Surgery versus no surgery in platinum-sensitive relapsed ovarian cancer: final overall survival analysis of the SOC-1 randomized phase 3 trial.

Surgery for platinum-sensitive, relapsed ovarian cancer (PSROC) is widely practiced but had contradictory survival outcomes in previous studies. In this multicenter, open-label, phase 3 trial, women with PSROC, and having had one previous therapy and no platinum-based chemotherapy (platinum-free interval) of 6 months or more, were randomly assigned to either the surgery group (182 patients) or the no-surgery group (control) (175 patients). Patients with resectable diseases were eligible according to the international model (iMODEL), combined with a positron emission tomography-computed tomography imaging. Overall survival (OS) and progression-free survival were coprimary endpoints in hierarchical testing, and a significantly longer progression-free survival with surgery was previously reported. Final analysis of OS was planned at data maturity of 59%. Between 19 July 2012 and 3 June 2019, 357 patients were enrolled. Median follow-up was 82.5 months. Median OS was 58.1 months with surgery and 52.1 months for control (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.61-1.05, P = 0.11). The predefined threshold for statistical significance was not met, but prespecified sensitivity analysis was performed. Overall, 61 of 175 (35%) patients in control had crossed over to surgery following subsequent relapse, and adjusted HR for death in the surgery group compared with control was 0.76, 95% CI 0.58-0.99. In subgroup analysis of relapse sites by imaging, median survival was not estimable in the surgery group and was 69.5 months in control in patients with <20 sites (HR 0.69, 95% CI 0.46-1.03). Patients with a complete resection had the most favorable outcome, with a median OS of 73.0 months. Twenty-four of 182 (13.2%) patients remained relapse free and alive >60 months in the surgery group as compared with five of 175 (2.9%) patients in the control group. In patients with PSROC, surgery did not increase OS in the intention-to-treat population but resulted in a prolongation of survival following adjustment of crossover.ClinicalTrials.gov registration: NCT01611766 .

Decreased snow depth inhibits litter decomposition via changes in litter microbial biomass and enzyme activity.

Decreased snow depth resulting from global warming has the potential to significantly impact biogeochemical cycles in cold forests. However, the specific mechanisms of how snow reduction affects litter decomposition and the underlying microbial processes remain unclear, this knowledge gap limits our ability to precisely predict ecological processes within cold forest ecosystems under climate change. Hence, a field experiment was conducted in a subalpine forest in southwestern China, involving a gradient of snow reduction levels (control, 50 %, 100 %) to investigate the effects of decreased snow on litter decomposition, as well as microbial biomass and activity, specifically focused on two common species: red birch (Betula albosinensis) and masters larch (Larix mastersiana). After one year of incubation, the decomposition rate (k-value) of the two types of litter ranged from 0.12 to 0.24 across three snow treatments. A significant lower litter mass loss, microbial biomass and enzyme activity were observed under decreased snow depth in winter. Furthermore, a hysteresis inhibitory effect of snow reduction on hydrolase activity was observed in the following growing season. Additionally, the high initial quality (lower C/N ratio) of red birch litter facilitated the colonization by a greater quantity of microorganisms, making it more susceptible to snow reduction compared to the low-quality masters larch litter. Structural equation models indicated that decreased snow depth hindered litter decomposition by altering the biological characterization of litter (e.g., microbial biomass and enzyme activity) and environmental variables (e.g., mean temperature and moisture content). The findings suggest that the potential decline in snow depth could inhibit litter decomposition by reducing microbial biomass and activity, implying that the future climate change may alter the material cycling processes in subalpine forest ecosystems.

Discrimination and characterization of volatile organic compounds and nutritional values of three varieties of chopped pepper seeds.

Fermented-chopped pepper is a widely consumed condiment in China due to its attractive flavor. Chopped pepper seed (CPS) is the byproduct generated during the production of chopped pepper and is generally discarded as waste. In this study, the volatile organic compounds (VOCs) and nutritional value of three varieties of CPS were investigated. Results indicated that the nutritional compositions of the three CPS varieties exhibited significant differences. All CPS samples contained 17 amino acids and were rich in fatty acids, with unsaturated fatty acids being predominant and accounting for 79 % of the total fatty acids. A total of 53 VOCs were identified by gas chromatography-ion mobility spectrometry, which could be classified into 9 groups, with aldehydes, esters, and alcohols comprising the three largest groups. The three varieties of CPS had remarkably varied aromas whereas there are five key VOCs (i.e., 2-pentylfuran, methional, ethyl 3-methylbutanoate, dimethyl disulfide, and nonanal) in all CPS samples. Network correlation analysis revealed that VOCs are closely correlated with amino and fatty acids. Thus, this study provides a useful basis for understanding the nutritional values and flavor characteristics of different CPS varieties, which could be used as an ingredient and might have great potential in the food industry.

