Mesoporous Nano-Badminton with Asymmetric Mass Distribution: How Nanoscale Architecture Affects the Blood Flow Dynamics.

While the nanobio interaction is crucial in determining nanoparticles' in vivo fate, a previous work on investigating nanoparticles' interaction with biological barriers is mainly carried out in a static state. Nanoparticles' fluid dynamics that share non-negligible impacts on their frequency of encountering biological hosts, however, is seldom given attention. Herein, inspired by badmintons' unique aerodynamics, badminton architecture Fe3O4&mPDA (Fe3O4 = magnetite nanoparticle and mPDA = mesoporous polydopamine) Janus nanoparticles have successfully been synthesized based on a steric-induced anisotropic assembly strategy. Due to the "head" Fe3O4 having much larger density than the mPDA "cone", it shows an asymmetric mass distribution, analogous to real badminton. Computational simulations show that nanobadmintons have a stable fluid posture of mPDA cone facing forward, which is opposite to that for the real badminton. The force analysis demonstrates that the badminton-like morphology and mass distribution endow the nanoparticles with a balanced motion around this posture, making its movement in fluid stable. Compared to conventional spherical Fe3O4@mPDA nanoparticles, the Janus nanoparticles with an asymmetric mass distribution have straighter blood flow trails and ∼50% reduced blood vessel wall encountering frequency, thus providing doubled blood half-life and ∼15% lower organ uptakes. This work provides novel methodology for the fabrication of unique nanomaterials, and the correlations between nanoparticle architectures, biofluid dynamics, organ uptake, and blood circulation time are successfully established, providing essential guidance for designing future nanocarriers.

DAGLß is the principal synthesizing enzyme of 2-AG and promotes aggressive phenotype of intrahepatic cholangiocarcinoma via AP-1/DAGLß/miR4516 feedforward circuitry.

The endocannabinoid system (ECS) is dysregulated in various liver diseases. Previously, we had shown that the major endocannabinoid 2-arachidonoyl glycerol (2-AG) promoted tumorigenesis of intrahepatic cholangiocarcinoma (ICC). However, biosynthesis regulation and clinical significance of 2-AG remain elusive. In the present study, we quantified 2-AG by gas chromatography/mass spectrometry (GC/MS) and showed that 2-AG was enriched in patients with ICC samples as well as in thioacetamide-induced orthotopic rat ICC model. Moreover, we found that diacylglycerol lipase ß (DAGLß) was the principal synthesizing enzyme of 2-AG that significantly upregulated in ICC. DAGLß promoted tumorigenesis and metastasis of ICC in vitro and in vivo and positively correlated with clinical stage and poor survival in patients with ICC. Functional studies showed that activator protein-1 (AP-1; heterodimers of c-Jun and FRA1) directly bound to the promoter and regulated transcription of DAGLß, which can be enhanced by lipopolysaccharide (LPS). miR-4516 was identified as the tumor-suppressing miRNA of ICC that can be significantly suppressed by LPS, 2-AG, or ectopic DAGLß overexpression. FRA1 and STAT3 were targets of miR-4516 and overexpression of miRNA-4516 significantly suppressed expression of FRA1, SATA3, and DAGLß. Expression of miRNA-4516 was negatively correlated with FRA1, SATA3, and DAGLß in patients with ICC samples. Our findings identify DAGLß as the principal synthesizing enzyme of 2-AG in ICC. DAGLß promotes oncogenesis and metastasis of ICC and is transcriptionally regulated by a novel AP-1/DAGLß/miR4516 feedforward circuitry.NEW & NOTEWORTHY Dysregulated endocannabinoid system (ECS) had been confirmed in various liver diseases. However, regulation and function of 2-arachidonoyl glycerol (2-AG) and diacylglycerol lipase ß (DAGLß) in intrahepatic cholangiocarcinoma (ICC) remain to be elucidated. Here, we demonstrated that 2-AG was enriched in ICC, and DAGLß was the principal synthesizing enzyme of 2-AG in ICC. DAGLß promotes tumorigenesis and metastasis in ICC via a novel activator protein-1 (AP-1)/DAGLß/miR4516 feedforward circuitry.

Streamlined Mesoporous Silica Nanoparticles with Tunable Curvature from Interfacial Dynamic-Migration Strategy for Nanomotors.

