Multi-omics analysis of immune-related microbiome and prognostic model in head and neck squamous cell carcinoma.

OBJECTIVES: The aim of our study is to explore the transcriptional and microbial characteristics of head and neck cancer's immune phenotypes using a multi-omics approach. MATERIALS AND METHODS: Employing TCGA data, we analyzed head and neck squamous cell carcinoma (HNSCC) immune cells with CIBERSORT and identified differentially expressed genes using DESeq2. Microbial profiles, obtained from the TCMA database, were analyzed using LEfSe algorithm to identify differential microbes in immune cell infiltration (ICI) subgroups. Random Forest algorithm and deep neural network (DNN) were employed to select microbial features and developed a prognosis model. RESULTS: We categorized HNSCC into three immune subtypes, finding ICI-2 with the worst prognosis and distinct microbial diversity. Our immune-related microbiome (IRM) model outperformed the TNM staging model in predicting survival, linking higher IRM model scores with poorer prognosis, and demonstrating clinical utility over TNM staging. Patients categorized as low-risk by the IRM model showed higher sensitivity to cisplatin and sorafenib treatments. CONCLUSIONS: This study offers a comprehensive exploration of the ICI landscape in HNSCC. We provide a detailed scenario of immune regulation in HNSCC and report a correlation between differing ICI patterns, intratumor microbiome, and prognosis. This research aids in identifying prime candidates for optimizing treatment strategies in HNSCC. CLINICAL RELEVANCE: This study revealed the microbial signatures associated with immunophenotyping of HNSCC and further found the microbial signatures associated with prognosis. The prognostic model based on IRM microbes is helpful for early prediction of patient prognosis and assisting clinical decision-making.

LncRNA AATBC indicates development and facilitates cell growth and metastasis of cervical cancer as a sponge of miR-1245b-5p.

With the increasing incidence and mortality rate, cervical cancer has been considered one of the most frequent malignant tumors in females. Exploration of tumor progression-related biomarkers could facilitate the identification of novel and targeted therapy strategies. To assess the significance of lncRNA AATBC (AATBC) and its potential regulatory mechanism in cervical cancer, and to identify a potential biomarker, this study enrolled 123 patients with cervical cancer. Paired tissue samples were collected. The expression levels of AATBC and miR-1245b-5p were analyzed by RT-qPCR and their significance in the development and prognosis of cervical cancer was evaluated using chi-square and Cox analyses. In vitro, the regulatory effect of AATBC on the cellular processes of cervical cancer was estimated by CCK8 and Transwell assay. The interaction between ATTBC and miR-1245b-5p was assessed by luciferase reporter assay. Significant upregulation of AATBC and reduced miR-1245b-5p level in cervical cancer were observed, which showed a negative correlation between their expression levels. Close relationships of AATBC and miR-1245b-5p with the FIGO stage and lymph node metastasis were revealed. AATBC showed a significant prognostic value and miR-1245b-5p was found to mediate the tumor inhibitory effect of AATBC knockdown, which is speculated to be the underlying molecular mechanism of AATBC in cervical cancer development. Upregulation of AATBC indicted the malignant development and adverse prognosis of cervical cancer. AATBC served as a tumor promoter of cervical cancer by modulating miR-1245b-5p.

Contrast-Enhanced Computed Tomography-Based Radiogenomics Analysis for Predicting Prognosis in Gastric Cancer.

Objective: The aim of this study is to identify prognostic imaging biomarkers and create a radiogenomics nomogram to predict overall survival (OS) in gastric cancer (GC). Material: RNA sequencing data from 407 patients with GC and contrast-enhanced computed tomography (CECT) imaging data from 46 patients obtained from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA) were utilized to identify radiogenomics biomarkers. A total of 392 patients with CECT images from the Nanfang Hospital database were obtained to create and validate a radiogenomics nomogram based on the biomarkers. Methods: The prognostic imaging features that correlated with the prognostic gene modules (selected by weighted gene coexpression network analysis) were identified as imaging biomarkers. A nomogram that integrated the radiomics score and clinicopathological factors was created and validated in the Nanfang Hospital database. Nomogram discrimination, calibration, and clinical usefulness were evaluated. Results: Three prognostic imaging biomarkers were identified and had a strong correlation with four prognostic gene modules (P < 0.05, FDR < 0.05). The radiogenomics nomogram (AUC = 0.838) resulted in better performance of the survival prediction than that of the TNM staging system (AUC = 0.765, P = 0.011; Delong et al.). In addition, the radiogenomics nomogram exhibited good discrimination, calibration, and clinical usefulness in both the training and validation cohorts. Conclusions: The novel prognostic radiogenomics nomogram that was constructed achieved excellent correlation with prognosis in both the training and validation cohort of Nanfang Hospital patients with GC. It is anticipated that this work may assist in clinical preferential treatment decisions and promote the process of precision theranostics in the future.

Circular RNA hsa_circ_0004543 Aggravates Cervical Cancer Development by Sponging MicroRNA hsa-miR-217 to Upregulate Hypoxia-Inducible Factor.