Low-Temperature Adaptive Single-Atom Iron Nanozymes against Viruses in the Cold Chain.

Outbreaks of viral infectious diseases, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV), pose a great threat to human health. Viral spread is accelerated worldwide by the development of cold chain logistics; Therefore, an effective antiviral approach is required. In this study, it is aimed to develop a distinct antiviral strategy using nanozymes with low-temperature adaptability, suitable for cold chain logistics. Phosphorus (P) atoms are added to the remote counter position of Fe-N-C center to prepare FeN4P2-single-atom nanozymes (SAzymes), exhibiting lipid oxidase (OXD)-like activity at cold chain temperatures (-20, and 4 °C). This feature enables FeN4P2-SAzymes to disrupt multiple enveloped viruses (human, swine, and avian coronaviruses, and H1-H11 subtypes of IAV) by catalyzing lipid peroxidation of the viral lipid envelope. Under the simulated conditions of cold chain logistics, FeN4P2-SAzymes are successfully applied as antiviral coatings on outer packaging and personal protective equipment; Therefore, FeN4P2-SAzymes with low-temperature adaptability and broad-spectrum antiviral properties may serve as key materials for developing specific antiviral approaches to interrupt viral transmission through the cold chain.

Discovery of 4-amino-1,6-dihydro-7H-pyrrolo[2,3-d]pyridazin-7-one derivatives as potential receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitors.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important regulatory factor in the necroptosis signaling pathway, and is considered an attractive therapeutic target for treating multiple inflammatory diseases. Herein, we describe the design, synthesis, and structure-activity relationships of 4-amino-1,6-dihydro-7H-pyrrolo [2,3-d]pyridazin-7-one derivatives as RIPK1 inhibitors. Among them, 13c showed favorable RIPK1 kinase inhibition activity with an IC50 value of 59.8 nM, and high RIPK1 binding affinity compared with other regulatory kinases of necroptosis (RIPK1 Kd = 3.5 nM, RIPK3 Kd = 1700 nM, and MLKL Kd > 30,000 nM). 13c efficiently blocked TNFα-induced necroptosis in both human and murine cells (EC50 = 1.06-4.58 nM), and inhibited TSZ-induced phosphorylation of the RIPK1/RIPK3/MLKL pathway. In liver microsomal assay studies, the clearance rate and half-life of 13c were 18.40 mL/min/g and 75.33 min, respectively. 13c displayed acceptable pharmacokinetic characteristics, with oral bioavailability of 59.55%. In TNFα-induced systemic inflammatory response syndrome, pretreatment with 13c could effectively protect mice from loss of body temperature and death. Overall, these compounds are promising candidates for future optimization studies.

Dietary Chito-oligosaccharide attenuates LPS-challenged intestinal inflammation via regulating mitochondrial apoptotic and MAPK signaling pathway.

To investigate the regulatory effects of Chito-oligosaccharide (COS) on the anti-oxidative, anti-inflammatory, and MAPK signaling pathways. A total of 40 28-day-old weaned piglets were randomly allotted to 4 equal groups [including the control group, lipopolysaccharide (LPS) group, COS group, and COS*LPS group]. On the morning of d 14 and 21, piglets were injected with saline or LPS. At 2 h post-injection, whole blood samples were collected on d 14 and 21, and small intestine and liver samples were collected and analyzed on d 21. The results showed that COS inhibited the LPS-induced increase of malondialdehyde (MDA) concentration and hepatic TNF-α cytokines. COS significantly increased the serum total antioxidant capability (T-AOC) value on d 14, and total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) activities in both serum and liver on d 21. Furthermore, it increased hepatic catalase (CAT) activity. COS also increased the LPS-induced decrease in serum IgG concentrations. Immunohistochemical analysis results showed that COS significantly increased the jejunal and ileal Caspase 3, and ileal CD4+ values challenged by LPS. Dietary COS decreased the LPS-induced jejunal and ileal BAX and CCL2 mRNA levels, markedly decreased ileal COX2 and SOD1 mRNA levels, while increasing ileal iNOS. Furthermore, COS significantly increased the LPS-induced jejunal and ileal p-P38 and MyD88, as well as jejunal P38, while it effectively suppressed jejunal JNK1, and jejunal and ileal JNK2, p-JNK1, and p-JNK2 protein expressions. These results demonstrated that COS could be beneficial by attenuating LPS-challenged intestinal inflammation via regulating mitochondrial apoptotic and MAPK signaling pathways.

