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Abstract Background Bone marrow mesenchymal stem cells (BMSCs) are a crucial component of the tumor microenvironment (TME), with hypoxic conditions promoting their migration to tumors. Exosomes play a vital role in cell-to-cell communication within the TME. Hypoxic TME have a great impact on the release, uptake and biofunctions of exosomes. This study aims to elucidate the communication between BMSC-derived exosomal miRNA and triple-negative breast cancer (TNBC) in a hypoxic environment. Methods Exosomes were isolated via ultracentrifugation and identified using scanning electron microscopy (SEM), nanoparticle tracking analysis (NTA) and western blot. A range of bioinformatics approaches were used to screen exosomal miRNAs and the target mRNAs of miRNAs and predict the possible signaling pathways. Expression levels of genes and proteins were assessed by quantitative real-time PCR and western blot. Cell proliferation, apoptosis, migration and invasion were analyzed using CCK-8 assay, EDU assay, transwell migration, wound healing assay and invasion assay, respectively. Dual luciferase reporter gene assay was conducted to confirm the binding between miRNAs and the target mRNAs. The impact of hypoxic BMSC-derived exosomal miRNA on TNBC progression in vivo was evaluated using tumor xenograft nude mouse models. Furthermore, the impact of patients’ serum exosomal miRNA on TNBC was implemented. Results Exosomes derived from hypoxic BMSCs promotes the proliferation, migration, invasion and epithelial-mesenchymal transition of TNBC and suppresses the apoptosis of TNBC. The expression of miR-210-3p in BMSC-derived exosomes is markedly elevated in hypoxic conditions. Exosome-mediated transfer of miR-210-3p from hypoxic BMSCs to TNBC targets NFIX and activates Wnt/β-Catenin signaling in TNBC. Deletion of miR-210-3p in hypoxic BMSC-derived exosomes attenuates TNBC in vivo. Additionally, human exosomal miR-210-3p from the serum of TNBC patients promotes TNBC progression. Moreover, we notably observed a marked downregulation of NFIX expression levels in cancerous tissues compared to paracancerous tissues. Conclusions Hypoxic BMSC-derived exosomal miR-210-3p promotes TNBC progression via NFIX-Wnt/β-catenin signaling axis.

Abstract The role of neoadjuvant chemotherapy and its benefits in patients with triple-negative breast cancer (TNBC) and small tumors are unclear. This study aims to compare survival differences between clinical T1 TNBC receiving neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC). Data for patients with clinical T1 TNBC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized according to whether they received chemotherapy before or after surgery. Propensity Score Matching (PSM) was used to minimize the influence of confounding factors. OS and BCSS were compared between the two treatment sequences using Kaplan–Meier and univariate and multivariable Cox proportional hazards regression analyses. The study included 6249 women with T1 TNBC. In multivariate analysis, compared with that in the AC group, the hazard ratio for death in the NAC group was 1.54 (95% confidence interval 1.26–1.89, p

Abstract Purpose To assess the efficacy of neoadjuvant endocrine therapy in female HR‐positive/HER2‐negative breast cancer patients. Data and Methods We identified female patients aged ≥18 years with cT1‐4N0‐XM0, HR(+), and HER2(−) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as “surgery‐first,” while those who received NET before surgery were classified as “NET.” Propensity score‐matching, Cox proportional‐hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes. Results Among 432,387 cases, 2914 NET patients and 2914 surgery‐first patients were matched. Compared with the surgery‐first group, the NET group received less adjuvant chemotherapy (p

Abstract Phosphorylation proteomics is the basis for the study of abnormally activated kinase signaling pathways in breast cancer, which facilitates the discovery of new oncogenic agents and drives the discovery of potential targets for early diagnosis and therapy of breast cancer. In this study, we have explored the aberrantly active kinases in breast cancer development and to elucidate the role of PRKCD_pY313 in triple negative breast cancer (TNBC) progression. We collected 47 pairs of breast cancer and paired far-cancer normal tissues and analyzed phosphorylated tyrosine (pY) peptides by Superbinder resin and further enriched the phosphorylated serine/threonine (pS/pT) peptides using TiO2 columns. We mapped the kinases activity of different subtypes of breast cancer and identified PRKCD_pY313 was upregulated in TNBC cell lines. Gain-of-function assay revealed that PRKCD_pY313 facilitated the proliferation, enhanced invasion, accelerated metastasis, increased the mitochondrial membrane potential and reduced ROS level of TNBC cell lines, while Y313F mutation and low PRKCD_pY313 reversed these effects. Furthermore, PRKCD_pY313 significantly upregulated Src_pY419 and p38_pT180/pY182, while low PRKCD_pY313 and PRKCD_Y313F had opposite effects. Dasatinib significantly inhibited the growth of PRKCD_pY313 overexpression cells, and this effect could be enhanced by Adezmapimod. In nude mice xenograft model, PRKCD_pY313 significantly promoted tumor progression, accompanied by increased levels of Ki-67, Bcl-xl and Vimentin, and decreased levels of Bad, cleaved caspase 3 and ZO1, which was opposite to the trend of Y313F group. Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

