Predictive models for delay in medical decision-making among older patients with acute ischemic stroke: a comparative study using logistic regression analysis and lightGBM algorithm.

OBJECTIVE: To explore the factors affecting delayed medical decision-making in older patients with acute ischemic stroke (AIS) using logistic regression analysis and the Light Gradient Boosting Machine (LightGBM) algorithm, and compare the two predictive models. METHODS: A cross-sectional study was conducted among 309 older patients aged ≥ 60 who underwent AIS. Demographic characteristics, stroke onset characteristics, previous stroke knowledge level, health literacy, and social network were recorded. These data were separately inputted into logistic regression analysis and the LightGBM algorithm to build the predictive models for delay in medical decision-making among older patients with AIS. Five parameters of Accuracy, Recall, F1 Score, AUC and Precision were compared between the two models. RESULTS: The medical decision-making delay rate in older patients with AIS was 74.76%. The factors affecting medical decision-making delay, identified through logistic regression and LightGBM algorithm, were as follows: stroke severity, stroke recognition, previous stroke knowledge, health literacy, social network (common factors), mode of onset (logistic regression model only), and reaction from others (LightGBM algorithm only). The LightGBM model demonstrated the more superior performance, achieving the higher AUC of 0.909. CONCLUSIONS: This study used advanced LightGBM algorithm to enable early identification of delay in medical decision-making groups in the older patients with AIS. The identified influencing factors can provide critical insights for the development of early prevention and intervention strategies to reduce delay in medical decisions-making among older patients with AIS and promote patients' health. The LightGBM algorithm is the optimal model for predicting the delay in medical decision-making among older patients with AIS.

Expression and Mutation of SLC45A2 Affects Iris Color in Quail.

Iris color is a prominent phenotypic feature of quail. To understand the mechanism of melanin deposition related to quail iris color, iris tissues were selected from Beijing white and Chinese yellow quail for transcriptome analysis. Differentially expressed genes (DEGs) associated with pigmentation were identified using RNA sequencing and validated by quantitative real-time polymerase chain reaction (RT-qPCR). The identified single nucleotide polymorphisms were studied using bioinformatics and iris color correlation analyses. A total of 485 DEGs were obtained, with 223 upregulated and 262 downregulated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Thirty-two genes were annotated using the GO database. Three important pigment synthesis pathways (Notch signaling, melanogenesis, and tyrosine metabolism) were identified in quail iris tissue (P < 0.05). The expression levels of solute carrier family 45 member 2 (SLC45A2), tyrosinase-related protein 1, vitamin D receptor, opsin 5, and docking protein 5 were significantly different between Beijing white and Chinese yellow quail, as verified by RT-qPCR. The c.1061C>T mutation in SLC45A2, which caused a single amino acid change at position 354 (threonine to methionine), was significantly associated with iris color in Beijing white and Chinese yellow quail, and might be the main reason for the different iris colors between these two quail species.

Assessment of the Conformation Stability and Glycosylation Heterogeneity of Lactoferrin by Native Mass Spectrometry.

Lactoferrin (LTF) has diverse biological activities and is widely used in functional foods and active additives. Nevertheless, evaluating the proteoform heterogeneity, conformational stability, and activity of LTF remains challenging during its production and storage processes. In this study, we describe the implementation of native mass spectrometry (nMS), glycoproteomics, and an antimicrobial activity assay to assess the quality of LTF. We systematically characterize the purity, glycosylation heterogeneity, conformation, and thermal stability of LTF samples from different sources and transient high-temperature treatments by using nMS and glycoproteomics. Meanwhile, the nMS peak intensity and antimicrobial activity of LTF samples after heat treatment decreased significantly, and the two values were positively correlated. The nMS results provide essential molecular insights into the conformational stability and glycosylation heterogeneity of different LTF samples. Our results underscore the great potential of nMS for LTF quality control and activity evaluation in industrial production.

Barriers and facilitators to patient education provided by nurses: A mixed-method systematic review.