Supragastric lesser sac: an insidious site for surgical exploration during the debulking surgery in advanced ovarian cancer.

OBJECTIVE: Metastases in the supragastric lesser sac (SGLS) are not only occult but are also barriers to complete resection of ovarian cancer. We describe a cohort of patients with SGLS disease undergoing debulking surgery. METHODS: We identified all patients who underwent evaluation and eventual resection of SGLS disease as part of cytoreductive surgery for stage IIIC-IVB high-grade epithelial ovarian cancer at our institution from January 2018 to August 2022. RESULTS: Thirty-three of 286 patients (11.5%) underwent resection of SGLS disease. Metastases in the SGLS were identified by preoperative imaging in 4 of 33 patients (12.1%). The median peritoneal cancer index score was 22 (range, 9-33). Through surgical exploration, metastases were frequently seen in the right diaphragm (100%), hepatorenal recess (97%), lesser omentum (81.8%), left diaphragm (78.8%), supracolic omentum (75.8%), anterior transverse mesocolon (72.7%), splenic hilum (63.6%), ligamentum teres hepatis (60.6%), and gallbladder fossa (51.5%). The lesser omentum was normal in 6 of 33 (18.2%) patients, despite metastases within the SGLS. A total of 54.5% of patients underwent complex surgery (surgical complexity scores; median, 8; range, 3-14). Complete resections were achieved in 19 (57.6%) patients. No complications were related to the resection of SGLS disease. The median length of progression-free survival was 24.8 months (95% confidence interval=16.6-32.9). CONCLUSION: Metastases to the SGLS are not uncommon in advanced ovarian cancer, particularly those with widely disseminated disease. Disease in this recess is rarely identified by preoperative imaging and deserves systematic surgical exploration to attain complete cytoreduction.

Effects of solid-state fermentation with Bacillus subtilis LK-1 on the volatile profile, catechins composition and antioxidant activity of dark teas.

In this study, the solid-state fermentation (SSF) of dark tea was carried out using Bacillus subtilis LK-1, which was isolated from Fu brick tea (FBT). The effects of SSF with B. subtilis on volatile organic compounds (VOCs), non-volatile metabolites, and antioxidant activities of dark tea was investigated. A total of 45 VOCs were identified, primarily consisting of ketones (18), hydrocarbons (8), aldehydes (7), and alcohols (6). Following fermentation, the content of key odor active substances such as linalool, ß-ionone, and 3,5-octadiene-2-one significantly increased, resulting in an enhanced floral and fruity aroma of dark tea. Furthermore, new flavor substances like geranyl isovalerate and decanal were produced during SSF, enriching the aroma profile of dark tea. Non-ester catechins demonstrated a drastic increase, while ester catechins remarkably decreased after SSF. Furthermore, SSF led to a slight decrease in the total polyphenols content and antioxidant activity of dark tea. There is a close relationship between VOCs and the main non-volatile metabolites during SSF. Overall, this study highlighted the great impact of SSF with B. subtilis on the metabolites of dark tea and provided valuable insights into the role of bacteria in shaping the metabolite profile of FBT.

Fruits are vehicles of drug-resistant pathogenic Candida tropicalis.

IMPORTANCE: Of 123 identified isolates from the fruit surface, C. tropicalis was the most frequently found species, followed by Meyerozyma caribbica and Candida krusei. All three fluconazole-resistant C. tropicalis were non-susceptible to voriconazole and belonged to the same predominant genotype of azole-resistant C. tropicalis causing candidemia in patients in Taiwan. Our findings provide evidence that fruit should be washed before eaten not only to remove chemicals but also potential drug-resistant pathogenic microbes, especially for immunocompromised individuals. To keep precious treatment options in patients, we not only continuously implement antimicrobial stewardship in hospitals but also reducing/stopping the use of agricultural fungicide classes used in human medicine.

