Does dual-layer spectral detector CT provide added value in predicting spread through air spaces in lung adenocarcinoma? A preliminary study.

OBJECTIVES: To examine the predictive value of dual-layer spectral detector CT (DLCT) for spread through air spaces (STAS) in clinical lung adenocarcinoma. METHODS: A total of 225 lung adenocarcinoma cases were retrospectively reviewed for demographic, clinical, pathological, traditional CT, and spectral parameters. Multivariable logistic regression analysis was carried out based on three logistic models, including a model using traditional CT features (traditional model), a model using spectral parameters (spectral model), and an integrated model combining traditional CT and spectral parameters (integrated model). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to assess these models. RESULTS: Univariable analysis showed significant differences between the STAS and non-STAS groups in traditional CT features, including nodule density (p < 0.001), pleural indentation types (p = 0.006), air-bronchogram sign (p = 0.031), the presence of spiculation (p < 0.001), long-axis diameter of the entire nodule (LD) (p < 0.001), and consolidation/tumor ratio (CTR) (p < 0.001). Multivariable analysis revealed that LD > 20 mm (odds ratio [OR] = 2.271, p = 0.025) and CTR (OR = 24.208, p < 0.001) were independent predictors in the traditional model, while electronic density (ED) in the venous phase was an independent predictor in the spectral (OR = 1.062, p < 0.001) and integrated (OR = 1.055, p < 0.001) models. The area under the curve (AUC) for the integrated model (0.84) was the highest (spectral model, 0.83; traditional model, 0.80), and the difference between the integrated and traditional models was statistically significant (p = 0.015). DCA showed that the integrated model had superior clinical value versus the traditional model. CONCLUSIONS: DLCT has added value for STAS prediction in lung adenocarcinoma. CLINICAL RELEVANCE STATEMENT: Spectral CT has added value for spread through air spaces prediction in lung adenocarcinoma so may impact treatment planning in the future. KEY POINTS: • Electronic density may be a potential spectral index for predicting spread through air spaces in lung adenocarcinoma. • A combination of spectral and traditional CT features enhances the performance of traditional CT for predicting spread through air spaces.

Watching Food Videos Leads to Postparotidectomy Salivary Fistula.

Salivary fistula is a common postparotidectomy complication, and eating sour or spicy food ranks among the leading causes. Here we report a rare postparotidectomy salivary fistula case, a 31-year-old female patient who affirmed that she did not eat any irritating foods but admitted that she had been watching food videos for up to 4 hours every day since she left hospital. This case offers a cautionary tale about postparotidectomy precautions.

[Role of Dual-layer Detector Energy Spectral CT in Resting Myocardial Perfusion Imaging for Patients with Normal Coronary Artery].

Objective To investigate the role of dual-layer detector energy spectral CT in resting myocardial perfusion imaging for patients with normal coronary artery. Methods One hundred and fifty-six patients with suspected coronary heart disease underwent dual-layer detector energy spectral CT coronary angiography,and resting myocardial perfusion imaging was performed for 28 patients with normal coronary artery.According to American Heart Association's 17-segmentmodel,the iodine density and effective atomic number(Zeff value)of each myocardial segment(except for apical segment)were measured and normalized to those of the aorta.All the data were quantitatively evaluated using ANOVA or Friedman test. Results Iodine density and Zeff value of myocardial segments in middle plane were significantly different(all P<0.001).The iodine density and Zeff value showed no significant difference between segments in basal and apical plane(all P > 0.05). Conclusions Iodine density and Zeff value of myocardial segments can be quantitatively evaluated using dual-layer detector energy spectral CT.Resting myocardial perfusion of segments in middle plane are significantly different in patients with normal coronary artery.

Overexpression of Malic Enzyme 2 Indicates Pathological and Clinical Significance in Oral Squamous Cell Carcinoma.

Our study investigated the expression of malic enzyme 2 (ME2) in human oral squamous cell carcinoma (OSCC) and associated pathological and clinical pattern. We demonstrated that human OSCC tissues expressed a high level of ME2, and the overexpression of ME2 is closely connected to a high pathological grade, lymphatic metastasis, large tumor size and human papillomavirus (HPV) (P < 0.001). Similarly, high levels of ME2 expression in OSCC tissue were shown to be correlated with poor prognosis (P < 0.05). The expression of ME2 was correlated with Slug, SOX2, and aldehyde dehydrogenase-1 (ALDH1) immunoreactivity.ME2 was shown to be overexpressed in OSCC tissue and indicated a poor prognosis for OSCC. ME2 may be correlated with several immune markers.