The objective of this study was to investigate the structural and antioxidative properties of royal jelly protein (RJP) at different degrees of hydrolysis (DH) by partial enzymatic hydrolysis. RJP was hydrolyzed by alcalase for 0 min, 15 min, 1 h, 5 h and 8 h to obtain hydrolysates at DH of 5.34 %, 11.65 %, 15.19 %, 21.38 % and 23.91 %, respectively. With the increased DH, the RJP hydrolysates showed elevated antioxidative activities. The molecular weight of RJP hydrolysates was significantly decreased but their primary backbone kept unchanged. Analysis of circular dichroism spectra revealed that the enzymolysis reduced the content of α-helix but increased the contents of β-sheet, β-turn and random coil. Meanwhile, the surface hydrophobicity and fluorescence intensity of RJP hydrolysates were decreased and a red shift occurred. As the enzymolysis continued, the surface morphology of RJP was gradually changed from a sheet-like structure into microparticles. Changes in antioxidative activities and structures generally followed a DH-dependent manner, however these changes became insignificant for samples at DH beyond 20 %. Taking into consideration of both effectiveness and productivity, the optimum enzymatic duration was determined at 5 h.

BackgroundUnderstanding the correlation between female breast cancer (BC) and the prevalence of coronary heart disease (CHD) is important for developing prevention strategies and reducing the burden of female social disease. This study aimed to evaluate the relationship between BC and CHD using data from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018.MethodsThe study cohort included 16,149 eligible non-pregnant female participants aged 20 years or older. Logistic regression was used to analyze the relationship between BC and CHD, excluding the interaction between covariates and BC through hierarchical subgroup analysis.ResultsThe study found that participants with BC had a 2.30 times greater risk of developing CHD compared to those without BC [95% confidence interval (CI): 2.29–2.31]. After adjusting for all included covariates, BC was still significantly associated with CHD risk (odds ratio: 1.11, 95% CI: 1.10–1.12). When participants were stratified by age, education level, and prevalence of hypertension, it was evident that participants with BC had a higher risk of developing CHD compared to those without BC, although the effect of BC on CHD varied across stratification.ConclusionsOur study demonstrates the close relationship between CHD and female BC. Therefore, it is necessary to screen patients with CHD for BC and monitor BC survivors for the long-term risk of developing CHD.

Highlights We performed single-cell transcriptome sequencing in one case carrying adenoma and carcinoma, and explored process of colon cancer progression. Results suggest the presence of dominant clones of same cells including C2 goblet cell, epithelial cell subtype 1 (Epi1), enterocyte cell subset 0 (Entero0), and Entero5 in colon carcinoma We discovered new colon cancer related genes including AC007952.4, NEK8, CHRM3, ANO7, B3GNT6, NEURL1, ODC1 and KCNMA1. The function of TBC1D4, LTB, C2CD4A, AND GBP4/5 in T cells needs to be clarified.

Abstract Introduction Immediate postmastectomy reconstruction for breast cancer has been widely used due to its unique esthetic and psychological effects. However, no other population‐based study has investigated the effects of different reconstruction types on the survival in patients with triple negative breast cancer (TNBC). Methods We selected patients who met the eligibility criteria from the Surveillance, Epidemiology, and End Results cancer registry (N = 9760). We then assessed the effect of different reconstructive surgical approaches (implant, autologous, implant and autologous combined reconstruction) on the overall survival (OS) and breast cancer‐specific survival (BCSS) by using the Kaplan–Meier survival curve and Cox proportional hazard regression analyses. The nomograms were used to predict OS and BCSS. And the competitive risk model was used to assess breast cancer‐specific death (BCSD) and non‐breast cancer‐specific death (NBCSD). Results Statistical analysis suggested that the three reconstruction methods had better OS and BCSS with lower hazard than mastectomy alone (log‐rank test, p 60 years of age. The survival prediction model quantified the survival benefits of TNBC patients undergoing different surgeries. Moreover, the C‐indexes showed the good predictive ability of the nomograms. Conclusions Our results suggest that for TNBC patients, there is a survival benefit of immediate postmastectomy reconstruction compared with mastectomy alone. Among them, implant reconstruction has the most obvious advantage.

