Unraveling the key role of chromatin structure in cancer development through epigenetic landscape characterization of oral cancer.

Epigenetic alterations, such as those in chromatin structure and DNA methylation, have been extensively studied in a number of tumor types. But oral cancer, particularly oral adenocarcinoma, has received far less attention. Here, we combined laser-capture microdissection and muti-omics mini-bulk sequencing to systematically characterize the epigenetic landscape of oral cancer, including chromatin architecture, DNA methylation, H3K27me3 modification, and gene expression. In carcinogenesis, tumor cells exhibit reorganized chromatin spatial structures, including compromised compartment structures and altered gene-gene interaction networks. Notably, some structural alterations are observed in phenotypically non-malignant paracancerous but not in normal cells. We developed transformer models to identify the cancer propensity of individual genome loci, thereby determining the carcinogenic status of each sample. Insights into cancer epigenetic landscapes provide evidence that chromatin reorganization is an important hallmark of oral cancer progression, which is also linked with genomic alterations and DNA methylation reprogramming. In particular, regions of frequent copy number alternations in cancer cells are associated with strong spatial insulation in both cancer and normal samples. Aberrant methylation reprogramming in oral squamous cell carcinomas is closely related to chromatin structure and H3K27me3 signals, which are further influenced by intrinsic sequence properties. Our findings indicate that structural changes are both significant and conserved in two distinct types of oral cancer, closely linked to transcriptomic alterations and cancer development. Notably, the structural changes remain markedly evident in oral adenocarcinoma despite the considerably lower incidence of genomic copy number alterations and lesser extent of methylation alterations compared to squamous cell carcinoma. We expect that the comprehensive analysis of epigenetic reprogramming of different types and subtypes of primary oral tumors can provide additional guidance to the design of novel detection and therapy for oral cancer.

Small Transjugular Intrahepatic Portosystemic Shunt Plus Variceal Embolization for Gastric Varices: A Multicenter Cohort Study.

BACKGROUND & AIMS: The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs. METHODS: This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at 7 medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality. RESULTS: A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% vs 13.6%; P = .005) and OHE (31.0% vs 39.4%; P = .02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% vs 9.7%; P = .42). In patients with GOV2 and IGV1, TIPS plus variceal embolization reduced both rebleeding (GOV2: 7.8% vs 25.1%; P = .01; IGV1: 5.6% vs 30.8%; P = .03) and OHE (GOV2: 31.8% vs 51.5%; P = .008; IGV1: 11.6% vs 38.5%; P = .04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% vs 8.7%; P = .37) or OHE (33.1% vs 35.3%; P = .60). CONCLUSIONS: Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.

SQLE-a promising prognostic biomarker in cervical cancer: implications for tumor malignant behavior, cholesterol synthesis, epithelial-mesenchymal transition, and immune infiltration.

BACKGROUND: Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development. METHODS: RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed. RESULTS: SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis. CONCLUSION: SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.

Xiashengella succiniciproducens gen. nov., sp. nov., a succinate-producing bacterium isolated from an anaerobic digestion tank in the family Marinilabiliaceae of the order Bacteroidales.