Expression levels of SIX1, ME2, and AP2M1 in adenoid cystic carcinoma and mucoepidermoid carcinoma.

OBJECTIVE: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the most frequent malignancies in the salivary glands. The purpose of this study was to explore the roles of sine oculis homeobox homolog 1 (SIX1), malic enzyme 2 (ME2), and AP-2 complex subunit mu (AP2M1) in AdCC and MEC, as well as the potential relationship between SIX1, ME2, AP2M1, and proliferation marker cyclin D1. MATERIAL AND METHODS: Immunohistochemistry was performed on human salivary gland tissue microarrays that contained 76 normal salivary glands (NSGs), 14 pleomorphic adenomas (PMAs), 81 AdCCs, and 52 MECs. RESULTS: We observed that the expression levels of SIX1 and ME2 were significantly elevated in AdCC and MEC when compared with NSG and PMA. In addition, we detected that AP2M1 was overexpressed in AdCC and MEC when compared with NSG. We also found that SIX1 and AP2M1 were positively associated with cyclin D1. CONCLUSIONS: These results may prove that SIX1 and AP2M1 are involved in the proliferation of AdCC and MEC to cause tumor growth.

Significantly increased amino acid accumulation in a novel albino branch of the tea plant (Camellia sinensis).

MAIN CONCLUSION: A normal tea plant with one albino branch was discovered. RNA sequencing, albinism phenotype and ultrastructural observations provided a valuable understanding of the albino mechanism in tea plants. Tea plants with a specific color (white or yellow) have been studied extensively. A normal tea plant (Camellia sinensis cv. quntizhong) with one albino branch was discovered in a local tea plantation in Huangshan, Anhui, China. The pure albino leaves on this special branch had accumulated a fairly high content of amino acids, especially theanine (45.31 mg/g DW), and had a low concentration of polyphenols and an extremely low chlorophyll (Chl) content compared with control leaves. Ultrastructural observation of an albino leaf revealed no chloroplasts, whereas it was viable in the control leaf. RNA sequencing and differentially expressed gene (DEG) analysis were performed on the albino leaves and on control leaves from a normal green branch. The related genes involved in theanine and polyphenol biosynthesis were also investigated in this study. DEG expression patterns in Chl biosynthesis or degradation, carotenoid biosynthesis or degradation, chloroplast development, and biosynthesis were influenced in the albino leaves. Chloroplast deletion in albino leaves had probably destroyed the balance of carbon and nitrogen metabolism, leading to a high accumulation of free amino acids and a low concentration of polyphenols in the albino leaves. The obtained results can provide insight into the mechanism underlying this special albino branch phenotype, and are a valuable contribution toward understanding the albino mechanism in tea plants.

Inhibition of SRC family kinases facilitates anti-CTLA4 immunotherapy in head and neck squamous cell carcinoma.

The immune system plays a critical role in the establishment, development, and progression of head and neck squamous cell carcinoma (HNSCC). As treatment with single-immune checkpoint agent results in a lower response rate in patients, it is important to investigate new strategies to maintain favorable anti-tumor immune response. Herein, the combination immunotherapeutic value of CTLA4 blockade and SFKs inhibition was assessed in transgenic HNSCC mouse model. Our present work showed that tumor growth was not entirely controlled when HNSCC model mice were administered anti-CTLA4 chemotherapeutic treatment. Moreover, it was observed that Src family kinases (SFKs) were hyper-activated and lack of anti-tumor immune responses following anti-CTLA4 chemotherapeutic treatment. We hypothesized that activation of SFKs is a mechanism of anti-CTLA4 immunotherapy resistance. We, therefore, carried out combined drug therapy using anti-CTLA4 mAbs and an SFKs' inhibitor, dasatinib. As expected, dasatinib and anti-CTLA4 synergistically inhibited tumor growth in Tgfbr1/Pten 2cKO mice. Furthermore, dasatinib and anti-CTLA4 combined to reduce the number of myeloid-derived suppressor cells and Tregs, increasing the CD8+ T cell-to-Tregs ratio. We also found that combining dasatinib with anti-CTLA4 therapy significantly attenuated the expression of p-STAT3Y705 and Ki67 in tumoral environment. These results suggest that combination therapy with SFKs inhibitors may be a useful therapeutic approach to increase the efficacy of anti-CTLA4 immunotherapy in HNSCC.