Cervical cancer (CC) is the 4th principal source of cancer death in females with 604,000 new patients and 342,000 deaths in 2020 worldwide. It has been extensively shown that circRNAs are involved in regulating CC development. Nevertheless, the function and mechanisms of hsa_circ_0004543 in regulating CC need to be clearly elucidated. Herein, hsa_circ_0004543 expressions were compared between 40 paired paracancerous and cancerous specimens from CC patients and between 6 CC cell lines and a normal human cervical epithelial cell line based on qRT-PCR. Potential complementary binding sites between hsa-miR-217 and hsa_circ_0004543 were predicted using the interactome, while binding sites for the hypoxia-inducible factor-1a (HIF-1a) were predicted by TargetScan. The function and mechanism of hsa_circ_0004543 in the development of CC were estimated by silencing hsa_circ_0004543 with/without hsa-miR-217 or HIF-1a overexpression. The association between gene expressions was evaluated with Pearson's correlation analysis. Molecular mechanisms were explored by ribonucleic acid (RNA) pulldown, dual-luciferase activity, and rescue experimental assays. Our results revealed that the hsa_circ_0004543 expression was considerably increased in CC tissues and cells. Its silencing repressed proliferation and metastasis, while it increased apoptosis of CC cells. The investigation of the mechanism showed that hsa-miR-217 silencing or HIF-1a overexpression rescued hsa_circ_0004543, and silencing inhibited malignant phenotypes of CC cells. hsa_circ_0004543 upregulated the HIF-1α expression by sponging hsa-miR-217 in CC development. Therefore, the hsa_circ_0004543 functioned as a competing endogenous RNA (ceRNA) of hsa-miR-217 to increase CC oncogenesis and metastasis by the upregulation of the HIF-1α expression. Consequently, targeting the hsa_circ_0004543/hsa-miR-217/HIF-1α axis might be a potential treatment approach for CC.

Discovery of 1,3,4-oxadiazole derivatives as potential antitumor agents inhibiting the programmed cell death-1/programmed cell death-ligand 1 interaction.

Inhibition of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction by small-molecule inhibitors is emerging cancer immunotherapy. A series of novel 1,3,4-oxadiazole derivatives were designed, synthesized, and evaluated for their activities in vitro and vivo to find potent inhibitors of the PD-1/PD-L1 interaction. Among them, compoundⅡ-14exhibited outstanding biochemical activity, with an IC50of 0.0380 µM. Importantly, compound II-14, with a TGI value of 35.74 %, had more potent efficacy in a mouse tumor model compared to that in the control group. Surprisingly, when compound II-14 combined with 5-FU in a mouse tumor model having a TGI value of 64.59 %, which showed potential anti-tumor synergistic effects. Furthermore, immunohistochemistry analysis demonstrated thatcompound II-14 activated the immune microenvironment by promoting the infiltration of CD4+ T cells into tumor tissues. These results indicate that compound II-14 is a promising lead compound for further development of small-molecule PD-1/PD-L1 inhibitors for cancer therapy.

A gastric cancer LncRNAs model for MSI and survival prediction based on support vector machine.

BACKGROUND: Recent studies have shown that long non-coding RNAs (lncRNAs) play a crucial role in the induction of cancer through epigenetic regulation, transcriptional regulation, post-transcriptional regulation and other aspects, thus participating in various biological processes such as cell proliferation, differentiation and apoptosis. As a new nova of anti-tumor therapy, immunotherapy has been shown to be effective in many tumors of which PD-1/PD-L1 monoclonal antibodies has been proofed to increase overall survival rate in advanced gastric cancer (GC). Microsatellite instability (MSI) was known as a biomarker of response to PD-1/PD-L1 monoclonal antibodies therapy. The aim of this study was to identify lncRNAs signatures able to classify MSI status and create a predictive model associated with MSI for GC patients. METHODS: Using the data of Stomach adenocarcinoma from The Cancer Genome Atlas (TCGA), we developed and validated a lncRNAs model for automatic MSI classification using a machine learning technology - support vector machine (SVM). The C-index was adopted to evaluate its accuracy. The prognostic values of overall survival (OS) and disease-free survival (DFS) were also assessed in this model. RESULTS: Using the SVM, a lncRNAs model was established consisting of 16 lncRNA features. In the training cohort with 94 GC patients, accuracy was confirmed with AUC 0.976 (95% CI, 0.952 to 0.999). Veracity was also confirmed in the validation cohort (40 GC patients) with AUC 0.950 (0.889 to 0.999). High predicted score was correlated with better DFS in the patients with stage I-III and lower OS with stage I-IV. CONCLUSION: This study identify 16 LncRNAs signatures able to classify MSI status. The correlation between lncRNAs and MSI status indicates the potential roles of lncRNAs interacting in immunotherapy for GC patients. The pathway of these lncRNAs which might be a target in PD-1/PD-L1 immunotherapy are needed to be further study.

All-Silicon Topological Semimetals with Closed Nodal Line.