A strictly anaerobic, motile bacterium, designated as strain Ai-910T, was isolated from the sludge of an anaerobic digestion tank in China. Cells were Gram-stain-negative rods. Optimal growth was observed at 38 °C (growth range 25-42 °C), pH 8.5 (growth range 5.5-10.5), and under a NaCl concentration of 0.06% (w/v) (range 0-2.0%). Major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The respiratory quinone was MK-7. Using xylose as the growth substrate, succinate was produced as the fermentation product. Phylogenetic analysis based on the 16 S rRNA gene sequences indicated that strain Ai-910T formed a distinct phylogenetic lineage that reflects a new genus in the family Marinilabiliaceae, sharing high similarities to Alkaliflexus imshenetskii Z-7010T (92.78%), Alkalitalea saponilacus SC/BZ-SP2T (92.51%), and Geofilum rubicundum JAM-BA0501T (92.36%). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain Ai-910T and its phylogenetic neighbors were below 65.27 and 16.90%, respectively, indicating that strain Ai-910T represented a novel species. The average amino acid identity between strain Ai-910T and other related members of the family Marinilabiliaceae were below 69.41%, supporting that strain Ai-910T was a member of a new genus within the family Marinilabiliaceae. Phylogenetic, genomic, and phenotypic analysis revealed that strain Ai-910T was distinguished from other phylogenetic relatives within the family Marinilabiliaceae. The genome size was 3.10 Mbp, and the DNA G + C content of the isolate was 42.8 mol%. Collectively, differences of the phenotypic and phylogenetic features of strain Ai-910T from its close relatives suggest that strain Ai-910T represented a novel species in a new genus of the family Marinilabiliaceae, for which the name Xiashengella succiniciproducens gen. nov., sp. nov. was proposed. The type strain of Xiashengella succiniciproducens is Ai-910T (= CGMCC 1.17893T = KCTC 25,304T).

Transjugular mesenteric-caval shunt for portal vein cavernous transformation with recurrent variceal bleeding: preliminary results.

OBJECTIVES: This study aimed to evaluate the feasibility, safety, and efficacy of the transjugular mesenteric-caval shunt (TMCS) as a treatment for the cavernous transformation of the portal vein (CTPV) and recurrent variceal bleeding. METHODS: This retrospective case series was conducted with approval from the institutional review board. It involved seven patients diagnosed with CTPV and recurrent variceal bleeding who underwent the TMCS procedure. We analyzed the rate of procedural complications, incidents of rebleeding, stent stenosis, hepatic encephalopathy, and overall survival to assess treatment outcomes. RESULTS: The TMCS was successfully performed in all seven patients without any life-threatening complications. Postoperatively, one patient developed a lung infection and pleural effusion, which resolved with appropriate treatment. Additionally, two patients experienced an increase in total bilirubin levels, but there was no further deterioration in liver function. The median portal pressure gradient significantly decreased from a preoperative value of 27 mmHg (range 20-36 mmHg) to a postoperative value of 6 mmHg (range 4-11 mmHg). A notable improvement was observed in one cirrhotic patient, with liver function progressing from Child-Pugh class B (score 9) to class A (score 6). Over a median follow-up period of 14 months (range 7-18 months), none of the patients encountered rebleeding, stent stenosis, hepatic encephalopathy, or mortality. CONCLUSION: The TMCS appears to be a viable and effective alternative for managing CTPV with recurrent variceal bleeding. Its long-term outcome requires further evaluation. CLINICAL RELEVANCE STATEMENT: TMCS provides a promising treatment for patients with life-threatening CTPV complications when occluded portal vein cannot be recanalized and portal vein recanalization TIPS is not an option. KEY POINTS: Performing TIPS in patients with portal vein cavernoma is complex due to the requirement for recanalization of the occluded portal vein. Creating a mesenteric-caval shunt through a transjugular approach is a feasible technique. Establishing a TMCS provides a means to manage life-threatening complications arising from portal vein cavernoma.

Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

CT-based radiomics analysis of different machine learning models for differentiating gnathic fibrous dysplasia and ossifying fibroma.

OBJECTIVE: In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery. MATERIALS AND METHODS: We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value. RESULTS: We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy. CONCLUSION: Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision-making.

Flexible and fast estimation method of far-field patterns for digital-coding metasurfaces.

We propose a flexible and fast estimation method to calculate the far-field patterns of digital-coding metasurfaces (DCMs) by performing chirp Z-transform (CZT), called the DCM-CZT method. Because of the expression form of convolution, CZT can be accelerated by fast Fourier transform. Compared with the traditional discrete Fourier transform (DFT) method, the DCM-CZT method can accurately estimate the far-field patterns with arbitrary element periods. More importantly, the DCM-CZT method can calculate partial far-field patterns for some specific orientations, instead of the global far-field patterns like DFT does. We show that the DCM-CZT method can efficiently improve the partial space-resolution to avoid the calculation error caused by the fence effect under acceptable computing time. We present six representative examples to demonstrate the capabilities of the proposed method. Results show that the far-field patterns calculated by the DCM-CZT method have good agreements with full-wave simulations and experimental measurements. However, the results of main-lobes calculated by the DFT method have obvious deviations when the element period is about 0.2 wavelengths. We believe that the DCM-CZT method has potential applications in wireless communications and radar detections.

