The potential of epigenetic therapy to target the 3D epigenome in endocrine-resistant breast cancer.

Three-dimensional (3D) epigenome remodeling is an important mechanism of gene deregulation in cancer. However, its potential as a target to counteract therapy resistance remains largely unaddressed. Here, we show that epigenetic therapy with decitabine (5-Aza-mC) suppresses tumor growth in xenograft models of pre-clinical metastatic estrogen receptor positive (ER+) breast tumor. Decitabine-induced genome-wide DNA hypomethylation results in large-scale 3D epigenome deregulation, including de-compaction of higher-order chromatin structure and loss of boundary insulation of topologically associated domains. Significant DNA hypomethylation associates with ectopic activation of ER-enhancers, gain in ER binding, creation of new 3D enhancer-promoter interactions and concordant up-regulation of ER-mediated transcription pathways. Importantly, long-term withdrawal of epigenetic therapy partially restores methylation at ER-enhancer elements, resulting in a loss of ectopic 3D enhancer-promoter interactions and associated gene repression. Our study illustrates the potential of epigenetic therapy to target ER+ endocrine-resistant breast cancer by DNA methylation-dependent rewiring of 3D chromatin interactions, which are associated with the suppression of tumor growth.

Low dose PFDA induces DNA damage and DNA repair inhibition by promoting nuclear cGAS accumulation in ovarian epithelial cells.

Per- and polyfluoroalkyl substances (PFAS), the versatile anthropogenic chemicals, are popular with the markets and manufactured in large quantities yearly. Accumulation of PFAS has various adverse health effects on human. Albeit certain members of PFAS were found to have genotoxicity in previous studies, the mechanisms underlying their effects on DNA damage repair remain unclear. Here, we investigated the effects of Perfluorodecanoic acid (PFDA) on DNA damage and DNA damage repair in ovarian epithelial cells through a series of in vivo and in vitro experiments. At environmentally relevant concentration, we firstly found that PFDA can cause DNA damage in primary mouse ovarian epithelial cells and IOSE-80 cells. Moreover, nuclear cGAS increased in PFDA-treated cells, which leaded to the efficiency of DNA homologous recombination (HR) decreased and DNA double-strand breaks perpetuated. In vivo experiments also verified that PFDA can induce more DNA double-strand breaks lesions and nuclear cGAS in ovarian tissue. Taken together, our results unveiled that low dose PFDA can cause deleterious effects on DNA and DNA damage repair (DDR) in ovarian epithelial cells and induce genomic instability.

E-Spin: A Stochastic Ising Spin Based on Electrically-Controlled MTJ for Constructing Large-Scale Ising Annealing Systems.

With its unique computer paradigm, the Ising annealing machine has become an emerging research direction. The Ising annealing system is highly effective at addressing combinatorial optimization (CO) problems that are difficult for conventional computers to tackle. However, Ising spins, which comprise the Ising system, are difficult to implement in high-performance physical circuits. We propose a novel type of Ising spin based on an electrically-controlled magnetic tunnel junction (MTJ). Electrical operation imparts true randomness, great stability, precise control, compact size, and easy integration to the MTJ-based spin. In addition, simulations demonstrate that the frequency of electrically-controlled stochastic Ising spin (E-spin) is 50 times that of the thermal disturbance MTJ-based spin (p-bit). To develop a large-scale Ising annealing system, up to 64 E-spins are implemented. Our Ising annealing system demonstrates factorization of integers up to 264 with a temporal complexity of around O(n). The proposed E-spin shows superiority in constructing large-scale Ising annealing systems and solving CO problems.

mBAT-combo: A more powerful test to detect gene-trait associations from GWAS data.

Gene-based association tests aggregate multiple SNP-trait associations into sets defined by gene boundaries and are widely used in post-GWAS analysis. A common approach for gene-based tests is to combine SNPs associations by computing the sum of χ2 statistics. However, this strategy ignores the directions of SNP effects, which could result in a loss of power for SNPs with masking effects, e.g., when the product of two SNP effects and the linkage disequilibrium (LD) correlation is negative. Here, we introduce "mBAT-combo," a set-based test that is better powered than other methods to detect multi-SNP associations in the context of masking effects. We validate the method through simulations and applications to real data. We find that of 35 blood and urine biomarker traits in the UK Biobank, 34 traits show evidence for masking effects in a total of 4,273 gene-trait pairs, indicating that masking effects is common in complex traits. We further validate the improved power of our method in height, body mass index, and schizophrenia with different GWAS sample sizes and show that on average 95.7% of the genes detected only by mBAT-combo with smaller sample sizes can be identified by the single-SNP approach with a 1.7-fold increase in sample sizes. Eleven genes significant only in mBAT-combo for schizophrenia are confirmed by functionally informed fine-mapping or Mendelian randomization integrating gene expression data. The framework of mBAT-combo can be applied to any set of SNPs to refine trait-association signals hidden in genomic regions with complex LD structures.