Ecological resilience (ER) is considered a key factor in resolving complex human and natural systems conflicts and managing risk during the period of rapid development. However, the importance of landscape patterns for ER is not given enough attention in previous studies. Therefore, we selected the Yangtze River Delta region as the study area, incorporated landscape patterns into the assessment of ER and proposed the way for identifying ecological sources based on the combination of ecosystem services and landscape patterns. Combining the multidimensional ecological resilience assessment indicators system, we calculated the ER for the Yangtze River Delta region and explored the importance and nonlinear effects of landscape patterns on the ER using a random forest regression model. The results showed that the comparative analysis of ecosystem services and landscape patterns enhanced the scientificity of ecological source identification. We identified 94 ecological sources mainly in the southern of the Yangtze River Delta region, including important mountain ranges and water bodies. In addition, the ER was significantly strengthened by considering the landscape patterns. The random forest regression results indicated the nonlinear relationship between the landscape patterns and the other elements in terms of ER. This study can contribute to a comprehensive and integrated approach to the identification of ecological sources and the evaluation of ER, which can promote the conservation of regional ecological functions.

Abstract Background Breast cancer (BC) is the most common malignant tumor worldwide. Apoptosis and hypoxia are involved in the progression of BC, but reliable biomarkers for these have not been developed. We hope to explore a gene signature that combined apoptosis and hypoxia‐related genes (AHGs) to predict BC prognosis and immune infiltration. Methods We collected the mRNA expression profiles and clinical data information of BC patients from The Cancer Genome Atlas database. The gene signature based on AHGs was constructed using the univariate Cox regression, least absolute shrinkage and selection operator, and multivariate Cox regression analysis. The associations between risk scores, immune infiltration, and immune checkpoint gene expression were studied using single‐sample gene set enrichment analysis. Besides, gene signature and independent clinicopathological characteristics were combined to establish a nomogram. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the potential functions of AHGs. Results We identified a 16‐AHG signature (AGPAT1, BTBD6, EIF4EBP1, ERRFI1, FAM114A1, GRIP1, IRF2, JAK1, MAP2K6, MCTS1, NFKBIA, NFKBIZ, NUP43, PGK1, RCL1, and SGCE) that could independently predict BC prognosis. The median score of the risk model divided the patients into two subgroups. By contrast, patients in the high‐risk group had poorer prognosis, less abundance of immune cell infiltration, and expression of immune checkpoint genes. The gene signature and nomogram had good predictive effects on the overall survival of BC patients. GO and KEGG analyses revealed that the differential expression of AHGs may be closely related to tumor immunity. Conclusion We established and verified a 16‐AHG BC signature which may help predict prognosis, assess potential immunotherapy benefits, and provide inspiration for future research on the functions and mechanisms of AHGs in BC.

BackgroundBreast cancer (BC) is the most common malignancy among women. Nicotinamide (NAM) metabolism regulates the development of multiple tumors. Herein, we sought to develop a NAM metabolism-related signature (NMRS) to make predictions of survival, tumor microenvironment (TME) and treatment efficacy in BC patients.MethodsTranscriptional profiles and clinical data from The Cancer Genome Atlas (TCGA) were analyzed. NAM metabolism-related genes (NMRGs) were retrieved from the Molecular Signatures Database. Consensus clustering was performed on the NMRGs and the differentially expressed genes between different clusters were identified. Univariate Cox, Lasso, and multivariate Cox regression analyses were sequentially conducted to develop the NAM metabolism-related signature (NMRS), which was then validated in the International Cancer Genome Consortium (ICGC) database and Gene Expression Omnibus (GEO) single-cell RNA-seq data. Further studies, such as gene set enrichment analysis (GSEA), ESTIMATE, CIBERSORT, SubMap, and Immunophenoscore (IPS) algorithm, cancer-immunity cycle (CIC), tumor mutation burden (TMB), and drug sensitivity were performed to assess the TME and treatment response.ResultsWe identified a 6-gene NMRS that was significantly associated with BC prognosis as an independent indicator. We performed risk stratification according to the NMRS and the low-risk group showed preferable clinical outcomes (P < 0.001). A comprehensive nomogram was developed and showed excellent predictive value for prognosis. GSEA demonstrated that the low-risk group was predominantly enriched in immune-associated pathways, whereas the high-risk group was enriched in cancer-related pathways. The ESTIMATE and CIBERSORT algorithms revealed that the low-risk group had a higher abundance of anti-tumor immunocyte infiltration (P < 0.05). Results of Submap, IPS, CIC, TMB, and external immunotherapy cohort (iMvigor210) analyses showed that the low-risk group were indicative of better immunotherapy response (P < 0.05).ConclusionsThe novel signature offers a promising way to evaluate the prognosis and treatment efficacy in BC patients, which may facilitate clinical practice and management.

