Nano-cutting mechanism of ion implantation-modified SiC: reducing subsurface damage expansion and abrasive wear.

This study utilized ion implantation to modify the material properties of silicon carbide (SiC) to mitigate subsurface damage during SiC machining. The paper analyzed the mechanism of hydrogen ion implantation on the machining performance of SiC at the atomic scale. A molecular dynamics model of nanoscale cutting of an ion-implanted SiC workpiece using a non-rigid regular tetrakaidecahedral diamond abrasive grain was established. The study investigated the effects of ion implantation on crystal structure phase transformation, dislocation nucleation, and defect structure evolution. Results showed ion implantation modification decreased the extension depth of amorphous structures in the subsurface layer, thereby enhancing the surface and subsurface integrity of the SiC workpiece. Additionally, dislocation extension length and volume within the lattice structure were lower in the ion-implanted workpiece compared to non-implanted ones. Phase transformation, compressive pressure, and cutting stress of the lattice in the shear region per unit volume were lower in the ion-implanted workpiece than the non-implanted one. Taking the diamond abrasive grain as the research subject, the mechanism of grain wear under ion implantation was explored. Grain expansion, compression, and atomic volumetric strain wear rate were higher in the non-implanted workpiece versus implanted ones. Under shear extrusion of the SiC workpiece, dangling bonds of atoms in the diamond grain were unstable, resulting in graphitization of the diamond structure at elevated temperatures. This study established a solid theoretical and practical foundation for realizing non-destructive machining at the atomic scale, encompassing both theoretical principles and practical applications. .

Classification of anatomical morphology of cystic duct and its association with gallstone.

BACKGROUND: Gallstones are common lesions that often require surgical intervention. Laparoscopic cholecystectomy is the treatment of choice for symptomatic gallstones. Preoperatively, the anatomical morphology of the cystic duct (CD), needs to be accurately recognized, especially when anatomical variations occur in the CD, which is otherwise prone to bile duct injury. However, at present, there is no optimal classification system for CD morphology applicable in clinical practice, and the relationship between anatomical variations in CDs and gallstones remains to be explored. AIM: To create a more comprehensive clinically applicable classification of the morphology of CD and to explore the correlations between anatomic variants of CD and gallstones. METHODS: A total of 300 patients were retrospectively enrolled from October 2021 to January 2022. The patients were divided into two groups: The gallstone group and the nongallstone group. Relevant clinical data and anatomical data of the CD based on magnetic resonance cholangiopancreatography (MRCP) were collected and analyzed to propose a morphological classification system of the CD and to explore its relationship with gallstones. Multivariate analysis was performed using logistic regression analyses to identify the independent risk factors using variables that were significant in the univariate analysis. RESULTS: Of the 300 patients enrolled in this study, 200 (66.7%) had gallstones. The mean age was 48.10 ± 13.30 years, 142 (47.3%) were male, and 158 (52.7%) were female. A total of 55.7% of the patients had a body mass index (BMI) ≥ 24 kg/m2. Based on the MRCP, the CD anatomical typology is divided into four types: Type I: Linear, type II: n-shaped, type III: S-shaped, and type IV: W-shaped. Univariate analysis revealed differences between the gallstone and nongallstone groups in relation to sex, BMI, cholesterol, triglycerides, morphology of CD, site of CD insertion into the extrahepatic bile duct, length of CD, and angle between the common hepatic duct and CD. According to the multivariate analysis, female, BMI (≥ 24 kg/m2), and CD morphology [n-shaped: Odds ratio (OR) = 10.97, 95% confidence interval (95%CI): 5.22-23.07, P < 0.001; S-shaped: OR = 4.43, 95%CI: 1.64-11.95, P = 0.003; W-shaped: OR = 7.74, 95%CI: 1.88-31.78, P = 0.005] were significantly associated with gallstones. CONCLUSION: The present study details the morphological variation in the CD and confirms that CD tortuosity is an independent risk factor for gallstones.