AIM: To investigate the factors that facilitate or hinder nurses in providing patient education. DESIGN: A mixed-method systematic review. DATA SOURCES: Six databases (Cochrane Library, PubMed, EMBASE, Web of Science, MEDLINE and ERIC) were systematically searched for relevant publications. METHODS: The study was conducted following the JBI for mixed-method systematic reviews, and the reporting followed the PRISMA guideline. Two researchers independently performed literature screening, literature evaluation, data extraction and synthesis. PROSPERO registration number: CRD42023427451. RESULTS: Twenty-six eligible articles were included, including 15 quantitative articles, 10 qualitative articles and 2 mixed-methods articles. The resultant synthesis of key findings led to the identification of these barriers and facilitators, categorised into five distinct levels: nurse-related factors, organisational factors, patient-related factors, the nurse-patient relationship and interdisciplinary collaboration. CONCLUSIONS: The findings highlight the factors that facilitate or hinder nurses in providing patient education, suggesting that multifaceted interventions can enhance the practice of patient education in nursing and support the development of appropriate patient education guidelines or public policies. RELEVANCE TO CLINICAL PRACTICE: This review delineates the facilitators and barriers influencing nurses' provision of patient education, offering an initial framework for nursing managers to craft interventions aimed at enhancing the quality of patient education provided by nurses, consequently elevating the overall quality of nursing.

RNA sequencing analysis reveals that missense mutation in SOX10 is associated with iris color phenotype in quail.

To investigate the molecular mechanisms underlying the differences in iris color in quail, the transcriptome of iris tissue from black quail and Korean quail at day 10 of hatching was RNA sequenced in this study. The differentially expressed genes (DEGs) were screened, functionally annotated and enriched after the quality control and mapping of the raw data. RT-qPCR validation was performed using EIF2S3 as an internal reference gene. The screened SNPs were studied by bioinformatics analysis and iris color correlation analysis. The results showed that there were 425 upregulated genes and 364 downregulated genes in 789 DEGs. Gene Ontology (GO) enrichment analysis revealed that 139 DEGs were significantly enriched in 154 GO terms. The Kyoto Encyclopedia of Genes and Genomes enrichment results showed that the Notch signaling pathway, melanogenesis and tyrosine metabolism were associated with pigment synthesis (p < 0.05). The expression levels of the ASIP, MLPH, PMEL, TYR and SOX10 genes were significantly different in black quail iris and Korean quail iris, as verified by RT-qPCR. The SOX10 gene c.324G>C mutation, which caused the replacement of p.Glu108Asp, had a highly significant correlation with iris color in black quail and Korean quail, which may be one of the reasons for different in iris color between these two quail species.

Molecular Structure Characterization of Micro/Nanoplastics by 193 nm Ultraviolet Photodissociation Mass Spectrometry.

The degradation of macroplastics results in micro/nanoplastics (MNPs) in the natural environment, inducing high health risks worldwide. It remains challenging to characterize the accurate molecular structures of MNPs. Herein, we integrate 193 nm ultraviolet photodissociation (UVPD) with mass spectrometry to interrogate the molecular structures of poly(ethylene glycol) terephthalate and polyamide (PA) MNPs. The backbones of the MNP polymer can be efficiently dissociated by UVPD, producing rich types of fragment ions. Compared to high-energy collision dissociation (HCD), the structural informative fragment ions and corresponding sequence coverages obtained by UVPD were all improved 2.3 times on average, resulting in almost complete sequence coverage and precise structural interrogation of MNPs. We successfully determine the backbone connectivity differences of MNP analogues PA6, PA66, and PA610 by improving the average sequence coverage from 26.8% by HCD to 89.4% by UVPD. Our results highlight the potential of UVPD in characterizing and discriminating backbone connectivity and chain end structures of different types of MNPs.

Novel casein antimicrobial peptides for the inhibition of oral pathogenic bacteria.

Milk casein is a rich source of antimicrobial peptides (AMPs) and the most common way to produce AMPs is enzymatic hydrolysis in vitro. In this study, active casein antimicrobial peptide (CAMPs) mixtures were generated by optimized proteolytic cleavage of milk casein. These natural-safe CAMPs mixtures exhibited high activity in the inhibition of Streptococcus mutans and Porphyromonas gingivalis. Morphological characterization suggested the pathogenic bacteria presented incomplete or irregular collapsed membrane surface after the treatment with active CAMPs mixtures. The CAMPs inhibition activity was also effective in the attachment and development of microbial biofilm. Potential CAMPs sequences were unambiguously determined by unbiased proteomic analysis and 301 potential CAMPs were obtained. The activity of 4 novel CAMPs was successfully confirmed by using synthetic standards. This study provides a promising milk CAMPs resource for the development of safe agents in oral bacteria inhibition and functional foods.

