ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.

ObjectiveTo identify potential influencing factors of urate crystal deposition at ankle/foot in patients with hyperuricemia （HUA）， and to analyze the predictive value of inflammatory indicators for urate crystal deposition in patients with different traditional Chinese medicine （TCM） syndromes， so as to provide potential reference for clinical risk assessment and individualized TCM intervention. MethodsA retrospective study was carried out with the enrollment of 231 HUA patients from The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2021 and December 2024. The enrolled patients were further divided into a crystal deposition-positive group （143 cases） and a crystal deposition-negative group （88 cases） according to the results of dual-energy computed tomography （CT）. Sociodemographic data， living habits， serum uric acid levels， and inflammatory indicators of the enrolled patients were collcted， and TCM syndrome differentiation was performed. Furthermore， univariate analysis was used to compare inter-group differences in clinical characteristics. MMultivariate Logistic regression was applied to identify the influencing factors of urate crystal deposition. In addition， the receiver operating characteristic （ROC） curves were plotted to evaluate the predictive efficacy of inflammatory indicators for crystal deposition across different TCM syndromes. ResultsThere were statistically significant inter-group differences in the proportion of males， age， body mass index， proportion of mental labor， rate of low water intake， and rate of high-sugar beverage consumption （P<0.05），whereas no significant difference in low exercise intensity was found between the two groups. Furthermore， compared with the negative group， the positive group had higher serum uric acid level， neutrophil-to-lymphocyte ratio （NLR）， and platelet-to-lymphocyte ratio （PLR）， but lower systemic immune-inflammation index （SIRI） （P<0.05）. Regarding the distribution of TCM syndromes， the positive group was dominated by the dampness-heat accumulation syndrome （55/143，38.46%）， while the negative group was mainly characterized by the phlegm-turbidity obstruction syndrome （44/88，50.00%）. Multivariate Logistic regression analysis revealed that high-sugar beverage consumption， elevated NLR， and elevated PLR were risk factors for urate crystal deposition ［odd ratio （OR） = 8.002， 5.377， 1.034， respectively； 95% CI 1.572-40.732， 2.179-13.270， 1.013-1.054，all P<0.05］， while SIRI was a protective factor （OR = 0.869， 95% CI 0.778-0.971， P<0.05）. In the positive group， patients with the dampness-heat accumulation syndrome exhibited the highest NLR， while the lowest PLR and SIRI， showing statistically significant differences with those of other syndromes （all P<0.05）. In addition， ROC curve analysis indicated that for the dampness-heat accumulation syndrome， the combined "NLR + PLR" model had an area under the curve （AUC） of 0.901 （95% CI 0.850-0.951， P<0.01）， with a sensitivity of 89.1% and a specificity of 79.5%； for the blood stasis-heat obstruction syndrome， the combined "NLR + PLR" model had an AUC of 0.880 （95% CI 0.825-0.934， P<0.01）， with a sensitivity of 100.0% and a specificity of 67.3%； for the liver-kidney Yin-deficiency syndrome， the single PLR model had an AUC of 0.842 （95% CI 0.731-0.952， P<0.01）， with a sensitivity of 83.3% and a specificity of 84.0%. ConclusionUrate crystal deposition in HUA patients exhibits intimate associations with high-sugar beverage consumption as well as elevated NLR and PLR levels. Meanwhile， TCM syndrome differentiation has potential correlation with inflammatory characteristics. The inflammatory indicator-based prediction model constructed based on TCM syndromes exhibits good predictive value.

ObjectiveTo develop a community-family management model for older adults with mild cognitive impairment (MCI) and to formulate detailed application specifications, and to fully leverage the initiative of communities and families under limited resource conditions, for achieving community-based early detection and early intervention for older adults with MCI. MethodsA systematic literature review was conducted to identify pertinent publications. Corpus-based research methodologies were employed to extract, refine, integrate and synthesize management elements, thereby establishing the specific content and service processes for each stage of the management model. Utilizing the 5W2H analytical framework, essential elements such as management stakeholders, target populations, content and methods for each stage were delineated. The model and its application guidelines were finalized through expert consultation and demonstration. ResultsAn expert evaluation of the management model yielded mean scores of 4.84, 4.32 and 4.84 for acceptability, feasibility and systematicity, respectively. By integrating the identified core elements with expert ratings and feedback, the final iteration of the community-family management model for older adults with MCI was formulated. This model comprised of five stages: screening and identification, comprehensive assessment, intervention planning, monitoring and referral pathways to ensure implementation, and enhanced support for communities, family members and caregivers. Additionally, it included 18 specific application guidelines. ConclusionThe proposed management model may theoretically help delay cognitive decline, improve cognitive function and potentially promote reversal from MCI to normal cognition. It may also enhance the awareness and coping capacity of older adults and their families, strengthen community healthcare professionals' ability to early identify and manage MCI.

