Osr2 functions as a biomechanical checkpoint to aggravate CD8 T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8 T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8 T cells.

Single cell glycan-linkages profiling for hepatocellular carcinoma early diagnosis using lanthanide encoded bacteriophage MS2 based ICP-MS.

Early diagnosis is paramount for enhancing survival rates and prognosis in the context of malignant diseases. Hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths worldwide, poses significant challenges for its early detection. In this study, we present an innovative approach which contributed to the early diagnosis of HCC.

Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis.

Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation (LT) is critical for precise clinical management strategies. Here, we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells (PBMCs) collected from LT patients (with and without acute cellular rejection [ACR]) at 13 time points. Validation was performed in two independent cohorts with additional LT patients and healthy controls.

TGF-β1/SMAD3-driven GLI2 isoform expression contributes to aggressive phenotypes of hepatocellular carcinoma.

Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-β1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-β1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified.

Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1.

PD-1 is a co-inhibitory receptor expressed by CD8 T cells which limits their cytotoxicity. PD-L1 expression on cancer cells contributes to immune evasion by cancers, thus, understanding the mechanisms that regulate PD-L1 protein levels in cancers is important. Here we identify tumor-cell-expressed otubain-2 (OTUB2) as a negative regulator of antitumor immunity, acting through the PD-1/PD-L1 axis in various human cancers.

Design of a dual Ir-Eu tag for fluorescent visualization and ICP-MS quantification of SIRPα and its host cells.

With the expansion of ICP-MS application into the field of bioanalysis, there is an urgent need for novel element tags today. Here, we report the design of a dual-element Ir-Eu tag, opening the door to simultaneous fluorescent imaging and ICP-MS quantification. The ratio of Eu/Ir may serve as a precision control of the labeling process, allowing internal validation of the quantitative results obtained.

SPTAN1/NUMB axis senses cell density to restrain cell growth and oncogenesis through Hippo signaling.

The loss of contact inhibition is a key step during carcinogenesis. The Hippo-Yes-associated protein (Hippo/YAP) pathway is an important regulator of cell growth in a cell density-dependent manner. However, how Hippo signaling senses cell density in this context remains elusive.

Value of Non-tumoral Liver Volume in the Prognosis of Large Hepatocellular Carcinoma Patients After R0 Resection.

Background And Aims: Hepatectomy is an effective treatment for selected patients with large hepatocellular carcinoma (HCC). This study aimed to develop a nomogram incorporating non-tumoral liver volume (non-TLV) and liver function markers to predict the patients' overall survival (OS) and disease-free survival (DFS).

Methods: Data of 198 consecutive large HCC patients who underwent hepatectomy at the Zhongshan Hospital Xiamen University were collected.

Hepatocellular carcinoma detection via targeted enzymatic methyl sequencing of plasma cell-free DNA.

Background: Epigenetic variants carried by circulating tumor DNA can be used as biomarkers for early detection of hepatocellular carcinoma (HCC) by noninvasive liquid biopsy. However, traditional methylation analysis method, bisulfite sequencing, with disadvantages of severe DNA damage, is limited in application of low-amount cfDNA analysis.

Results: Through mild enzyme-mediated conversion, enzymatic methyl sequencing (EM-seq) is ideal for precise determination of cell-free DNA methylation and provides an opportunity for HCC early detection.

Prospective, randomized, controlled, noninferiority clinical trial to evaluate the safety and efficacy of absorbable macroporous polysaccharide composites as adjunct to hemostasis during open surgery.

Background: To address intraoperative bleeding in cardiac surgery, reducing blood transfusion requirements, is mandatory to achieve effective hemostasis. Hemostatic agents may limit localized persistent bleeding. The introduction of carboxymethyl-chitosan component into the hemostatic agent and the application of the radiation crosslinking technique maintain its capacity for achieving intraoperative hemostasis, thus increasing the clinical utility.