Identification of key pathways and genes in nasopharyngeal carcinoma based on WGCNA.

OBJECTIVE: We aim to identify the potential genes and signaling pathways associated with the nasopharyngeal carcinoma (NPC) prognosis using Weighted Gene Co-Expression Network Analysis (WGCNA). METHODS: Gene Expression Omnibus (GEO) query was utilized to download two NPC mRNA microarray data. WGCNA was conducted on differentially expressed genes (DEGs) to obtain tumor-associated gene modules. Genes in core modules were intersected with DEGs for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. GSE102349 dataset was devoted to identifying prognostic hub genes by survival analysis and the results were confirmed by quantitative polymerase chain reaction (qPCR). RESULTS: Co-expression networks were built, and we detected 12 gene modules. The Brown module and Magenta module were extremely associated with NPC samples. GO functional analysis and KEGG pathway analysis was carried out to the genes in the Brown and Magenta modules. Our data indicated that DEGs in Brown module and Magenta module were correlated with the biological regulation, metabolic process, reproduction, and cellular proliferation. Twenty-six hub genes were obtained and were considered to be closely related to NPC. GSE102349 dataset was devoted to identifying prognostic hub genes by survival analysis. The expression of IL33, MPP3 and SLC16A7 in GSE102349 dataset was significantly correlated with the progression-free survival (PFS). The results of qPCR indicated a strong correlation between SLC16A7 expression and the overall survival (OS). CONCLUSIONS: WGCNA contributed to the detection of gene modules and identification of hub genes and crucial genes. These crucial genes might be potential targets for pharmaceutic therapies with potential clinical significance.

Interface Engineering in 2D/2D Heterogeneous Photocatalysts.

Assembling different 2D nanomaterials into heterostructures with strong interfacial interactions presents a promising approach for novel artificial photocatalytic materials. Chemically implementing the 2D nanomaterials' construction/stacking modes to regulate different interfaces can extend their functionalities and achieve good performance. Herein, based on different fundamental principles and photochemical processes, multiple construction modes (e.g., face-to-face, edge-to-face, interface-to-face, edge-to-edge) are overviewed systematically with emphasis on the relationships between their interfacial characteristics (e.g., point, linear, planar), synthetic strategies (e.g., in situ growth, ex situ assembly), and enhanced applications to achieve precise regulation. Meanwhile, recent efforts for enhancing photocatalytic performances of 2D/2D heterostructures are summarized from the critical factors of enhancing visible light absorption, accelerating charge transfer/separation, and introducing novel active sites. Notably, the crucial roles of surface defects, cocatalysts, and surface modification for photocatalytic performance optimization of 2D/2D heterostructures are also discussed based on the synergistic effect of optimization engineering and heterogeneous interfaces. Finally, perspectives and challenges are proposed to emphasize future opportunities for expanding 2D/2D heterostructures for photocatalysis.

Multiomics Integrative Analysis Identifying EPC1 as a Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma.

Background: Biomarker research in head and neck squamous cell carcinoma (HNSCC) is constantly revealing promising findings. An enhancer of polycomb homolog 1 (EPC1) was found to play a procancer role in nasopharyngeal carcinoma (NPC), but its role in HNSCC with strong heterogeneity is still unclear. Herein, we investigated the prognostic significance and related mechanisms of EPC1 in HNSCC. Methods: The Kaplan-Meier plotter was used to evaluate the prognostic significance of EPC1. Based on a range of published public databases, the multiomics expression of EPC1 in HNSCC was explored to investigate the mechanisms affecting prognosis. Results: According to the clinical data, high EPC1 expression in HNSCC was a predictor of patient prognosis (hazard ratio (HR) = 0.64; 95% confidence interval (CI) 0.49-0.83; P < 0.01). EPC1 expression varied among clinical subtypes and was related to key factors, such as TP53 and human papillomavirus (HPV) (P < 0.05). At the genetic level, EPC1 expression level may be associated with protein phosphorylation, cell adhesion, cancer-related pathways, etc. For the noncoding region, a competing endogenous RNA network was constructed, and 6 microRNAs and 12 long noncoding RNAs were identified. At the protein level, a protein-protein interaction (PPI) network related to EPC1 expression was constructed and found to be involved in HPV infection, endocrine resistance, and multiple cancer pathways. At the immune level, EPC1 expression was correlated with a variety of immune cells and immune molecules, which together constituted the immune microenvironments of tumors. Conclusion: High EPC1 expression may predict a better prognosis in HNSCC, as it is more frequently found in HNSCC with HPV infection. EPC1 may participate in the genomics, transcriptomics, proteomics, and immunomics of HNSCC, and the results can provide a reference for the development of targeted drugs and evaluation of patient prognosis.