Streamlined architectures with a low fluid-resistance coefficient have been receiving great attention in various fields. However, it is still a great challenge to synthesize streamlined architecture with tunable surface curvature at the nanoscale. Herein, we report a facile interfacial dynamic migration strategy for the synthesis of streamlined mesoporous nanotadpoles with varied architectures. These tadpole-like nanoparticles possess a big streamlined head and a slender tail, which exhibit large inner cavities (75-170 nm), high surface areas (424-488 m2 g-1), and uniform mesopore sizes (2.4-3.2 nm). The head curvature of the streamlined mesoporous nanoparticles can be well-tuned from ∼2.96 × 10-2 to ∼5.56 × 10-2 nm-1, and the tail length can also be regulated from ∼30 to ∼650 nm. By selectively loading the Fe3O4 catalyst in the cavity of the streamlined silica nanotadpoles, the H2O2-driven mesoporous nanomotors were designed. The mesoporous nanomotors with optimized structural parameters exhibit outstanding directionality and a diffusion coefficient of 8.15 µm2 s-1.

On-Chip Rolling Design for Controllable Strain Engineering and Enhanced Photon-Phonon Interaction in Graphene.

On-chip strain engineering is highly demanded in 2D materials as an effective route for tuning their extraordinary properties and integrating consistent functionalities toward various applications. Herein, rolling technique is proposed for strain engineering in monolayer graphene grown on a germanium substrate, where compressive or tensile strain could be acquired, depending on the designed layer stressors. Unusual compressive strains up to 0.30% are achieved in the rolled-up graphene tubular structures. The subsequent phonon hardening under compressive loading is observed through strain-induced Raman G band splitting, while distinct blueshifts of characteristic peaks (G+ , G- , or 2D) can be well regulated on an asymmetric tubular structure with a strain variation. In addition, due to the strong confinement of the local electromagnetic field under 3D tubular geometry, the photon-phonon interaction is highly strengthened, and thus, the Raman scattering of graphene in rolled-up tubes is enhanced. Such an on-chip rolling approach leads to a superior strain tuning method in 2D materials and could improve their light-matter interaction in a tubular configuration, which may hold great capability in 2D materials integration for on-chip applications such as in mechanics, electronics, and photonics.

Rolling up MoSe2 Nanomembranes as a Sensitive Tubular Photodetector.

Transition metal dichalcogenides, as a kind of 2D material, are suitable for near-infrared to visible photodetection owing to the bandgaps ranging from 1.0 to 2.0 eV. However, limited light absorption restricts photoresponsivity due to the ultrathin thickness of 2D materials. 3D tubular structures offer a solution to solve the problem because of the light trapping effect which can enhance optical absorption. In this work, thanks to mechanical flexibility of 2D materials, self-rolled-up technology is applied to build up a 3D tubular structure and a tubular photodetector is realized based on the rolled-up molybdenum diselenide microtube. The tubular device is shown to present one order higher photosensitivity compared with planar counterparts. Enhanced optical absorption arising from the multiple reflections inside the tube is the main reason for the increased photocurrent. This tubular device offers a new design for increasing the efficiency of transition metal dichalcogenide-based photodetection and could hold great potential in the field of 3D optoelectronics.

Rolled-up single-layered vanadium oxide nanomembranes for microactuators with tunable active temperature.

Multilayer vanadium dioxide (VO2) actuators are a widespread concern as these micro/nano-actuators present a fast and efficient dynamic response when VO2 occurs in metal-insulator transition (MIT) at 68 °C. By tuning the O2 flow rate during oxide deposition and rolled-up nanotechnology, a microactuator based on a single-layered vanadium oxide nanomembrane with vertical component gradient is fabricated. Upward bending of the nanomembrane is driven by the release of the compressive strain gradient which is revealed through the difference in Raman shift of the vibration mode. Combining strain engineering, the initial curvature of microactuators is tuned in a wide range by the thickness of the nanomembranes. The actuation behavior from low curvature to high final curvature across the MIT is observed which depends on the nanomembrane thickness. Initial compressive strain distribution of the rolled-up nanomembrane decreases the MIT temperature simultaneously. Thus, taking advantage of the tunable MIT and reversible shape transformation, micro/nano-actuators with tunable triggering temperature, controllable initial curvature and large-displacement actuation are fabricated for curvature engineering in micromechanical systems.

Thermal-controlled releasing and assembling of functional nanomembranes through polymer pyrolysis.

