The Presence of Small-Size Circulating Tumor Cells Predicts Worse Prognosis in Non-Small Cell Lung Cancer Patients.

CONTEXT.­: Most patients with non-small cell lung cancers (NSCLC) are diagnosed at advanced stages. The 5-year survival rate of patients with advanced lung cancer is less than 20%, which makes lung cancer the leading cause of cancer-related deaths worldwide. OBJECTIVE.­: To identify indicators that can predict the prognosis of lung cancer patients. DESIGN.­: To determine the correlation between circulating tumor cells (CTCs), circulating tumor-derived endothelial cells (CTECs), and their subtypes and the prognosis of patients with NSCLC, 80 patients with lung cancer were recruited and 48 patients who met the enrollment criteria were selected in this study. Peripheral blood was collected from the enrolled patients before any treatment and analyzed by the subtraction enrichment and immunostaining-fluorescence in situ hybridization technique to determine the correlation between CTCs and CTECs and lung cancer disease progression and to identify prognostic indicators. RESULTS.­: In all patients, the positive rate of CTCs was 100% and the positive rate of CTECs was 81.3%. The CTEC positivity rate was higher in late-stage patients than in early-stage patients (P = .03). Patients with advanced or lymph node metastases had a higher rate of small-size CTC positivity than those with early or no lymph node metastases. Large-size CTEC positivity was higher in patients with advanced NSCLC than in early-stage patients. Patients with ≥1 small-size CTC had shorter progression-free survival, and it was an independent prognostic factor. CONCLUSIONS.­: Small-size CTCs are a reliable prognostic indicator and a probable predictor of the severity of disease in NSCLC patients.

Consistency Analysis of Programmed Death Ligand 1 Expression in Non-Small Cell Lung Cancer Between Pleural Effusion and Matched Primary Lung Cancer Tissues by Immunohistochemical Double Staining.

In clinical practice, programmed death ligand 1 (PD-L1) detection is prone to nonspecific staining due to the complex cellular composition of pleural effusion smears. In this study, diaminobenzidine (DAB) and 3-amino-9-ethylcarbazole (AEC) immunohistochemistry double staining was performed to investigate PD-L1 expression in tumor cells from malignant pleural effusion (MPE). MPE was considered as a metastasis in non-small cell lung cancer patients; thus, the heterogeneity between metastatic and primary lung cancer was revealed as well. Ninety paired specimens of MPE cell blocks and matched primary lung cancer tissues from non-small cell lung cancer patients were subjected to PD-L1 and thyroid transcription factor-1(TTF-1)/p63 immunohistochemistry double staining. Two experienced pathologists independently evaluated PD-L1 expression using 3 cutoffs (1%, 10%, and 50%). PD-L1 expression in MPE was strongly correlated with that in matched primary lung cancer tissues (R = 0.813; P < .001). Using a 4-tier scale (cutoffs: 1%, 10%, and 50%), the concordance was 71.1% (Cohen's κ = .534). Using a 2-tier scale, the concordance was 75.6% (1%, Cohen's κ = 0.53), 78.9% (10%, Cohen's κ = 0.574), and 95.6% (50%, Cohen's κ = 0.754). The rates of PD-L1 positivity in MPE (56.7%) were higher than that in lung tissues (32.2%). All 27 discordant cases had higher scores in MPE. The double-staining method provided superior identification of PD-L1-positive tumor cells on a background with nonspecific staining. In conclusion, PD-L1 expression was moderately concordant between metastatic MPE cell blocks and matched primary lung carcinoma tissues, with variability related to tumor heterogeneity. MPE should be considered to detect PD-L1 when histological specimens are unattainable, especially when PD-L1 expression is >50%. PD-L1 positivity rates were higher in MPE. Double staining can improve PD-L1 detection by reducing false-negative/positive results.

The SOC1 gene plays an important role in regulating litchi flowering time.