KCNK3 inhibits proliferation and glucose metabolism of lung adenocarcinoma via activation of AMPK-TXNIP pathway.

Non-small cell lung cancer (NSCLC) is a primary histological subtype of lung cancer with increased morbidity and mortality. K+ channels have been revealed to be involved in carcinogenesis in various malignant tumors. However, TWIK-related acid-sensitive potassium channel 1 (TASK-1, also called KCNK3), a genetic member of K2P channels, remains an enigma in lung adenocarcinoma (LUAD). Herein, we investigated the pathological process of KCNK3 in proliferation and glucose metabolism of LUAD. The expressions of KCNK3 in LUAD tissues and corresponding adjacent tissues were identified by RNA sequencing, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry. Gain and loss-of-function assays were performed to estimate the role of KCNK3 in proliferation and glucose metabolism of LUAD. Additionally, energy metabolites of LUAD cells were identified by targeted metabolomics analysis. The expressions of metabolic molecules and active biomarkers associated with AMPK-TXNIP signaling pathway were detected via western blot and immunofluorescence. KCNK3 was significantly downregulated in LUAD tissues and correlated with patients' poor prognosis. Overexpression of KCNK3 largely regulated the process of oncogenesis and glycometabolism in LUAD in vitro and in vivo. Mechanistic studies found that KCNK3-mediated differential metabolites were mainly enriched in AMPK signaling pathway. Furthermore, rescue experiments demonstrated that KCNK3 suppressed proliferation and glucose metabolism via activation of the AMPK-TXNIP pathway in LUAD cells. In summary, our research highlighted an emerging role of KCNK3 in the proliferative activity and glycometabolism of LUAD, suggesting that KCNK3 may be an optimal predictor for prognosis and a potential therapeutic target of LUAD.

C1QTNF6 regulated by miR-29a-3p promotes proliferation and migration in stage I lung adenocarcinoma.

OBJECTIVE: C1QTNF6 has been implicated as an essential component in multiple cellular and molecular preliminary event, including inflammation, glucose metabolism, endothelial cell modulation and carcinogenesis. However, the biological process and potential mechanism of C1QTNF6 in lung adenocarcinoma (LUAD) are indefinite and remain to be elucidated. Therefore, we investigated the interaction among the traits of C1QTNF6 and LUAD pathologic process. METHODS: RT-qPCR and western blot were conducted to determine the expression levels of C1QTNF6. RNA interference and overexpression of C1QTNF6 were constructed to identify the biological function of C1QTNF6 in cellular proliferative, migratory and invasive potentials in vitro. Dual-luciferase reporter assay was applied to identify the possible interaction between C1QTNF6 and miR-29a-3p. Moreover, RNA sequencing analysis of C1QTNF6 knockdown was performed to identify the potential regulatory pathways. RESULTS: C1QTNF6 was upregulated in stage I LUAD tissues compared with adjacent non-cancerous tissues. Concurrently, C1QTNF6 knockdown could remarkably inhibit cell proliferation, migratory and invasive abilities, while overexpression of C1QTNF6 presented opposite results. Additionally, miR-29a-3p may serve as an upstream regulator of C1QTNF6 and reduce the expression of C1QTNF6. Subsequent experiments showed that miR-29a-3p could decrease the cell mobility and proliferation positive cell rates, as well as reduce the migratory and invasive possibilities in LUAD cells via downregulating C1QTNF6. Moreover, RNA sequencing analysis demonstrated that the cytokine-cytokine receptor interaction pathway may participate in the process of C1QTNF6 regulating tumor progression. CONCLUSION: Our study first demonstrated that downregulation of C1QTNF6 could inhibit tumorigenesis and progression in LUAD cells negatively regulated by miR-29a-3p. These consequences could reinforce our awareness and understanding of the underlying mechanism and provide a promising therapeutic target for LUAD.