Recent Advances of CeO2-Based Composite Materials for Photocatalytic Applications.

Photocatalysis has the advantages of practical, sustainable and environmental protection, so it plays a significant role in energy transformation and environmental utilization. CeO2 has attracted widespread attention for its unique 4 f electrons, rich defect structures, high oxygen storage capacity and great chemical stability. In this paper, we review the structure of CeO2 and the common methods for the preparation of CeO2-based composites in the first part. In particular, we highlight the co-precipitation method, template method, and sol-gel method methods. Then, in the second part, we introduce the application of CeO2-based composites in photocatalysis, including photocatalytic CO2 reduction, hydrogen production, degradation, selective organic reaction, and photocatalytic nitrogen fixation. In addition, we discuss several modification techniques to improve the photocatalytic performance of CeO2-based composites, such as elemental doping, defect engineering, constructing heterojunction and morphology regulation. Finally, the challenges faced by CeO2-based composites are analyzed and their development prospects are prospected. This review provides a systematic summary of the recent advance of CeO2-based composites in the field of photocatalysis, which can provide useful references for the rational design of efficient CeO2-based composite photocatalysts for sustainable development.

Identification of Treg-related prognostic molecular subtypes and individualized characteristics in clear cell renal cell carcinoma through single-cell transcriptomes and bulk RNA sequencing.

BACKGROUND: In clear cell renal cell carcinoma (ccRCC), the role of Regulatory T cells (Treg cells) as prognostic and immunotherapy response predictors is not fully explored. METHODS: Analyzing renal clear cell carcinoma datasets from TISCH, TCGA, and GEO, we focused on 8 prognostic Treg genes to study patient subtypes in ccRCC. We assessed Treg subtypes in relation to patient prognosis, tumor microenvironment, metabolism. Using Cox regression and principal component analysis, we devised Treg scores for individual patient characterization and explored the molecular role of C1QL1, a critical gene in the Treg model, through in vivo and in vitro studies. RESULTS: Eight Treg-associated prognostic genes were identified, classifying ccRCC patients into cluster A and B. Cluster A patients showed poorer prognosis with distinct clinical and molecular profiles, potentially benefiting more from immunotherapy. Low Treg scores correlated with worse outcomes and clinical progression. Low scores also suggested that patients might respond better to immunotherapy and targeted therapies. In ccRCC, C1QL1 knockdown reduced tumor proliferation and invasion via NF-kb-EMT pathways and decreased Treg cell infiltration, enhancing immune efficacy. CONCLUSIONS: The molecular subtype and Treg score in ccRCC, based on Treg cell marker genes, are crucial in personalizing ccRCC treatment and underscore C1QL1's potential as a tumor biomarker and target for immunotherapy.

BatchEval Pipeline: batch effect evaluation workflow for multiple datasets joint analysis.

As genomic sequencing technology continues to advance, it becomes increasingly important to perform joint analyses of multiple datasets of transcriptomics. However, batch effect presents challenges for dataset integration, such as sequencing data measured on different platforms, and datasets collected at different times. Here, we report the development of BatchEval Pipeline, a batch effect workflow used to evaluate batch effect on dataset integration. The BatchEval Pipeline generates a comprehensive report, which consists of a series of HTML pages for assessment findings, including a main page, a raw dataset evaluation page, and several built-in methods evaluation pages. The main page exhibits basic information of the integrated datasets, a comprehensive score of batch effect, and the most recommended method for removing batch effect from the current datasets. The remaining pages exhibit evaluation details for the raw dataset, and evaluation results from the built-in batch effect removal methods after removing batch effect. This comprehensive report enables researchers to accurately identify and remove batch effects, resulting in more reliable and meaningful biological insights from integrated datasets. In summary, the BatchEval Pipeline represents a significant advancement in batch effect evaluation, and is a valuable tool to improve the accuracy and reliability of the experimental results. Availability & Implementation: The source code of the BatchEval Pipeline is available at https://github.com/STOmics/BatchEval.