Litchi (Litchi chinensis Sonn.) is a valuable subtropical fruit tree with high-quality fruit. However, its economic benefits and sustainable development are restrained by a number of challenges. One major challenge is the lack of extremely early and late maturing high-quality varieties due to limited availability of varieties suitable for commercial cultivation and outdated breeding methods, resulting in an imbalanced supply and low price of litchi. Flowering time is a crucial genetic factor influencing the maturation period of litchi. Our previous research has highlighted the pivotal role of the LcFT1 gene in regulating the flowering time of litchi and identified a gene associated with LcFT1 (named as LcSOC1) based on RNA-Seq and weight gene co-expression network (WGCNA) analysis. This study further investigated the function of LcSOC1. Subcellular localization analysis revealed that LcSOC1 is primarily localized in the nucleus, where it acts as a transcription factor. LcSOC1 overexpression in Nicotiana tabacum and Arabidopsis thaliana resulted in significant early flowering. Furthermore, LcSOC1 was found to be expressed in various tissues, with the highest expression in mature leaves. Analysis of spatial and temporal expression patterns of LcSOC1 in litchi varieties with different flowering time under low temperature treatment and across an annual cycle demonstrated that LcSOC1 is responsive to low temperature induction. Interestingly, early maturing varieties exhibited higher sensitivity to low temperature, with significantly premature induction of LcSOC1 expression relative to late maturing varieties. Activation of LcSOC1 triggered the transition of litchi into the flowering phase. These findings demonstrate that LcSOC1 plays a pivotal role in regulating the flowering process and determining the flowering time in litchi. Overall, this study provides theoretical guidance and important target genes for molecular breeding to regulate litchi production period.

Heterogeneity of Lipid Metabolism and its Clinical and Immune Correlation in Lung Adenocarcinoma.

INTRODUCTION: The role of lipid metabolism in lung adenocarcinoma (LUAD) is not completely researched. Lipid metabolism reprogramming is a characteristic of malignancies and contributes to carcinogenesis and progression. The transcriptome and scRNA- seq data and clinical information were downloaded from the public databases. METHODS: Lipid metabolism pathways were collected from the MSigDB database, and molecular subtypes were classified based on lipid metabolism features via consensus clustering. The bidirectional crosstalk between immune cells and malignant cells was analyzed. Differences in lipid metabolism at the single-cell level and their correlation with the tumor microenvironment (TME) were also studied. LUAD patients were classified into two subtypes, showing distinct mutation and lipid metabolism features based on lipid metabolism characteristics. Meanwhile, significant differences in the overall survival, clinical characteristics, and immune landscape were observed between the two subtypes. We also found that clust1 had higher oxidative stress status. There were 116 differentially expressed genes between the two subtypes, which were significantly associated with cell cycle progression. We identified 4001 immune cells, including 483 malignant cells and 3518 normal cells, and found active intercellular communication and significant differences in lipid metabolism characteristics between the malignant cells and normal cells. Furthermore, several lipid metabolism pathways were found to be associated with TME factors, including hypoxia and angiogenesis. RESULT: The current findings indicated that lipid metabolism was involved in the development and cellular heterogeneity of LUAD and revealed widespread reprogramming across multiple cellular elements in the TME of LUAD. CONCLUSION: This characterization improved the current understanding of tumor biology and enabled the identification of novel targets for immunotherapy.

MUC15 is an independent prognostic factor that promotes metastases of MYCN non-amplified neuroblastoma.