Investigating Acupoint Selection and Combinations of Acupuncture for Tic Disorders: An Association Rule Mining and Network Analysis Study.

Objective: Tic disorders (TDs) are common mental disorders in children and adolescents, and the clinical application of acupuncture for treating TDs is becoming increasingly widespread. However, the criteria for selecting acupoint prescriptions and combinations have not been summarized. Therefore, data mining was used herein to determine the treatment principles and the most effective acupoint selection and compatibility criteria for the treatment of TDs. Methods: Clinical studies and observations of the efficacy of acupuncture treatment for TDs were obtained from the PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and Chinese Biomedical (CBM) databases. The data on the acupoint prescriptions applied in these studies were collected, and network and association analyses were used to reveal the relationships between acupoints and to identify acupoint combinations. Additionally, the principles of acupuncture for TDs were determined through cluster analysis. Subgroup analysis of acupuncture prescriptions based on specific categorical diagnoses was performed to further assess the selection of acupoints. Results: Eighty-six trials were identified, and 257 groups of effective prescriptions involving 121 acupoints were extracted. Bai-hui (DU20), Feng-chi (GB20), Tai-chong (LR3), He-gu (LI4), and San-yin-jiao (SP6) were the most regularly used acupoints for treating TDs. The Governor Vessel, gallbladder, and large intestine meridians were more commonly used than other meridians. Moreover, most acupoint sites focused on the head and neck. Network analysis revealed potentially effective acupoint prescriptions for their commonly used acupoints, namely, Bai-hui (DU20), Si-shen-cong (EX-HN1), Feng-chi (GB20), Nei-guan (PC6), Shen-men (HT7), He-gu (LI4), Zu-san-li (ST36), San-yin-jiao (SP6) and Tai-chong (LR3). Association rule mining indicated that potential point combinations that should be prioritized in TD treatment are Bai-hui (DU20), Neiguan (PC6) and Sanyinjiao (SP6). Cluster analysis revealed the treatment principle of "coordinating yin and yang, tonifying qi and blood, dispelling pathogenic wind and eliminating phlegm". The core acupoint prescription of TS treatment comprised He-gu (LI4), Feng-chi (GB20), Tai-chong (LR3), Bai-hui (DU20), Yin-tang (EX-HN3), Si-shen-cong (EX-HN1), San-yin-jiao (SP6), and Nei-guan (PC6). The core group included He-gu (LI4) and Feng-chi (GB20). Proximal points were usually used in TS as an additional method of point selection. Conclusion: Using data mining analysis of published studies, this study provides valuable information regarding the selection of the most effective acupoints and point combinations for clinical acupuncture practice for treating TDs.

Whole genome deep sequencing analysis of cell-free DNA in samples with low tumour content.

BACKGROUND: Circulating cell-free DNA (cfDNA) in the plasma of cancer patients contains cell-free tumour DNA (ctDNA) derived from tumour cells and it has been widely recognized as a non-invasive source of tumour DNA for diagnosis and prognosis of cancer. Molecular profiling of ctDNA is often performed using targeted sequencing or low-coverage whole genome sequencing (WGS) to identify tumour specific somatic mutations or somatic copy number aberrations (sCNAs). However, these approaches cannot efficiently detect all tumour-derived genomic changes in ctDNA. METHODS: We performed WGS analysis of cfDNA from 4 breast cancer patients and 2 patients with benign tumours. We sequenced matched germline DNA for all 6 patients and tumour samples from the breast cancer patients. All samples were sequenced on Illumina HiSeqXTen sequencing platform and achieved approximately 30x, 60x and 100x coverage on germline, tumour and plasma DNA samples, respectively. RESULTS: The mutational burden of the plasma samples (1.44 somatic mutations/Mb of genome) was higher than the matched tumour samples. However, 90% of high confidence somatic cfDNA variants were not detected in matched tumour samples and were found to comprise two background plasma mutational signatures. In contrast, cfDNA from the di-nucleosome fraction (300 bp-350 bp) had much higher proportion (30%) of variants shared with tumour. Despite high coverage sequencing we were unable to detect sCNAs in plasma samples. CONCLUSIONS: Deep sequencing analysis of plasma samples revealed higher fraction of unique somatic mutations in plasma samples, which were not detected in matched tumour samples. Sequencing of di-nucleosome bound cfDNA fragments may increase recovery of tumour mutations from plasma.