Bendable transmission line and amplifier of spoof surface plasmon polaritons at microwave frequencies.

A bendable transmission line (TL) of spoof surface plasmon polaritons (SSPPs) is presented, which can maintain good transmission performance despite of the deformation caused by bending. Such a TL consists of flexible dielectric substrate and ultrathin metallic strip with zigzag decorations that are designed to support the propagation of SSPPs with strong field confinement and low radiation loss. Furthermore, the proposed SSPP TL is used to excite an amplifier chip efficiently, reaching high and stable gains with nearly no degradation of amplification in the bending states. Numerical and experimental results are demonstrated to verify the bendable merits of both passive TL and active amplifier from 12 GHz to 18 GHz. The flexible and stable characteristics of this design may find utility in novel applications like wearable electronics and conformal plasmonic circuits in the microwave frequencies.

Ka-band beam-scanning leaky-wave antenna fed by reconfigurable spoof surface plasmon polaritons.

A leaky-wave antenna (LWA) based on reconfigurable spoof surface plasmon polaritons (SSPP) is proposed for beam scanning in the Ka band, which consists of a reconfigurable SSPP waveguide and a periodic array of metal rectangular split rings. Both numerical simulations and experimental measurements show that the reconfigurable SSPP-fed LWA has good performance in the frequency range from 25 to 30 GHz. Specifically, as the bias voltage changes from 0 to 15 V, we can achieve the maximum sweep range of 24° at a single frequency and 59° at multiple frequency points, respectively. Owing to the wide-angle beam-steering feature, as well as the field confinement and wavelength compression properties derived from the SSPP architecture, the proposed SSPP-fed LWA possesses great potential applications in the compact and miniaturized devices and systems of the Ka band.

Hepatic hydrothorax does not increase the risk of death after transjugular intrahepatic portosystemic shunt in cirrhosis patients.

OBJECTIVES: Hepatic hydrothorax (HH) is a predictor of poor survival in cirrhosis patients. However, whether HH increases the mortality risk of cirrhosis patients treated with transjugular intrahepatic portosystemic shunt (TIPS) is unknown. Our objective was to evaluate the influence of HH on the survival of cirrhosis patients after TIPS. METHODS: Cirrhosis patients with portal hypertension complications were selected from a prospective database of consecutive patients treated with TIPS in Xijing Hospital from January 2015 to June 2021. Cirrhosis patients with HH were treated as the experimental group. A control group of cirrhosis patients without HH was created using propensity score matching. Survival after TIPS and the related risk factors were analysed. RESULTS: There were 1292 cirrhosis patients with portal hypertension complications treated with TIPS, among whom 255 patients had HH. Compared with patients without HH, patients with HH had worse liver function (MELD, 12 vs. 10, p < 0.001), but no difference in survival after TIPS was observed. After propensity score matching, 243 patients with HH and 243 patients without HH were enrolled. There was no difference in cumulative survival between patients with and without HH. Cox regression analysis showed that HH was not associated with survival after TIPS, and main portal vein thrombosis (> 50%) was a prognostic factor of long-term survival after TIPS in cirrhosis patients (hazard ratio, 1.386; 95% CI, 1.030-1.865, p = 0.031). CONCLUSION: Hepatic hydrothorax does not increase the risk of death after TIPS in cirrhosis patients. KEY POINTS: • Hepatic hydrothorax is a decompensated event of cirrhosis and increases the risk of death. • Hepatic hydrothorax is associated with worse liver function. • Hepatic hydrothorax does not increase the mortality of cirrhosis treated with TIPS.