Association analysis of PMEL gene expression and single nucleotide polymorphism with plumage color in quail.

To explore the relationship between PMEL gene and quail plumage color, to provide a reference for subsequent quail plumage color breeding. In this experiment, RT-qPCR technology was used to analyze the relative mRNA expression levels of Korean quail (maroon) and Beijing white quail embryos at different developmental stages. Two SNPs in PMEL gene were screened based on the RNA-Seq data of skin tissues of Korean quail and Beijing white quail during embryonic stage. The KASP technology was used for genotyping in the resource population and correlation analysis was carried out with the plumage color traits of quail. Finally, the bioinformatics technology was used to predict the effects of these two SNPs on the structure and function of the encoded protein. The results showed that the expression levels of PMEL gene during the embryonic development of Beijing white quail were extremely significantly higher than that of Korean quail (p < 0.01). The frequency distribution of the three genotypes (AA, AB, and BB) of the Beijing white quail at the c. 1030C > T and c. 1374A > G mutation sites were extremely significantly different from that of the Korean quail (p < 0.01). And there was a significant correlation between the c. 1374A > G mutation site with white plumage phenotype. Bioinformatics analysis showed that SNP1 (c. c1030t) located in exon 6 was a harmful mutation site, and SNP2 (c. a1374g) located in exon 7 was a neutral mutation site. Protein conservation prediction showed that the coding protein P344S site caused by SNP1 (c. c1030t) site and the coding protein I458M site caused by SNP2 (c. g2129a) site were non-conservative sites. The results of this experiment showed that the PMEL gene was associated with the plumage color traits of quail and could be used as a candidate gene for studying the plumage color of quail.

Association analysis of melanophilin (MLPH) gene expression and polymorphism with plumage color in quail.

We explore the relationship between the melanophilin (MLPH) gene and quail plumage color and provide a reference for subsequent quail plumage color breeding. In this experiment, real-time quantitative PCR (RT-qPCR) technology was used to analyze the relative mRNA expression levels of Korean quail (maroon) and Beijing white quail embryos at different developmental stages. Two single-nucleotide polymorphisms (SNPs) in the MLPH gene were screened based on the RNA-sequencing (RNA-Seq) data of skin tissues of Korean quail and Beijing white quail during the embryonic stage. Kompetitive allele-specific PCR (KASP) technology was used for genotyping in the resource population, and correlation analysis was carried out with the plumage color traits of quail. Finally, bioinformatics was used to predict the effects of these two SNPs on the structure and function of the encoded protein. The results showed that the expression level of the MLPH gene during embryonic development of Beijing white quail was significantly higher than that of Korean quail ( P < 0.01 ). The frequency distribution of the three genotypes (CC, CA and AA) of the Beijing white quail at the c.1807C  >  A mutation site was significantly different from that of the Korean quail ( P < 0.01 ). The frequency distribution of the three genotypes (GG, GA and AA) of the Beijing white quail at the c.2129G  >  A mutation site was significantly different from that of the Korean quail ( P < 0.01 ). And there was a significant correlation between the c.1807C  >  A mutation site and the white plumage phenotype. Bioinformatics showed that SNP1 (c.1807C  >  A) was a neutral mutation and that SNP2 (c.2129G  >  A) was a deleterious mutation. The prediction of protein conservation showed that the mutation sites of coding proteins R603S and G710D caused by SNP1 (c.1807C  >  A) and SNP2 (c.2129G  >  A) were highly conserved.

Identification of Polymorphisms in the HERC2-OCA2 Gene Locus and their Association with Feather Color in Quail.

Mutations in the HERC2 and OCA2 genes have the potential to affect pigment deposition and alter feather color in birds. Therefore, in this study, we evaluated HERC2-OCA2 gene locus polymorphisms in Korean and Beijing white quails using RNA-Seq and KASP technology. The expression levels of HERC2 and OCA2 mRNA in skin tissues were analyzed using RT-qPCR. Ten single nucleotide polymorphisms were identified by RNA-Seq, of which three (n.117627564T>A, n.117674275T>G, n.117686226A>C) exhibited significant association with feather color in quail. The expression of OCA2 mRNA was significantly lower in the skin of Beijing white quails than that in the skin of Korean quails. These results suggested that variants in HERC2-OCA2 intergenic region could influence the expression of OCA2, which may underlie diluted feather color in the Beijing white quail.

