Polymethoxylated flavonoids in citrus fruits: absorption, metabolism, and anticancer mechanisms against breast cancer.

Polymethoxylated flavonoids (PMFs) are a subclass of flavonoids found in citrus fruits that have shown multifunctional biological activities and potential anticancer effects against breast cancer. We studied the absorption, metabolism, species source, toxicity, anti-cancer mechanisms, and molecular targets of PMFs to better utilize their anticancer activity against breast cancer. We discuss the absorption and metabolism of PMFs in the body, including the methylation, demethylation, and hydroxylation processes. The anticancer mechanisms of PMFs against breast cancer were also reviewed, including the estrogen activity, cytochrome P-450 enzyme system, and arylhydrocarbon receptor (AhR) inhibition, along with various molecular targets and potential anticancer effects. Although PMFs may be advantageous in the prevention and treatment for breast cancer, there is a lack of clinical evidence and data to support their efficacy. Despite their promise, there is still a long way to go before PMFs can be applied clinically.

Targeting LSD1 in tumor immunotherapy: rationale, challenges and potential.

Lysine-specific demethylase 1 (LSD1) is an enzyme that removes lysine methylation marks from nucleosome histone tails and plays an important role in cancer initiation, progression, metastasis, and recurrence. Recent research shows that LSD1 regulates tumor cells and immune cells through multiple upstream and downstream pathways, enabling tumor cells to adapt to the tumor microenvironment (TME). As a potential anti-tumor treatment strategy, immunotherapy has developed rapidly in the past few years. However, most patients have a low response rate to available immune checkpoint inhibitors (ICIs), including anti-PD-(L)1 therapy and CAR-T cell therapy, due to a broad array of immunosuppressive mechanisms. Notably, inhibition of LSD1 turns "cold tumors" into "hot tumors" and subsequently enhances tumor cell sensitivity to ICIs. This review focuses on recent advances in LSD1 and tumor immunity and discusses a potential therapeutic strategy for combining LSD1 inhibition with immunotherapy.

Using the Baidu index to understand Chinese interest in thyroid related diseases.

Common thyroid diseases are hyperthyroidism, hypothyroidism, thyroiditis, thyroid tumor and so on. Baidu is currently the most widely used online search tool in China, has developed an internet search trends collection and analysis tool called the Baidu Index. The aim of the present study was to understand the trend and characteristics of public's online attention to thyroid diseases, and to explore the value of Baidu Index in monitoring online retrieval behavior of thyroid-related information. Taking the period from January 1, 2011 to December 31, 2019 as the time range into consideration, we used the big data analysis tool of Baidu Index and took "thyroid nodules", "thyroid cancer", "thyroiditis" "hyperthyroidism" and "hypothyroidism" as the keywords, the data of "search index" and "media index" were recorded on a weekly basis, and all information were aggregated into quarterly and annual to generate the final data which was carried out for secondary analysis. Pearson correlation analysis was used to analyze the correlation between the search index of keywords and the year. One-way Analysis of Variance was used to analyze the differences between search index and media index. Among the five keywords, thyroid nodule search index had the highest growth rate (640%), followed by thyroid cancer (298%). The media's attention to thyroid diseases had been declining year by year. Unlike the public's attention, the media index of hyperthyroidism was significantly higher than other keywords. Over the past nine years, the public's attention to thyroid-related diseases has been increasing gradually. Baidu Index is an effective tool to track the health information query behavior of Chinese internet users, which can provide a cost-effective supplement to traditional monitoring system.

Molecular Characteristics of T Cell-Mediated Tumor Killing in Hepatocellular Carcinoma.

Background: Although checkpoint blockade is a promising approach for the treatment of hepatocellular carcinoma (HCC), subsets of patients expected to show a response have not been established. As T cell-mediated tumor killing (TTK) is the fundamental principle of immune checkpoint inhibitor therapy, we established subtypes based on genes related to the sensitivity to TKK and evaluated their prognostic value for HCC immunotherapies. Methods: Genes regulating the sensitivity of tumor cells to T cell-mediated killing (referred to as GSTTKs) showing differential expression in HCC and correlations with prognosis were identified by high-throughput screening assays. Unsupervised clustering was applied to classify patients with HCC into subtypes based on the GSTTKs. The tumor microenvironment, metabolic properties, and genetic variation were compared among the subgroups. A scoring algorithm based on the prognostic GSTTKs, referred to as the TCscore, was developed, and its clinical and predictive value for the response to immunotherapy were evaluated. Results: In total, 18 out of 641 GSTTKs simultaneously showed differential expression in HCC and were correlated with prognosis. Based on the 18 GSTTKs, patients were clustered into two subgroups, which reflected distinct TTK patterns in HCC. Tumor-infiltrating immune cells, immune-related gene expression, glycolipid metabolism, somatic mutations, and signaling pathways differed between the two subgroups. The TCscore effectively distinguished between populations with different responses to chemotherapeutics or immunotherapy and overall survival. Conclusions: TTK patterns played a nonnegligible role in formation of TME diversity and metabolic complexity. Evaluating the TTK patterns of individual tumor will contribute to enhancing our cognition of TME characterization, reflects differences in the functionality of T cells in HCC and guiding more effective therapy strategies.