Background: Neuroblastoma (NB) is a cancer that arises from neural-crest-derived sympathoadrenal lineage. Less is known about the pathogenesis and molecular characteristics of MYCN non-amplified (MYCN-NA) NB. Methods: We constructed a signature model targeting mucin family according to RNA sequencing data from GSE49710 dataset, and validated the prognostic performance. We also analyzed the gene expression matrix using DESeq2 R packages to screen the most differential mucin in high-risk NB samples. We further assessed its prognostic value, particularly in MYCN-NA NB samples. Moreover, we performed functional experiments to evaluate the impact of MUC15 overexpression on the migration of MYCN-NA NB cell lines. Results: The 8-mucin signature model showed good prognostic performance in the GSE49710 dataset. Among the mucin genes, MUC15 was significantly upregulated in the high-risk NB cohort and was associated with poor prognosis, especially in MYCN-NA NB samples. Furthermore, MUC15 overexpression and exogenous MUC15 protein enhanced the migration of MYCN-NA NB cell lines. Mechanistically, MUC15 promoted the phosphorylation of focal adhesion kinase (FAK) by inhibiting the expression of MYCT1, a target of c-Myc. Conclusions: Our findings suggested a potential network in controlling NB cell metastasis. Targeting MUC15 in MYCN-NA NB patients could be a promising therapeutic strategy.

IMM47, a humanized monoclonal antibody that targets CD24, exhibits exceptional anti-tumor efficacy by blocking the CD24/Siglec-10 interaction and can be used as monotherapy or in combination with anti-PD1 antibodies for cancer immunotherapy.

This study evaluates the anti-tumor mechanism of IMM47, a humanized anti-CD24 mAb. Biolayer interferometry, ELISA and flow cytometry methods were used to measure the IMM47 binding, affinity, ADCC, ADCP, ADCT and CDC activities. In vivo therapeutical efficacy was measured in transplanted mouse models. IMM47 significantly binds granulocytes but not human erythrocytes and blocks CD24's ability to bind to Siglec-10. IMM47 has strong ADCC, ADCT and ADCP activity against REH cells. IMM47's in vivo pharmacodynamics showed that IMM47 has strong anti-tumor effects in human siglec-10 transgenic mouse models with a memory immune response. IMM47 also has powerful synergistic therapeutic efficacy when combined with Tislelizumab, Opdivo and Keytruda, by blocking CD24/Siglec-10 interaction through macrophage antigen presentation with strong ADCC, ADCP, ADCT and CDC activities and with a safe profile. IMM47 binding to CD24 is independent of N-glycosylation modification of the extracellular domain.

The novel high-affinity humanized antibody IMM40H targets CD70, eliminates tumors via Fc-mediated effector functions, and interrupts CD70/CD27 signaling.

Background: A significant level of CD70 can be detected in various types of tumor tissues and CD27 is expressed on Treg cells, but CD70 expression is low in normal tissues. The interaction between CD70 and CD27 can stimulate the proliferation and survival of cancer cells and increase the level of soluble CD27, which is associated with poor prognosis in patients with lymphoma and certain solid tumors. Thus, it is a promising therapeutic target for the treatment of many major CD70+ cancer indications, including CD70+ lymphoma, RCC, NSCLC, HNSCC and OC. Methods: IMM40H was obtained through hybridoma screening and antibody humanization techniques. IMM40H was evaluated for its binding, blocking, Fc-dependent effector functions and antitumor activity characteristics in various in vitro and in vivo systems. The safety and tolerability profile of IMM40H were evaluated through single and repeated administration in cynomolgus monkeys. Results: In vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively. IMM40H also exhibited potent Fc-dependent effector functions (ADCC/CDC/ADCP), and could make a strong immune attack on tumor cells and enhance therapeutic efficacy. Preclinical findings showed that IMM40H had potent antitumor activity in multiple myeloma U266B1 xenograft model, and could eradicate subcutaneously established tumors at a low dose of 0.3 mg/kg. IMM40H (0.3 mg/kg) showed therapeutic effects faster than cusatuzumab (1 mg/kg). A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt's lymphoma Raji and renal carcinoma cell A498 tumor models. In cynomolgus monkeys, the highest non-severely toxic dose (HNSTD) for repeat-dose toxicity was up to 30 mg/kg, while the maximum tolerated dose (MTD) for single-dose toxicity was up to 100 mg/kg, confirming that IMM40H had a good safety and tolerability profile. Conclusion: IMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling.

Sequential liquid-based cytology based on exfoliative cells of 18-gauge core needle groove to improve renal mass core needle biopsy yield: a real-world observational study.