Identification of a ZC3H12D-regulated competing endogenous RNA network for prognosis of lung adenocarcinoma at single-cell level.

BACKGROUND: To identify hub genes from the competing endogenous RNA (ceRNA) network of lung adenocarcinoma (LUAD) and to explore their potential functions on prognosis of patients from a single-cell perspective. METHODS: We performed RNA-sequencing of LUAD to construct ceRNA regulatory network, integrating with public databases to identify the vital pathways related to patients' prognosis and to reveal the expression level of hub genes under different conditions, the functional enrichment of co-expressed genes and their potential immune-related mechanisms. RESULTS: ZC3H12D-hsa-miR-4443-ENST00000630242 axis was found to be related with LUAD. Lower ZC3H12D expression was significantly associated with shorter overall survival (OS) of patients (HR = 2.007, P < 0.05), and its expression was higher in early-stage patients, including T1 (P < 0.05) and N0 (P < 0.05). Additionally, ZC3H12D expression was higher in immune cells displayed by single-cell RNA-sequencing data, especially in Treg cells of lung cancer and CD8 T cells, B cells and CD4 T cells of LUAD. The functional enrichment analysis showed that the co-expressed genes mainly played a role in lymphocyte activation and cytokine-cytokine receptor interaction. In addition, ZC3H12D was associated with multiple immune cells and immune molecules, including immune checkpoints CTLA4, CD96 and TIGIT. CONCLUSION: ZC3H12D-hsa-miR-4443-ENST00000630242 ceRNA network was identified in LUAD. ZC3H12D could affect prognosis of patients by regulating mRNA, miRNA, lncRNA, immune cells and immune molecules. Therefore, it may serve as a vital predictive marker and could be regarded as a potential therapeutic target for LUAD in the future.

Improved analyses of GWAS summary statistics by reducing data heterogeneity and errors.

statistics from genome-wide association studies (GWAS) have facilitated the development of various summary data-based methods, which typically require a reference sample for linkage disequilibrium (LD) estimation. Analyses using these methods may be biased by errors in GWAS summary data or LD reference or heterogeneity between GWAS and LD reference. Here we propose a quality control method, DENTIST, that leverages LD among genetic variants to detect and eliminate errors in GWAS or LD reference and heterogeneity between the two. Through simulations, we demonstrate that DENTIST substantially reduces false-positive rate in detecting secondary signals in the summary-data-based conditional and joint association analysis, especially for imputed rare variants (false-positive rate reduced from >28% to <2% in the presence of heterogeneity between GWAS and LD reference). We further show that DENTIST can improve other summary-data-based analyses such as fine-mapping analysis.

Study on High Frequency Surface Discharge Characteristics of SiO2 Modified Polyimide Film.

Polyimide (PI) can be used as a cladding insulation for high frequency power transformers, and along-side discharge can lead to insulation failure, so material modification techniques are used. In this paper, different doped nano-SiO2 are introduced into polyimide for nanocomposite modification. The results of testing the life time of high-frequency electrical stress along-side discharge show that the 10% SiO2 doping has the longest life time. The results show that: for composites prone to corona, their flashover causes more damage, and both positive half-cycle and polarity reversal discharges are more violent; compared to pure PI, the positive half-cycle and overall discharge amplitude and number of modified films are smaller, but the negative half-cycle is larger; at creeping development stages, the number of discharges is smaller, and the discharge amplitude of both films fluctuates in the mid-term, with the modified films having fewer discharges and the PI films discharging more violently in the later stages. The increase in the intensity of the discharge was greater in the later stages, and the amplitude and number of discharges were much higher than those of the modified film, which led to a rapid breakdown of the pure polyimide film. Further research found that resistivity plays an important role in the structural properties of the material in the middle and late stages, light energy absorption in the modified film plays an important role, the distribution of traps also affects the discharge process, and in the late stages of the discharge, the heating of the material itself has a greater impact on the breakdown, so the pure polyimide film as a whole discharges more severely and has the shortest life.

Expression and Biological Functions of EPC1 in Nasopharyngeal Carcinoma.