KDM1A Identified as a Potential Oncogenic Driver and Prognostic Biomarker via Multi-Omics Analysis.

BACKGROUND: Lysine-specific demethylase 1A (KDM1A) is a histone demethylation enzyme and a crucial epigenetic factor for multiple pathological pathways that mediate carcinogenesis and immunogenicity. Although increasing evidence supposes the association between KDM1A and cancers, no systematic multi-omics analysis of KDM1A is available. METHODS: We systematically evaluated the KDM1A expression of various cancer and normal tissues and the unique relationship between KDM1A expression and prognosis of cancer cases based on The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The genetic variations, phosphorylation, and DNA methylation of KDM1A were analyzed via various tools. We further analyzed the correlation of KDM1A expression and fibroblasts and immune cell infiltration score of TCGA samples via TIMER2.0. RESULTS: KDM1A was highly expressed in 17 types of total 33 cancers, while it expressed low levels in only 4 cancers. High KDM1A expression was associated with worse survival status in various cancers. KDM1A expression was positively correlated with the cancer-associated fibroblasts and myeloid-derived suppressor cells infiltration levels in most cancer types. Additionally, KDM1A in most cancer types was negatively correlated with Th1 cell infiltration and positively correlated with Th2 cells. Moreover, spliceosome, cell cycle, and RNA transport pathways were involved in the functional mechanisms of KDM1A via enrichment analysis. CONCLUSIONS: Our study describes the epigenetic factor KDM1A as an oncogene and prognostic biomarker. Our findings provide valuable guidance for further analysis of KDM1A function in pathogenesis and potential clinical treatment.

The acaricidal activity and mechanism of eugenol on Psoroptes cuniculi.

In this study, the acaricidal effect of eugenol was measured and its mechanism of action investigated. The results showed that eugenol possessed the effect of killing Psoroptes cuniculi, and could regulate the mRNA expression of glutathione S-transferase (GST), catechinic acid (Ca) and thioredoxin (Trx). PPAR, NF-kappa B, TNF, Rap 1 and Ras signaling pathways might be the main pathways that involved into the process of killing mites. These findings suggested that eugenol could be developed into a new kind of acaricide, and further expand current knowledge on the mechanisms of eugenol for killing Psoroptes cuniculi of eugenol.

Geometric detection based on one-dimensional laser range profiles of dynamic conical target.

One-dimensional laser range profiles (LRPs) contain abundant information regarding the shape, size, and attitude of detected objects. For a dynamic conical target, the variation of its size and attitude could have a significant effect on the projections of LRP peaks. Ground coordinates, target coordinates, and incident field coordinates are established to compute the LRP of dynamic cones. In order to inverse the size, a genetic algorithm is adopted. The cone heights and half-cone angles of three different cones are inversed. Moreover, the results are used to inverse the attitude angles at any sampling time in order to verify accuracy of the theory. The inversion mentioned in this paper can be applied in any targets of arbitrary material, shape, and attitude with great efficiency.

Experimental study on viscoelasticity of lumbar yellow ligament in young and old people / 医用生物力学

Objective To compare the stress relaxation and mechanical properties of creep viscoelasticity in the young and old’s spine and to provide the reference for the mechanical mechanism of viscoelasticity of yellow ligament degeneration. Method Twenty specimens of elderly patients with degenerative lumbar yellow ligament degeneration as the older group, and twenty specimens of young patients with lumbar yellow ligament injuries as the youth group were used respectively. All the yellow ligament specimens were from the yellow ligament between the fourth and fifth of lumbar vertebra (L4~L5). Stress relaxation experiment and creep experiment were conducted on the specimens by the strain increasing speed as 1%/s and the stress increasing speed as 0.5 MPa/s respectively. The experimental temperature was (36.5±0.5) ℃ and the experimental time was 7 200 s. Ninety stress relaxation and creep data were collected, and the data were dealt with the statistical analysis and normalization methods. Results The 7 200 s stress of yellow ligament in the youth group decreased by 1.42 MPa, while the 7 200 s stress of yellow ligament in the older group decreased by 1.91 MPa. The 7 200 s strain of yellow ligament in the youth group increased by 3.39%, while the 7 200 s strain of yellow ligament in the older group increased by 2.07%. The 7 200 s stress in two groups all increased and the increased strain data showed statistically significance (P<0.05). The stress relaxation curve changed in the form of logarithm and the creep curve changed in the form of index. Conclusions The 7 200 s stress relaxation and creep in the yellow ligament of the older group all decreased and the mechanical properties of viscoelasticity changed.