Objective To investigate the effects and potential mechanisms of polystyrene micro/nanoplastics(PS-MNPs)on testicular Sertoli cells.Methods Sixty male C57BL/6N mice(8 weeks old)were randomly divided into a control group(deionized water),a PS-NPs group[particle size of 20 nm,2.5 mg/(kg·d)],and a PS-MPs group[particle size of 5 μm,2.5 mg/(kg·d)],with 20 mice in each group.The corresponding agents were gavaged once daily for 6 months.HE staining was used to observe the histopathological and morphological changes in the testicular tissues.Immunohistochemistry of marker proteins was employed to evaluate the changes in the number of Sertoli cells.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to identify functions and signaling pathways enriched in the testicular transcriptome.Mouse testicular Sertoli cell line TM4 was divided into a control group(deionized water),a 2.5NPs group(2.5 μg/mL),and a 2.5MPs group(2.5 μg/mL).All groups received continuous exposure through 130 cell passages.Cell viability and proliferative capacity were evaluated using CCK-8 assay and EdU incorporation,while cell migration was assessed using transwell and cell scratch assays.RT-qPCR and Western blotting were used to detect the changes in the expression of key molecules regulating mesenchymal phenotypic transformation(MPT)at mRNA and protein levels.Results Pathological analysis revealed that,when compared to the control group,PS-NPs and PS-MPs treatment resulted in extended spaces between testicular seminiferous tubules,loosely arranged spermatogenic cells,and enhanced vacuolization.Immunohistochemical analysis of marker proteins indicated a decreasing trend in the number of testicular Sertoli cells in the PS-NPs and PS-MPs groups than the control group,with the PS-NPs group having statistical significance(P<0.01).GO and KEGG enrichment analyses revealed that PS-MNPs exposure-related altered genes were significantly enriched in cell adhesion signaling pathways(P<0.05).PS-MPs exposure significantly inhibited the growth and migration ability of TM4 cells(P<0.05),but PS-NPs exposure had no such effect on cell growth but notably enhanced cell migration ability.PS-NPs exposure inhibited the expression levels of E-cadherin and ZO-1(P<0.01)and up-regulated the expression of N-cadherin and vimentin(P<0.01),and PS-MPs exposure led to significant up-regulation of vimentin(P<0.01)and down-regulation of E-cadherin,N-cadherin,and ZO-1(P<0.05).Both PS-MPs and PS-NPs exposure up-regulated the mRNA levels of Snail2,Twist1,and Zeb2(P<0.01).Conclusion Exposure of PS-MNPs leads to abnormal proliferation and migration of TM4 cells,induces decreases in cell-cell contacts among Sertoli cells and spermatogenic cells at all levels possibly through MPT,and thus results in testicular damage.

Objective To investigate whether long-term low-dose exposure to polystyrene microplastics(PS-MPs)induces ferroptosis in testicular Sertoli cells and then leads to testicular injury.Methods Forty 8-week-old male C57BL/6 mice were randomly divided into a control group(deionized water group)and a PS-MPs group[2.5 mg/(kg·d)],with 20 mice in each group.Corresponding agents were gavaged once a day for 12 consecutive months.HE staining and Prussian blue staining were used to detect histopathological damage and accumulation of ferrous ions in the testes.Electron transmission microscopy was employed to observe the mitochondrial morphology of testicular Sertoli cells.Mouse Sertoli cell line TM4 was divided into a Con group(standard culture)and an MPs group(2.5 μg/mL PS-MPs).After both groups underwent continuous exposure and passed up to the 100th generation,morphological changes were observed under the microscope;cell viability was detected with CCK8 assay,and production of reactive oxygen species(ROS)and mitochondrial membrane potential(MMP)were detected with a ROS probe and a mitochondrial membrane potential probe(JC-1),respectively.Flow cytometry,ferrous ion(Fe2+)kit and Western blotting were applied to detect cell apoptosis,intracellular iron ion content,and protein levels of key molecules of ferroptosis in tissues and cells.Results Long-term exposure to PS-MPs resulted in significantly reduced diameter and thickness of mouse varicocele(P<0.01),fewer testicular Sertoli cells(P<0.05),with characteristic ferroptosis alterations in the mitochondria,and increased accumulation of ferrous ions in testicular tissue.Exposure to PS-MPs down-regulated the key molecules of ferroptosis,glutathione peroxidase 4(GPX4)and ferritin light chain(FTL)when compared with the control group(P<0.05).In the cell model,long-term PS-MPs exposure led to morphological changes and decreased cell viability(P<0.05),more production of ROS(P<0.01),and decrease in MMP(P<0.05)of TM4 cells.The exposure had no effect on cell apoptosis,but elevated the intracellular content of ferric ions(P<0.01),and down-regulated GPX4 and FTL protein levels(P<0.05).Conclusion Long-term low-dose exposure to PS-MPs induces mitochondrial damage and oxidative stress in testicular Sertoli cells,activates the ferroptosis pathway,and ultimately leads to testicular injury in mice.