Quantification of active selenols in cells: a selenol-specific recognition europium-switched signal-amplification ICP-MS approach.

Selenium (Se) is a mysterious thus tempting element playing a dual bio-chemical function, mainly through selenol, during life processes. Quantification of the selenols is thus of great significance for understanding the biological roles of Se, but remains a big challenge. Herein we report a selenol-specific recognition-mediated and europium (Eu) signal-switched amplification inductively coupled plasma mass spectrometry (ICP-MS) approach for quantifying the free active selenols (act-SeH) in cells.

Genome-wide long noncoding RNA and mRNA expression profiles demonstrate associations between exposure to inorganic elements and the risk of developing hepatocellular carcinoma.

Background: Long noncoding RNAs (lncRNAs) are closely associated with the development of hepatocellular carcinoma (HCC). The present study conducted a genome-wide microarray analysis and qPCR validation to obtain comprehensive insights into this issue.

Methods: Thirty male HCC patients with chronic HBV infection were included in the present study.

Contrast-Enhanced Multispectral Photoacoustic Imaging for Irregular Hepatectomy Navigation: A Pilot Study.

Irregular hepatectomy plays a prominent role in the treatment of small hepatocellular carcinoma (HCC) patients with severe cirrhosis and localized liver metastasis. In clinical practices, intraoperative tumor boundaries delineation facilitates to accomplish tumor resection with negative margin, remarkably decreasing the recurrence rates. Currently, ultrasound (US) and ICG fluorescence-guided surgery has been used for intraoperative navigation in irregular hepatectomy, but insufficient specificity results in a limited prevalence.

Organelle-Partitioned Sugar-Rhodamine Diad for In Vivo Tumor Imaging.

Current tumor imaging agents are often limited by their liability to dissipate from tumor tissues. As cell sugar sorting enables exogenous sugars to be delivered into predetermined subcellular locations, we synthesized sialic acid (Sia) derivatives with rhodamine-X conjugated at C-9 (Sia), which hitchhikes cell sialic acid sorting to target tumor cell lysosomes, exhibiting pH-independent long-term probe retention in lysosomes. Sia gives selective, bright, and endured fluorescence signals in subcutaneous tumors and orthotopic tumors in mice models.

Tumor-targeting oncolytic virus elicits potent immunotherapeutic vaccine responses to tumor antigens.

Oncolytic viruses represent a promising therapeutic modality, but they have yet to live up to their therapeutic potential. Safety and efficacy concerns impel us to identify least toxic oncolytic agents that would generate durable and multifaceted anti-tumor immune responses to disrupt the tumors. Here we describe a rational engineered oncolytic herpes virus (OVH) that is a selective killer for targeting tumors, has strong safety records, induces complete regression of tumors in multiple tumor models, and elicits potent antitumor immunity.

Intravenous Injections of a Rationally Selected Oncolytic Herpes Virus as a Potent Virotherapy for Hepatocellular Carcinoma.

As a clinical setting in which novel treatment options are urgently needed, hepatocellular carcinoma (HCC) exhibits intriguing opportunities for oncolytic virotherapy. Here we report the rational generation of a novel herpes simplex virus type 1 (HSV-1)-based oncolytic vector for targeting HCC, named Ld0-GFP, which was derived from oncolytic ICP0-null virus (d0-GFP), had a fusogenic phenotype, and was a novel killer against HCC as well as other types of cancer cells. Compared with d0-GFP, Ld0-GFP exhibited superior cancer cell-killing ability and .

Elevated N-methyltransferase expression induced by hepatic stellate cells contributes to the metastasis of hepatocellular carcinoma via regulation of the CD44v3 isoform.