Abstract Bioinformatics methods are used to construct an immune gene prognosis assessment model for patients with non-small cell lung cancer (NSCLC), and to screen biomarkers that affect the occurrence and prognosis of NSCLC. The transcriptomic data and clinicopathological data of NSCLC and cancer-adjacent normal tissues were downloaded from the Cancer Genome Atlas (TCGA) database and the immune-related genes were obtained from the IMMPORT database ( http://www.immport.org/ ); then, the differentially expressed immune genes were screened out. Based on these genes, an immune gene prognosis model was constructed. The Cox proportional hazards regression model was used for univariate and multivariate analyses. Further, the correlations among the risk score, clinicopathological characteristics, tumor microenvironment, and the prognosis of NSCLC were analyzed. A total of 193 differentially expressed immune genes related to NSCLC were screened based on the "wilcox.test" in R language, and Cox single factor analysis showed that 19 differentially expressed immune genes were associated with the prognosis of NSCLC (P

IntroductionPropolis is a beneficial bioactive food with rich polyphenols content. Nowadays, an increasing interest is attracted to the extraction of polyphenols from raw propolis. This study utilized the novel ultrasound-assisted approach for polyphenol extraction from Chinese propolis, aiming to improve its extraction yield and reveal the relevant mechanisms via extraction kinetic study as well as the compositional and structural analysis.MethodsThe optimum ultrasound-assisted extraction conditions were optimized according to the total phenolic content and total flavonoids content. Compositional and structural analysis were conducted using high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry, high-performance liquid chromatography, Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM).Results and discussionThe optimum ultrasound-assisted extraction conditions were as follows: ratio of liquid to solid, 60:1; ultrasound power, 135 W; ultrasound duration, 20 min. Under the optimum conditions, the antioxidant activities of the extract were increased by 95.55% and 64.46% by 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability assay and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging ability assay, respectively, compared to those obtained by traditional maceration. The second-order kinetics model was employed to study the extraction process; it was found that ultrasound significantly accelerated the extraction of propolis and increased the maximum extraction volume of phenolic compounds. The qualitative and quantitative analysis of polyphenol compositions showed that ultrasound did not change the polyphenol types in the extract but it significantly improved the contents of various flavonoids and phenolic acids such as galangin, chrysin, pinocembrin, pinobanksin and isoferulic acid. Likewise, the FT-IR analysis indicated that the types of functional groups were similar in the two extracts. The SEM analysis revealed that the ultrasound-assisted extraction enhanced the contact areas between propolis and ethanol by breaking down the propolis particles and eroding the propolis surface.

Tourism is an important economic and social activity with distinct characteristics of human-land interaction, which creates increasingly pronounced ecological and environmental challenges. The changes in four ecosystem services, including water yield (WY), carbon storage (CS), soil retention (SR) and habitat quality (HQ) in the coastal and noncoastal zones of Sanya were analysed, and the influencing factors were discussed. We found that from 2000 to 2018, the built-up land area of the coastal zone of Sanya quadrupled; CS, SR and HQ of the coastal zone were lower than those of the non-coastal zone with a clear downwards trend; and WY was higher than that of the noncoastal zone, indicating that the development of coastal tourism in Sanya damaged the surrounding ecological environment. The decline in ecosystem services in Sanya from 2010 to 2018 was smaller than that from 2000 to 2010, indicating that Sanya's ecological and environmental protection measures have been effective in recent years. The ecosystem services of Sanya were mainly affected by the natural environment, such as precipitation(P), and fractional vegetation coverage (FVC), but the impact of tourism factors, such as total tourism attraction (TA) and accommodation capacity (AC) also gradually became significant. Based on these findings, we propose to adhere to the sustainable development of coastal ecotourism, implement dynamic planning and dynamic monitoring, and strengthen the protection of coastal and its buffer zone. This study is of great significance to the scientific decision-making and comprehensive regulation of tourism-oriented cities and towns to improve ecosystem services.