Background: Renal mass biopsy (RMB) has regained clinical interest in recent years due to the pursuit of individualized and precision medicine. Renal mass core needle biopsy (RMCNB) for histopathology (HP), with or without liquid-based cytology (LBC), has been used increasingly in our hospital. This study investigated factors influencing the HP diagnostic yield of RMCNB, and compared the diagnostic rate between HP alone and HP plus LBC. Methods: In this retrospective cross-sectional study, a total of 134 patients who underwent ultrasound-guided percutaneous RMCNB in the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 and May 2022 were enrolled. All biopsies were performed using an 18-gauge core needle biopsy gun, and the sampling tissues and exfoliative cells of 18-gauge core needle groove were delivered for HP and LBC diagnosis, respectively. The patient demographics, clinical indications, tumor characteristics, number of biopsies, final pathological diagnosis, and follow-up data were reviewed. Univariate and multivariate logistic regression analyses were performed to evaluate the association between variables and HP diagnostic yield of RMCNB. The diagnostic rate between HP and HP plus LBC was compared using McNemar's test and agreement was evaluated using the Kappa score. Results: The most common indication of RMCNB was renal masses with a radiological diagnosis of locally advanced disease or distant metastasis (86.6%). The HP diagnostic yield was established in 88.1% (118/134) of cases, and the diagnostic rate of HP plus LBC was 94.0% (126/134). Logistic regression analyses revealed that non-enhanced area exceeding 50% [odds ratio (OR): 0.021, 95% confidence interval (CI): 0.003-0.134, P<0.001] and number of core biopsies (OR: 9.479, 95% CI: 1.528-58.794, P=0.016) were associated with the HP diagnostic yield of RMCNB. The diagnostic rate of HP plus LBC was significantly higher than that of HP alone (94.0% vs. 88.1%, P=0.008), and they showed substantial agreement (Kappa =0.638, P<0.001). Meanwhile, in the non-enhanced area ≥50% subgroup, the diagnostic rate between HP plus LBC and HP alone was significantly different (86.7% vs. 60%, P=0.008), and the agreement was fair (Kappa =0.375, P=0.009). Conclusions: RMCNB has a high diagnostic yield with a minimum of two high-quality core biopsies, LBC can improve the diagnostic yield of HP alone, especially in masses with large non-enhanced area.

Oat ß-D-glucan ameliorates type II diabetes through TLR4/PI3K/AKT mediated metabolic axis.

Diabetes is one of the major global public health problems. Our previous results found that oat ß-D-glucan exhibited ameliorative effects on diabetic mice, but the underlying mechanism is unclear. The present study indicates that oat ß-D-glucan increased glycogen content, decreased glycogen synthase (GS) phosphorylation and increased hepatic glycogen synthase kinase 3ß (GSK3ß) phosphorylation for glycogen synthesis via PI3K/AKT/GSK3-mediated GS activation. Moreover, oat ß-D-glucan inhibited gluconeogenesis through the PI3K/AKT/Foxo1-mediated phosphoenolpyruvate carboxykinase (PEPCK) decrease. In addition, oat ß-D-glucan enhanced glucose catabolism through elevated protein levels of COQ9, UQCRC2, COXIV and ATP5F complexes involved in oxidative phosphorylation, as well as that of TFAM, a key regulator of mitochondrial gene expression. Importantly, our results showed that oat ß-D-glucan maintained hepatic glucose balance via TLR4-mediated intracellular signal. After TLR4 blocking with anti-TLR4 antibody, oat ß-D-glucan had almost no effect on high glucose-induced HepG2 cells. These data revealed that oat ß-D-glucan maintains glucose balance by regulating the TLR4/PI3K/AKT signal pathway.

Screening of Endometrial Cancer Related to Lynch Syndrome in China by Suction Curettage-Based Cytology and Histology: A Retrospective Study.

