Five new flavonoids and their pharmacological activities from Iris tenuifolia Pall.

Five new components including two new isoflavones, 5, 7, 2', 3'-tetrahydroxy-6-methoxyisoflavone (1), 5, 7, 2', 3'-tetrahydroxy-8-methoxyisoflavone (2), one flavonol 3, 5, 3', 4'-tetrahydroxy-7, 2'-dimethoxyflavonol (3), one flavanone (2S)-5, 7, 3'-trihydroxy-2'-methoxyflavanone (4), and one flavanonol (2R, 3R)-3, 5, 3', 4'-tetrahydroxy-7, 2'-dimethoxyflavanonol (5), along with nine known flavonoids (6-14) were isolated from under ground parts of Iris tenuifolia Pall. Their structures were elucidated by NMR and HRESIMS data and by comparison of CD spectra with compounds having similar structure. The separated compounds were evaluated for in vitro antioxidant activities by DPPH and ABTS. The α-glucosidase inhibitory activity of the compounds were evaluated with the pNPG method, the results indicated flavonoids were potential inhibitors of α-glucosidase. Moreover, in vitro anti-oxidative assay using flow cytometry indicated that compounds 1-5 showed strong oxidation resistance ability on C8D1A cells without affecting the cell viability.

Robust and accurate measurement of optical freeform surfaces with wavefront deformation correction.

The non-null test to detect the modulated wavefront is a widely used method in optical freeform surface measurement. In this study, the wavefront deformation in the non-null test of an optical freeform surface measurement was corrected based on the wavefront propagation model to improve measurement accuracy. A freeform surface wavefront correction (FSWC) measurement system was established to validate the proposed method. Simulation and experimental studies indicated that the proposed method can reduce the influence of freeform surface wavefront deformation in space propagation. Moreover, the freeform surface form accuracy measured by FSWC can reach a root-mean-squared value of 10 nm.

Measuring corner cube reflectors through ray tracing of a reflected wavefront.

The corner cube plays a key role in many advanced optical systems as the critical retrieval component, while the errors such as dihedral deviation will lead to unacceptable results. We present a method to obtain the right-angle plane deviation of the corner cube only by measuring and calculating the normal incident reflection wavefront. The calculation process is an iterative method of ray tracing based on the corner cube reflection process. The three-dimensional shape of the right-angle plane of the corner cube can be obtained accurately by this method. The proposed method is easy to implement and reliable, and it avoids the complicated operation of the traditional measurement method, which can also be applied to the measurement of the errors in the assembly and adjustment process where corner cube reflectors are used.

Subtyping of head and neck squamous cell cancers based on immune signatures.

Although head and neck squamous cell cancer (HNSCC) is one of the cancer types in which immune checkpoint inhibitors (ICIs) has achieved a certain success, only a subset of HNSCC patients respond to ICIs. Thus, identification of HNSCC subtypes responsive to ICIs is crucial. Using hierarchical clustering, we identified three subtypes of HNSCC, termed Immunity-H, Immunity-M, and Immunity-L, based on the enrichment scores of 28 immune cells generated by the single-sample gene-set enrichment analysis of transcriptome data. We demonstrated that this subtyping method was stable and producible in four different HNSCC cohorts. Immunity-H had the highest levels of immune infiltrates and PD-L1 expression, lowest levels of stemness, intratumor heterogeneity and genomic instability, and favorable prognosis. In contrast, Immunity-L had the lowest levels of immune infiltrates and PD-L1 expression, highest levels of stemness, intratumor heterogeneity and genomic instability, and unfavorable prognosis. We found that somatic copy number alteration had a significant negative association with anti-tumor immunity in HNSCC, while tumor mutation burden showed no significant association. TP53, COL11A1, NSD1, and PKHD1L1 were more frequently mutated in Immunity-H versus Immunity-L, and their mutations were associated with increased immune signatures in HNSCC. Besides immune-related pathways, many stromal and oncogenic pathways were highly enriched in Immunity-H, including cell adhesion molecules, focal adhesion, ECM-receptor interaction, calcium signaling, MAPK signaling, apoptosis, VEGF signaling, and PPAR signaling. The high levels of PD-L1 expression and immune infiltration in Immunity-H indicate that this subtype responds best to ICIs. Our study recaptures the immunological heterogeneity in HNSCC and provide clinical implications for the immunotherapy of HNSCC.

Comparisons of the immunological landscape between COVID-19, influenza, and respiratory syncytial virus patients by clustering analysis.

BACKGROUND: COVID-19 has stronger infectivity and a higher risk for severity than most other contagious respiratory illnesses. The mechanisms underlying this difference remain unclear. METHODS: We compared the immunological landscape between COVID-19 and two other contagious respiratory illnesses (influenza and respiratory syncytial virus (RSV)) by clustering analysis of the three diseases based on 27 immune signatures' scores. RESULTS: We identified three immune subtypes: Immunity-H, Immunity-M, and Immunity-L, which displayed high, medium, and low immune signatures, respectively. We found 20%, 35.5%, and 44.5% of COVID-19 cases included in Immunity-H, Immunity-M, and Immunity-L, respectively; all influenza cases were included in Immunity-H; 66.7% and 33.3% of RSV cases belonged to Immunity-H and Immunity-L, respectively. These data indicate that most COVID-19 patients have weaker immune signatures than influenza and RSV patients, as evidenced by 22 of the 27 immune signatures having lower enrichment scores in COVID-19 than in influenza and/or RSV. The Immunity-M COVID-19 patients had the highest expression levels of ACE2 and IL-6 and lowest viral loads and were the youngest. In contrast, the Immunity-H COVID-19 patients had the lowest expression levels of ACE2 and IL-6 and highest viral loads and were the oldest. Most immune signatures had lower enrichment levels in the intensive care unit (ICU) than in non-ICU patients. Gene ontology analysis showed that the innate and adaptive immune responses were significantly downregulated in COVID-19 versus healthy individuals. CONCLUSIONS: Compared to influenza and RSV, COVID-19 displayed significantly different immunological profiles. Elevated immune signatures are associated with better prognosis in COVID-19 patients.

Correlate the TP53 Mutation and the HRAS Mutation with Immune Signatures in Head and Neck Squamous Cell Cancer.

Although immunotherapy has emerged as an effective therapeutic strategy for various cancers including head and neck squamous cell carcinomas (HNSCCs), only a subset of patients can benefit from such therapy. Hence, it is pressing to discover predictive biomarkers for cancer immunotherapy response. TP53 and HRAS mutations frequently occur in HNSCC and correlate with a worse prognosis in HNSCC. We extensively characterized the associations of TP53 mutations and HRAS mutations with HNSCC immunity based on multiple cancer genomics datasets. We compared the enrichment levels of 20 immune signatures between TP53-mutated and TP53-wildtype HNSCCs, and between HRAS-mutated and HRAS-wildtype HNSCCs, and found that TP53 mutations were associated with depressed immune signatures while HRAS mutations were associated with enhanced immune signatures in HNSCC. Moreover, we found multiple p53- and RAS-mediated pathways showing significant correlations with HNSCC immunity. Furthermore, we demonstrated that the association between TP53 mutation and tumor immunity was independent of the human papillomavirus (HPV) infection and smoking status in HNSCC. These data suggest that p53 and RAS may play important roles in regulating HNSCC immunity and that the TP53 and HRAS mutation status could be useful biomarkers for stratifying HNSCC patients responsive to immunotherapy.