IntroductionIt is still unclear whether radiotherapy affects the long-term survival of breast cancer (BC) patients after immediate breast reconstruction (IBR). This study aims to evaluate the actual prognostic impact of radiotherapy on BC patients undergoing IBR, and to construct survival prediction models to predict the survival benefit of radiotherapy.MethodsData on eligible BC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Competing risk models were used to assess breast cause-specific death (BCSD) and non-breast cancer cause-specific death (NBCSD). Kaplan‐Meier curve, Cox risk regression model and forest map were used to evaluate and demonstrate overall survival (OS) and breast cancer-specific survival (BCSS). Survival prediction nomograms were used to predict OS and BCSS probabilities.ResultsA total of 22,218 patients were selected, 24.9% received radiotherapy and 75.1% were without radiotherapy. Competing risk models showed that whether BCSD or NBCSD, the cumulative long-term risk of death in the radiotherapy group was higher than that in the non-radiotherapy group. The Kaplan‐Meier curve showed that patients with different lymph node metastasis had different radiotherapy benefits. Multivariate stratified analysis showed that radiotherapy after autologous reconstruction was associated with poor BCSS in patients with stage N0, and radiotherapy after autologous reconstruction and combined reconstruction improved OS and BCSS in patients with stage N3. The C-indexes of nomogram (between 0.778 and 0.847) and calibration curves showed the good prediction ability of survival prediction model.ConclusionsRadiotherapy can improve OS and BCSS in N3 stage BC patients undergoing immediate autologous reconstruction after mastectomy. The practical nomograms can be used to predict OS and BCSS of patients with or without radiotherapy, which is helpful for individualized treatment.

ObjectiveThe efficacy of primary tumor surgery on survival in female patients with de novo stage IV breast cancer (BC) remains unclear. Our study endeavored to develop comprehensive competing risk nomograms to predict clinical outcomes and guide precision treatment in these patients.Participants and MethodsA total of 12281 patients who had distant metastasis at initial BC diagnosis between 2010 and 2017 in the Surveillance Epidemiology and End Results (SEER) database, were enrolled in this study. First, we assessed the impacts of primary tumor surgery on overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier curves. Then subgroup analyses stratified by different metastatic patterns were performed using Cox and competing risk models (CRM). Based on the filtered independent prognostic parameters by CRM, we established two nomograms to predict the probability of breast cancer-specific death (BCSD) at 1-,2- and 3-year intervals. Furthermore, calibration curves and area under the curves (AUC) were conducted for validation.ResultsKaplan-Meier analysis revealed that surgery was associated with better OS and BCSS (P

Early warning during sky survey provides a crucial opportunity to detect low-mass, free-floating planets. In particular, to search short-timescale microlensing (ML) events from high-cadence and wide- field survey in real time, a hybrid method which combines ARIMA (Autoregressive Integrated Moving Average) with LSTM (Long-Short Time Memory) and GRU (Gated Recurrent Unit) recurrent neural networks (RNN) is presented to monitor all observed light curves and identify ML events at their early stages. Experimental results show that the hybrid models perform better in accuracy and less time consuming of adjusting parameters. ARIMA+LSTM and ARIMA+GRU can achieve improvement in accuracy by 14.5% and 13.2%, respectively. In the case of abnormal detection of light curves, GRU can achieve almost the same result as LSTM with less time by 8%. Same models are also applied to MIT-BIH Arrhythmia Databases ECG dataset with similar abnormal pattern and we yield from both sets that we can reduce up to 40% of time consuming for researchers to adjust the model to 90% accuracy.