Objective: To explore the feasibility of sampling Chinese patients by suction curettage for cytological and histological screening of endometrial cancer related to Lynch syndrome. Methods: This retrospective study enrolled patients who underwent endometrial biopsy at our hospital between May 2018 and January 2019. Endometrial sampling (cytological and micro-histological specimens) was conducted by suction curettage. The gold standard for diagnosis was traditional sharp dilation and curettage (D&C). The sensitivity, specificity, and diagnostic accuracy of cytology, micro-histology, and the combination of cytology and micro-histology were calculated. Additionally, receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficiency of three screening methods. Mismatch repair proteins were further detected using immunohistochemistry (IHC) in endometrial cancer. Results: This retrospective finally enrolled 100 patients, which satisfactory samples were obtained from 96 patients for liquid-based cytology and 93 patients for microtissue histology. The concordance rates with D&C, sensitivity, and specificity were 94.8%, 76.9%, and 97.5% for liquid-based cytology, 96.8%, 84.6%, and 98.8% for microtissue histology, and 99.0%, 92.3%, and 100.0% for liquid-based cytology and microtissue histology combined, respectively. The AUC of ROC curves in liquid-based cytology, microtissue histology, and the combined methods for diagnostic ability were 0.873, 0.917, and 0.962, respectively. Absence rates of MLHl, MSH2, MSH6, and PMS2 proteins were 15.3% (2/13), 0% (0/13), 7.7% (1/13), and 15.3% (2/13) in the 13 endometrial cancer samples. Conclusion: Liquid-based cytology and microtissue histology samples from suction curettage combined IHC are useful for endometrial cancer screening.

PTBP2-Mediated Alternative Splicing of IRF9 Controls Tumor-Associated Monocyte/Macrophage Chemotaxis and Repolarization in Neuroblastoma Progression.

The recurrence and metastasis of children with mediastinal neuroblastoma (NB) are also occurred after surgery, chemotherapy, or radiotherapy. Strategies targeting the tumor microenvironment have been reported to improve survival; however, thorough investigations of monocytes and tumor-associated macrophages (Mϕs) with specialized functions in NB are still lacking. Our data first demonstrated polypyrimidine tract binding protein 2 (PTBP2) as a possible identifier in patients with mediastinal NB screened by proteomic profiling and that PTBP2 predicted good outcomes. Functional studies revealed that PTBP2 in NB cells induced the chemotactic activity and repolarization of tumor-associated monocytes and Mϕs, which, in turn, inhibited NB growth and dissemination. Mechanistically, PTBP2 prevents interferon regulatory factor 9 alternative splicing and upregulates signal transducers and activators of transcription 1 to stimulate C-C motif chemokine ligand 5 (CCL5) and interferon-stimulated gene factor-dependent type I interferon secretion, to induce monocyte/Mϕs chemotaxis, and to sustain monocytes in a proinflammatory phenotype. Our study defined a critical event of PTBP2-induced monocytes/Mϕs in NB progression and revealed that RNA splicing occurred by PTBP2 benefits immune compartmentalization between NB cells and monocytes. This work revealed the pathological and biological role of PTBP2 in NB development and indicates that PTBP2-induced RNA splicing benefits immune compartmentalization and predicted a favorable prognosis in mediastinal NB.

The Pathogenesis of Diabetes.

Diabetes is the most common metabolic disorder, with an extremely serious effect on health systems worldwide. It has become a severe, chronic, non-communicable disease after cardio-cerebrovascular diseases. Currently, 90% of diabetic patients suffer from type 2 diabetes. Hyperglycemia is the main hallmark of diabetes. The function of pancreatic cells gradually declines before the onset of clinical hyperglycemia. Understanding the molecular processes involved in the development of diabetes can provide clinical care with much-needed updates. This review provides the current global state of diabetes, the mechanisms involved in glucose homeostasis and diabetic insulin resistance, and the long-chain non-coding RNA (lncRNA) associated with diabetes.

