), and six SCPL genes from conserved tandem repeat clusters that are involved in gallotannin biosynthesis and hydrolysis in CG. We then constructed a regulatory network of these genes based on co-expression and transcription factor motif analysis. Our findings provide a genomic resource for the exploration of the underlying mechanisms of plant-galling insect interaction and highlight the importance of the functional divergence of tandem duplicate genes in the accumulation of secondary metabolites.

Sialic acids as attachment factors in mosquitoes mediating Japanese encephalitis virus infection.

The role of Culex mosquitoes in the transmission of Japanese encephalitis virus (JEV) is crucial, yet the mechanisms of JEV infection in these vectors remain unclear. Previous research has indicated that various host factors participate in JEV infection. Herein, we present evidence that mosquito sialic acids enhance JEV infection both in vivo and in vitro. By treating mosquitoes and C6/36 cells with neuraminidase or lectin, the function of sialic acids is effectively blocked, resulting in significant inhibition of JEV infection. Furthermore, knockdown of the sialic acid biosynthesis genes in Culex mosquitoes also leads to a reduction in JEV infection. Moreover, our research revealed that sialic acids play a role in the attachment of JEV to mosquito cells, but not in its internalization. To further explore the mechanisms underlying the promotion of JEV attachment by sialic acids, we conducted immunoprecipitation experiments to confirm the direct binding of sialic acids to the last α-helix in JEV envelope protein domain III. Overall, our study contributes to a molecular comprehension of the interaction between mosquitoes and JEV and offers potential strategies for preventing the dissemination of flavivirus in natural environments.IMPORTANCEIn this study, we aimed to investigate the impact of glycoconjugate sialic acids on mosquito infection with Japanese encephalitis virus (JEV). Our findings demonstrate that sialic acids play a crucial role in enhancing JEV infection by facilitating the attachment of the virus to the cell membrane. Furthermore, our investigation revealed that sialic acids directly bind to the final α-helix in the JEV envelope protein domain III, thereby accelerating virus adsorption. Collectively, our results highlight the significance of mosquito sialic acids in JEV infection within vectors, contributing to a better understanding of the interaction between mosquitoes and JEV.

NLRP3 Phosphorylation Is an Essential Priming Event for Inflammasome Activation.

Many infections and stress signals can rapidly activate the NLRP3 inflammasome to elicit robust inflammatory responses. This activation requires a priming step, which is thought to be mainly for upregulating NLRP3 transcription. However, recent studies report that the NLRP3 inflammasome can be activated independently of transcription, suggesting that the priming process has unknown essential regulatory steps. Here, we report that JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation. We show that NLRP3 inflammasome activation is disrupted in NLRP3-S194A knockin mice. JNK1-mediated NLRP3 S194 phosphorylation is critical for NLRP3 deubiquitination and facilitates its self-association and the subsequent inflammasome assembly. Importantly, we demonstrate that blocking S194 phosphorylation prevents NLRP3 inflammasome activation in cryopyrin-associated periodic syndromes (CAPS). Thus, our study reveals a key priming molecular event that is a prerequisite for NLRP3 inflammasome activation. Inhibiting NLRP3 phosphorylation could be an effective treatment for NLRP3-related diseases.

Identification of the potential active site of the septal peptidoglycan polymerase FtsW.

SEDS (Shape, Elongation, Division and Sporulation) proteins are widely conserved peptidoglycan (PG) glycosyltransferases that form complexes with class B penicillin-binding proteins (bPBPs, with transpeptidase activity) to synthesize PG during bacterial cell growth and division. Because of their crucial roles in bacterial morphogenesis, SEDS proteins are one of the most promising targets for the development of new antibiotics. However, how SEDS proteins recognize their substrate lipid II, the building block of the PG layer, and polymerize it into glycan strands is still not clear. In this study, we isolated and characterized dominant-negative alleles of FtsW, a SEDS protein critical for septal PG synthesis during bacterial cytokinesis. Interestingly, most of the dominant-negative FtsW mutations reside in extracellular loops that are highly conserved in the SEDS family. Moreover, these mutations are scattered around a central cavity in a modeled FtsW structure, which has been proposed to be the active site of SEDS proteins. Consistent with this, we found that these mutations blocked septal PG synthesis but did not affect FtsW localization to the division site, interaction with its partners nor its substrate lipid II. Taken together, these results suggest that the residues corresponding to the dominant-negative mutations likely constitute the active site of FtsW, which may aid in the design of FtsW inhibitors.

