The Role of Surgery for Primary Pulmonary Synovial Sarcoma: A Population-Based Study.

INTRODUCTION: The rarity of primary pulmonary synovial sarcoma (PPSS) and the lack of prospective clinical trials resulted in poorly understood treatment modality and clinical outcomes. This study aimed to better understand PPSS based on patients from the Surveillance, Epidemiology, and End Results database. MATERIALS AND METHODS: Clinical and survival data of PPSS patients who were diagnosed during 1989 through 2016 and retrieved from the Surveillance, Epidemiology, and End Results database were studied. Kaplan-Meier analyses and Cox proportional hazards model were applied to evaluate the overall survival (OS) and disease-specific survival (DSS) of PPSS patients. RESULTS: A total of 122 patients with PPSS were included (median age: 50 y). PPSS accounted for 4.5% (122/2741) of total primary synovial sarcoma. Most of the patients were diagnosed as poor or undifferentiated grade (52.0% and 34.0%). Cancer-directed surgery was performed for 74.4% of PPSS patients and 28.2% of patients received radiotherapy. The 1-year, 3-year, 5-year, and 10-year OS rates of PPSS patients were 75.4%, 50.8%, 41.8%, and 39.3%, respectively. Cancer-directed surgery was shown to improve the survival of PPSS patients with localized or regional stage (P < 0.05), yet surgical resection did not prolong the OS and DSS of patients with distant stage (P > 0.1). Postoperational radiotherapy was associated with shortened survival time (P < 0.05). PPSS patients who received lobectomy had statistically prolonged OS and DSS than those with pneumonectomy (P < 0.001). CONCLUSIONS: PPSS is a rare and special subtype of synovial sarcoma. Treatment with lobectomy or sublobar resection alone may contribute to a superior prognosis compared with other managements.

Expression of RRM1 and RRM2 as a novel prognostic marker in advanced non-small cell lung cancer receiving chemotherapy.

The aim of this study was to examine the prognostic value of BRCA1, RRM1, and RRM2 in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy. A total of 418 patients who underwent curative pulmonary resection were obtained between January 2007 and November 2009. The relative cDNA quantification for BRCA1, RRM1, and RRM2 was conducted using a fluorescence-based, real-time detection method, and ß-actin was used as a reference gene. The low expression of RRM1 and RRM2 significantly increased the platinum-based chemotherapy response (For RRM1: odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.38-3.18; For RRM2: OR = 1.64, 95% CI = 1.09-2.48). The univariate analysis indicated that low expression of RRM1 attained a longer time to progression and overall survival time, with HR (95% CI) of 0.50 (0.33-0.77) and 0.60 (0.39-0.92), respectively. Similarly, low expression of RRM2 had a longer time to progression and overall survival, with HR (95% CI) of 0.57 (0.38-0.86) and 0.47 (0.31-0.71), respectively. In conclusion, low expression of RRM1 and RRM2 could be used to predict the treatment response to platinum-based chemotherapy and survival in NSCLC. The RRM1 and RRM2 could substantially contribute to the future design of individualized cancer treatment in NSCLC patients.

Macrophage-Related Gene Signatures for Predicting Prognosis and Immunotherapy of Lung Adenocarcinoma by Machine Learning and Bioinformatics.

Background: In recent years, the immunotherapy of lung adenocarcinoma has developed rapidly, but the good therapeutic effect only exists in some patients, and most of the current predictors cannot predict it very well. Tumor-infiltrating macrophages have been reported to play a crucial role in lung adenocarcinoma (LUAD). Thus, we want to build novel molecular markers based on macrophages. Methods: By non-negative matrix factorization (NMF) algorithm and Cox regression analysis, we constructed macrophage-related subtypes of LUAD patients and built a novel gene signature consisting of 12 differentially expressed genes between two subtypes. The gene signature was further validated in Gene-Expression Omnibus (GEO) datasets. Its predictive effect on prognosis and immunotherapy outcome was further evaluated with rounded analyses. We finally explore the role of TRIM28 in LUAD with a series of in vitro experiments. Results: Our research indicated that a higher LMS score was significantly correlated with tumor staging, pathological grade, tumor node metastasis stage, and survival. LMS was identified as an independent risk factor for OS in LUAD patients and verified in GEO datasets. Clinical response to immunotherapy was better in patients with low LMS score compared to those with high LMS score. TRIM28, a key gene in the gene signature, was shown to promote the proliferation, invasion and migration of LUAD cell. Conclusion: Our study highlights the significant role of gene signature in predicting the prognosis and immunotherapy efficacy of LUAD patients, and identifies TRIM28 as a potential biomarker for the treatment of LUAD.