Because of the natural compatibility with current semiconductor industry, silicon allotropes with diverse structural and electronic properties provide promising platforms for next-generation Si-based devices. After screening 230 all-silicon crystals in the zeolite frameworks by first-principles calculations, we disclose two structurally stable Si allotropes (AHT-Si24 and VFI-Si36) containing open channels as topological node-line semimetals with Dirac nodal points forming a nodal loop in the k z = 0 plane of the Brillouin zone. Interestingly, their nodal loops protected by inversion and time-reversal symmetries are robust against SU(2) symmetry breaking because of the very weak spin-orbit coupling of Si. When the nodal lines are projected onto the (001) surface, flat surface bands can be observed because of the nontrivial topology of the bulk band structures. Our discoveries extend the topological physics to the three-dimensional Si materials, highlighting the possibility of realizing low-cost, nontoxic, and semiconductor-compatible Si-based electronics with topological quantum states.

Characterization of Potent Aroma Compounds in Preserved Egg Yolk by Gas Chromatography-Olfactometry, Quantitative Measurements, and Odor Activity Value.

To characterize potent odor-active compounds in preserved egg yolk (PEY), volatile compounds were isolated by headspace solid-phase microextraction and solvent-assisted flavor evaporation. Gas chromatography-olfactometry (GC-O) and gas chromatography-mass spectrometry (GC-MS) analyses identified a total of 53 odor-active compounds by comparing the odor characteristics, MS data, and retention indices with those of reference compounds. Twenty-seven odorants were detected in at least five isolates that were extracted and analyzed by the same method, and their flavor dilution (FD) factors, ranging from 1 to 2048, were measured by aroma extract dilution analysis (AEDA). To further determine their contribution to the overall aroma profile of PEY, 22 odorants with FD factors ≥16 and GC-MS responses were quantitated, and their odor activity values (OAVs) were calculated. According to the OAV results, 19 odorants with OAVs ≥ 1 are the potent odorants that greatly contribute to the characteristic aroma of PEY. Nine compounds were identified for the first time: (E,Z)-2,6-nonadienal, (E)-2-nonenal, 2-methylbutanal, dimethyl disulfide, trimethylamine, methional, dimethyl trisulfide, diisopropyl disulfide, and diethyl disulfide.

Characterization of the Potent Odorants Contributing to the Characteristic Aroma of Beijing Douzhi by Gas Chromatography-Olfactometry, Quantitative Analysis, and Odor Activity Value.

Beijing douzhi (BD) is a traditional snack in Beijing, China, and it has been listed as a part of Beijing's intangible cultural heritage. The potent odorants that contribute to the characteristic aroma of BD were investigated by analyzing the isolates from solvent-assisted flavor evaporation (SAFE) and simultaneous distillation-extraction. Using aroma extract dilution analysis based on gas chromatography-mass spectrometry and gas chromatography-olfactometry, 31 aroma-active compounds with flavor dilution (FD) factors ranging from 1 to 2187 were identified by comparison of their odor characteristics, MS data, and retention indices with those of reference compounds. To further determine their contribution to the aroma of BD, the odorants isolated using SAFE with FD factors ≥9 were quantified, and their odor activity values (OAVs; ratio of concentration to the respective odor threshold in water) were calculated. Eleven compounds were found to have OAVs ≥ 1, which indicated they were the potent odorants that contributed substantially to the characteristic aroma of BD. Among the 11 odorants, (E,Z)-2,6-nonadienal, eugenol, methional, p-cresol, 1-octen-3-one, and 3-methylbutanoic acid were not previously identified in BD.

Epidemiology and genotype distribution of high risk human papillomavirus in population of hospital opportunistic screening.

This study aimed to determine the prevalence of high-risk human papillomavirus (HR-HPV) in population of hospital opportunistic screening and to identify the correlation of prevalent genotypes and cervical cytological abnormalities. A cross-sectional study was employed between July 2013 and July 2014 in the Chaoyang hospital, in Beijing. Cervical samples were collected for the Type-specific HPV and the cervical cytological analyses in the population of hospital opportunistic screening. Total of 8975 samples from female patients aged 17-86 years were tested. Of these, 10.4% were infected by HR-HPV, the highest prevalence of HR-HPV in the youngest group and decreasing with aging (X(2)=19.68, P=0.02). Of these, 78.73% were single infections and 21.27% were multiple infections. Age-specific prevalence of multiple HPV exhibited a "U" shaped curve (X(2)=19.98, P=0.018). The most prevalent genotype is HPV 52, then descending order of frequency were HPV-58, 16, 39, 51, 56, 59, 18, 31, 33, 35, 68 and 45. 15.9% had an abnormal cytology in HR-HPV positive women, vs 4.13% in HR-HPV negative women. The prevalence of HR-HPV were 9.2%, 26.8%, 32%, 35.3% and 36.4% in normal cell, ASCUS, LSIL, ASC-H and HSIL, respectively (X(2)=234.67, P=0.000). Women with HPV 52, 16, 18, 58, 39, 51, 59, 56, 33, 31 infections related to the abnormal cytology, while the HPV68, 45, 35 didn't. The prevalent characteristic in population of the hospital opportunistic screening is similar to the population of cervical screen, But the most five prevalent genotype in rank are different .Women with HR-HPV infections were more likely to have the cervical abnormal cytology.