Pyrolysis, which involves thermal decomposition of materials at elevated temperatures, has been commonly applied in the chemical industry. Here we explored the pyrolysis process for 3D nanofabrication. By strain engineering of nanomembranes on a thermal responsive polymer as the sacrificial layer, we demonstrated that diverse 3D rolled-up microstructures with different functions could be achieved without any additional solution and drying process. We carefully studied the effect of molecular weight of the polymer in the pyrolysis process and identified that the rapid breakdown of molecular backbone to a monomer is the key for nanomembrane releasing and rolling. Preferential rolling direction and corresponding dynamics were studied by analyzing the real-time video of the rolling process. We further demonstrated the versatile functions of the fabricated 3D structures as catalytic microengines and optical resonators. The simple fabrication methodology developed here may have great potential in producing functional 3D tubular micro-/nanostructures.

Anisotropic Rolling and Controlled Chirality of Nanocrystalline Diamond Nanomembranes toward Biomimetic Helical Frameworks.

Future advances in materials will be aided by improved dimensional control in fabrication of 3D hierarchical structures. Self-rolling technology provides additional degrees of freedom in 3D design by enabling an arbitrary rolling direction with controllable curvature. Here, we demonstrate that deterministic helical structures with variable rolling directions can be formed through releasing a strained nanomembrane patterned in a "utility knife" shape. The asymmetry of the membrane shape provides anisotropic driving force generated by the disparity between the etching rates along different sides in this asymmetric shape. A transient finite element method (FEM) model of diagonal rolling is established to analyze the relationships among geometries, elastic properties, and boundary conditions. On the basis of this model, a diamond-based helical framework consisting of two or three helical segments has been fabricated to mimic the shapes of natural plants. Further experiment has been done to extend this approach to other materials and material combinations, such as MoSe2/Cr, Cr/Pt, and VO2. To demonstrate the possible application accessible by our technology to new fields, VO2-based helical microscale actuation has been demonstrated with photocontrollable bending in a selected region, as well as morphable and recognizable helix. This study offers a new way to construct helical mesostructures that combine special properties of the advanced materials, thus possess novel features and potential applications.

Reconfigurable Vanadium Dioxide Nanomembranes and Microtubes with Controllable Phase Transition Temperatures.

Two additional structural forms, free-standing nanomembranes and microtubes, are reported and added to the vanadium dioxide (VO2) material family. Free-standing VO2 nanomembranes were fabricated by precisely thinning as-grown VO2 thin films and etching away the sacrificial layer underneath. VO2 microtubes with a range of controllable diameters were rolled-up from the VO2 nanomembranes. When a VO2 nanomembrane is rolled-up into a microtubular structure, a significant compressive strain is generated and accommodated therein, which decreases the phase transition temperature of the VO2 material. The magnitude of the compressive strain is determined by the curvature of the VO2 microtube, which can be rationally and accurately designed by controlling the tube diameter during the rolling-up fabrication process. The VO2 microtube rolling-up process presents a novel way to controllably tune the phase transition temperature of VO2 materials over a wide range toward practical applications. Furthermore, the rolling-up process is reversible. A VO2 microtube can be transformed back into a nanomembrane by introducing an external strain. Because of its tunable phase transition temperature and reversible shape transformation, the VO2 nanomembrane-microtube structure is promising for device applications. As an example application, a tubular microactuator device with low driving energy but large displacement is demonstrated at various triggering temperatures.

Selected and Enhanced Single Whispering-Gallery Mode Emission from a Mesostructured Nanomembrane Microcavity.

Quantum sciences are revolutionizing computing and communication technologies, in which single-photon emitters are the key components for creating strong quantum entanglement. Color centers in diamonds in coupled-cavity systems are considered great candidates for the efficient generation of quantum carriers over other solid-state emitters. Owing to the multi-mode nature of high quality factor ( Q) diamond cavities, however, it is a grand challenge to the achievement of single photon emission with high rate and indistinguishability. To this end, a single-mode high- Q diamond cavity is highly desired. Here, we report a diamond mesostructured nanomembrane microcavity of a discrete rotational symmetry that selectively produces the desired single-mode emission in a broad spectrum. The strategic rolling up of a flexible diamond nanomembrane with aligned holes effectively defines the designed symmetry while maintaining the high- Q resonance through the whispering-gallery mode supported in the central hollow microcavity. The demonstrated diamond mesostructured microcavity features a distinct and enhanced single-mode emission, a step toward efficient quantum sources with designed positions or bands for quantum information technology.