Effect of Ultrasonic Treatment on the Physicochemical Properties of Bovine Plasma Protein-Carboxymethyl Cellulose Composite Gel.

In order to improve the stability of bovine plasma protein-carboxymethyl cellulose composite gels and to expand the utilization of animal by-product resources, this study investigated the impact of different ultrasound powers (300, 400, 500, 600, and 700 W) and ultrasound times (0, 10, 20, 30, and 40 min) on the functional properties, secondary structure and intermolecular forces of bovine plasma protein-carboxymethyl cellulose composite gel. The results showed that moderate ultrasonication resulted in the enhancement of gel strength, water holding capacity and thermal stability of the composite gels, the disruption of hydrogen bonding and hydrophobic interactions between gel molecules, the alteration and unfolding of the internal structure of the gels, and the stabilization of the dispersion state by electrostatic repulsive forces between the protein particles. The content of α-helices, ß-turns, and ß-sheets increased and the content of random curls decreased after sonication (p < 0.05). In summary, appropriate ultrasound power and time can significantly improve the functional and structural properties of composite gels. It was found that controlling the thermal aggregation behavior of composite gels by adjusting the ultrasonic power and time is an effective strategy to enable the optimization of composite gel texture and water retention properties.

Involvement of ICAM5 in Carcinostasis Effects on LUAD Based on the ROS1-Related Prognostic Model.

Background: Lung cancer is the most common type of cancer in the world. In lung adenocarcinoma (LUAD), studies on receptor tyrosine kinase ROS proto-oncogene 1 (ROS1) have mainly focused on the oncogenic effects of its fusion mutations, whereas ROS1 has been reported to be aberrantly expressed in a variety of cancers and can extensively regulate the growth, survival, and proliferation of tumor cells through multiple signaling pathways. The comprehensive analysis of ROS1 expression has not been fully investigated regarding its predictive value for LUAD patients. Methods: Gene expression profiles collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to build and validate prognostic risk models. The association of ROS1 with overall survival and the immune landscape was obtained from the Tumor Immune Estimation Resource (TIMER) database. The following analyses were performed using the R package to determine the model's validity: pathway dysregulation analysis, gene set enrichment analysis, Gene Oncology analysis, immune invasion analysis, chemotherapy, radiotherapy, and immunotherapy sensitivity analysis. Finally, we conducted a pan-cancer analysis and performed in vitro experiments to explore the regulatory role of intercellular adhesion molecule 5 (ICAM5) in the progression of LUAD. Results: We constructed a 17-gene model that categorized patients into two risk groups. The model had predictive accuracy for tumor prognosis and was specific for patients with high ROS1 expression. Comprehensive analysis showed that patients in the high-risk group were characterized by marked dysregulation of multiple pathways (eg, unfolded protein response), immune suppression of the tumor microenvironment, and poor benefit from immunotherapy and radiotherapy compared with patients in the low-risk group. PLX4720 may be a suitable treatment for the high-risk patient population. The ICAM5 gene has been demonstrated to inhibit the proliferation, cell cycle, invasion, and migration of LUAD cells. Conclusion: We constructed a 17-gene prognostic risk model and found differences in immune-related cells, biological processes, and prognosis among patients in different risk groups based on the correlation between ROS1 and immunity. Personalized therapy may play an essential role in treatment. We further investigated the role of ICAM5 in inhibiting the malignant bioactivity of LUAD cells.

UBASH3B-mediated MRPL12 Y60 dephosphorylation inhibits LUAD development by driving mitochondrial metabolism reprogramming.