Blockage of the NLRP3 inflammasome by MCC950 improves anti-tumor immune responses in head and neck squamous cell carcinoma.

The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1ß, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1ß concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1ß levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues. Blocking NLRP3 inflammasome activation using MCC950 remarkably reduced IL-1ß production in an HNSCC mouse model and reduced the numbers of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Moreover, inhibiting NLRP3 inflammasome activation increased the numbers of CD4+ and CD8+ T cells in HNSCC mice. Notably, the numbers of exhausted PD-1+ and Tim3+ T cells were significantly reduced. A human HNSCC tissue microarray showed that NLRP3 inflammasome expression was correlated with the expression of CD8 and CD4, the Treg marker Foxp3, the MDSC markers CD11b and CD33, and the TAM markers CD68 and CD163, PD-1 and Tim3. Overall, our results demonstrate that the NLRP3 inflammasome/IL-1ß pathway promotes tumorigenesis in HNSCC and inactivation of this pathway delays tumor growth, accompanied by decreased immunosuppressive cell accumulation and an increased number of effector T cells. Thus, inhibition of the tumor microenvironment through the NLRP3 inflammasome/IL-1ß pathway may provide a novel approach for HNSCC therapy.

Identification of geographical origin of Keemun black tea based on its volatile composition coupled with multivariate statistical analyses.

BACKGROUND: Keemun black tea (KBT) is one of the most popular tea beverages in China as a result of its unique flavor and potential health benefits. The geographical origin of KBT influences its quality and price. The present study aimed to apply a head-space solid phase microextraction approach and gas chromatography-mass spectrometry combined with chemometric analysis to profile the volatile compounds of KBT collected from five production areas. RESULTS: Thirty-one peaks were detected in 61 KBT samples. Hierarchical cluster analysis, principal component analysis (PCA), k-nearest neighbor (k-NN) and stepwise linear discriminant analysis (SLDA) were employed to visualize the volatile fractions. The results of unsupervised statistical tools were compared using a test for similarities and distinctions, which showed that different sources may be associated. A satisfying combination of average recognition (91.7%) and cross-validation prediction abilities (84.6%) was obtained for the PCA-k-NN. Among all of the statistical tools, SLDA provided promising results, with 100% recognition and 96.4% prediction ability. CONCLUSION: The results obtained in the present study indicate that the volatile compounds can be used as indicators to identify the geographical origin of KBT. © 2019 Society of Chemical Industry.

Geographical origin traceability of Keemun black tea based on its non-volatile composition combined with chemometrics.

BACKGROUND: Non-volatile compounds play a key role in the quality and price of Keemun black tea (KBT). The non-volatile compounds in KBT samples from different producing areas normally vary greatly. The development of rapid methods for tracing the geographical origin of KBT is useful. In this study, we develop models for the discrimination of KBT's geographical origin based on non-volatile compounds. RESULTS: Seventy-two KBT samples were collected from five towns in Anhui province to determine 13 KBT compounds by high-performance liquid chromatography (HPLC). Analysis of variance showed that the content of 13 compounds in KBT indicated significant differences (P < 0.05) among five towns. Three multivariate statistical models including principal component analysis (PCA), soft independent modeling of class analogy (SIMCA), and linear discriminant analysis (LDA) were built to discriminate origin. Principal component analysis effectively extracted three principal components, namely theaflavins, galloylated catechins, and simple catechins. The high sensitivity (64.5%-99.2%) was achieved of SIMCA model. To establish the discriminant functions, six variables (gallic acid, (+)-catechin, (-)-epigallocatechin gallate, theaflavin-3-gallate, theaflavin-3,3'-di-gallate, and total theaflavins) were chosen from 13 variables, and LDA was applied. This gave a satisfactory overall correct classification rate (94.4%) and cross-validation rate (88.9%) for KBT samples. CONCLUSION: The results showed that HPLC analysis together with chemometrics is a reliable approach for tracing KBT and guaranteeing its authenticity. © 2019 Society of Chemical Industry.