Generating single-cell gene expression profiles for high-resolution spatial transcriptomics based on cell boundary images.

In spatially resolved transcriptomics, Stereo-seq facilitates the analysis of large tissues at the single-cell level, offering subcellular resolution and centimeter-level field-of-view. Our previous work on StereoCell introduced a one-stop software using cell nuclei staining images and statistical methods to generate high-confidence single-cell spatial gene expression profiles for Stereo-seq data. With advancements allowing the acquisition of cell boundary information, such as cell membrane/wall staining images, we updated our software to a new version, STCellbin. Using cell nuclei staining images, STCellbin aligns cell membrane/wall staining images with spatial gene expression maps. Advanced cell segmentation ensures the detection of accurate cell boundaries, leading to more reliable single-cell spatial gene expression profiles. We verified that STCellbin can be applied to mouse liver (cell membranes) and Arabidopsis seed (cell walls) datasets, outperforming other methods. The improved capability of capturing single-cell gene expression profiles results in a deeper understanding of the contribution of single-cell phenotypes to tissue biology. Availability & Implementation: The source code of STCellbin is available at https://github.com/STOmics/STCellbin.

Machinability and Surface Properties of Cryogenic Poly(methyl methacrylate) Machined via Single-Point Diamond Turning.

Poly(methyl methacrylate) (PMMA), with a glass transition temperature (Tg) over 100 °C, shows good mechanical and optical properties and has broad applications after being machined with single-point diamond turning (SPDT) at room temperature. Because of the high Tg, current efforts mostly focus on optimizing machining parameters to improve workpiece precision without considering the modification of material properties. Cryogenic cooling has been proven to be an effective method in assisting ultra-precision machining for certain types of metals, alloys, and polymers, but has never been used for PMMA before. In this work, cryogenic cooling was attempted during the SPDT of PMMA workpieces to improve surface quality. The machinability and surface properties of cryogenically cooled PMMA were investigated based on the mechanical properties at corresponding temperatures. Nanoindentation tests show that, when temperature is changed from 25 °C to 0 °C, the hardness and Young's modulus are increased by 37% and 22%, respectively. At these two temperature points, optimal parameters including spindle speed, feed rate and cut depth were obtained using Taguchi methods to obtain workpieces with high surface quality. The surface quality was evaluated based on the total height of the profile (Pt) and the arithmetic mean deviation (Ra). The measurement results show that the values of Pt and Ra of the workpiece machined at 0 °C are 124 nm and 6 nm, respectively, while the corresponding values of that machined at 25 °C are 291 nm and 11 nm. The test data show that cryogenic machining is useful for improving the form accuracy and reducing the surface roughness of PMMA. Moreover, the relationship between temperature, material properties and machinability weas established with dynamic mechanical analysis (DMA) data and a theoretical model. This can explain the origin of the better surface quality of the cryogenic material. The basis of this is that temperature affects the viscoelasticity of the polymer and the corresponding mechanical properties due to relaxation. Then, the material property changes will affect surface profile formation during machining. The experimental results and theoretical analysis show that cryogenically cooled PMMA has good machinability and improved surface quality when using SPDT compared to that at ambient temperature.

EAGS: efficient and adaptive Gaussian smoothing applied to high-resolved spatial transcriptomics.

BACKGROUND: The emergence of high-resolved spatial transcriptomics (ST) has facilitated the research of novel methods to investigate biological development, organism growth, and other complex biological processes. However, high-resolved and whole transcriptomics ST datasets require customized imputation methods to improve the signal-to-noise ratio and the data quality. FINDINGS: We propose an efficient and adaptive Gaussian smoothing (EAGS) imputation method for high-resolved ST. The adaptive 2-factor smoothing of EAGS creates patterns based on the spatial and expression information of the cells, creates adaptive weights for the smoothing of cells in the same pattern, and then utilizes the weights to restore the gene expression profiles. We assessed the performance and efficiency of EAGS using simulated and high-resolved ST datasets of mouse brain and olfactory bulb. CONCLUSIONS: Compared with other competitive methods, EAGS shows higher clustering accuracy, better biological interpretations, and significantly reduced computational consumption.