TLK2 promotes progression of hepatocellular carcinoma through Wnt/ß-catenin signaling.

Background: Hepatocellular carcinoma is a widespread cancer worldwide, ranking as the fifth most frequent cancer and the fourth leading cause of cancer-related deaths. According to comprehensive research, TLK2, a phosphorylated kinase, has been discovered to play a crucial role in promoting tumor development. However, the prognostic significance and influence of TLK2 on hepatocellular carcinoma tumor cells and the immune microenvironment remain unexplored, warranting further investigation. The aim of this study was to investigate the role of TLK2 in promoting the development of hepatocellular carcinoma. Methods: The present study utilized The Cancer Genome Atlas (TCGA) database and other databases as training sets to examine the expression of TLK2 and its prognostic significance. The findings were subsequently validated through cell proliferation assays and cell colony assays. Gene set enrichment analysis (GSEA) was employed to investigate the tumor-related biological processes associated with TLK2 in hepatocellular carcinoma, while the relationship between TLK2 expression and Wnt/ß-catenin signaling pathway was analyzed via TCGA dataset analysis. Western blotting and immunofluorescence assays were used to confirm the experimental results. Results: TLK2 showed higher expression levels in tumor tissues than in normal tissues. Alpha fetoprotein (AFP), T stage, pathological stage, and histological grade were significantly associated with TLK2 expression. High TLK2 expression correlated with worse overall survival (OS) [hazard ratio (HR) =1.62, 95% confidence interval (CI): 1.14-2.29, P=0.007], progression-free survival (PFS) (HR =1.88, 95% CI: 1.40-2.52, P<0.001) and disease specific survival (DSS) (HR =1.86, 95% CI: 1.18-2.93, P=0.007) in the training and validation sets. Both univariate and multivariate analyses showed that TLK2 was an independent prognostic factor. GSEA showed that TLK2 was significantly enriched in tumor-related biological processes. TLK2 induced the activation of ß-catenin signaling, resulting in sustained tumor growth. Methyl thiazolyl tetrazolium (MTT) and colony formation assays demonstrated that TLK2 could promote hepatocellular carcinoma progression. Furthermore, TLK2 showed a significant association with ß-catenin in the Wnt pathway. Conclusions: TLK2 represents an independent prognostic factor in hepatocellular carcinoma and can promote cancer progression via the ß-catenin signaling pathway.

A Novel Oncogenic Role of Disulfidptosis-related Gene SLC7A11 in Anti-tumor Immunotherapy Response to Human Cancers.

BACKGROUND: The protein Solute Carrier Family 7 Member 11 (SLC7A11) plays a pivotal role in cellular redox homeostasis by suppressing disulfidptosis, which restricts tumor growth. Yet, its relevance in prognosis, immunity, and cancer treatment efficacy is not well understood. METHODS: We conducted a comprehensive analysis of the expression of SLC7A11 across 33 cancer types, employing datasets from public databases. Methods, such as Cox regression and survival analyses assessed its prognostic significance, while functional enrichment explored the biological processes tied to SLC7A11. The association between SLC7A11 expression, immune cell infiltration, and immune-related gene expression was also scrutinized. RESULTS: Notably, SLC7A11 expression was more pronounced in cancerous compared to normal samples and correlated with higher tumor grades. Increased SLC7A11 expression was linked to poor outcomes, particularly in liver hepatocellular carcinoma (LIHC). This protein's expression also showcased significant relationships with diverse molecular and immune subtypes. Additionally, a prognostic nomogram was devised, integrating SLC7A11 expression and clinical variables. High SLC7A11 levels corresponded with cell growth and senescence pathways in various cancers and with lipid and cholesterol metabolism in LIHC. Furthermore, potential therapeutic compounds for LIHC with high SLC7A11 were identified. Real-time PCR (qPCR) and Western blot were conducted to explore the expression of SLC7A11 in tumor tissues and cancer cell lines. CONCLUSION: In summation, this study emphasizes the prognostic and immunological importance of SLC7A11, spotlighting its potential as a therapeutic target in LIHC.

Label-free investigation of infected acute pyelonephritis tissue by FTIR microspectroscopy with unsupervised and supervised analytical methods.