Notch activation promotes bone metastasis via SPARC inhibition in adenoid cystic carcinoma.

OBJECTIVES: We aimed to investigate bone metastasis induced by Notch signalling pathway dysregulation and to demonstrate that SPARC is a potential therapeutic target in adenoid cystic carcinoma (AdCC) with Notch dysregulation. MATERIALS AND METHODS: This retrospective study enrolled 144 AdCC patients. RNA-sequencing and enrichment analyses were performed using 32 AdCC samples. Osteonectin/SPARC and the Notch activation indicator Notch intracellular domain (NICD) were detected using immunohistochemistry. Cell proliferation and migration assays were conducted using stably NICD over-expressing cells. The effect of SPARC on osteoclast differentiation in NICD cells was investigated using western blotting, quantitative reverse transcription PCR, tartrate-resistant acid phosphatase staining and resorption assays. RESULTS: RNA-sequencing analysis showed that genes down-regulated in Notch-mutant AdCCs, such as SPARC, were enriched in ossification and osteoblast differentiation. Most (75/110, 68.2%) Notch1-wild-type AdCCs showed SPARC over-expression, whereas 30 out of 34 (88.2%) Notch1-mutant tumours showed low SPARC expression. SPARC over-expression was then found negatively to be correlated with NICD expression in 144 AdCCs. NICD over-expression promoted cell growth, migration and osteoclast differentiation, which could be partly reversed by exogenous SPARC. CONCLUSIONS: Notch activation in AdCC contributes to bone metastasis through SPARC inhibition. The study results suggest that SPARC may represent a prognostic biomarker and potential therapeutic target.

A Comprehensive Analysis of Chloroplast Genome Provides New Insights into the Evolution of the Genus Chrysosplenium.

Chrysosplenium, a perennial herb in the family Saxifragaceae, prefers to grow in low light and moist environments and is divided into two sections of Alternifolia and Oppositifolia based on phyllotaxy. Although there has been some progress in the phylogeny of Chrysosplenium over the years, the phylogenetic position of some species is still controversial. In this study, we assembled chloroplast genomes (cp genomes) of 34 Chrysosplenium species and performed comparative genomic and phylogenetic analyses in combination with other cp genomes of previously known Chrysosplenium species, for a total of 44 Chrysosplenium species. The comparative analyses revealed that cp genomes of Chrysosplenium species were more conserved in terms of genome structure, gene content and arrangement, SSRs, and codon preference, but differ in genome size and SC/IR boundaries. Phylogenetic analysis showed that cp genomes effectively improved the phylogenetic support and resolution of Chrysosplenium species and strongly supported Chrysosplenium species as a monophyletic taxon and divided into three branches. The results also showed that the sections of Alternifolia and Oppositifolia were not monophyletic with each other, and that C. microspermum was not clustered with other Chrysosplenium species with alternate leaves, but with C. sedakowii into separate branches. In addition, we identified 10 mutational hotspot regions that could serve as potential DNA barcodes for Chrysosplenium species identification. In contrast to Peltoboykinia, the clpP and ycf2 genes of Chrysosplenium were subjected to positive selection and had multiple significant positive selection sites. We further detected a significant positive selection site on the petG gene between the two sections of Chrysosplenium. These evolutionary characteristics may be related to the growth environment of Chrysosplenium species. This study enriches the cp genomes of Chrysosplenium species and provides a reference for future studies on its evolution and origin.

Chloroplast Genomes and Phylogenetic Analysis of Three Carthamus (Asteraceae) Species.