Cellular nucleic acid binding protein facilitates cardiac repair after myocardial infarction by activating ß-catenin signaling.

The regenerative capacity of the adult mammalian heart is limited, while the neonatal heart is an organ with regenerative and proliferative ability. Activating adult cardiomyocytes (CMs) to re-enter the cell cycle is an effective therapeutic method for ischemic heart disease such as myocardial infarction (MI) and heart failure. Here, we aimed to reveal the role and potential mechanisms of cellular nucleic acid binding protein (CNBP) in cardiac regeneration and repair after heart injury. CNBP is highly expressed within 7 days post-birth while decreases significantly with the loss of regenerative ability. In vitro, overexpression of CNBP promoted CM proliferation and survival, whereas knockdown of CNBP inhibited these processes. In vivo, knockdown of CNBP in CMs robustly hindered myocardial regeneration after apical resection in neonatal mice. In adult MI mice, CM-specific CNBP overexpression in the infarct border zone ameliorated myocardial injury in acute stage and facilitated CM proliferation and functional recovery in the long term. Quantitative proteomic analysis with TMT labeling showed that CNBP overexpression promoted the DNA replication, cell cycle progression, and cell division. Mechanically, CNBP overexpression increased the expression of ß-catenin and its downstream target genes CCND1 and c-myc; Furthermore, Luciferase reporter and Chromatin immunoprecipitation (ChIP) assays showed that CNBP could directly bind to the ß-catenin promoter and promote its transcription. CNBP also upregulated the expression of G1/S-related cell cycle genes CCNE1, CDK2, and CDK4. Collectively, our study reveals the positive role of CNBP in promoting cardiac repair after injury, providing a new therapeutic option for the treatment of MI.

Evaluation of the TLR3 involvement during Schistosoma japonicum-induced pathology.

BACKGROUND: Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to Schistosoma japonicum infections. The aim of this study was to investigate the properties of TLR3 in the liver of C57BL/6 mice infected by S. japonicum. METHODS: The production of TLR3+ cells in CD4+T cells (CD4+CD3+), CD8+T cells (CD8+CD3+), γδT cells (γδTCR+CD3+), NKT cells (NK1.1+CD3+), B cells (CD19+CD3-), NK (NK1.1-CD3+) cells, MDSC (CD11b+Gr1+), macrophages (CD11b+F4/80+), DCs (CD11c+CD11b+) and neutrophils (CD11b+ Ly6g+) were assessed by flow cytometry. Sections of the liver were examined by haematoxylin and eosin staining in order to measure the area of granulomas. Hematological parameters including white blood cell (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (HGB) were analyzed. The levels of ALT and AST in the serum were measured using biochemical kits. The relative titers of anti-SEA IgG and anti-SEA IgM in the serum were measured by enzyme-linked immunosorbent assay (ELISA). CD25, CD69, CD314 and CD94 molecules were detected by flow cytometry. RESULTS: Flow cytometry results showed that the expression of TLR3 increased significantly after S. japonicum infection (P < 0.05). Hepatic myeloid and lymphoid cells could express TLR3, and the percentages of TLR3-expressing MDSC, macrophages and neutrophils were increased after infection. Knocking out TLR3 ameliorated the damage and decreased infiltration of inflammatory cells in infected C57BL/6 mouse livers.,The number of WBC was significantly reduced in TLR3 KO-infected mice compared to WT-infected mice (P < 0.01), but the levels of RBC, platelet and HGB were significantly increased in KO infected mice. Moreover, the relative titers of anti-SEA IgG and anti-SEA IgM in the serum of infected KO mice were statistically decreased compared with the infected WT mice. We also compared the activation-associated molecules expression between S.japonicum-infected WT and TLR3 KO mice. CONCLUSIONS: Taken together, our data indicated that TLR3 played potential roles in the context of S. japonicum infection and it may accelerate the progression of S. japonicum-associated liver pathology.