BACKGROUND: Metabolic reprogramming plays a pivotal role in tumorigenesis and development of lung adenocarcinoma (LUAD). However, the precise mechanisms and potential targets for metabolic reprogramming in LUAD remain elusive. Our prior investigations revealed that the mitochondrial ribosomal protein MRPL12, identified as a novel mitochondrial transcriptional regulatory gene, exerts a critical influence on mitochondrial metabolism. Despite this, the role and regulatory mechanisms underlying MRPL12's transcriptional activity in cancers remain unexplored. METHODS: Human LUAD tissues, Tp53fl/fl;KrasG12D-driven LUAD mouse models, LUAD patient-derived organoids (PDO), and LUAD cell lines were used to explored the expression and function of MRPL12. The posttranslational modification of MRPL12 was analyzed by mass spectrometry, and the oncogenic role of key phosphorylation sites of MRPL12 in LUAD development was verified in vivo and in vitro. RESULTS: MRPL12 was upregulated in human LUAD tissues, Tp53fl/fl;KrasG12D-driven LUAD tissues in mice, LUAD PDO, and LUAD cell lines, correlating with poor patient survival. Overexpression of MRPL12 significantly promoted LUAD tumorigenesis, metastasis, and PDO formation, while MRPL12 knockdown elicited the opposite phenotype. Additionally, MRPL12 deletion in a Tp53fl/fl;KrasG12D-driven mouse LUAD model conferred a notable survival advantage, delaying tumor onset and reducing malignant progression. Mechanistically, we discovered that MRPL12 promotes tumor progression by upregulating mitochondrial oxidative phosphorylation. Furthermore, we identified UBASH3B as a specific binder of MRPL12, dephosphorylating tyrosine 60 in MRPL12 (MRPL12 Y60) and inhibiting its oncogenic functions. The decrease in MRPL12 Y60 phosphorylation impeded the binding of MRPL12 to POLRMT, downregulating mitochondrial metabolism in LUAD cells. In-depth in vivo, in vitro, and organoid models validated the inhibitory effect of MRPL12 Y60 mutation on LUAD. CONCLUSION: This study establishes MRPL12 as a novel oncogene in LUAD, contributing to LUAD pathogenesis by orchestrating mitochondrial metabolism reprogramming towards oxidative phosphorylation (OXPHOS). Furthermore, it confirms Y60 as a specific phosphorylation modification site regulating MRPL12's oncogenic functions, offering insights for the development of LUAD-specific targeted drugs and clinical interventions.

Expression of HGF and Met in human tissues of colorectal cancers: biological and clinical implications for synchronous liver metastasis.

BACKGROUND AND AIMS: Synchronous liver metastasis (SLM) remains a significant problem in newly diagnosed colorectal cancer (CRC). The system of hepatocyte growth factor (HGF) and Met plays an important role in cancer invasion and metastasis and is being developed to be targeted drugs. We aimed to investigate the role of HGF/Met in SLM based on a case-matched study and comparison between primary tumors and matched metastases. METHODS: A group of 30 patients with SLM and other two groups of patients without SLM in a hospital database were collected. They were matched into according to clinicopathological factors. 81 patients were included in the study. Their tissues of primary colorectal cancers, lymph nodes and liver metastases were collected to detect HGF and Met expression by immunohistochemistry and RT-PCR. RESULTS: Expression of HGF and Met at the protein level and the RNA level in primary CRCs with SLM were significantly higher than that in primary colorectal carcinomas without liver metastases (all P value<0.05). Their expression was only related to SLM when concurrent with regional lymph node metastasis (all P value<0.05) but had little influence on SLM without involvement of lymph node metastasis (all P value>0.05). Comparison their expression between primary tumors and matched metastases, major concordance and minor difference existed. CONCLUSIONS: HGF and Met may exert functions in the development of SLM when concurrent with lymph node metastases but had little influence on SLM without lymph node metastasis, further indicating their roles and potential values for a subtype of colorectal cancer metastasis. Major concordance and minor difference exist between primary tumors and matched metastases, which further provides evidence for evaluating the response to their inhibitors based on primary tumors or metastases.

Effects of muscle-specific oxidative stress on protein phosphorylation and its relationship with mitochondrial dysfunction, muscle oxidation, and apoptosis.

This study aimed to investigate the effects of muscle-specific oxidative stress on phosphorylation and its relationship with mitochondrial dysfunction, muscle oxidation, and apoptosis of porcine PM (psoas major) and LL (longissimus lumborum) during the first 24 h postmortem. The global phosphorylation level decreased and the mitochondrial dysfunction, oxidation level, and apoptosis increased significantly at 12 h postmortem compared with 2 h postmortem, suggesting that lower phosphorylation level was related to more mitochondrial dysfunction and apoptosis during the early postmortem, regardless of muscle type. PM exhibited a higher global phosphorylation level but showed greater mitochondrial dysfunction, oxidation level, and apoptosis than LL, regardless of aging time. The increased mitochondrial dysfunction and oxidative stress accelerated apoptosis, but their relationship with phosphorylation was different in various muscle types at different aging times. These findings provide insight regarding the roles of coordinated regulation of phosphorylation and apoptosis in development of quality of different muscles.