Knocking out Selenium Binding Protein 1 Induces Depressive-Like Behavior in Mice.

Selenium binding protein 1 (SELENBP1) is involved in neurologic disorders, such as multiple sclerosis, spinal cord injury, Parkinson's disease, epilepsy, and schizophrenia. However, the role of SELENBP1 in the neurogenesis of depression, which is a neurologic disorder, and the underlying mechanisms of oxidative stress and inflammation in depression remain unknown. In this study, we evaluated the changes in the expression levels of SELENBP1 in the hippocampus of a mouse model of depression and in the serum of human patients with depression using the Gene Expression Omnibus database. These changes were validated using blood samples from human patients with depression and mouse models with chronic unpredictable mild stress (CUMS)-induced depressive-like behavior. We also investigated the effects of SELENBP1 knockout (KO) on inflammation, oxidative stress, and hippocampal neurogenesis in mice with CUMS-induced depression. Our results revealed that SELENBP1 levels was decreased in the blood of human patients with depression and in the hippocampus of mice with CUMS-induced depression. SELENBP1 KO increased CUMS-induced depressive behavior in mice and caused dysregulation of inflammatory cytokines and oxidative stress. This led to a decrease in the numbers of doublecortin- and Ki67-positive cells, which might aggravate CUMS-induced depressive symptoms. These findings suggest that SELENBP1 might be involved in the regulation of neurogenesis in mice with depression and could be served as a potential target for diagnosing and treating depression.

The Way to Malignant Transformation: Can Epigenetic Alterations Be Used to Diagnose Early-Stage Head and Neck Cancer?

Identifying and treating tumors early is the key to secondary prevention in cancer control. At present, prevention of oral cancer is still challenging because the molecular drivers responsible for malignant transformation of the 11 clinically defined oral potentially malignant disorders are still unknown. In this review, we focused on studies that elucidate the epigenetic alterations demarcating malignant and nonmalignant epigenomes and prioritized findings from clinical samples. Head and neck included, the genomes of many cancer types are largely hypomethylated and accompanied by focal hypermethylation on certain specific regions. We revisited prior studies that demonstrated that sufficient uptake of folate, the primary dietary methyl donor, is associated with oral cancer reduction. As epigenetically driven phenotypic plasticity, a newly recognized hallmark of cancer, has been linked to tumor initiation, cell fate determination, and drug resistance, we discussed prior findings that might be associated with this hallmark, including gene clusters (11q13.3, 19q13.43, 20q11.2, 22q11-13) with great potential for oral cancer biomarkers, and successful examples in screening early-stage nasopharyngeal carcinoma. Although one-size-fits-all approaches have been shown to be ineffective in most cancer therapies, the rapid development of epigenome sequencing methods raises the possibility that this nonmutagenic approach may be an exception. Only time will tell.

Risk Factors of Postoperative Cerebrospinal Fluid Leak After Craniovertebral Junction Anomalies Surgery: A Case-Control Study.

OBJECTIVE: To identify potential risk factors for cerebrospinal fluid (CSF) leakage after craniovertebral junction (CVJ) anomaly surgery and to provide a reference for clinical practice. METHODS: Sixty-six patients who underwent elective CVJ anomaly surgery during a 6-year period (April 2013 to September 2019) were retrospectively included. Research data were collected from the patients' medical records and imaging systems. Patients were divided into CSF leak and no CSF leak groups. Univariate tests were performed to identify potential risk factors. For statistically significant variables in the univariate tests, a logistic regression test was used to identify independent risk factors for CSF leakage. RESULTS: The overall prevalence of CSF leakage was 13.64%. Univariate tests showed that a basion-dental interval (BDI) > 10 mm and occipitalized atlas had significant intergroup differences (p < 0.05). Multivariate analysis indicated that a BDI > 10 mm was an independent risk factor for CSF leakage, and patients with CVJ anomalies with a BDI > 10 mm were more likely to have postoperative CSF leaks (odds ratio, 14.67; 95% confidence interval, 1.48-30.88; p = 0.004). CONCLUSION: It is necessary to maintain vigilance during CVJ anomaly surgery in patients with a preoperative BDI > 10 mm to avoid postoperative CSF leaks.