Photocatalytic Conversion of Diluted CO2 into Tunable Syngas via Modulating Transition Metal Hydroxides.

The conversion of diluted CO2 into tunable syngas via photocatalysis is critical for implementing CO2 reduction practically, although the efficiency remains low. Herein, we report the use of graphene-modified transition metal hydroxides, namely, NiXCo1-X-GR, for the conversion of diluted CO2 into syngas with adjustable CO/H2 ratios, utilizing Ru dyes as photosensitizers. The Ni(OH)2-GR cocatalyst can generate 12526 µmol g-1 h-1 of CO and 844 µmol g-1 h-1 of H2, while the Co(OH)2-GR sample presents a generation rate of 2953 µmol g-1 h-1 for CO and 10027 µmol g-1 h-1 for H2. Notably, by simply altering the addition amounts of nickel and cobalt in the transition metal composite, the CO/H2 ratios in syngas can be easily regulated from 18:1 to 1:4. Experimental characterization of composites and DFT calculations suggest that the differing adsorption affinities of CO2 and H2O over Ni(OH)2-GR and Co(OH)2-GR play a significant role in determining the selectivity of CO and H2 products, ultimately affecting the CO/H2 ratios in syngas. Overall, these findings demonstrate the potential of graphene-modified transition metal hydroxides as efficient photocatalysts for CO2 reduction and syngas production.

A comprehensive review for machine learning on neuroimaging in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a common mental disease, which can exist as a separate disease or become one of the symptoms of other mental diseases. With the development of society, statistically, the incidence rate of obsessive-compulsive disorder has been increasing year by year. At present, in the diagnosis and treatment of OCD, The clinical performance of patients measured by scales is no longer the only quantitative indicator. Clinical workers and researchers are committed to using neuroimaging to explore the relationship between changes in patient neurological function and obsessive-compulsive disorder. Through machine learning and artificial learning, medical information in neuroimaging can be better displayed. In this article, we discuss recent advancements in artificial intelligence related to neuroimaging in the context of Obsessive-Compulsive Disorder.

Tumor Microenvironment-Responsive One-for-All Molecular-Engineered Nanoplatform Enables NIR-II Fluorescence Imaging-Guided Combinational Cancer Therapy.

The activable NIR-based phototheranostic nanoplatform (NP) is considered an efficient and reliable tumor treatment due to its strong targeting ability, flexible controllability, minimal side effects, and ideal therapeutic effect. This work describes the rational design of a second near-infrared (NIR-II) fluorescence imaging-guided organic phototheranostic NP (FTEP-TBFc NP). The molecular-engineered phototheranostic NP has a sensitive response to glutathione (GSH), generating hydrogen sulfide (H2S) gas, and delivering ferrocene molecules in the tumor microenvironment (TME). Under 808 nm irradiation, FTEP-TBFc could not only simultaneously generate fluorescence, heat, and singlet oxygen but also greatly enhance the generation of reactive oxygen species to improve chemodynamic therapy (CDT) and photodynamic therapy (PDT) at a biosafe laser power of 0.33 W/cm2. H2S inhibits the activity of catalase and cytochrome c oxidase (COX IV) to cause the enhancement of CDT and hypothermal photothermal therapy (HPTT). Moreover, the decreased intracellular GSH concentration further increases CDT's efficacy and downregulates glutathione peroxidase 4 (GPX4) for the accumulation of lipid hydroperoxides, thus causing the ferroptosis process. Collectively, FTEP-TBFc NPs show great potential as a versatile and efficient NP for specific tumor imaging-guided multimodal cancer therapy. This unique strategy provides new perspectives and methods for designing and applying activable biomedical phototheranostics.