In this paper, emulsions stabilized by Tremella fuciformis polysaccharides (TFP) were prepared and the physiochemical properties were assessed. Results showed that the TFP emulsions illustrated the highest emulsifying activity (EAI) and emulsifying stability (ESI) when the concentration of TFP and oil were 0.8% and 10% (wt%). The higher pH value was in favor of the emulsifying properties, while the addition of NaCl impaired the stability, and the greater the concentration, the lower the EAI and ESI. Besides, the emulsifying and rheological properties and stability analysis were evaluated in comparison with gum arabic, pectin, and carboxymethyl cellulose emulsions. It was discovered that TFP illustrated better storage and freeze-thaw stability, which was proved by the result of zeta-potential and particle size. The rheological measurement revealed that all the emulsions behaved as pseudoplastic fluids, while TFP displayed a higher viscosity. Meanwhile, TFP emulsions tended to form a more stable network structure according to the analysis of the parameters obtained from the Herschel–Bulkley model. FTIR spectra suggested that the O-H bond could be destructed without the formation of new covalent bonds during the emulsion preparation. Therefore, this study would be of great importance for the research of emulsions stabilized by TFP as a natural food emulsifier.

Background: Oxidative stress is related to oncogenic transformation in kidney renal clear cell carcinoma (KIRC). We intended to identify a prognostic antioxidant gene signature and investigate its relationship with immune infiltration in KIRC.Methods: With the support of The Cancer Genome Atlas (TCGA) database, we researched the gene expression and clinical data of KIRC patients. Antioxidant related genes with significant differences in expression between KIRC and normal samples were then identified. Through univariate and multivariate Cox analysis, a prognostic gene model was established and all patients were divided into high- and low-risk subgroups. Single sample gene set enrichment analysis was adopted to analyze the immune infiltration, HLA expression, and immune checkpoint genes in different risk groups. Finally, the prognostic nomogram model was established and evaluated.Results: We identified six antioxidant genes significantly correlated with the outcome of KIRC patients as independent predictors, namely DPEP1 (HR = 0.97, P < 0.05), GSTM3 (HR = 0.97, P < 0.05), IYD (HR = 0.33, P < 0.05), KDM3B (HR = 0.96, P < 0.05), PRDX2 (HR = 0.99, P < 0.05), and PRXL2A (HR = 0.96, P < 0.05). The high- and low-risk subgroups of KIRC patients were grouped according to the six-gene signature. Patients with higher risk scores had poorer prognosis, more advanced grade and stage, and more abundance of M0 macrophages, regulatory T cells, and follicular helper T cells. There were statistically significant differences in HLA and checkpoint gene expression between the two risk subgroups. The performance of the nomogram was favorable (concordance index = 0.766) and reliably predicted the 3-year (AUC = 0.792) and 5-year (AUC = 0.766) survival of patients with KIRC.Conclusion: The novel six antioxidant related gene signature could effectively forecast the prognosis of patients with KIRC, supply insights into the interaction between cellular antioxidant mechanisms and cancer, and is an innovative tool for selecting potential patients and targets for immunotherapy.

In this study, we employed the ultrasound-prepared electrostatic complex and covalent conjugate of soy protein isolate (SPI) and citrus pectin (CP) to prepare β-carotene-loaded nanoemulsions. The in vitro digestion and storage stability of nanoemulsions stabilized by different types of emulsifiers were investigated and compared. Nanoemulsions stabilized by ultrasound-treated complex/conjugate showed the highest encapsulation efficiency; during gastric digestion, these nanoemulsions also demonstrated the smallest droplet sizes and the highest absolute values of zeta potential, indicating that both electrostatic complexation/covalent conjugation and ultrasound treatment could significantly improve the stability of the resulting nanoemulsions. In comparison, complexes were more beneficial for the controlled release of β-carotene; however, the conjugate-stabilized nanoemulsion showed an overall higher bioaccessibility. The results were also confirmed by optical micrographs. Furthermore, nanoemulsions stabilized by ultrasound-prepared complexes/conjugates exhibited the highest stability during 14-day storage at 25 °C. The results suggested that ultrasound-prepared SPI–CP complexes and conjugates had great application potential for the delivery of hydrophobic nutrients.

In the present work, chitin suspensions after enzymolysis and sonoenzymolysis were taken as adsorbents to evaluate the adsorption properties of Congo red (CR) dyes. Compared with untreated chitin suspension, the CR adsorption performance was significantly improved after enzymolysis and even more after sonoenzymolysis. According to different adsorption kinetic and isotherm models, Langmuir isotherm and the pseudo-second order model were more reliable to describe the adsorption process of CR onto different chitin samples and demonstrated a monolayer and favorable physisorption process. What’s more, negative values of ΔG (Gibbs free energy change) and the shifts to higher negative values with the temperature increasing from adsorption thermodynamic study proved a spontaneous CR adsorption process. The structural characterization before and after adsorption further verified the physical adsorption between chitin and CR, and a larger specific area and higher porosity of chitin suspension was obtained after sonoenzymolysis with more available active sites.

