FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma.

Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer and is highly lethal. Clonorchis sinensis (C. sinensis) infection is an important risk factor for iCCA.

Th17 Cells Secrete TWEAK to Trigger Epithelial-Mesenchymal Transition and Promote Colorectal Cancer Liver Metastasis.

Unlabelled: Liver metastasis is the leading cause of mortality in patients with colorectal cancer. Given the significance of both epithelial-mesenchymal transition (EMT) of tumor cells and the immune microenvironment in colorectal cancer liver metastasis (CRLM), the interplay between them could hold the key for developing improved treatment options. We employed multiomics analysis of 130 samples from 18 patients with synchronous CRLM integrated with external datasets to comprehensively evaluate the interaction between immune cells and EMT of tumor cells in liver metastasis.

Diffusion-driven fabrication of calcium and phosphorous-doped zinc oxide heterostructures on titanium to achieve dual functions of osteogenesis and preventing bacterial infections.

Conventional Ti-based implants are vulnerable to postsurgical infection and improving the antibacterial efficiency without compromising the osteogenic ability is one of the key issues in bone implant design. Although zinc oxide (ZnO) nanorods grown on Ti substrates hydrothermally can improve the antibacterial properties, but cannot meet the stringent requirements of bone implants, as rapid degradation of ZnO and uncontrolled leaching of Zn are detrimental to peri-implant cells and tissues. To solve these problems, a lattice-damage-free method is adopted to modify the ZnO nanorods with thin calcium phosphate (CaP) shells.

Personalized drug screening in patient-derived organoids of biliary tract cancer and its clinical application.

Patients with biliary tract cancer (BTC) show different responses to chemotherapy, and there is no effective way to predict chemotherapeutic response. We have generated 61 BTC patient-derived organoids (PDOs) from 82 tumors (74.4%) that show similar histological and genetic characteristics to the corresponding primary BTC tissues.

Spatial proteomics of immune microenvironment in nonalcoholic steatohepatitis-associated hepatocellular carcinoma.

Background And Aims: NASH-HCC is inherently resistant to immune checkpoint blockade, but its tumor immune microenvironment is largely unknown.

Approach And Results: We applied the imaging mass cytometry to construct a spatially resolved single-cell atlas from the formalin-fixed and paraffin-embedded tissue sections from patients with NASH-HCC, virus-HCC (HBV-HCC and HCV-HCC), and healthy donors. Based on 35 biomarkers, over 750,000 individual cells were categorized into 13 distinct cell types, together with the expression of key immune functional markers.

Hepatitis B virus-related intrahepatic cholangiocarcinoma originates from hepatocytes.

Background: Hepatitis B virus (HBV) infection is one of the most common risk factors for intrahepatic cholangiocarcinoma (ICC). However, there is no direct evidence of a causal relationship between HBV infection and ICC. In this study, we attempted to prove that ICC may originate from hepatocytes through a pathological study involving ICC tissue-derived organoids.

Cross-talk between Myeloid and B Cells Shapes the Distinct Microenvironments of Primary and Secondary Liver Cancer.

Unlabelled: The tumor microenvironment is distinctive in primary and secondary liver cancer. B cells represent an important component of immune infiltrates. Here, we demonstrated that B cells are an important regulator in hepatocellular carcinoma (HCC) and colorectal cancer liver metastasis (CRLM) microenvironments.

Maintenance of multipotency of bone marrow mesenchymal stem cells on poly(ε-caprolactone) nanoneedle arrays through the enhancement of cell-cell interaction.

Mesenchymal stem cells (MSCs), with high self-renewal ability and multipotency, are commonly used as the seed cells for tissue engineering. However, the reduction and loss of multipotential ability after necessary expansion set up a heavy obstacle to the clinical application of MSCs. Here in this study, we exploit the autologous crystallization ability of biocompatible poly (ε-caprolactone) (PCL) to obtain uniformly distributed nanoneedle arrays.

Distinct single-cell immune ecosystems distinguish true and de novo HBV-related hepatocellular carcinoma recurrences.

Objective: Revealing the single-cell immune ecosystems in true versus de novo hepatocellular carcinoma (HCC) recurrences could help the optimal development of immunotherapies.

Design: We performed 5'and VDJ single-cell RNA-sequencing on 34 samples from 20 recurrent HCC patients. Bulk RNA-sequencing, flow cytometry, multiplexed immunofluorescence, and in vitro functional analyses were performed on samples from two validation cohorts.