Trisulfide Bond-Mediated Molecular Phototheranostic Platform for "Activatable" NIR-II Imaging-Guided Enhanced Gas/Chemo-Hypothermal Photothermal Therapy.

Tumor microenvironment (TME)-triggered phototheranostic platform offers a feasible strategy to improve cancer diagnosis accuracy and minimize treatment side effects. Developing a stable and biocompatible molecular phototheranostic platform for TME-activated second near-infrared (NIR-II) fluorescence imaging-guided multimodal cascade therapy is a promising strategy for creating desirable anticancer agents. Herein, a new NIR-II fluorescence imaging-guided activatable molecular phototheranostic platform (IR-FEP-RGD-S-S-S-Fc) is presented for actively targeted tumor imaging and hydrogen sulfide (H2 S) gas-enhanced chemodynamic-hypothermal photothermal combined therapy (CDT/HPTT). It is revealed for the first time that the coupling distance between IR-FE and ferrocene is proportional to the photoinduced electron transfer (PET), and the aqueous environment is favorable for PET generation. The part of Cyclic-RGDfK (cRGDfk) peptides can target the tumor and benefit the endocytosis of nanoparticles. The high-concentration glutathione (GSH) in the TME will separate the fluorescence molecule and ferrocene by the GSH-sensitive trisulfide bond, realizing light-up NIR-II fluorescence imaging and a cascade of trimodal synergistic CDT/HPTT/gas therapy (GT). In addition, the accumulation of hydroxyl radicals (•OH) and down-regulation of glutathione peroxidase 4 (GPX4) can produce excessive harmful lipid hydroperoxides, ultimately leading to ferroptosis.

Brucine suppresses proliferation and promotes apoptosis of human cholangiacarcinoma cells via the inhibition of COX2 expression.

Aims The aim of this study was to investigate the anti-tumor efficacy of brucine on intrahepatic cholangiocarcinoma (ICC). Methods ICC QBC939 cells were treated with brucine, cell viability, cell cycle and apoptosis were analyzed using CCK-8 and flow cytometry. The expression of COX-2 and apoptosis related proteins Casp3, Bax and Bcl-2 were detected by Western blot analysis. QBC939 cells were subcutaneously transplanted into nude mice and the mice were injected with brucine intraperitoneally. The expression of Ki67, COX-2 and apoptosis related proteins were detected by immunohistochemical staining and Western blot analysis. Results Brucine significantly inhibited the proliferation and cell cycle progression while promoted the apoptosis of QBC939 cells. The expression of the apoptotic proteins Casp3 and Bax was upregulated, while the expression of Bcl-2 and COX-2 was downregulated in QBC939 cells with brucine treatment. Moreover, the overexpression of COX-2 could antagonize the effects of brucine on QBC939 cells. In vivo, brucine inhibited subcutaneous tumor formation in nude mice, and the expression of Ki67, COX-2 and Bcl-2 decreased while the expression of Casp3 and Bax increased in tumor tissues from nude mice with brucine treatment. Conclusions Brucine can significantly inhibit the progression of cholangiocarcinoma in vitro and in vivo, and the mechanism may be related to the inhibition of COX-2 expression.