The genus Carthamus Linnaeus, which belongs to the tribe Cardueae in the Asteraceae family, originated in the Mediterranean region and consists of approximately 20 species worldwide. Understanding the phylogeny of the Carthamus is crucial for the cultivation of C. tinctorius. Although chloroplast genomes are widely used for species identification and evolutionary studies, there have been limited investigations on the chloroplast genomes of Carthamus species. In this study, we assembled the chloroplast genomes of C. persicus, C. tinctorius × C. persicus, and C. lanatus and combined them with the five chloroplast genomes of C. tinctorius for comparative genomic analysis. The sizes of the chloroplast genomes of C. lanatus, C. persicus, and C. tinctorius × C. persicus were 152,602 bp, 153,177 bp, and 153,177 bp, respectively. Comparative analysis showed that the chloroplast genome structures of the four Carthamus species were highly conserved. Additionally, the phylogenomic analysis demonstrated that the plastid genome and angiosperms353 dataset significantly improved the phylogenetic support of Carthamus species. This analysis supported Carthamus as a monophyletic taxon and its internal division into the sect. Carthamus and sect. Atractylis. The Carthamus was closely related to Carduncellus, Femeniasia, Phonus, and Centaurea. In conclusion, this study not only expands our understanding of the cp genomes of Carthamus species but also provides support for more comprehensive phylogenetic studies of Carthamus.

Lysine Deprivation Suppresses Adipogenesis in 3T3-L1 Cells: A Transcriptome Analysis.

Growing evidence proves that amino acid restriction can reverse obesity by reducing adipose tissue mass. Amino acids are not only the building blocks of proteins but also serve as signaling molecules in multiple biological pathways. The study of adipocytes' response to amino acid level changes is crucial. It has been reported that a low concentration of lysine suppresses lipid accumulation and transcription of several adipogenic genes in 3T3-L1 preadipocytes. However, the detailed lysine-deprivation-induced cellular transcriptomic changes and the altered pathways have yet to be fully studied. Here, using 3T3-L1 cells, we performed RNA sequencing on undifferentiated and differentiated cells, and differentiated cells under a lysine-free environment, and the data were subjected to KEGG enrichment. We found that the differentiation process of 3T3-L1 cells to adipocytes required the large-scale upregulation of metabolic pathways, mainly on the mitochondrial TCA cycle, oxidative phosphorylation, and downregulation of the lysosomal pathway. Single amino acid lysine depletion suppressed differentiation dose dependently. It disrupted the metabolism of cellular amino acids, which could be partially reflected in the changes in amino acid levels in the culture medium. It inhibited the mitochondria respiratory chain and upregulated the lysosomal pathway, which are essential for adipocyte differentiation. We also noticed that cellular interleukin 6 (IL6) expression and medium IL6 level were dramatically increased, which was one of the targets for suppressing adipogenesis induced by lysine depletion. Moreover, we showed that the depletion of some essential amino acids such as methionine and cystine could induce similar phenomena. This suggests that individual amino acid deprivation may share some common pathways. This descriptive study dissects the pathways for adipogenesis and how the cellular transcriptome was altered under lysine depletion.

The action of topical application of Vitamin B12 ointment on radiodermatitis in a porcine model.

Radiodermatitis is an inevitable side effect of radiotherapy in cancer treatment and there is currently no consensus on effective drugs for treating the condition. Vitamin B12 is known to be effective for repairing and regenerating damaged skin. However, there are few studies on the use of Vitamin B12 for treating radiodermatitis. This study explored the therapeutic efficacy and mechanism of action of Vitamin B12 ointment on radiodermatitis. A porcine model of grade IV radiodermatitis was established. The ointment was applied for 12 weeks after which histological staining, transmission electron microscopy, RT-qPCR, western blotting, and gene sequencing were performed for the evaluation of specific indicators in skin samples. After 12 weeks of observation, the Vitamin B12 treatment was found to have significantly alleviated radiodermatitis. The treatment also significantly reduced the expression levels of NF-κB, COX-2, IL-6, and TGF-ß in the skin samples. The pathways involved in the effects of the treatment were identified by analysing gene expression. In conclusion, Vitamin B12 ointment was found to be highly effective for treating radiodermatitis, with strong anti-radiation, anti-inflammatory, and anti-fibrosis effects. It is thus a promising drug candidate for the treatment of severe radiodermatitis.

["Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation].

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Increased expression of Myosin X contributes to the metastasis in patients with laryngeal squamous cell carcinoma.

Laryngeal Squamous Cell Carcinoma (LSCC) is one of the most common malignancy in Head and neck cancer for which the mechanism underlying its metastasis is poorly understood. Myosin X, a molecular motor in cells has been demonstrated to play an important role in cell migration. However, whether Myosin X is involved in the metastasis of LSCC remains unclear. To investigate the expression of Myosin X and its implication in the metastasis of LSCC, we recruited 30 patients with LSCC and 6 patients with vocal cord polyp range from October 2016 to October 2018. Tissue samples were obtained during surgery and the expression of Myosin X, Cortactin, MMP2, MMP9, E-cadherin, and ß-catenin in tissue samples were evaluated by RT-PCR, Western blot, immunohistochemistry or ELISA. Patients with LSCC were further followed-up 2 year after surgery for metastasis analysis. We found that the level of Myosin X, Cortactin, MMP2, and MMP9 was much higher in poorly differentiated LSCC compared to that in moderately and highly LSCC, as well as the control tissues. In contrast, the expression of epithelial-mesenchymal transition related marker, E-cadherin, and ß-catenin, were much lower in poorly differentiated LSCC tissues compared to that in moderately and highly differentiated LSCC tissues, as well as the control tissues. Moreover, the expression of Myosin X was positively correlated with Cortactin, MMP2, and MMP9 levels. Increased expression of Myosin X in LSCC tissues was related to higher risk of metastasis. In conclusion, our findings showed that. Myosin X augments the expression of Cortactin, MMP2 and MMP9, which could upregulate the cell migration and the matrix degradation, and consequently reduce the expression of E-cadherin and ß-catenin, thereby activating epithelial-mesenchymal transformation and promoting the metastasis of LSCC. Targeting Myosin X may have potential therapeutic effect in the metastasis of LSCC.

Touch-Programmable Metasurface for Various Electromagnetic Manipulations and Encryptions.

Previous programmable metasurfaces integrated with diodes or varactors require external instructions for field programmable gate arrays (FPGAs), which usually rely on computer-inputs or pre-loaded algorithms. But the complicated external devices make the coding regulation process of the programmable metasurfaces cumbersome and difficult to use. To simplify the process and provide a new interaction manner, a touch-programmable metasurface (TPM) based on touch sensing modules is proposed to realize various electromagnetic (EM) manipulations and encryptions. By simply touching the meta-units of the TPM, the state of the diodes can be changed. Through the touch controls, the TPM can achieve independent and direct manipulations of meta-units and efficient inputs of coding patterns without using a FPGA or other control modules. Various coding patterns are demonstrated to achieve diverse scattering-field control and flexible near-field EM information encryptions, which verifies the feasibility of the TPM design. The presented TPM will have wide application prospects in imaging displays, wireless communications, and EM information encryptions.

Dual-band chiral metasurface for independent controls of spin-selective reflections.

The development of chiral metasurfaces with spin-selective reflection or transmission provides a new way to control the circularly polarized (CP) waves. However, it is still a great challenge to independently manipulate the polarization, frequency, and phase of the spin-selective reflected waves in different operating bands, which may have potential applications in improving the data capacity of microwave and optical communication systems. Here, a dual-band chiral metasurface is proposed to generate gigantic intrinsic chirality with strong circular dichroism (CD) in two different frequency bands by piecing two typical mono-chiral units together. The polarization, frequency and phase of the spin-selective reflected waves can also be independently designed in the two operating bands by adjusting the configuration of the chiral unit structures. Based on the proposed chiral structures, a dual-band chiral metasurface with spin-selective anomalous reflections is designed and demonstrated by both simulations and experiments. The results show that the polarization of spin-selective reflected waves can be customized by selecting appreciate chiral structures, while the wavefront of the spin-selective reflected waves can be further controlled by designing their arrangement.