Specific blockade CD73 alters the "exhausted" phenotype of T cells in head and neck squamous cell carcinoma.

The adenosine-induced immunosuppression hampers the immune response toward tumor cells and facilitates the tumor cells to evade immunosurveillance. CD73, an ecto-5-nucleotidase, is the ectoenzyme dephosphorylating extracellular AMP to adenosine. Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model, immune profiling showed high expression of CD73 on CD4+ and CD8+ T cells was associated with an "exhausted" phenotype. Further, treatment with anti-CD73 monoclonal antibody (mAb) significantly blunted the tumor growth in the mouse model, and the blockade of CD73 reversed the "exhausted" phenotype of CD4+ and CD8+ T cells through downregulation of total expression of PD-1 and CTLA-4 on T cells. Whereas the population of CD4+ CD73hi /CD8+ CD73hi T cells expressed higher CTLA-4 and PD-1 as compared to untreated controls. In addition, the human tissue microarrays showed the expression of CD73 is upregulated on tumor infiltrating immune cells in patients with primary HNSCC. Moreover, CD73 expression is an independent prognostic factor for poor outcome in our cohort of HNSCC patients. Altogether, these findings highlight the immunoregulatory role of CD73 in the development of HNSCC and we propose that CD73 may prove to be a promising immunotherapeutic target for the treatment of HNSCC.

γ-Secretase inhibitor reduces immunosuppressive cells and enhances tumour immunity in head and neck squamous cell carcinoma.

Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signaling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signaling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment. In addition, flow cytometry analysis indicated that Notch signaling inhibition reduced the sub-population of myeloid-derived suppressor cells (MDSCs), tumour-associated macrophages (TAMs) and regulatory T cells (Tregs), as well as immune checkpoint molecules (PD1, CTLA4, TIM3 and LAG3), in the circulation and in the tumour. Immunohistochemistry (IHC) of human HNSCC tissues demonstrated that elevation of the Notch1 downstream target HES1 was correlated with MDSC, TAM and Treg markers and with immune checkpoint molecules. These results suggest that modulating the Notch signaling pathway may decrease MDSCs, TAMs, Tregs and immune checkpoint molecules in HNSCC.

Inhibition of JAK2/STAT3 reduces tumor-induced angiogenesis and myeloid-derived suppressor cells in head and neck cancer.

Angiogenesis is an essential event in tumor growth and metastasis, and immune system also contributes to the tumor evasion. Emerging evidences have suggested the bidirectional link between angiogenesis and immunosuppression. Myeloid-derived suppressor cell (MDSC) is a kind of immunosuppressive cells and plays an important role in this process. However, the actual regulatory mechanisms of angiogenesis and MDSCs in head and neck squamous cell carcinoma (HNSCC) were unclear. In this study, through analyzing the immunohistochemistry staining of human HNSCC tissue microarray, we found that the microvascular density (MVD) was significantly increased in HNSCC patients. We also characterized angiogenic factors p-STAT3, VEGFA, CK2, and MDSCs marker CD11b in HNSCC tissue array, and found the close expression correlation among these markers. To determine the role of JAK2/STAT3 pathway in tumor microenvironment of HNSCC, we utilized AG490 (an inhibitor of JAK2/STAT3) for further research. Results showed that inhibition of JAK2/STAT3 suppressed angiogenesis by decreasing VEGFA and HIF1-α both in vitro and vivo. Moreover, in HNSCC transgenic mouse model, inhibiting JAK2/STAT3 not only suppressed angiogenesis but also reduced MDSCs in the tumor microenvironment through suppressing VEGFA and CK2. Our findings demonstrated the close relationship between angiogenesis and MDSCs in HNSCC, and inhibition of JAK2/STAT3 could reduce tumor-induced angiogenesis and decrease MDSCs.

Overexpression of p21-activated kinase 2 is correlated with high-grade oral squamous cell carcinomas.