Identification of characteristic genes and construction of regulatory network in gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) is a highly malignant tumor with a poor overall prognosis. This study aimed to identify the characteristic microRNAs (miRNAs) of GBC and the competing endogenous RNA (ceRNA) regulatory mechanisms. METHODS: The microarray data of GBC tissue samples and normal gallbladder (NGB) tissue samples from the Gene Expression Omnibus (GEO) database was downloaded. GBC-related differentially expressed miRNAs (DE-miRNAs) were identified by inter-group differential expression analysis and weighted gene co-expression network analysis (WGCNA). Machine learning algorithms were used to screen the characteristic miRNA based on the intersect between least absolute shrinkage and selection operator (LASSO) and Support vector machine-recursive feature elimination (SVM-RFE). Based on the differential expression analysis of GEO database, the ceRNA network of characteristic miRNA was predicted and constructed. The biological functions of the ceRNA network were revealed by carrying out the gene enrichment analysis was implemented. We further screened the key genes of ceRNA network and constructed a protein-protein interaction (PPI) network, and predicted and generated the transcription factors (TFs) network of signature miRNAs. The expression of characteristic miRNA in clinical samples was verified by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: A total of 131 GBC-related DE-miRNAs were obtained. The hsa-miR-4770 was defined as characteristic miRNA for GBC. The ceRNA network containing 211 mRNAs, one miRNA, two lncRNAs, and 48 circRNAs was created. Gene enrichment analysis suggested that the downstream genes were mainly involved in actin filament organization, cell-substrate adhesion, cell-matrix adhesion, reactive oxygen species metabolic process, glutamine metabolic process and extracellular matrix (ECM)-receptor interaction pathway. 10 key genes in the network were found to be most correlated with disease, and involved in cell cycle-related processes, p53, and extrinsic apoptotic signaling pathways. The qRT-PCR result demonstrated that hsa-miR-4770 is down-regulated in GBC, and the expression trend is consistent with the public database. CONCLUSIONS: We identified hsa-miR-4770 as the characteristic miRNA for GBC. The ceRNA network of hsa-miR-4770 may play key roles in GBC. This study provided some basis for potential pathogenesis of GBC.

Integrating Co(OH)2 nanosheet arrays on graphene for efficient noble-metal-free EY-sensitized photocatalytic H2 evolution.

The development of an efficient noble-metal-free cocatalyst is the key to photocatalytic hydrogen production technology. In this study, hierarchical Co(OH)2 nanosheet array-graphene (GR) composite cocatalysts are developed. With Eosin Y (EY) as a photosensitizer, the optimal Co(OH)2-10%GR hybrid cocatalyst presents excellent photocatalytic activity with an H2 production rate of 17 539 µmol g-1 h-1, and the apparent quantum yield for hydrogen production can reach 12.8% at 520 nm, which remarkably surpasses that of pure Co(OH)2 and most similar hybrid cocatalyst systems. Experimental investigations demonstrate that the excellent photocatalytic activity of Co(OH)2-GR arises from its unique nanosheet array architecture, which can collaboratively expose rich active sites for photocatalytic hydrogen evolution and facilitate the migration and separation of photogenerated charge carriers. It is desired that this study would supply a meaningful direction for the rational optimization of the constitute and structure of cocatalysts to achieve efficient photocatalytic hydrogen generation.

Exploring the nonlinear piezoresistive effect of 4H-SiC and developing MEMS pressure sensors for extreme environments.

Microelectromechanical system (MEMS) pressure sensors based on silicon are widely used and offer the benefits of miniaturization and high precision. However, they cannot easily withstand high temperatures exceeding 150 °C because of intrinsic material limits. Herein, we proposed and executed a systematic and full-process study of SiC-based MEMS pressure sensors that operate stably from -50 to 300 °C. First, to explore the nonlinear piezoresistive effect, the temperature coefficient of resistance (TCR) values of 4H-SiC piezoresistors were obtained from -50 to 500 °C. A conductivity variation model based on scattering theory was established to reveal the nonlinear variation mechanism. Then, a piezoresistive pressure sensor based on 4H-SiC was designed and fabricated. The sensor shows good output sensitivity (3.38 mV/V/MPa), accuracy (0.56% FS) and low temperature coefficient of sensitivity (TCS) (-0.067% FS/°C) in the range of -50 to 300 °C. In addition, the survivability of the sensor chip in extreme environments was demonstrated by its anti-corrosion capability in H2SO4 and NaOH solutions and its radiation tolerance under 5 W X-rays. Accordingly, the sensor developed in this work has high potential to measure pressure in high-temperature and extreme environments such as are faced in geothermal energy extraction, deep well drilling, aeroengines and gas turbines.