Abstract c‐Myc overexpression has been implicated in several malignancies including gastric cancer. Here, we report that acidified bile acids enhance tumor progression and telomerase activity in gastric cancer via c‐Myc activation both in vivo and in vitro. c‐Myc mRNA and protein levels were assessed in ten primary and five local recurrent gastric cancer samples by quantitative real‐time polymerase chain reaction and western blotting analysis. The gastric cancer cell line MGC803 was exposed to bile salts (100 μmol/L glycochenodeoxycholic acid and deoxycholic acid) in an acid medium (pH 5.5) for 10 min daily for 60 weeks to develop an MGC803‐resistant cell line. Control MGC803 cells were grown without acids or bile salts for 60 weeks as a control. Cell morphology, proliferation, colony formation and apoptosis of MGC803‐resistant cells were analyzed after 60 weeks. To determine the involvement of c‐Myc in tumor progression and telomere aging in MGC803‐resistant cells, we generated xenografts in nude mice and measured xenograft volume and in vivo telomerase activity. The c‐Myc and hTERT protein and mRNA levels were significantly higher in local recurrent gastric cancer samples than in primary gastric cancer samples. MGC803‐resistant cells showed a marked phenotypic change under normal growth conditions with more clusters and acini, and exhibited increased cell viability and colony formation and decreased apoptosis in vitro. These phenotypic changes were found to be dependent on c‐Myc activation using the c‐Myc inhibitor 10058‐F4. MGC803‐resistant cells also showed a c‐Myc‐dependent increase in xenograft growth and telomerase activity in vivo. In conclusion, these observations support the hypothesis that acidified bile acids enhance tumor progression and telomerase activity in gastric cancer and that these effects are dependent on c‐Myc activity. These findings suggest that acidified bile acids play an important role in the malignant progression of local recurrent gastric cancer.

In order to remove the flocculent precipitation in Huyou juice after frozen storage and thawing process, the thawed juice was ultrasonically treated with different power (45–360 W) and time (10–60 min) in ice bath (~0 °C), and its sedimentation behavior during storage was observed. After optimization, the cloud stability of juice could be improved by ultrasonic treatment with ultrasonic power of 360 W or more for at least 30 min, which could be stable during 7 days of storage at 4 °C. Under this optimal condition (360 W, 30 min), the effects of ultrasound on the physicochemical properties and bioactive compounds of thawed Huyou juice during storage were investigated. The results showed that with smaller particle size and lower polymer dispersity index, ultrasonic treatment did not significantly change the color, soluble solids, titratable acidity, and bioactive compounds including flavonoids and other phenolics. In addition, all properties of samples were at the same level during storage. Thus, ultrasound was applicable since it can improve the cloud stability of Huyou juice with minimal impact on its physicochemical properties and nutritional quality compared to the untreated one.

Immune checkpoint blockade (ICB) therapy has emerged as a promising approach in clinical oncology. For brain metastases, the presence of the robust blood-brain barrier (BBB) and potential immune-related adverse events (irAEs) pose significant challenges. Here, a multistage-responsive antibody-delivery strategy is developed for non-small cell lung cancer (NSCLC) brain metastases, with the ultra-pH sensitivity borate bonds. The antibody-delivery nanoformulation (MB-aPDL1) is able to maintain the "silent state" in health tissue, cross the BBB/BTB by the GLUT1-mediated transcytosis, release the functionalized aPDL1 responsively, and promote the aPDL1 tumor-anchoring. In the in vivo tumor region, the MB-aPDL1 rapidly releases the activated BPA6-aPDL1, which successfully anchors to the tumor cells and improves the efficiency of ICB therapy. The two in vivo ICB therapy studies show a significant tumor growth inhibition from the MB-aPDL1 with an encouraging cure rate of 20% for the NSCLC brain metastases, due to enhanced immune response in tumor, commendably with less behavioral adverse reactions and liver damage. Taken together, this antibody-delivery strategy holds substantial potential for application in clinical treatment of brain metastases. [ABSTRACT FROM AUTHOR]