Bidirectionally Regulating Viral and Cellular Ferroptosis with Metastable Iron Sulfide Against Influenza Virus.

Influenza virus with numerous subtypes and frequent variation limits the development of high-efficacy and broad-spectrum antiviral strategy. Here, a novel multi-antiviral metastable iron sulfides (mFeS) against various influenza A/B subtype viruses is developed. This work finds that mFeS induces high levels of lipid peroxidation and •OH free radicals in the conservative viral envelope, which depends on Fe2+ . This phenomenon, termed as a viral ferroptosis, results in the loss of viral infectibility and pathogenicity in vitro and in vivo, respectively. Furthermore, the decoction of mFeS (Dc(mFeS)) inhibits cellular ferroptosis-dependent intracellular viral replication by correcting the virus-induced reprogrammed sulfur metabolism, a conserved cellular metabolism. Notably, personal protective equipment (PPE) that is loaded with mFeS provides good antiviral protection. Aerosol administration of mFeS combined with the decoction (mFeS&Dc) has a potential therapeutic effect against H1N1 lethal infection in mice. Collectively, mFeS represents an antiviral alternative with broad-spectrum activity against intracellular and extracellular influenza virus.

Study on the effect of additives on microbial diversity, predicted functional profiles, and fermentation quality of Broussonetia papyrifera and Pennisetum sinese mixed ensilage in the karst region.

In this research, we evaluated the effect of exogenous lactic acid bacteria and Amomum villosum essential oil (AVEO) on the chemical composition, microbial community composition, microbial functional diversity, and fermentation quality of Broussonetia papyrifera (BP) and Pennisetum sinese (PS) mixed silages. The BP:PS mixing ratios were 100:0, 70:30, 50:50, 30:70, and 0:100. After 3 and 30 days of ensiling at 22°C-25°C, microbial diversity and function, and fermentation quality, were assessed. Increasing PS content resulted in decreased ammoniacal nitrogen and pH, increased water-soluble carbohydrate content, increased relative abundance of Lactococcus and Acinetobacter, and reduced relative abundance of Caproiciproducens and Pseudomonas. A 50:50 BP:PS ratio effectively improved the fermentation quality compared to anaerobic fermentation with BP or PS alone, while AVEO treatment further improved fermentation quality by increasing Lactococcus relative abundance. Moreover, as fermentation proceeded, ensiling enhanced the 'Human diseases', 'Environmental information processing', and 'Cellular processes' functions at the first level, as well as the 'Two-component system' and 'ABC transporters' functions at the third level. Different additives affected the fermentation of BP and PS mixed silage by regulating microbial community succession and metabolic pathways during ensiling.

MRI texture-based machine learning models for the evaluation of renal function on different segmentations: a proof-of-concept study.

BACKGROUND: To develop and validate an MRI texture-based machine learning model for the noninvasive assessment of renal function. METHODS: A retrospective study of 174 diabetic patients (training cohort, n = 123; validation cohort, n = 51) who underwent renal MRI scans was included. They were assigned to normal function (n = 71), mild or moderate impairment (n = 69), and severe impairment groups (n = 34) according to renal function. Four methods of kidney segmentation on T2-weighted images (T2WI) were compared, including regions of interest covering all coronal slices (All-K), the largest coronal slices (LC-K), and subregions of the largest coronal slices (TLCO-K and PIZZA-K). The speeded-up robust features (SURF) and support vector machine (SVM) algorithms were used for texture feature extraction and model construction, respectively. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of models. RESULTS: The models based on LC-K and All-K achieved the nonsignificantly highest accuracy in the classification of renal function (all p values > 0.05). The optimal model yielded high performance in classifying the normal function, mild or moderate impairment, and severe impairment, with an area under the curve of 0.938 (95% confidence interval [CI] 0.935-0.940), 0.919 (95%CI 0.916-0.922), and 0.959 (95%CI 0.956-0.962) in the training cohorts, respectively, as well as 0.802 (95%CI 0.800-0.807), 0.852 (95%CI 0.846-0.857), and 0.863 (95%CI 0.857-0.887) in the validation cohorts, respectively. CONCLUSION: We developed and internally validated an MRI-based machine-learning model that can accurately evaluate renal function. Once externally validated, this model has the potential to facilitate the monitoring of patients with impaired renal function.