Objective:To investigate the interaction between non-alcoholic fatty liver disease (NAFLD) and overweight/obesity on the risk of mild cognitive impairment (MCI) in elderly individuals.Methods:This cross-sectional study was based on the Hubei Memory and Aging Cohort Study (HMACS). Cluster random sampling was used to select 5 661 elderly individuals aged≥65 years in Wuhan from 2018 to 2023. Standardized neuropsychological assessments and clinical examinations results were collected. The NAFLD was diagnosed by abdominal ultrasound. The logistic regression analysis was used to analyze the association of NAFLD and overweight/obesity with MCI. The impacts of interaction between NAFLD and overweight/obesity on the risk of MCI were analyzed using both multiplicative and additive models.Results:Among the 5 661 elderly individuals included in the analysis, 2 563 were male and 3 098 were female, with a mean age of (72.24±5.51) years. A total of 2 239 participants (39.6%) resided in rural areas, 2 841 (50.2%) were overweight/obesity, 2 390 (42.2%) had NAFLD, and 1 694 (29.9%) were diagnosed with MCI. The risk of MCI in elderly individuals with NAFLD and overweight/obesity was 2.975 times ( OR=2.975, 95% CI: 2.489-3.557, P<0.001) of that in non-overweight/obese individuals without NAFLD. There was a multiplicative interaction between NAFLD and overweight/obesity on MCI ( OR=1.508, 95% CI: 1.169-1.944, P=0.002). NAFLD and overweight/obesity had an additive interaction effect on the risk of MCI, and the relative excess risk of interaction, attributable proportion of interaction and the synergy index was 1.099 (95% CI: 0.630-1.593), 0.369 (95% CI: 0.222-0.487), 2.256 (95% CI: 1.457-3.492), respectively. Conclusion:There is an interaction between NAFLD and overweight/obesity in elderly individuals, and the co-existence of NAFLD and overweight/obesity increases the risk of MCI in this population.

AIM To explore the clinical effects of Jinfukang Oral Liquid combined with thymosin α1 on patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin.METHODS Seventy-five patients were randomly assigned into thymosin α1 group(15 cases)for 4-week administration,Jinfukang Oral Liquid group(30 cases)for 4-week administration,and combination group(30 cases)for 4-week administration.The changes in TCM clinical syndrome effects,immunity indices(CD3+T,Th,CTL,total NK,CD56dim CD16+NK,NKT,Treg,MDSC),lethality/inhibition ratios(CTL/Treg,total NK/Treg,NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC)and FACT-L scores were detected.RESULTS The Jinfukang Oral Liquid group and combination group demonstrated higher total effective rates than the thymosin α1 group(P＜0.05).After the treatment,the Jinfukang Oral Liquid group and combination group displayed increased NKT(P＜0.05)and decreased MDSC(P＜0.05),which were more obvious than those in the thymosin α1 group(P＜0.05),and higher NKT was observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group and combination group displayed increased lethality/inhibition ratios(P＜0.05),among which NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC were higher than those in the thymosin α1 group(P＜0.05),and higher CTL/MDSC,NKT/MDSC were observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group(except for physiological status,society and family status)and combination group(except for society and family status)displayed increased FACT-L scores(P＜0.05).CONCLUSION For the patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin,Jinfukang Oral Liquid single use or combined with thymosin α1 can enhance peripheral blood immune surveillance,inhibit immune escape,restore the balanced state of tumor immune responses,and improve TCM syndromes and life quality.

Objective West Nile virus(WNV)is one of the most common mosquito-borne zoonotic viruses worldwide,with unique transmission dynamics and varied hosts.Lots of ecological and host factors have been reported to influence the host adaptation and transmission of WNVs,however,general genomic features of WNVs are less focused,except for some exact host-specific genotypes at molecular level.Artificial intelligence that analyzes genome composition characteristics currently shows significant advantages in identifying and predicting viral host adaptability.This research aimed to establish a convolutional neural network(CNN)model to predict the host adaptability of WNVs based on general genomic features.Methods Presently available WNV gene sequences were embedded for their genomic features with an embedding approach of dinucleotide composition representation(DCR).And DCR-based distribution difference of WNV samples among various hosts was performed with unsupervised learning methods.Then a classification model was built with a convolutional neural network(CNN)framework based on genomic DCR to evaluate the adaptation of the WNVs from birds,mammals and mosquitos.Additionally,host-specific amino acids in WNV proteins were inferred via Bayes method.Results DCR features could effectively distinguish host-specific WNVs.The trained CNN model predicted accurately mammalian susceptible WNVs from avian susceptible WNVs,however,much less accurately for mosquito/mammalian WNVs.Such predicted host adaptation was interpreted as host specified significance of biased amino acid distribution on the bayes-inferred sites in WNV proteins,implying a possible high significance of these sites for WNV adaptive phenotypes.Conclusions Genomic compositional features of WNVs are host-specific,and such genomic bias facilitates predicting the adaptation of WNVs to avian or mammalian hosts via deep learning methods.DCR-based decomposition is helpful to recognize the high risk of infecting mammals of WNVs.The present study provides a general knowledge of genomic features contributing to host adaptation to WNVs.