Advances in common in vitro cellular models of pulmonary fibrosis.

The development of in vitro models is essential for a comprehensive understanding and investigation of pulmonary fibrosis (PF) at both cellular and molecular levels. This study presents a literature review and an analysis of various cellular models used in scientific studies, specifically focusing on their applications in elucidating the pathogenesis of PF. Our study highlights the importance of taking a comprehensive approach to studing PF, emphasizing the necessity of considering multiple cell types and organs and integrating diverse analytical perspectives. Notably, primary cells demonstrate remarkable cell growth characteristics and gene expression profiles; however, their limited availability, maintenance challenges, inability for continuous propagation and susceptibility to phenotypic changes over time significantly limit their utility in scientific investigation. By contrast, immortalized cell lines are easily accessible, cultured and continuously propagated, although they may have some phenotypic differences from primary cells. Furthermore, in vitro coculture models offer a more practical and precise method to explore complex interactions among cells, tissues and organs. Consequently, when developing models of PF, researchers should thoroughly assess the advantages, limitations and relevant mechanisms of different cell models to ensure their selection is consistent with the research objectives.

Bridging Eulerian and Lagrangian Poisson-Boltzmann solvers by ESES.

The Poisson-Boltzmann (PB) model is a widely used electrostatic model for biomolecular solvation analysis. Formulated as an elliptic interface problem, the PB model can be numerically solved on either Eulerian meshes using finite difference/finite element methods or Lagrangian meshes using boundary element methods. Molecular surface generators, which produce the discretized dielectric interfaces between solutes and solvents, are critical factors in determining the accuracy and efficiency of the PB solvers. In this work, we investigate the utility of the Eulerian Solvent Excluded Surface (ESES) software for rendering conjugated Eulerian and Lagrangian surface representations, which enables us to numerically validate and compare the quality of Eulerian PB solvers, such as the MIBPB solver, and the Lagrangian PB solvers, such as the TABI-PB solver. Furthermore, with the ESES software and its associated PB solvers, we are able to numerically validate an interesting and useful but often neglected source-target symmetric property associated with the linearized PB model.

Bovine Serum Albumin Template-Mediated Fabrication of Ruthenium Dioxide/Multiwalled Carbon Nanotubes: High-Performance Electrochemical Dopamine Biosensing in Human Serum.

The presence of abnormal dopamine (DA) levels may cause serious neurological disorders, therefore, the quantitative analysis of DA and its related research are of great significance for ensuring health. Herein, the bovine serum albumin (BSA) template method has been proposed for the preparation of catalytically high-performance ruthenium dioxide/multiwalled carbon nanotube (RuO2/MWCNT) nanocomposites. The incorporation of MWCNTs has improved the active surface area and conductivity while effectively preventing the aggregation of RuO2 nanoparticles. The outstanding electrocatalytic performance of RuO2/MWCNTs has promoted the electro-oxidation of DA at neutral pH. The electrochemical sensing platform based on RuO2/MWCNTs has demonstrated a wide linear range (0.5 to 111.1 µM), low detection limit (0.167 µM), excellent selectivity, long-term stability, and good reproducibility for DA detection. The satisfactory recovery range of 94.7% to 103% exhibited by the proposed sensing podium in serum samples signifies its potential for analytical applications. The aforementioned results reveal that RuO2/MWCNT nanostructures hold promising aptitude in the electrochemical sensor to detect DA in real samples, further offering broad prospects in clinical and medical diagnosis.