High-performance micro/nanoplastics characterization by MALDI-FTICR mass spectrometry.

Micro/nanoplastics (MNPs) are widespread environmental pollutants that cause high health risks. However, high heterogeneity in particle sizes and chemical compositions of MNPs make their accurate characterization extremely challenging. Herein, we established a matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) strategy for the unambiguous characterization of different types of MNPs with high performance, including polystyrene, polyethylene glycol terephthalate, polyamide, polymethyl methacrylate, acrylonitrile butadiene styrene copolymer, and polycarbonate. The MNP sample preparation and detection conditions were systematically optimized by using response surface methodology, and the MS detection signal-to-noise ratios were improved 1.5 times on average. The ultrahigh mass resolution of FTICR MS is crucial to the unambiguous elucidation of MNP structures. We demonstrate that this MS strategy is highly efficient in the characterization of polymer constitutions of environmental MNPs derived from foam, bottles, cable ties, and compact discs, providing a promising tool for MNP detection and safety evaluation.

Efficacy Evaluation of Zoledronic Acid Combined with Chemotherapy in the Treatment of Lung Cancer Spinal Metastases on Computed Tomography Images on Intelligent Algorithms.

To analyze the effectiveness and safety of zoledronic acid combined with chemotherapy for lung cancer spinal metastases, 96 patients with lung cancer spinal metastases were averagely classified into the experimental group (gemcitabine, cisplatin, and zoledronic acid) and the control group (gemcitabine and cisplatin). An optimized noise variance estimation algorithm (OMAPB) was proposed based on the maximum a posteriori Bayesian method (MAPB), and the algorithm was applied to the patient's computed tomography (CT) scan. The results indicated that in terms of curative effect, the number of complete remission (CR), partial remission (PR) cases, effective rate, and clinical benefit rate of the test group was significantly higher than those of the control group. The number of progress disease (PD) cases was significantly lower than that of the control group (P < 0.05). The disease progression time of the test group patients was 6.2 months, and the disease progression time of the control group patients was 3.7 months (P < 0.05). The test group patients had 8 cases of bone marrow suppression and gastrointestinal reactions after treatment. In the test group, there were 8 cases of bone marrow suppression, 9 cases of gastrointestinal reaction, 3 cases of fever, 4 cases of pain, and 2 cases of hair loss. The patients in the control group were complicated with bone marrow suppression in 14 cases, gastrointestinal reaction in 17 cases, fever in 5 cases, pain in 4 cases, and hair loss in 6 cases. The difference was statistically significant (P < 0.05). It showed that zoledronic acid combined with chemotherapy could effectively improve the treatment efficiency and clinical benefit rate of patients with lung cancer spinal metastases, prolong the progression of the disease, reduce the degree of bone tissue damage, and would not increase chemotherapy adverse events.

Comprehensive proteomic analysis of sea cucumbers (Stichopus japonicus) in thermal processing by HPLC-MS/MS.

Thermal processing is the most frequently adopted processing technology for sea cucumbers, which can significantly affect their protein composition. In this paper, three thermal processing methods high pressure steaming (HPS), atmospheric pressure boiling (APB), and atmospheric pressure steaming (APS) were adopted and protein compositions of both body walls and cooking liquors by thermal processing stichopus japonicus were systematically analysis by proteomic strategy. The total proteins loss rates of body walls were 11.6%, 13.0%, and 14.8% for HPS, APS, and APB methods, respectively. However, the main types of protein composition were retained. Similar mechanisms of protein loss may exist even if different thermal processing were applied. The most frequent hydrolysis sites in thermal processing were phenylalanine, leucine, asparagine, and tyrosine at both C and N terminals. This study provides theoretical guidance for optimizing the industry thermal processing of sea cucumbers.

Marine Sulfated Polysaccharides: Preventive and Therapeutic Effects on Metabolic Syndrome: A Review.