Patient-derived cancer organoids for drug screening: Basic technology and clinical application.

Cancer organoids, a three-dimensional (3D) culture system of cancer cells derived from tumor tissues, recapitulate physiological structure of the parental tumor. Different tumor organoids have been established for a variety of tumor types, such as colorectal, liver, stomach, pancreatic and brain tumors. Some tumor organoid biobanks are built to screen and discover novel antitumor drug targets.

Programmed surface on poly(aryl-ether-ether-ketone) initiating immune mediation and fulfilling bone regeneration sequentially.

The immune responses are involved in every stage after implantation but the reported immune-regulated materials only work at the beginning without fully considering the different phases of bone healing. Here, poly(aryl-ether-ether-ketone) (PEEK) is coated with a programmed surface, which rapidly releases interleukin-10 (IL-10) in the first week and slowly delivers dexamethasone (DEX) up to 4 weeks. Owing to the synergistic effects of IL-10 and DEX, an aptly weak inflammation is triggered within the first week, followed by significant M2 polarization of macrophages and upregulation of the autophagy-related factors.

Rational integration of defense and repair synergy on PEEK osteoimplants via biomimetic peptide clicking strategy.

Polyetheretherketone (PEEK) has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance. However, its biological inertness, poor osteoinduction, and weak antibacterial activity make the clinical applications in a dilemma. Inspired by the mussel adhesion mechanism, here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins (Mfps)-mimic peptide with clickable azido terminal.

Multiomic Analysis Reveals Comprehensive Tumor Heterogeneity and Distinct Immune Subtypes in Multifocal Intrahepatic Cholangiocarcinoma.

Purpose: Targeted therapy and immunotherapy are transforming the treatment approach for intrahepatic cholangiocarcinoma (ICC). However, little is known about the intertumor heterogeneity (ITH) of multifocal ICC and its impacts on patient response to these treatments. We aimed to characterize the immunogenomic and epigenomic heterogeneity of multifocal ICC to guide treatment decision making.

N-Methylguanosine tRNA modification enhances oncogenic mRNA translation and promotes intrahepatic cholangiocarcinoma progression.

Cancer cells selectively promote translation of specific oncogenic transcripts to facilitate cancer survival and progression, but the underlying mechanisms are poorly understood. Here, we find that N-methylguanosine (mG) tRNA modification and its methyltransferase complex components, METTL1 and WDR4, are significantly upregulated in intrahepatic cholangiocarcinoma (ICC) and associated with poor prognosis. We further reveal the critical role of METTL1/WDR4 in promoting ICC cell survival and progression using loss- and gain-of-function assays in vitro and in vivo.

Comparison of the Anterior Tooth and Lip Esthetic Characteristics of Hani and Han Youth in China When Speaking.

Objective: This study aims to measure and analyze the lip and tooth dynamic esthetic characteristics at rest and during speech in order to provide a reference for its esthetic design and restoration among the Hani and Han populations in Yunnan Province, China.

Methods: Subjects of Hani and Han ethnicity in Yunnan were selected using multistage stratified sampling and inclusive criteria. The lip and tooth dynamic esthetic characteristics of the subjects at rest and during the pinyin pronunciation of "me", "yi", "fu", and "si" were recorded using digital photography and analyzed with computer software.

Phenotype Regulation of Smooth Muscle Cells Through Facial Crystallization of Poly(-Caprolactone).

Phenotype conversion of smooth muscle cells (SMCs) plays a key role in the formation of atherosclerosis. Understanding how SMCs respond to a micro/nano-topology and elucidating the cellular mechanism of phenotype conversion is critical to the atherosclerosis treatment. Herein, we prepared poly(-caprolactone) (PCL) spherulites with a radius more than 350 m for the studying of radial microstructure influence on SMCs behaviors.

Confinement of carbon dots localizing to the ultrathin layered double hydroxides toward simultaneous triple-mode bioimaging and photothermal therapy.

It is a great challenge to develop multifunctional nanocarriers for cancer diagnosis and therapy. Herein, versatile CDs/ICG-uLDHs nanovehicles for triple-modal fluorescence/photoacoustic/two-photon bioimaging and effective photothermal therapy were prepared via a facile self-assembly of red emission carbon dots (CDs), indocyanine green (ICG) with the ultrathin layered double hydroxides (uLDHs). Due to the J-aggregates of ICG constructed in the self-assembly process, CDs/ICG-uLDHs was able to stabilize the photothermal agent ICG and enhanced its photothermal efficiency.