Method to Measure Radial Thermal Conductivity for Cylindrical Samples.

Anisotropy is a prevailing property in most substances in the real world. The thermal conductivity characteristic of anisotropy must be determined for utilizing geothermal resources and assessing battery performances. Most core samples were primarily obtained by drilling and intended to be cylindrical in shape, with the cores resembling quantities of familiar batteries. Although Fourier's law could be used to measure the axial thermal conductivity of square or cylindrical samples, there is still a need to develop a new method to measure the radial thermal conductivity of cylindrical samples and evaluate their anisotropy. Thus, we established a testing method for cylindrical samples using the theory of complex variable functions following the heat conduction equation and implemented a numerical simulation to determine the difference between this method and typical ones via a finite element model for various samples. Results show that the method could perfectly gauge the radial thermal conductivity of cylindrical samples with more powerful availability.

HS6ST1 overexpressed in cancer-associated fibroblast and inhibited cholangiocarcinoma progression.

BACKGROUD: Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumor microenvironment, which play an important role in tumor progression. However, the mechanism is unclear. AIMS: To investigate the role of CAFs with HS6ST1-overexpression in cell migration and invasion effects. METHODS: Human primary CAFs were isolated and identified from intrahepatic cholangiocarcinoma. mRNA profiles differences between CAFs and NFs were examined by using transcriptome sequencing. Using Transwell® migration assays, ICCA cells (RBE and HUCCT1) with NF-CM, CAF-CM, CAFsNC-CM, and CAFsHS6ST1-CM were analyzed. Immunohistochemical staining were used to analyze the expression of HS6ST1 in CAF in 152 patients with ICCA. Overall survival (OS) was compared based on CAF HS6ST1 expression were analysed. The relationship between clinicopathological parameters and survival was also examined. RESULTS: Successfully isolated CAFs is positive staining with αSMA, FSP-1, FAP, and PDGFR-ß. Transcriptome sequencing showed that differently expressed genes were enriched in the function of the extracellular matrix and chemokine signaling pathway. HS6ST1 is differentially expressed between CAFs and NFs, and associated with the migration and invasion of ICCA cells. Moreover, HS6ST1 positive expression of CAFs predicted unfavorable prognosis in patients with intrahepatic cholangiocarcinoma and showed correlation with the presence of lymph node metastasis. CONCLUSION: HS6ST1 is new possibilities for targeting the CAFs to reduce cholangiocarcinoma growth and metastasis.

Loss of Human Epidermal Receptor 2 Expression in Formalin-Fixed Paraffin-Embedded Breast Cancer Samples and the Rescuing Effect of Enhanced Antigen Retrieval and Signal Amplification.

As an important therapeutic target in breast cancer, HER2 expression assessed by immunohistochemistry plays a critical role in breast cancer treatment. Recent advances in HER2 antibody-drug conjugate therapy have enabled patients with HER2-low expression breast cancer to benefit from the drugs. However, it is not known whether the HER2-low expression in breast cancer FFPE blocks would be lost as storage time increased. In this study, we aimed to assess the loss of HER2 antigenicity in stored FFPE blocks of breast cancer and the rescue effect of modifying the protocol of antigen staining. We selected archived HER2-low breast cancer FFPE blocks with stored time ranging from 1 year to over 15 years and re-detected the expression of HER2. Our study showed that HER2 antigenicity loss increased with storage time and could cause false negativity in HER2-low detection. Moreover, we showed that by either increasing the antigen retrieval time or applying the tyramide signal amplification (TSA) kit, the HER2 signal can be rescued and detected in about half of the cases with HER2-low loss without causing false positivity.