Systematic analysis reveals a pan-cancer SNHG family signature predicting prognosis and immunotherapy response.

Small nucleolar RNA host genes (SNHGs) are a special family of long non-coding RNAs (lncRNAs), which not only function in a way similar to other lncRNAs but also influence the intracellular level of small nucleolar RNAs to modulate cancers. However, the features of SNHGs and their role in the prognosis and immunotherapeutic response of human cancer have not been explored. We found that SNHGs were commonly deregulated and correlated with patient survival in various cancers. The critical role of DNA methylation and somatic alterations on deregulation was also identified. SNHG family score was significantly associated with survival, multiple tumor characteristics, and tumor microenvironment. SNHG-related risk score could serve as a prognostic and immunotherapeutic response biomarker based on multiple databases. This study emphasizes the potential of SNHGs as biomarkers for prognosis and immunotherapeutic response, enabling further research into the immune regulatory mechanism and therapeutic potentials of SNHGs in cancer.

LF-NMR determination of water distribution and its relationship with protein- related properties of yak and cattle during postmortem aging.

The water distribution have a profound influence on meat quality, and proteins play a critical role in water distribution. The water distribution detected with proton NMR and its relationship with protein related properties were investigated. Three populations of water were detected: bound water (T21, P21), immobilized water (T22, P22), and free water (T23, P23). The decreased T22 and T23 indicated an increase in water-holding capacity in both muscles from 3 days of aging. The P22 in cattle was higher than that in yak and the P23 in cattle was lower than that in yak, suggesting that cattle exhibited a greater water-holding capacity compared to yak. Moreover, postmortem aging affected muscle protein oxidation, denaturation, and degradation. Correlation analysis suggested that protein oxidation and denaturation caused muscle water loss and protein degradation could allow the muscle to retain water. It provides a basis for the optimization of quality of meat and products.

Incidence and prognostic nomogram for resected non-small cell neuroendocrine tumor: A population-based respective study in China and the SEER database.

Background: Pulmonary neuroendocrine tumors, including small cell lung cancer (SCLC) and non-small cell neuroendocrine tumor (NSCLC-NET), have obvious heterogeneity. The comparison between SCLC and NSCLC-NET, and prognostic nomogram of resected NSCLC-NET have not been performed. Methods: We retrieved data from SEER database. The incidence and prognostic factors were compared between SCLC and NSCLC-NET. By Cox regression, we constructed prognostic nomogram of resected NSCLC-NET. The nomogram was evaluated by ROC, calibration plot and decision curve analysis (DCA) and compared with 8th TNM staging system. A Chinese cohort was used for external validation. Results: The age-adjusted incidence of SCLC declined after 1991 but the incidence of NSCLC-NET continuously rose. Patients with typical carcinoid had the best prognosis in both overall survival and lung cancer specific survival, followed by atypical carcinoid, large cell neuroendocrine tumor and SCLC after operation. Patients receiving sleeve resection in NSCLC-NET had longer survival but segmental resection was more recommended in SCLC. High-smoking index was associated with worse overall survival in both SCLC and NSCLC-NET. Histological subtype, age, surgery type, N, M stage and chemotherapy were independent prognostic factors and used to construct prognostic nomogram of resected NSCLC-NET. The nomogram performed well with good discrimination, calibration and clinical usefulness, which was validated by a Chinese cohort (1, 3, 5-year AUC: SEER cohort 0.873, 0.901, 0.875; Chinese cohort 0.867, 0.892, 0.874). Compared to the 8th staging system, the nomogram had higher C-index (0.87 vs 0.728, P < 0.001), clinical usefulness, increasing AUC value over time and improved 68%. Conclusion: The prognostic nomogram of resected NSCLC-NET performed better than the 8th TNM staging system. It may have certain value in risk stratification and survival prediction of patients with resected NSCLC-NET and help clinicians to take measures for high-risk patients in advance.

Comprehensive analysis of suppressor of cytokine signaling 2 protein in the malignant transformation of NSCLC.