Construction of Co-ZIF-derived CoS2@Cu hollow heterogeneous nanotube array for the detection of hydrazine in environmental water samples.

As a neurotoxin, it is necessary to establish a low cost, stable and sensitive method for the quantitative detection of hydrazine. Using Co-ZIF (zeolite imidazole framework) nanorods as precursor, CoS2 hollow nanotube array heterogeneous structure loaded with Cu nanoparticles were prepared on carbon cloth (CC) by etching, calcination and plasma magnetron sputtering (CoS2@Cu HNTA/CC). As a self-supporting electrode, its hollow heterogeneous structure provides a large area of electron transfer channel for the oxidation of the food pollutant hydrazine. In addition, bimetallic synergies and in situ N doping regulated the electronic structure of CoS2@Cu HNTA/CC, and thus significantly improved the electrical conductivity and catalytic activity. As an efficient hydrazine sensor with a wide linear range of 1 µM L-1-10 mM (1 µM-1 mM and 1 mM-10 mM), its sensitivity and the limit of detection are 7996 µA mM-1 cm-2, 3772 µA mM-1 cm-2 and 0.276 µM (S/N = 3), respectively. This study provides a new strategy for the construction of MOFs (Metal Organic Framework)-derived bimetallic composites and their application in electrochemical sensing.

Current therapy and drug resistance in metastatic castration-resistant prostate cancer.

Castration-resistant prostate cancer (CRPC), especially metastatic castration-resistant prostate cancer (mCRPC) is one of the most prevalent malignancies and main cause of cancer-related death among men in the world. In addition, it is very difficult for clinical treatment because of the natural or acquired drug resistance of CRPC. Mechanisms of drug resistance are extremely complicated and how to overcome it remains an urgent clinical problem to be solved. Thus, a comprehensive and thorough understanding for mechanisms of drug resistance in mCRPC is indispensable to develop novel and better therapeutic strategies. In this review, we aim to review new insight of the treatment of mCRPC and elucidate mechanisms governing resistance to new drugs: taxanes, androgen receptor signaling inhibitors (ARSIs) and poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Most importantly, in order to improve efficacy of these drugs, strategies of overcoming drug resistance are also discussed based on their mechanisms respectively.

Deciphering feedback regulation of prostaglandin F2α in blood stasis syndrome using nitrogen-doped porous transition metal carbides.

Blood stasis syndrome (BSS) has persistent health risks; however, its pathogenesis remains elusive. This obscurity may result in missed opportunities for early intervention, increased susceptibility to chronic diseases, and reduced accuracy and efficacy of treatments. Metabolomics, employing the matrix-assisted laser desorption/ionization (MALDI) strategy, presents distinct advantages in biomarker discovery and unraveling molecular mechanisms. Nonetheless, the challenge is to develop efficient matrices for high-sensitivity and high-throughput analysis of diverse potential biomarkers in complex biosamples. This work utilized nitrogen-doped porous transition metal carbides and nitrides (NP-MXene) as a MALDI matrix to delve into the molecular mechanisms underlying BSS pathogenesis. Structural optimization yielded heightened peak sensitivity (by 1.49-fold) and increased peak numbers (by 1.16-fold) in clinical biosamples. Validation with animal models and clinical serum biosamples revealed significant differences in metabolic fingerprints between BSS and control groups, achieving an overall diagnostic efficacy of 0.905 (95% CI, 0.76-0.979). Prostaglandin F2α was identified as a potential biomarker (diagnostics efficiency of 0.711, specificity = 0.7, sensitivity = 0.6), and pathway enrichment analysis disclosed disruptions in arachidonic acid metabolism in BSS. This innovative approach not only advances comprehension of BSS pathogenesis, but also provides valuable insights for personalized treatment and diagnostic precision.

Using Auricular Cartilage-fascia Composite Tissue Free Grafting Technique to Improve Cartilage Survival Outcomes.