AIM: p21-activated kinase 2 (PAK2) is overexpressed in several tumors but the expression of PAK2 in oral squamous cell carcinomas (OSCCs) remains unclear. MATERIALS & METHODS: Immunohistochemistry was performed on human tissue microarrays containing 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa. RESULTS: PAK2 expression was increased in primary OSCC compared with normal mucosa and significantly increased in primary OSCC grade III compared with grade I, but independent of overall survival rate. Moreover, the expression of PAK2 was statistically correlated with Lck/Yes novel tyrosine kinase (LYN), zinc finger transcription factor Slug, tumor-associated macrophage marker CD163 and LAG3. CONCLUSION: Overexpression of PAK2 in OSCC may be associated with an advanced pathology grade.

Selective blockade of B7-H3 enhances antitumour immune activity by reducing immature myeloid cells in head and neck squamous cell carcinoma.

Immature myeloid cells including myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7-H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa. Using immunocompetent transgenic HNSCC models, we observed that targeting inhibition of B7-H3 reduced tumour size. Flow cytometry analysis revealed that targeting inhibition of B7-H3 increases antitumour immune response by decreasing immunosuppressive cells and promoting cytotoxic T cell activation in both tumour microenvironment and macroenvironment. Our study provides direct in vivo evidence for a rationale for B7-H3 blockade as a future therapeutic strategy to treat patients with HNSCC.

Blockade of adenosine A2A receptor enhances CD8+ T cells response and decreases regulatory T cells in head and neck squamous cell carcinoma.

BACKGROUND: Cancer immunotherapy offers a promising approach in cancer treatment. The adenosine A2A receptor (A2AR) could protect cancerous tissues from immune clearance via inhibiting T cells response. To date, the role of A2AR in head and neck squamous cell carcinoma (HNSCC) has not been investigated. Here, we sought to explore the expression and immunotherapeutic value of A2AR blockade in HNSCC. METHODS: The expression of A2AR was evaluated by immunostaining in 43 normal mucosae, 48 dysplasia and 165 primary HNSCC tissues. The immunotherapeutic value of A2AR blockade was assessed in vivo in genetically defined immunocompetent HNSCC mouse model. RESULTS: Immunostaining of HNSCC tissue samples revealed that increased expression of A2AR on tumor infiltrating immune cells correlated with advanced pathological grade, larger tumor size and positive lymph node status. Elevated A2AR expression was also detected in recurrent HNSCC and HNSCC tissues with induction chemotherapy. The expression of A2AR was found to be significantly correlated with HIF-1α, CD73, CD8 and Foxp3. Furthermore, the increased population of CD4+Foxp3+ regulatory T cells (Tregs), which partially expressed A2AR, was observed in an immunocompetent mouse model that spontaneously develops HNSCC. Pharmacological blockade of A2AR by SCH58261 delayed the tumor growth in the HNSCC mouse model. Meanwhile, A2AR blockade significantly reduced the population of CD4+ Foxp3+ Tregs and enhanced the anti-tumor response of CD8+ T cells. CONCLUSIONS: These results offer a preclinical proof for the administration of A2AR inhibitor on prophylactic experimental therapy of HNSCC and suggest that A2AR blockade can be a potential novel strategy for HNSCC immunotherapy.

Inhibition of SRC family kinases reduces myeloid-derived suppressor cells in head and neck cancer.

SRC family kinases (SFKs), a group of nonreceptor tyrosine kinases, modulate multiple cellular functions, such as cell proliferation, differentiation and metabolism. SFKs display aberrant activity in progressive stages of human cancers. However, the precise role of SFKs in the head and neck squamous cell carcinoma (HNSCC) signaling network is far from clear. In this study, we found that the inhibition of SFKs activity by dasatinib effectively reduced the tumor size and population of MDSCs in the HNSCC mouse model. Molecular analysis indicates that phosphorylation of LYN, rather than SRC, was inhibited by dasatinib treatment. Next, we analyzed LYN expression by immunostaining and found that it was overexpressed in the human HNSCC specimens. Moreover, LYN expression in stromal cells positively correlated with myeloid-derived suppressor cells (MDSCs) makers CD11b and CD33 in human HNSCC. The dual positive expression of LYN in epithelial and stromal cells (EPI+ SRT+ ) was associated with unfavorable overall survival of HNSCC patients. These findings indicate that SFKs may be a potential target for an effective immunotherapy of HNSCC by decreasing MDSCs and moreover, LYN will have an impact on such therapeutic strategy.