Metabolic syndrome is the pathological basis of cardiovascular and cerebrovascular diseases and type 2 diabetes. With the prevalence of modern lifestyles, the incidence of metabolic syndrome has risen rapidly. In recent years, marine sulfate polysaccharides (MSPs) have shown positive effects in the prevention and treatment of metabolic syndrome, and they mainly come from seaweeds and marine animals. MSPs are rich in sulfate and have stronger biological activity compared with terrestrial polysaccharides. MSPs can alleviate metabolic syndrome by regulating glucose metabolism and lipid metabolism. In addition, MSPs prevent and treat metabolic syndrome by interacting with gut microbiota. MSPs can be degraded by gut microbes to produce metabolites such as short chain fatty acids (SCFAs) and free sulfate and affect the composition of gut microbiota. The difference between MSPs and other polysaccharides lies in the sulfation pattern and sulfate content, therefore, which is very important for anti-metabolic syndrome activity of MSPs. This review summarizes the latest findings on effects of MSPs on metabolic syndrome, mechanisms of MSPs in treatment/prevention of metabolic syndrome, interactions between MSPs and gut microbiota, and the role of sulfate group and sulfation pattern in MSPs activity. However, more clinical trials are needed to confirm the potential preventive and therapeutic effects on human body. It may be a better choice to develop new functional foods containing MSPs for dietary intervention in metabolic syndrome.

Polysaccharide from Patinopecten yessoensis Skirt Boosts Immune Response via Modulation of Gut Microbiota and Short-Chain Fatty Acids Metabolism in Mice.

Polysaccharide from marine shellfish has various bioactivities. In this study, the effects of polysaccharide from Patinopecten yessoensis skirt (PS) on boosting immune response in mice were evaluated, and the potential mechanisms were explored. The results showed that PS administration effectively increased the serum IgG and IgM levels, implying that PS had immune response-boosting properties. Moreover, PS administration could modulate the composition of the gut microbiota, and significantly improve short-chain fatty acids (SCFAs) metabolism, especially butyrate metabolism. Of note, the expression of the Tlr2, Tlr7, MyD88, Tnfa, and Il1b genes in toll-like receptor (TLR) signaling pathway was significantly increased. In summary, PS could boost immune response by modulating the gut microbiota and SCFAs metabolism correlating with the activation of the TLR signaling pathway. Therefore, PS can be developed as a special ingredient for functional product.

Red-to-blue paper-based colorimetric sensor integrated with smartphone for point-of-use analysis of cerebral AChE upon Cd2+ exposure.

Herein, combined with a pervasive smartphone installed with a color recognition app, dual-responsive CDs@Eu/GMP ICPs were designed as a red-to-blue paper-based colorimetric sensor for the point-of-use analysis of cerebral acetylcholinesterase (AChE) upon Cd2+ exposure. Blue-emitting CDs with multi-functional groups as guests were encapsulated into the network of Eu/GMP ICPs to obtain CDs@Eu/GMP ICPs with the sensitized red fluorescence of Eu3+. With the presence of thiocholine (TCh), derived from acetylthiocholine (ATCh) hydrolyzed by AChE, the coordination environment of the CDs@Eu/GMP ICPs was interrupted, leading to the collapse of the CDs@Eu/GMP ICP network and the corresponding release of guest CDs into the surrounding environment. Consequently, the sensitized red fluorescence of Eu3+ decreased and the blue fluorescence of the CDs increased. This obvious red-to-blue fluorescent color changes of CDs@Eu/GMP ICPs on test paper could then be integrated with the smartphone for point-of-use analysis of cerebral AChE upon Cd2+ exposure, which not only offers a new analytical platform for a better understanding of the environmental risk of Alzheimer's Dementia (AD), but also holds great potential in the early diagnosis of AD even at the asymptomatic stage with the decrease in CSF AChE as an early biomarker.

[Investigation of human milk proteins by proteomics].

Human milk is the optimal food for infant nutrition and growth. Proteins are abundant and represent a key element in human milk. With recent developments in proteomics, more tools are available to explore human milk proteins. This article aims to review the recent investigations of human milk proteins using proteomic methodologies. This review focuses on using proteomics as a tool to study the components of human milk proteins; dynamics of human milk proteins during lactation; comparison of proteome from human milk and other source milk, phosphoprotein and glycoprotein analysis of human milk; endogenous peptides in human milk; and the human milk proteome and its correlation to curing of various diseases. Proteomics technology has enabled the study of human milk proteins in the era of micronutrient research, and the results of these studies will be helpful for further analysis of mother and infant health.

Effects of processing method on chemical compositions and nutritional quality of ready-to-eat sea cucumber (Apostichopus japonicus).