OBJECTIVES: Auricular cartilage graft has a wide range of applications in plastic and reconstructive surgery. However, there is still a risk of absorption of the grafts over time. Intrinsic postauricular fascia (IPF) with a rich vascular network may play an important role in the nutrition and repair of auricular cartilage. This study aimed to investigate the effect of IPF on the survival viability of free auricular cartilage grafts. METHODS: 24 auricular cartilages were obtained from 6 New Zealand white rabbits which were divided into the cartilage-fascia composite graft group (FC group, n=12) and the cartilage without fascia group (C group, n=12). Two groups of cartilage were implanted into each side of the subcutaneous pocket of the rabbit's dorsum. The rabbits were sacrificed after 3 months and all cartilage grafts were obtained. Macroscopic observation, histopathological staining, and biomechanical testing were performed on all specimens. RESULTS: There were significant differences between the 2 groups regarding proliferating chondrocytes, apoptotic chondrocytes, vascularization, and matrix collagen. Compared to the auricular cartilage grafts without fascia, the auricular cartilage-fascia composite grafts had more neovascularization, proliferative chondrocytes, and type II collagen, with a homogeneous cartilage matrix and no obvious areas of heterogeneous staining. Young's modulus and ultimate tensile strength of cartilage were reduced in both groups compared to pretransplantation, but the composite graft group was superior to the fascia-free group. CONCLUSIONS: Auricular cartilage-fascial composite tissue free graft could improve cartilage survival outcomes with higher viability and mechanical properties.

YOLOv7-TS: A Traffic Sign Detection Model Based on Sub-Pixel Convolution and Feature Fusion.

In recent years, significant progress has been witnessed in the field of deep learning-based object detection. As a subtask in the field of object detection, traffic sign detection has great potential for development. However, the existing object detection methods for traffic sign detection in real-world scenes are plagued by issues such as the omission of small objects and low detection accuracies. To address these issues, a traffic sign detection model named YOLOv7-Traffic Sign (YOLOv7-TS) is proposed based on sub-pixel convolution and feature fusion. Firstly, the up-sampling capability of the sub-pixel convolution integrating channel dimension is harnessed and a Feature Map Extraction Module (FMEM) is devised to mitigate the channel information loss. Furthermore, a Multi-feature Interactive Fusion Network (MIFNet) is constructed to facilitate enhanced information interaction among all feature layers, improving the feature fusion effectiveness and strengthening the perception ability of small objects. Moreover, a Deep Feature Enhancement Module (DFEM) is established to accelerate the pooling process while enriching the highest-layer feature. YOLOv7-TS is evaluated on two traffic sign datasets, namely CCTSDB2021 and TT100K. Compared with YOLOv7, YOLOv7-TS, with a smaller number of parameters, achieves a significant enhancement of 3.63% and 2.68% in the mean Average Precision (mAP) for each respective dataset, proving the effectiveness of the proposed model.

CXCL8 Knockout: A Key to Resisting Pasteurella multocida Toxin-Induced Cytotoxicity.

Pasteurella multocida, a zoonotic pathogen that produces a 146-kDa modular toxin (PMT), causes progressive atrophic rhinitis with severe turbinate bone degradation in pigs. However, its mechanism of cytotoxicity remains unclear. In this study, we expressed PMT, purified it in a prokaryotic expression system, and found that it killed PK15 cells. The host factor CXCL8 was significantly upregulated among the differentially expressed genes in a transcriptome sequencing analysis and qPCR verification. We constructed a CXCL8-knockout cell line with a CRISPR/Cas9 system and found that CXCL8 knockout significantly increased resistance to PMT-induced cell apoptosis. CXCL8 knockout impaired the cleavage efficiency of apoptosis-related proteins, including Caspase3, Caspase8, and PARP1, as demonstrated with Western blot. In conclusion, these findings establish that CXCL8 facilitates PMT-induced PK15 cell death, which involves apoptotic pathways; this observation documents that CXCL8 plays a key role in PMT-induced PK15 cell death.