Suppressor of cytokine signaling 2 (SOCS2) plays an essential role in a number of physiological phenomena and functions as a tumor suppressor. Understanding the predictive effects of SOCS2 on non-small cell lung cancer (NSCLC) is urgently needed. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to assess SOCS2 gene expression levels in NSCLC. The clinical significance of SOCS2 was evaluated through Kaplan-Meier curve analysis and the analysis of related clinical factors. Gene Set Enrichment Analysis (GSEA) was used to identify the biological functions of SOCS2. Subsequently proliferation, wound-healing, colony formation and Transwell assays, and carboplatin drug experiments were used for verification. The results revealed that SOCS2 expression was low in the NSCLC tissues of patients in TCGA and GEO database analyses. Downregulated SOCS2 was associated with poor prognosis, as determined by Kaplan-Meier survival analysis (HR 0.61, 95% CI 0.52-0.73; P<0.001). GSEA showed that SOCS2 was involved in intracellular reactions, including epithelial-mesenchymal transition (EMT). Cell experiments indicated that knockdown of SOCS2 caused the malignant progression of NSCLC cell lines. Furthermore, the drug experiment showed that silencing of SOCS2 promoted the resistance of NSCLC cells to carboplatin. In conclusion, low expression of SOCS2 was associated with poor clinical prognosis by effecting EMT and causing drug resistance in NSCLC cell lines. Furthermore, SOCS2 could act as a predictive indicator for NSCLC.

Preparation of Complementary Food for Infants and Young Children with Beef Liver: Process Optimization and Storage Quality.

In this study, fuzzy mathematics and response surface modeling were applied to optimize the preparation process of beef liver paste and characterize the proximate composition, sensory and physicochemical qualities, and in vitro simulated digestive properties while refrigerated at 0-4 °C (0, 3, 7, 15, 30, 45, and 60 days). The results showed that the optimal preparation process was 4.8% potato starch, 99.4% water, 10.2% olive oil, and a 3:2 ratio of chicken breast and beef liver. The beef liver paste prepared contained essential amino acids for infants and children, with a protein content of 10.29 g/100 g. During storage, the pH of the beef liver paste decreased significantly (p < 0.05) on day 7, texture and rheological properties decreased significantly after 30 days, a* values increased, L* and b* values gradually decreased, and TVB-N and TBARS values increased significantly (p < 0.05) on day 7 but were below the limit values during the storage period (TVB-N value ≤ 15 mg/100 g, TBARS value ≤ 1 mg/Kg). In vitro simulated digestion tests showed better digestibility and digestive characteristics in the first 15 days. The results of this study provide a reference for the development of beef liver products for infant and child supplementation.

Inhibitory effects of longan seed extract on polycyclic aromatic hydrocarbons formation and muscle oxidation in baked mutton kebabs.

Longan seeds, rich in phenolic compounds with antioxidant properties, are an underestimated by-product of longan processing. Polycyclic aromatic hydrocarbons (PAHs), which are carcinogenic and mutagenic, are produced during the cooking of meat products at high temperatures. The effects of different concentrations of longan seed extract (LSE, 0.2, 0.6, 1.0 mg/mL) on the formation of PAHs and muscle oxidation in mutton kebabs were investigated. Mutton kebabs were baked at 150, 200, 250 °C for 20 min, respectively, and the contents of PAHs, the degree of lipid and protein oxidation were evaluated. The results showed that LSE exhibited positive effects in inhibiting total PAHs formation (range from 14.9 to 48.8 %), decreasing the thiobarbituric acid reactive substances (TBARS) values (range from 17.1 to 39.1 %), reducing carbonyl content (range from 22.0 to 51.2 %) and increasing sulfhydryl content (range from 18.6 to 51.8 %). This study provided a guidance and potential solution for reducing the content of PAHs and muscle oxidation levels in baked meat.

Preparation of Bovine Hides Gelatin by Ultra-High Pressure Technique and the Effect of Its Replacement Fat on the Quality and In Vitro Digestion of Beef Patties.