Immunocytochemical detection by a fully automated immunostainer for assisting subclassification of pulmonary tumors on ThinPrep slides in real-life clinical samples: A single-institution experience.

INTRODUCTION: This study aims to investigate the feasibility and reliability of ThinPrep slides in detecting the subclassification of lung cancer and develop a process for immunocytochemistry (ICC) with optimized staining steps of an automated immunostainer. METHODS: Cytomorphology and ancillary ICC by automated immunostainer on ThinPrep slides were performed to subclassify 271 cytology cases of pulmonary tumor, which were stained with 2 or more of the following antibodies: p40, p63, thyroid transcription factor-1 (TTF-1), Napsin A, synaptophysin (Syn), and CD56. RESULTS: The accuracy of cytological subtyping was improved from 67.2% to 92.7% (p < .0001) after ICC. The accuracy of cytomorphology combined with ICC results for lung squamous-cell carcinoma (LUSC), lung adenocarcinomas (LUAD), and small cell carcinoma (SCLC) was 89.5% (51 of 57), 97.8% (90 of 92), and 98.8% (85 of 86), respectively. The sensitivity and specificity of 6 antibodies were as follows: p63 (91.2%, 90.4%) and p40 (84.2%, 95.1%) for LUSC, TTF-1(95.6%, 64.6%) and Napsin A (89.7%, 96.7%) for LUAD and Syn (90.7%, 60.0%) and CD56 (97.7%, 50.0%) for SCLC, respectively. P40 expression on ThinPrep slides had the highest agreement (κ = 0.881) with immunohistochemistry (IHC) results, followed by p63 (κ = 0.873), Napsin A (κ = 0.795), TTF-1 (κ = 0.713), CD56 (κ = 0.576), and Syn (κ = 0.491). CONCLUSION: The result of ancillary ICC on ThinPrep slides by fully automated immunostainer was in good agreement with the gold standard in pulmonary tumors subtype and immunoreactivity, objectively achieving accurate subtyping in cytology.

Coprococcus eutactus, a Potent Probiotic, Alleviates Colitis via Acetate-Mediated IgA Response and Microbiota Restoration.

Inflammatory bowel disease (IBD) is a complex disease characterized by relapsing episodes of inflammation of the colonic mucosa. Research into IBD suggests that this disease condition is caused by alterations in resident mucosal bacterial populations. Our previous study showed that Coprococcus was significantly elevated during the improvement of IBD. Human metagenome database GMrepo also indicates Coprococcus, in particular, Coprococcus eutactus (C. eutactus), which was negatively associated with IBD. The current study implied the alleviated effects and mechanisms of C. eutactus on dextran sodium sulfate-induced experimental colitis mice. Gavage with C. eutactus-ameliorated acute colitis, as evidenced, relieved weight loss, decreased concentrations of proinflammatory cytokines TNF-α, IL-1ß, and IL-6, and increased anti-inflammatory factors, IL-4, IL-5, and IL-10. In addition, C. eutactus enhanced the maturation of goblet cells and the expressions of mucins and restored the expressions of tight junction proteins such as claudin-1, occludin, and ZO-1. As a short-chain fatty acid-producing bacterium, C. eutactus mainly generates acetic acid. Interestingly, not only high levels of secretory immunoglobulin A (SIgA) but also increased IgA-producing plasma cells were observed in colitis mice during the administration of C. eutactus. Importantly, our data demonstrated that colonic SIgA is specifically coated on pathogens of Enterobacteriaceae. Owing to the selective binding effect of SIgA on microorganisms, the microbial diversity in the intestinal lumen and mucosa of C. eutactus-treated colitis mice was significantly restored, and the microbiota structure was remodeled. These findings provide substantial insight that C. eutactus as a promising probiotic can ameliorate colitis. In conclusion, our findings may deliver a novel approach to the prevention and biotherapy of IBD.

Aptima HR-HPV Testing of Cytology Specimens Is an Effective Supplement for p16 Staining to Improve Diagnostic Accuracy for HPV-Related Oropharyngeal Squamous Cell Carcinoma.