Expression of VISTA correlated with immunosuppression and synergized with CD8 to predict survival in human oral squamous cell carcinoma.

V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint regulatory molecule, suppresses T cell mediated immune responses. The aim of the present study was to profile the immunological expression, clinical significance and correlation of VISTA in human oral squamous cell carcinoma (OSCC). Human tissue microarrays, containing 165 primary OSCCs, 48 oral epithelial dysplasias and 43 normal oral mucosae, were applied to investigate the expression levels of VISTA, CD8, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death ligand 1 (PD-L1), PI3Kα p110, IL13Rα2, phospho-STAT3 at tyrosine 705 (p-STAT3) and myeloid-derived suppressor cell (MDSC) markers (CD11b and CD33) by immunohistochemistry and digital pathology analysis. The results demonstrated that the protein level of VISTA was significantly higher in human OSCC specimens, and that VISTA expression in primary OSCCs was correlated with lymph node status. VISTA expression did not serve as an independent predictor for poor prognosis, while patient subgroup with VISTA high and CD8 low expression (22/165) had significantly poorer overall survival compared with other subgroups based on the multivariate and Cox hazard analyses among the primary OSCC patients in the present cohort. Additionally, the expression of VISTA was significantly correlated with PD-L1, CTLA-4, IL13Rα2, PI3K, p-STAT3, CD11b and CD33 according to Pearson's correlation coefficient test. Taken together, the results indicated that the VISTA high and CD8 low group, as an immunosuppressive subgroup, might be associated with a poor prognosis in primary OSCC. These findings indicated that VISTA might be a potential immunotherapeutic target in OSCC treatment.

B7-H4 expression indicates poor prognosis of oral squamous cell carcinoma.

Checkpoint blockade therapy utilizing monoclonal antibodies to reactivate T cells and recover their antitumor activity makes an epoch in cancer immunotherapy. The role of B7-H4, a novel negative immune checkpoint, in oral squamous cell carcinoma (OSCC) has still not been elucidated. In this study, tissue samples from human OSCC, which contains 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa specimens, and Tgfbr1/Pten 2cKO mice OSCC model were stained with B7-H4 antibody to analyze the correlations between B7-H4 expression and clinicopathological characteristics. Kaplan-Meier analysis was used to compare the survival of patients with high B7-H4 expression and patients with low B7-H4 expression. We found B7-H4 is highly expressed in human OSCC tissue, and the B7-H4 expression level was associated with the clinicopathological parameters containing pathological grade and lymph node status. Moreover, we confirmed that B7-H4 was overexpressed in Tgfbr1/Pten 2cKO mice OSCC model. Our data also indicated that patients with high B7-H4 expression had poor overall survival compared with those with low B7-H4 expression. Furthermore, this study demonstrated that B7-H4 was positively associated with PD-L1, CD11b, CD33, PI3Kα p110, and p-S6 (S235/236). Taken together, these findings suggest B7-H4 is a potential target in the treatment of OSCC.

Exploring the effect of different tea varieties on the quality of Lu'an Guapian tea based on metabolomics and molecular sensory science.

Lu'an Guapian (LAGP) tea is one of the most famous teas in China. However, research on its suitable processing varieties is still lacking. This study analyzed the quality of LAGP tea made from three different tea varieties, namely, 'Anhui1' (AH1), 'Quntizhong' (QTZ), and 'Shuchazao' (SCZ), using molecular sensory science and metabolomics techniques. The results showed that AH1 had a strong floral aroma and the strongest umami flavor, while QTZ had a distinct roasted aroma and a mellow taste. SCZ had a cooked corn-like aroma and the highest bitterness and astringency owing to the high tea polyphenol contents and low free amino acid contents. The study also identified 12 key aroma-active compounds, with trans-beta-ionone and 2-ethyl-3,5-dimethyl-pyrazine contributing the most to floral and roasted aromas, respectively. The results of this study provide a theoretical and practical basis for selecting and breeding high-quality varieties of LAGP tea and stabilizing its quality.