Beef skin gelatin can be used as a good substitute for animal fat in meat patties. In this paper, the effect of different parameters on low-fat beef patties with cowhide gelatin substituted for beef fat (0, 25%, 50%, 75%, 100%) prepared by ultra-high pressure assisted technology was investigated by texture, cooking loss, and sensory scores. The beef patties were also stored at 0-4 °C for 0, 7, 14, 21, and 28 d. The differences and changing rules of fatty acid and amino acid compositions and contents of beef patties with different fat contents were investigated by simulating gastrointestinal digestion in vitro. The optimal process formulation of low-fat beef patties with cowhide gelatin was determined by experimental optimization as follows: ultra-high pressure 360 MPa, ultra-high of pressure time of 21 min, NaCl addition of 1.5%, compound phosphate addition of 0.3%. The addition of cowhide gelatin significantly increased monounsaturated fatty acids, polyunsaturated fatty acids, amino acid content, and protein digestibility of beef patties (p < 0.05). Moreover, with the extension of storage time, the content of saturated fatty acids was significantly higher (p < 0.05), the content of monounsaturated and polyunsaturated fatty acids was significantly lower (p < 0.05), the content of amino acids was significantly lower (p < 0.05), and protein digestibility was significantly lower (p < 0.05) under all substitution ratios. Overall, beef patties with 75% and 100% substitution ratios had better digestibility characteristics. The results of this study provide a theoretical basis for gelatin's potential as a fat substitute for beef patties and for improving the quality of low-fat meat products.

Effects of Salt Soaking Treatment on the Deodorization of Beef Liver and the Flavor Formation of Beef Liver Steak.

In this study, based on the evaluation of fishy value and sensory evaluation, this study determined that soaking in a 1% salt solution for 60 min had a significant impact on the deodorization of beef liver (p < 0.05). The results showed that salt infiltration promoted the release of fishy substances, improving the edible and processing performance of beef liver. The identification of flavor compounds in raw and roasted beef liver via GC-IMS implies that (E)-2-octenal-M, (E)-3-penten-2-one-M, ethyl acetate-M, ethyl acetate-D, and methanethiol are closely related to improving the flavor of beef liver; among them, (E)-2-octenal-M, (E)-3-penten-2-one-M, and methanethiol can cause beef liver odor, while nonanal-M, octanal-M, benzene acetaldehyde, n-hexanol-D, butyl propanoate-M, heptanal-D, heptanal-M, and 3-methylthiopropanal-M had significant effects on the flavor formation of beef liver steak. The determination of reducing sugars revealed that salt soaking had no significant effect on the reducing sugar content of beef liver, and the beef liver steak was significantly reduced (p < 0.05), proving that reducing sugars promoted the formation of beef liver steak flavor under roasting conditions. Fatty acid determination revealed that salt soaking significantly reduced the content of polyunsaturated fatty acids in beef liver (p < 0.05), promoting the process of fat degradation and volatile flavor production in the beef liver steak. Salt plays a prominent role in salting-out and osmosis during deodorization and flavor improvement. Through controlling important biochemical and enzymatic reactions, the release of flavor substances in a food matrix was increased, and a good deodorization effect was achieved, which lays a foundation for further research on the deodorization of beef liver and the flavor of beef liver steak.

Distinct gene mutation profiles among multiple and single primary lung adenocarcinoma.

With the development of technologies, multiple primary lung cancer (MPLC) has been detected more frequently. Although large-scale genomics studies have made significant progress, the aberrant gene mutation in MPLC is largely unclear. In this study, 141 and 44 lesions from single and multiple primary lung adenocarcinoma (SP- and MP-LUAD) were analyzed. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tumor tissue and sequenced by using the next-generation sequencing-based YuanSu450TM gene panel. We systematically analyzed the clinical features and gene mutations of these lesions, and found that there were six genes differently mutated in MP-LUAD and SP-LUAD lesions, including RBM10, CDK4, ATRX, NTRK1, PREX2, SS18. Data from the cBioPortal database indicated that mutation of these genes was related to some clinical characteristics, such as TMB, tumor type, et al. Besides, heterogeneity analysis suggested that different lesions could be tracked back to monophyletic relationships. We compared the mutation landscape of MP-LUAD and SP-LUAD and identified six differentially mutated genes (RBM10, CDK4, ATRX, NTRK1, PREX2, SS18), and certain SNV loci in TP53 and EGFR which might play key roles in lineage decomposition in multifocal samples. These findings may provide insight into personalized prognosis prediction and new therapies for MP-LUAD patients.

Prediction of prognosis, immunogenicity and efficacy of immunotherapy based on glutamine metabolism in lung adenocarcinoma.