INTRODUCTION: Regarding a small proportion of oropharyngeal squamous cell carcinoma (OPSCC) patients who tested p16-positive but human papillomavirus (HPV)-negative, we attempted to perform HPV testing to improve the accuracy of HPV detection in OPSCC patients. METHODS: We simultaneously performed Aptima HPV testing of cytological specimens and p16 immunohistochemistry (IHC) staining of histologic biopsies from the same cohort of patients with head and neck SCC (HNSCC). The cytological specimens included fine-needle aspiration specimens from patients with enlarged nodes and endoscopic brushing specimens from the primary lesions of patients without enlarged nodes. Cases with discordant results for p16 IHC staining and Aptima HPV testing were reexamined by a third method, RNAscope testing. RESULTS: Sixty patients with HNSCC (39 OPSCC and 21 non-OPSCC) were recruited for examination of HPV status. Among these patients, 28 were p16+/HPV+, 29 were p16-/HPV-, 2 were p16+/HPV-, and 1 was p16-/HPV+. The overall concordance rate between Aptima HPV testing and p16 IHC was 95.0%. Three cases with discordant results for these two methods were reexamined by RNAscope testing, and all were confirmed to be HPV negative. The prevalence of HPV in OPSCC and non-OPSCC patients was 61.5% (24/39) and 19.0% (4/21), respectively. The sensitivity and negative predictive values of Aptima HPV testing and p16 IHC were consistent at 100%, while the specificity and positive predictive values were 96.9% and 96.6% versus 93.8% and 93.3%, respectively. Additionally, 30 OPSCCs were simultaneously examined and diagnosed by both brush cytology and biopsy pathology; six of these SCCs were underdiagnosed by histopathology but accurately diagnosed by supplemental brush cytology. CONCLUSION: Aptima HPV testing of cytology specimens can be used as an adjuvant examination to identify false-positive OPSCC patients after p16 IHC of biopsies, while brush cytology may be a supplemental method for the histologic diagnosis of malignant oropharyngeal tumors.

Oat ß-glucan ameliorates diabetes in high fat diet and streptozotocin-induced mice by regulating metabolites.

Oats are widely distributed worldwide and oat ß-glucan has positive effects on human health. Particularly, oat ß-glucan is reported to be beneficial in the management of type 2 diabetes. The aim of the present study is to investigate the effects of oat ß-glucan and its possible underlying mechanisms on diabetes in type 2 diabetic mice that was induced by streptozotocin/high-fat diet (STZ/HFD). The data indicated that oat ß-glucan significantly reduced the fasting blood glucose, improved glucose tolerance, and insulin sensitivity. The results further showed that oat ß-glucan remarkably decreased the levels of total cholesterol (TCHO), total triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and free fatty acids. Moreover, oat ß-glucan remarkably increased the hepatic glycogen content, but largely decreased the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in STZ/HFD-induced diabetic mice. Histological analysis showed that oat ß-glucan alleviated visceral lesions. Finally, the metabolomic analysis indicated that the metabolic profile was remarkably changed after oat ß-glucan intervention in diabetic mice. There were 88 and 106 differential metabolites screened as biomarkers in negative ion mode (NEG) and positive ion mode (POS) after oat ß-glucan treatment, respectively. In addition, oat ß-glucan significantly affected the serum metabolites of amino acids, organic acids and bile acids. Collectively, the current study elucidates oat ß-glucan displays an effective nutritional intervention in diabetes.

Selective Photocatalytic Transformation of Lignin to Aromatic Chemicals by Crystalline Carbon Nitride in Water-Acetonitrile Solutions.