Acute pyelonephritis (AP) is a severe urinary tract infection (UTI) syndrome with a large population of patients worldwide. Current approaches to confirming AP are limited to urinalysis, radiological imaging methods and histological assessment. Fourier transform infrared (FTIR) microspectroscopy is a promising label-free modality that can offer information about both morphological and molecular pathologic alterations from biological tissues. Here, FTIR microspectroscopy serves to investigate renal biological histology of a rat model with AP and classify normal cortex, normal medulla and infected acute pyelonephritis tissues. The spectra were experimentally collected by FTIR with an infrared Globar source through raster scanning procedure. Unsupervised analysis methods, including integrating, clustering and principal component analysis (PCA) were performed on such spectra data to form infrared histological maps of entire kidney section. In comparison to Hematoxylin & Eosin-stained results of the adjacent tissue sections, these infrared maps were proved to enable the differentiation of the renal tissue types. The results of both integration and clustering indicated that the concentration of amide II decreases in the infected acute pyelonephritis tissues, with an increased presence of nucleic acids and lipids. By means of PCA, the infected tissue was linearly separated from normal ones by plotting confident ellipses with the score values of the first and second principal components. Moreover, supervised analysis was performed based on the supported vector machines (SVM). Normal cortex, normal medulla and infected acute pyelonephritis tissues were classified by SVM models with the best accuracy of 96.11% in testing dataset. In addition, these analytical methods were further employed on synchrotron-based FTIR spectra data and successfully form high-resolution infrared histological maps of glomerulus and necrotic cell mass. This work demonstrates that FTIR microspectroscopy will be a powerful manner to investigate AP tissue and differentiate infected tissue from normal tissue in a renal infected model system.

Fatty acid metabolism affects hepatocellular carcinoma progression via the PPAR-γ signaling pathway and fatty acid ß-oxidation.

PURPOSE: This study aimed to explore novel targets for hepatocellular carcinoma (HCC) treatment by investigating the role of fatty acid metabolism. METHODS: RNA-seq and clinical data of HCC were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatic analyses were employed to identify differentially expressed genes (DEGs) related to prognosis. A signature was then constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression to classify HCC patients from the TCGA database into low-risk and high-risk groups. The predictive performance of the signature was evaluated through principal components analysis (PCA), Kaplan Meier (KM) survival analysis, receiver operating characteristics (ROC) curves, nomogram, genetic mutations, drug sensitivity analysis, immunological correlation analysis, and enrichment analysis. Single-cell maps were constructed to illustrate the distribution of core genes. Immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and western blot were employed to verify the expression of core genes. The function of one core gene was validated through a series of in vitro assays, including cell viability, colony formation, wound healing, trans-well migration, and invasion assays. The results were analyzed in the context of relevant signaling pathways. RESULTS: Bioinformatic analyses identified 15 FAMGs that were related to prognosis. A 4-gene signature was constructed, and patients were divided into high- and low-risk groups according to the signature. The high-risk group exhibited a poorer prognosis compared to the low-risk group in both the training (P < 0.001) and validation (P = 0.020) sets. Furthermore, the risk score was identified as an independent predictor of OS (P < 0.001, HR = 8.005). The incorporation of the risk score and clinicopathologic features into a nomogram enabled the effective prediction of patient prognosis. The model was able to effectively predict the immune microenvironment, drug sensitivity to chemotherapy, and gene mutation for each group. Single-cell maps demonstrated that FAMGs in the model were distributed in tumor cells. Enrichment analyses revealed that the cell cycle, fatty acid ß oxidation and PPAR signaling pathways were the most significant pathways. Among the four key prognostically related FAMGs, Spermine Synthase (SMS) was selected and validated as a potential oncogene affecting cell cycle, PPAR-γ signaling pathway and fatty acid ß oxidation in HCC. CONCLUSIONS: The risk characteristics based on FAMGs could serve as independent prognostic indicators for predicting HCC prognosis and could also serve as evaluation criteria for gene mutations, immunity, and chemotherapy drug therapy in HCC patients. Meanwhile, targeted fatty acid metabolism could be used to treat HCC through related signaling pathways.

A Multi-foci Sparse-Aperture Metalens.