The effect of commercial processing methods on the nutritional value of ready-to-eat (RTE) sea cucumber Apostichopus japonicas was examined in this study. RTE sea cucumber products named RTE-T and RTE-V were prepared by two commercial methods, traditional processing, and vacuum cooking, respectively. Proximate, polysaccharide and mineral element composition, amino acid profiles, and true retention values of RTE sea cucumber products were evaluated and compared. Both commercial processing methods significantly changed the nutrient composition in RTE products, except that of Zn and Cu. Comparison of true retention values among RTE products showed that novel commercial method of vacuum cooking resulted in lower nutrient loss and had a shorter processing time than traditional processing. However, soaking after vacuum cooking significantly increased the nutrient loss of RTE sea cucumber. Therefore, vacuum cooking without soaking may be a promising alternative for producing RTE sea cucumber products with high nutritional quality.

Construction of MC1R and ASIP Eukaryotic Expression Vector and its Regulation of Plumage Color in Japanese Quail (Coturnix japonica).

The Japanese quail expresses polymorphism in plumage colors, including black, yellow, white, wild-type (maroon), and various intermediate colors through hybridization of quail with different plumage colors. The expression levels of MC1R and ASIP play important roles in the regulation of plumage colors in birds. In this study, the eukaryotic expression vector of pcDNA 3.1 + was used to analyze the effects of forced expression of MC1R and ASIP on the plumage colors of Japanese quail embryos. The constructed eukaryotic expression vectors of pcDNA 3.1 (+)-MC1R and pcDNA 3.1(+)-ASIP were transfected into wild-type Japanese quail embryos by Lipofectamine™ 2000 liposome at 6 days of incubation. After 3 days, the embryos were collected to analyze the plumage colors and the expression levels of MC1R, ASIP, and DCT genes in skin tissue. Forced expression of the MC1R gene by transfection of the pcDNA 3.1(+)-MC1R vector led to hyperpigmentation (similar to black plumage), whereas forced expression of the ASIP gene by transfection of the pcDNA 3.1(+)-ASIP vector led to hypopigmentation (similar to white plumage) in wild-type quail embryos. Two kinds of ASIP alternative splicing (ASIP1 and ASIP2) were found in Japanese quail, which did not have a significant effect on the plumage color or the main motifs of the ASIP protein. This study indicated that the black plumage color may be caused by increased production of MC1R and the white plumage color may be caused by increased production of ASIP in Japanese quail.

Notch1 signaling in melanoma cells promoted tumor-induced immunosuppression via upregulation of TGF-ß1.

BACKGROUND: The receptors of Notch family play an important role in controlling the development, differentiation, and function of multiple cell types. The aim of this study is to investigate the role of Notch1 signaling upon immune suppression induced by melanoma cells. METHODS: Melanoma cell line B16 cells were transfected by lentivirus containing mouse Notch1 gene or Notch1 shRNA to generate B16 cell line that highly or lowly expressed Notch1. Notch1 in anti-tumor immune response was comprehensively appraised in murine B16 melanoma tumor model in immunocompetent and immunodeficient mice. The ratios of CD3+CD8+ cytotoxic T cells, CD49b+NK cells, CD4+CD25+FoxP3+ Tregs and Gr1+CD11b+ MDSCs in tumor-DLN or spleen were examined by flow cytometry. After the co-culture of B16 cells and CD8+ T cells, the effects of Notch1 on the proliferation and activation of T cells were assessed by CCK8 assay, CFSE dilution and Chromium-release test. The mRNA expression and supernatant secretion of immunosuppressive cytokines, TGF-ß1, VEGF, IL-10 and IFN-γ were measured by RT-PCR and ELISA, respectively. RESULTS: Downregulation or overexpression of Notch1 in B16 melanoma cells inhibited or promoted tumor growth in immunocompetent mice, respectively. Notch1 expression in B16 melanoma cells inhibited the infiltration of CD8+ cytotoxic T lymphocytes and NK cells and reduced IFN-γ release in tumor tissue. It could also enhance B16 cell-mediated inhibition of T cell proliferation and activation, and upregulate PD-1 expression on CD4+ and CD8+ T cells. The percentage of CD4+CD25+FoxP3+ Tregs and Gr1+CD11b+MDSCs were significantly increased in tumor microenvironment, and all these were attributed to the upregulation of TGF-ß1. CONCLUSION: These findings suggested that Notch1 signaling in B16 melanoma cells might inhibit antitumor immunity by upregulation of TGF-ß1.