BACKGROUND: Comb homolog enhancer 1 (EPC1) gene is one of the important members of epigenetic inhibitor PCG family. It shows carcinogenic potential in a variety of malignant tumors, but the expression and role of EPC1 in nasopharyngeal carcinoma are unclear. The aim of this study was to explore the expression and function of enhancer of polycomb homolog 1 (EPC1) in nasopharyngeal carcinoma (NPC). METHODS: The differential expression of EPC1 in the cancer tissues and cell lines of NPC was examined by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). EPC1 expression, cell proliferation, and apoptosis were detected in NPC cell lines after EPC1 silencing, and the levels of the epithelial-mesenchymal transition (EMT)-related proteins E-cadherin and vimentin were detected in NPC cells after EPC1 silencing. The study was performed at Fujian Provincial Hospital, Fujian, China, from 2018 to 2019. RESULTS: We found that EPC1 was significantly upregulated in the cancer tissues and cell lines of NPC (P<0.001). Furthermore, knockdown of EPC1 inhibited the growth and metastasis of NPC cells. E-cadherin and vimentin were detected in NPC cells after EPC1 was knocked out. It was confirmed that inhibition of EPC1 resulted in increased E-cadherin expression (P<0.001) and decreased vimentin expression (P<0.001), suggesting that inhibition of EPC1 could inhibit the EMT in NPC cells. CONCLUSION: EPC1 expression was upregulated in NPC tissues and cell lines. Knockout of EPC1 effectively inhibited the growth of NPC cells, induced apoptosis, and inhibited invasion and metastasis. Inhibition of EPC1 could inhibit the EMT in NPC cells. All of the above findings support the viewpoint that EPC1 plays a pro-cancer role in NPC.

Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most predomintnt lung cancer subtype with increasing morbidity and mortality. Previous studies have shown that aquaporin (AQP) family genes were correlated with tumor progression and metastasis in several kinds of malignancies. However, their biological behaviors and prognostic values in LUAD have not been comprehensively elucidated. Methods: RNA sequencing and real-time reverse transcription PCR (RT-PCR) were used to assess AQP1/3/4/5 gene expressions in LUAD patients using GEPIA and UALCAN databases. And then Kaplan-Meier analysis, cBioPortal, Metascape, GeneMANIA, TISIDB, and TIMER were utilized to determine the prognostic value, mutation frequency, and immune cell infiltration of AQP family members in LUAD. Results: We found that AQP3 expression was significantly elevated and AQP1 expression was markedly reduced in LUAD patients, whereas the expression levels of AQP4 and AQP5 exhibited no significant changes. The Kaplan-Meier survival analysis indicated that the higher expressions of AQP1/4/5 were related to longer overall survival (OS). Of interest, AQP3 was significantly correlated with the clinical tumor stage and lower AQP3 expression showed favorable prognosis in stage I LUAD patients, which indicated that AQP3 may be a potential prognostic biomarker for patients. Through functional enrichment analysis, the functions of these four AQPs genes were mainly involved in the passive transport by aquaporins, water homeostasis, and protein tetramerization. Moreover, AQP1/3/4/5 expression was strongly associated with tumor-infiltrating lymphocytes (TILs) in LUAD. Conclusion: AQP3 can be used as a prognosis and survival biomarker for stage I LUAD. These findings may provide novel insights into developing molecular targeted therapies in LUAD.

The influence of the chemical composition of essential oils of Clausena lansium seeds on the growth of Candida strains.

Clausena lansium (Lour.) Skeels seeds have been shown to have diverse beneficial medical value due to their unique active components. This study analysed the composition of essential oils (EOs) of C. lansium seeds and investigated their potential antifungal effects against Candida strains. A total of forty-six components were identified in all samples by gas chromatography-mass spectrometry (GC-MS). The main components were sabinene, ß-phellandrene and 4-terpineol. Thirteen EOs of C. lansium seeds were classified into three clusters based on their components. Cluster analysis showed that the difference between the tropics and subtropics was the greatest. These EOs and the three main chemicals showed different antifungal activities against five Candida species (C. albicans, C. tropicalis, C. glabrata, C. krusei and C. parapsilosis). The antifungal activity against C. glabrata and C. krusei was higher than that against other Candida strains. EOs of C. lansium seeds displayed noteworthy antifungal activity against both sensitive and fluconazole-resistant strains, with inhibition zone diameters in the range of 9.4-23.4 mm. Comprehensive analysis illustrated the importance of sabinene, ß-phellandrene and 4-terpineol to antifungal activity, and there may be some synergistic effects with other components. These results represent the first report about the correlation between the chemical composition of EOs of C. lansium seeds and antifungal activity. Taken together, the results obtained provide scientific evidence for the traditional use of C. lansium seeds waste.