Background: Glutamine (Gln) metabolism has been reported to play an essential role in cancer. However, a comprehensive analysis of its role in lung adenocarcinoma is still unavailable. This study established a novel system of quantification of Gln metabolism to predict the prognosis and immunotherapy efficacy in lung cancer. Further, the Gln metabolism in tumor microenvironment (TME) was characterized and the Gln metabolism-related genes were identified for targeted therapy. Methods: We comprehensively evaluated the patterns of Gln metabolism in 513 patients diagnosed with lung adenocarcinoma (LUAD) based on 73 Gln metabolism-related genes. Based on differentially expressed genes (DEGs), a risk model was constructed using Cox regression and Lasso regression analysis. The prognostic efficacy of the model was validated using an individual LUAD cohort form Shandong Provincial Hospital, an integrated LUAD cohort from GEO and pan-cancer cohorts from TCGA databases. Five independent immunotherapy cohorts were used to validate the model performance in predicting immunotherapy efficacy. Next, a series of single-cell sequencing analyses were used to characterize Gln metabolism in TME. Finally, single-cell sequencing analysis, transcriptome sequencing, and a series of in vitro experiments were used to explore the role of EPHB2 in LUAD. Results: Patients with LUAD were eventually divided into low- and high-risk groups. Patients in low-risk group were characterized by low levels of Gln metabolism, survival advantage, "hot" immune phenotype and benefit from immunotherapy. Compared with other cells, tumor cells in TME exhibited the most active Gln metabolism. Among immune cells, tumor-infiltrating T cells exhibited the most active levels of Gln metabolism, especially CD8 T cell exhaustion and Treg suppression. EPHB2, a key gene in the model, was shown to promote LUAD cell proliferation, invasion and migration, and regulated the Gln metabolic pathway. Finally, we found that EPHB2 was highly expressed in macrophages, especially M2 macrophages. It may be involved in the M2 polarization of macrophages and mediate the negative regulation of M2 macrophages in NK cells. Conclusion: This study revealed that the Gln metabolism-based model played a significant role in predicting prognosis and immunotherapy efficacy in lung cancer. We further characterized the Gln metabolism of TME and investigated the Gln metabolism-related gene EPHB2 to provide a theoretical framework for anti-tumor strategy targeting Gln metabolism.

Effects of low-dose sodium nitrite on the structure of yak meat myoglobin during wet curing.

The effects of low doses of sodium nitrite on yak meat colouring, myoglobin oxygenation status, myoglobin aggregation and myoglobin structure were evaluated using Fourier transform infrared spectroscopy, laser micro-Raman spectroscopy and liquid chromatography-electrospray ionization tandem mass spectrometry. The results showed that the yak meat redness value increased steadily relative to that of the control after the addition of low dose sodium nitrite. The nitrosomyoglobin level gradually increased and was significantly higher in the sodium nitrite-treated group than in the control group. The secondary structures were also transformed. The Cα-N bond extended and then contracted, the area of the haem core decreased and then increased and the frequency of contraction increased. A total of 34 nitrosylated peptides were identified, of which 15 were stable and 19 were unstable. These findings show that low doses of sodium nitrite facilitated the dynamic transformation of the myoglobin nitrosylated peptide fragment, which in turn preserved the colour of the meat.

H2O2-induced oxidative stress improves meat tenderness by accelerating glycolysis via hypoxia-inducible factor-1α signaling pathway in postmortem bovine muscle.

Reactive oxygen species (ROS) affect meat quality through multiple biochemical pathways. To investigate the effect of ROS on postmortem glycolysis and tenderness of bovine muscle, ROS content, glycolytic potential, glycolysis rate-limiting enzyme activities, expression of hypoxia-inducible factor-1α (HIF-1α), phosphatidylinositol 3-kinase (PI3K), serine-threonine kinase (AKT), phosphorylated AKT (p-AKT), and tenderness were determined in the H2O2 group and control group. Results showed that the H2O2 group exhibited significantly higher ROS content within 48 h, coupled with increased glycolytic potential, pH decline, hexokinase (HK), and phosphofructokinase activities (PFK) early postmortem. These were attributed to ROS-induced PI3K/AKT signaling pathway activation and resultant HIF-1α accumulation. Moreover, shear force in the H2O2 group reached the peak 12 h earlier and decreased obviously after 24 h, accompanied by a significantly higher myofibril fragmentation index (MFI). These findings suggested that ROS drive HIF-1α accumulation by activating PI3K/AKT signaling pathway, thereby accelerating glycolysis and tenderization of postmortem bovine muscle.