The cross-talk between hepatic stellate cells (HSCs) and hepatic carcinoma cells contributes to hepatocellular carcinoma (HCC) progression, but the underlying mechanism is largely unknown. We report here that activated HSCs induce upregulation of nicotinamide N-methyltransferase (NNMT), which is known to regulate multiple metabolic pathways in hepatoma cells of the liver. High levels of NNMT in HCC tissues were positively correlated with vascular invasion, increased serum HBV-DNA levels, and distant metastasis.

Competing endogenous RNA network and prognostic nomograms for hepatocellular carcinoma patients who underwent R0 resection.

The prognosis of hepatocellular carcinoma (HCC) after R0 resection is unsatisfactory due to the high rate of recurrence. In this study, we investigated the recurrence-related RNAs and the underlying mechanism. The long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression data and clinical information of 247 patients who underwent R0 resection patients with HCC were obtained from The Cancer Genome Atlas.

Abnormal expression of YEATS4 associates with poor prognosis and promotes cell proliferation of hepatic carcinoma cell by regulation the TCEA1/DDX3 axis.

YEATS domain containing 4 (YEATS4) is usually amplified and functions as an oncogene in several malignancies, such as colorectum, ovarian, breast and lung. However, the biological role of YEATS4 in hepatocellular carcinoma (HCC) has not yet been discussed. Herein, we found that YEATS4 was significantly upregulated in HCC compared to para-cancerous tissues, and was associated with poor prognosis, large tumor size, poor differentiation and distant metastasis.

GABPA predicts prognosis and inhibits metastasis of hepatocellular carcinoma.

Background: Increasing evidence indicates that abnormal expression of GABPA is associated with tumor development and progression. However, the function and clinicopathological significance of GABPA in hepatocellular carcinoma (HCC) remain obscure.

Methods: The mRNA and protein expression of GABPA in HCC clinical specimens and cell lines was examined by real-time PCR and western blotting, respectively.

Analysis of risk factors related to gastrointestinal fistula in patients with severe acute pancreatitis: a retrospective study of 344 cases in a single Chinese center.

Background: Gastrointestinal fistula (GIF) in severe acute pancreatitis (SAP) is considered as a sparse episode and studied sporadically in the literature. There is paucity of data on the prediction of the effect on risk of GIF in patient with SAP. This study was aimed to investigate risk factors related to GIF in the development of SAP.

Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells.

Dysregulation of inhibitor of apoptosis (IAP) proteins (IAPs) in hepatocellular carcinoma (HCC) is often associated with poor prognosis. Here we showed that AT406, an IAP antagonist, was cytotoxic and pro-apoptotic to both established (HepG2, SMMC-7721 lines) and primary HCC cells. Activation of mTOR could be a key resistance factor of AT406 in HCC cells.

An HBV-tolerant immunocompetent model that effectively simulates chronic hepatitis B virus infection in mice.

Hepatitis B virus (HBV) is the leading cause of liver disease and hepatic carcinoma (HCC). Approximately 350 million people worldwide are infected with HBV and at risk of chronicity. An efficient HBV-tolerant murine model that mimics HBV infection in humans is desirable for HBV-related research.

Microarray analysis on the lncRNA expression profile in male hepatocelluar carcinoma patients with chronic hepatitis B virus infection.

Long non-coding RNAs are involved with development and progression of cancer, and the advance of microarray technology allows the researchers to investigate the complete expression profile of lncRNA in various kinds of sample. We enrolled 5 male primary HCC cases with chronic HBV infection and the HCC and normal tissues have been obtained during the resection surgery. After total RNA extraction, the lncRNA microarray analysis was conducted to determine the lncRNA and mRNA expression signals.

Simultaneous SPECT imaging of multi-targets to assist in identifying hepatic lesions.

Molecular imaging technique is an attractive tool to detect liver disease at early stage. This study aims to develop a simultaneous dual-isotope single photon emission computed tomography (SPECT)/CT imaging method to assist diagnosis of hepatic tumor and liver fibrosis. Animal models of liver fibrosis and orthotopic human hepatocellular carcinoma (HCC) were established.