The photocatalytic conversion of lignin to aromatic compounds in aqueous solutions is a promising approach. We herein report a crystalline carbon nitride prepared by high-temperature thermal polymerization and alkali-metal molten salt treatment, which was then applied in the selective conversion of lignin to aromatic compounds. The results showed that the tri-s-tri-C3N4 presented a relatively high activity and selectivity for the conversion of lignin in aqueous solutions. In a 95% water-acetonitrile solution, it achieved a relatively high conversation rate of lignin, reaching 62.00%, and the selectivity of the C-C bond cleavage was high, at 86.8%. The characterization results obtained by TEM, UV-vis/DRS, PL, and transient photocurrent response showed that the ultra-high activity of tri-s-tri-C3N4 was mainly due to the improvements in crystallinity and light absorption. Mechanism studies showed that the dispersion of the catalyst and the combination of lignin and catalyst in aqueous solvents with different acetonitrile ratios were the main factors affecting lignin conversion. As the water content in the solutions increased, the primary active sites were converted from h+ to ·O2-. This study revealed the interactions between lignin, photocatalysts, and reaction solutions, providing a theoretical basis for the photocatalytic conversion of lignin in aqueous solutions.

SIRPα-Fc fusion protein IMM01 exhibits dual anti-tumor activities by targeting CD47/SIRPα signal pathway via blocking the "don't eat me" signal and activating the "eat me" signal.

A novel recombinant SIRPα-Fc fusion protein, IMM01, was constructed and produced using an in-house developed CHO-K1 cell expression system, and the anti-tumor mechanism of IMM01 targeting the CD47-SIRPα pathway was explored. The phagocytosis and in vitro anti-tumor activity of IMM01 were evaluated by antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) assays. In vivo mouse tumor model studies were used to explore therapeutic efficacy as well as the mechanism of action. An in vitro binding assay revealed that IMM01 has a strong binding affinity to CD47 with an EC50 of 0.4967 nM. IMM01 can induce strong ADCP and moderate ADCC, but not CDC. IMM01-induced strong phagocytosis against tumor cells was attributed to dual activities of blocking the "don't eat me" signal and activating the "eat me" signal, and IMM01 exhibits strong and robust in vivo anti-tumor activities either as monotherapy on hematological malignancies, or in combination therapy with PD-L1 monoclonal antibody (mAb), PD-1 mAb, and HER-2 mAb on solid tumors. Finally, IMM01 demonstrated a favorable safety profile with no human RBC binding activity or hemagglutination induction. IMM01 inhibits the growth of tumor cells by the following three possible mechanisms: (1) directly activating macrophages to phagocytize tumor cells; (2) activated macrophages degrade phagocytized tumor cells and present tumor antigens to T cells through MHC molecules to activate T cells; (3) activated macrophages can convert "cold tumors" into "hot tumors" and increase the infiltration of immune cells through chemotaxis by secreting some cytokines and chemokines.

The Mixture of Ferulic Acid and P-Coumaric Acid Suppresses Colorectal Cancer through lncRNA 495810/PKM2 Mediated Aerobic Glycolysis.

Polyphenol-rich foods are gaining popularity due to their potential beneficial effects in the prevention and treatment of cancer. Foxtail millet is one of the important functional foods, riches in a variety of biologically active substance. Our previous study showed that ferulic acid (FA) and p-coumaric acid (p-CA) are the main anticancer components of foxtail millet bran, and the two have a significant synergistic effect. In the present study, the clinical application potential of FA and p-CA (FA + p-CA) were evaluated in vivo and in vitro. The FA and p-CA target gene enrichment analysis discovered that FA + p-CA were associated with aerobic glycolysis. It was further shown that FA + p-CA remodel aerobic glycolysis by inhibiting the glycolysis-associated lncRNA 495810 and the glycolytic rate-limiting enzyme M2 type pyruvate kinase (PKM2). Moreover, PKM2 expression was positively correlated with lncRNA 495810. More interestingly, the exogenous expression of lncRNA 495810 eliminated the inhibitory effects of FA + p-CA on aerobic glycolysis. Collectively, FA + p-CA obstruct the aerobic glycolysis of colorectal cancer cells via the lncRNA 495810/PKM2 axis, which provides a nutrition intervention and treatment candidate for colorectal cancer.