Restoration of lipid homeostasis between TG and PE by the LXRα-ATGL/EPT1 axis ameliorates hepatosteatosis.

Converting lipid disturbances in response to energy oversupply into healthy lipid homeostasis is a promising therapy to alleviate hepatosteatosis. Our clinical studies found that a further elevation of triglyceride (TG) in obese patients with the body mass index (BMI) greater than 28 was accompanied by a further reduction of phosphatidylethanolamine (PE). Shorter survival and poor prognosis were shown for the patients with high TG and low PE levels. Liver X receptor alpha (LXRα) knockout mice aggravated high-fat diet (HFD)-induced obesity and lipid disorders, making the TG enrichment and the PE decrease more pronounced according to the liver lipidomics analysis. The RNA-seq from mice liver exhibited that these metabolism disorders were attributed to the decline of Atgl (encoding the TG metabolism enzyme ATGL) and Ept1 (encoding the PE synthesis enzyme EPT1) expression. Mechanistic studies uncovered that LXRα activated the ATGL and EPT1 gene via direct binding to a LXR response element (LXRE) in the promoter. Moreover, both the supplement of PE in statin or fibrate therapy, and the LXRα inducer (oridonin) ameliorated cellular lipid deposition and lipotoxicity. Altogether, restoration of lipid homeostasis of TG and PE via the LXRα-ATGL/EPT1 axis may be a potential approach for the management of hepatosteatosis and metabolic syndrome.

Network Pharmacology Approach to Investigate the Mechanism of Danggui-Shaoyao-San against Diabetic Kidney Disease.

Background: Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine formula that has been widely used to treat a variety of disorders, including renal diseases. Despite being well-established in clinical practice, the mechanisms behind the therapeutic effects of DSS on diabetic nephropathy (DN) remain elusive. Methods: To explore the therapeutic mechanism, we explored the action mechanism of DSS on DN using network pharmacology strategies. All ingredients were selected from the relevant databases, and active ingredients were chosen on the basis of their oral bioavailability prediction and drug-likeness evaluation. The putative proteins of DSS were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas the potential genes of DN were obtained from the GeneCards and OMIM databases. Enrichment analysis using gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) was performed to discover possible hub targets and gene-related pathways. Afterwards, the underlying molecular mechanisms of DSS against DN were validated experimentally in vivo against db/db mice. Results: We identified 91 phytochemicals using the comprehensive network pharmacology technique, 51 of which were chosen as bioactive components. There were 40 proteins and 20 pathways in the target-pathway network. The experimental validation results demonstrated that DSS may reduce the expression of TNF-α, IL-6, and ICAM-1, as well as extracellular matrix deposition, by blocking the JNK pathway activation, which protects against kidney injury. Conclusion: This study discovered the putative molecular mechanisms of action of DSS against diabetic kidney damage through a network pharmacology approach and experimental validation.

PA-X protein of H9N2 subtype avian influenza virus suppresses the innate immunity of chicken bone marrow-derived dendritic cells.

H9N2 subtype avian influenza (AI) is an infectious disease associated with immunosuppression in poultry. Here, the regulation function of PA-X protein was determined on the host innate immune response of H9N2-infected chicken bone marrow-derived DCs (chBM-DCs). Based on 2 mutated viruses expressing PA-X protein (rTX) or deficient PA-X protein (rTX-FS), and the established culture system of chBM-DCs, results showed PA-X protein inhibited viral replication in chBM-DCs but not in non-immune chicken cells (DF-1). Moreover, PA-X protein downregulated the expression of phenotypic markers (CD40, CD86, and MHCII) and proinflammatory cytokine (IL-12 and IL-1ß) of chBM-DCs. The mixed lymphocyte reaction between chBM-DCs and chicken T cells showed PA-X protein significantly decreased H9N2-infected chBM-DCs to induce T cell proliferation, implying a suppression of the DC-induced downstream T cell response. Taken together, these findings indicated that PA-X protein is a key viral protein to help H9N2 subtype AIVs escape the innate immunity of chBM-DCs.