FCGR2A Could Function as a Prognostic Marker and Correlate with Immune Infiltration in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: We aim to investigate the correlation between FCGR2A mRNA level and prognosis of head and neck squamous cancer (HNSC) in public databases. In addition, we investigated the correlation between FCGR2A expression and clinicopathological characteristics and tumor-infiltrating immune cells in HNSC patients. METHODS: FCGR2A mRNA expression in multiple cancers was analyzed based on Gene Expression Profiling Interactive Analysis. A protein-protein interaction network was obtained based on the STRING database. The 10 proteins most closely related to FCGR2A (i.e., CD3G, PLCG2, LAT, LYN, SYK, FCGR3A, PIK3R1, HCK, ITGAM, and ITGB2) were screened, followed by establishing the protein-protein interaction network. The correlation between FCGR2A expression and immunocytes was investigated, together with the effects of FCGR2A on the metastasis, recurrence, and survival of HNSC. RESULTS: FCGR2A expression in several carcinoma tissues was significantly higher than that of adjacent tissues. Significant differences were noticed in the HNSC samples and the adjacent tissue samples except the seven samples of grade 4. There were statistical differences between the FCGR2A expression in tissues of grade 1, grade 2, and grade 3 (P < 0.05). In the tissues of grade 4, the expression of FCGR2A was the lowest. The FCGR2A protein was a type of II-a receptor in γFc of the low-affinity immunoglobulin, which could bind with the Fc region of the immunoglobulin γ. There was a correlation between the FCGR2A gene and the distal HNSC metastasis. FCGR2A gene expression was correlated with the survival and prognosis. The GSE65858 dataset was selected for the validation. The FCGR2A expression was significantly correlated with total survival (P = 0.0107) and progression-free survival (P = 0.0362). CONCLUSIONS: Our findings shed light on the importance of FCGR2A in HNSC and illustrated a potential relationship between FCGR2A and tumor-immune interactions.

Anaerobic co-digestion of chicken manure and cardboard waste: Focusing on methane production, microbial community analysis and energy evaluation.

This study aimed to investigate the synergistic effect and microbial community changes between chicken manure (CM) and cardboard (CB) during anaerobic co-digestion. Meanwhile, the energy balance of biogas engineering was extrapolated based on the batch tests. In batch tests, co-digestion system achieved the highest improvement (14.2%) and produced 319.62 mL CH4/gVS with a 65:35 ratio of CB: CM. More extracellular polymeric substance secretion promoted the electron transfer for acidogenesis and more hydrolase was provided with 31.6% improvement. The microbial analysis illustrated that higher acetoclastic Methanosaeta abundance was achieved, leading to 211% enhancement of acetoclastic pathway. Moreover, associated network illustrated that the higher methane production was mainly achieved through matching of hydrolytic bacteria and acidogenesis bacteria. As for energy balance, the synergistic effect increased the energy output by 38% and energy recovery to 46.4%.

Bent crystal Laue analyser combined with total reflection fluorescence X-ray absorption fine structure (BCLA + TRF-XAFS) and its application to surface studies.

A bent crystal Laue analyser (BCLA) is an X-ray energy analyser used for fluorescence X-ray absorption fine-structure (XAFS) spectroscopy to separate the fluorescence X-ray emission line of a target atom from the elastic scattering X-rays and other fluorescence emission lines. Here, the feasibility of the BCLA for total reflection fluorescence XAFS (TRF-XAFS), which has a long X-ray footprint on the substrate surface owing to grazing incidence, was tested. The focal line of the BCLA was adjusted on the X-ray footprint and the XAFS signal for one monolayer of Pt deposited on a 60 nm Au film with high sensitivity was obtained. Although range-extended XAFS was expected by the rejection of Au fluorescence arising from the Au substrate, a small glitch was found in the Au L3 edge because of the sudden change of the complex refraction index of the Au substrate at the Au edge. This abnormal spectrum feature can be removed by reflectivity correction using Au foil absorption data. BCLA combined with TRF-XAFS spectroscopy (BCLA + TRF-XAFS) is a new technique for the in situ surface analysis of highly dispersed systems even in the presence of a liquid overlayer.