Multi-foci lenses are essential components for optical communications, virtual reality display and microscopy, yet the bulkiness of conventional counterparts has significantly hindered their widespread applications. Benefiting from the unprecedented capability of metasurfaces in light modulation, metalenses are able to provide multi-foci functionality with a more compact footprint. However, achieving imaging quality comparable to that of corresponding single-foci metalenses at each focal point poses a challenge for existing multi-foci metalenses. Here, a polarization-independent all-dielectric multi-foci metalens is proposed and experimentally demonstrated by spatially integrating single-foci optical sparse-aperture sub-metalenses. Such design enables the metalens to generate multiple focal points, while maintaining the ability to capture target information comparable to that of a single-foci metalens. The proposed multi-foci metalens is composed of square-nanohole units array fabricated by two-photon polymerization. The focusing characteristic and imaging capability are demonstrated upon the illumination of an unpolarized light beam. This work finds a novel route toward multi-foci metalenses and may open a new avenue for dealing with the trade-off between multi-foci functionality and high-quality imaging performance.

Pan-Cancer Analysis Reveals Disulfidoptosis-Associated Genes as Promising Immunotherapeutic Targets: Insights Gained from Bulk Omics and Single-Cell Sequencing Validation.

Disulfidoptosis, a novel form of cell death, is distinct from other well-known cell death mechanisms. Consequently, a profound investigation into disulfidoptosis elucidates the fundamental mechanisms underlying tumorigenesis, presenting promising avenues for therapeutic intervention. Comprehensive analysis of disulfidoptosis-associated gene (DRG) expression in pan cancer utilized TCGA, GEO, and ICGC datasets, including survival and Cox-regression analyses for prognostic evaluation. We analyzed the association between DRG expression and both immune cell infiltration and immune-related gene expression using the ESTIMATE and TISDIB datasets. We obtained our single-cell RNA sequencing (scRNA-seq) data from the GEO repository. Subsequently, we assessed disulfidoptosis activity in various cell types. Evaluation of immune cell infiltration and biological functions was analyzed via single-sample gene set enrichment (ssGSEA) and gene set variation analysis (GSVA). For in vitro validation experiments, the results from real-time PCR (RT-qPCR) and Western blot were used to explore the expression of SLC7A11 in hepatocellular carcinoma (HCC) tissues and different cancer cell lines, while siRNA-mediated SLC7A11 knockdown effects on HCC cell proliferation and migration were examined. Expression levels of DRGs, especially SLC7A11, were significantly elevated in tumor samples compared to normal samples, which was associated with poorer outcomes. Except for SLC7A11, DRGs consistently exhibited high CNV and SNV rates, particularly in HCC. In various tumors, DRGs were negatively associated with DNA promoter methylation. TME analyses further illustrated a negative correlation of DRG expression with ImmuneScore and StromalScore and a positive correlation with tumor purity. Our analysis unveiled diverse cellular subgroups within HCC, particularly focusing on Treg cell populations, providing insights into the intricate interplay of immune activation and suppression within the tumor microenvironment (TME). These findings were further validated through RT-qPCR, Western blot analyses, and immunohistochemical analyses. Additionally, the knockdown of SLC7A11 induced a suppression of proliferation and migration in HCC cell lines. In conclusion, our comprehensive pan-cancer analysis research has demonstrated the significant prognostic and immunological role of disulfidoptosis across a spectrum of tumors, notably HCC, and identified SLC7A11 as a promising therapeutic target.

High Bile Titer and High Bile to Serum Ratio of CYFRA 21 - 1 Reliably Discriminate Malignant Biliary Obstruction Caused by Cholangiocarcinoma.

INTRODUCTION: Previously we demonstrated that elevated serum CYFRA 21 - 1 is a reliable diagnostic and prognostic biomarker for biliary tract cancers. This study aims to explore the diagnostic performance of bile CYFRA 21 - 1 (bCYFRA 21 - 1) in discriminating malignant biliary obstruction (MBO) caused by cholangiocarcinoma (CCA). METHODS: 77 CCA patients ((17 intrahepatic CCA (iCCA), 49 perihilar CCA (pCCA) and 11 distal CCA (dCCA)) and 43 benign patients with biliary obstruction were enrolled. Serum and bile levels of CYFRA 21 - 1, carcinoembryonic antigen (CEA) and carbohydrate antigen 19 - 9 (CA19-9) were quantified. Diagnostic performances of these biomarkers were estimated by receiver operator characteristic curves. Subgroups analysis of these tumor markers among CCA subtypes was performed. RESULTS: High bCYFRA 21 - 1 (cut-off value of 59.25 ng/mL with sensitivity of 0.889 and specificity of 0.750) and high bile to serum ratio of CYFRA 21 - 1 (b/sCYFRA 21 - 1, cut-off value of 31.55 with sensitivity of 0.741 and specificity of 0.778) achieved better diagnostic performance than any other biomarker in discriminating MBO. Subgroup analysis revealed that bCYFRA 21 - 1 was significantly elevated in all CCA subtypes; moreover b/sCYFRA 21 - 1 was upregulated in pCCA and dCCA (the mean b/sCYFRA 21 - 1 of pCCA was highest among CCA subtypes: 57.90, IQR 29.82-112.27). CONCLUSIONS: Both high biliary CYFRA 21 - 1 and high bile to serum ratio of CYFRA 21 - 1 were reliable diagnostic biomarkers for MBO caused by CCA.

Single-Cell RNA Sequencing and Microarray Analysis Reveal the Role of Lipid-Metabolism-Related Genes and Cellular Immune Infiltration in Pre-Eclampsia and Identify Novel Biomarkers for Pre-Eclampsia.

Pre-eclampsia (PE) is a gestational hypertensive disorder that is characterized by hypertension and proteinuria, typically occurring after 20 weeks of gestation. Despite its global impact on pregnant women, the precise pathogenic mechanisms of PE remain unclear. Dysregulated lipid metabolism and immune cell infiltration contribute to PE development. Our study aimed to identify lipid-metabolism-related genes (LMRG-PEs) and investigate their association with immune infiltration. We utilized the "Seurat" R package for data quality control, cell clustering, and marker gene identification. The "SingleR" package enabled the matching of marker genes to specific cell types. Pseudotemporal ordering analysis was conducted using the "Monocle" package. Weighted correlation network analysis (WGCNA), gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA) approaches were employed to explore lipid-metabolism-related genes, while potential targeted drugs were predicted using the drug-gene interaction database (DGIdb). Hub gene expression was validated through RT-qPCR. By analyzing single-cell RNA sequencing data, we identified and classified 20 cell clusters into 5 distinct types. Differential gene expression analysis revealed 186 DEGs. WGCNA identified 9 critical modules and 265 genes significantly associated with PE diagnosis, emphasizing the importance of the core genes PLA2G7 and PTGS2. RT-qPCR confirmed the significantly decreased expression of PLA2G7 and PTGS2 in PE patient tissues. These findings offer valuable insights into the molecular mechanisms of PE, particularly those involving lipid metabolism and immune infiltration. The identified hub genes have potential as therapeutic targets and biomarkers for future research and clinical applications.

Effectiveness of interventions to reduce aerosol generation in dental environments: A systematic review.

Certain dental procedures produce high levels of aerosols containing pathogenic microorganisms, posing a risk for the transmission of infections in dental settings. This study aimed to assess the effectiveness of various aerosol mitigation interventions during clinical dental procedures in real-world environments. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Embase for English studies up to March 2023 according to the PRISMA guidelines. Only peer-reviewed controlled clinical trials (CCT) or randomized controlled trials (RCT) studies involving human subjects were included. The risk of bias of selected researches were evaluated by two independent authors using the Cochrane Collaboration tool. The literature search yielded 3491 articles, of which 42 studies met the inclusion criteria and were included in this study. Most studies evaluated bacterial contamination in bio-aerosols, while the viral and fungal contamination was assessed in only three studies. Overall, various approaches have been applied in reducing aerosol contamination in clinical scenarios, including high-volume evacuators (HVE), mouse rinses and rubber dams, air cleaning systems, and high-efficiency particulate air (HEPA) filters. The available evidence suggests that various aerosol mitigation strategies could be implemented to decrease the risk of cross-infection during clinical dental procedures in real-world environments. However, further clinical trials are necessary to establish statistical validity in measuring aerosol contamination and mitigation, as well as to evaluate the risk of infection transmission for viral and fungal contamination.

RabbitTClust: enabling fast clustering analysis of millions of bacteria genomes with MinHash sketches.

We present RabbitTClust, a fast and memory-efficient genome clustering tool based on sketch-based distance estimation. Our approach enables efficient processing of large-scale datasets by combining dimensionality reduction techniques with streaming and parallelization on modern multi-core platforms. 113,674 complete bacterial genome sequences from RefSeq, 455 GB in FASTA format, can be clustered within less than 6 min and 1,009,738 GenBank assembled bacterial genomes, 4.0 TB in FASTA format, within only 34 min on a 128-core workstation. Our results further identify 1269 redundant genomes, with identical nucleotide content, in the RefSeq bacterial genomes database.