Nano-enabled repurposing of Benproperine phosphate enhances pancreatic Cancer chemotherapy through lethal autophagy arrest and immune activation.

Gemcitabine-based chemotherapy remains a cornerstone in pancreatic cancer treatment, yet its efficacy is hindered by poor bioavailability and adaptive resistance mechanisms, such as autophagy. In this study, we developed a hyaluronic acid (HA) modified zeolitic imidazolate framework-8 (ZIF-8) drug-repurposing nanoplatform (HA/ZIF-8@BPP/Gem) against pancreatic cancer through the co-delivery of the antitussive benproperine phosphate (BPP) and gemcitabine (Gem). Using cell lines, patient-derived xenograft models, and orthotopic tumor models, we demonstrated that BPP and Gem, rapidly released from the nanoplatform in the acidic tumor microenvironment, exhibited synergistic cytotoxicity without causing significant biochemical abnormalities or organ toxicity.

Dissecting cross-lineage tumourigenesis under p53 inactivation through single-cell multi-omics and spatial transcriptomics.

Background: Tumour suppressor genes, exemplified by TP53 (encoding the human p53), function as critical guardians against tumourigenesis. Germline TP53-inactivating mutations underlie Li-Fraumeni syndrome, a hereditary cancer predisposition disorder characterised by early-onset pan-tissue malignancies. However, the context-dependent tumour-suppressive mechanisms of p53 remain incompletely elucidated.

Targeting spermine metabolism to overcome immunotherapy resistance in pancreatic cancer.

While dysregulation of polyamine metabolism is frequently observed in cancer, it is unknown how polyamines alter the tumor microenvironment (TME) and contribute to therapeutic resistance. Analysis of polyamines in the plasma of pancreatic cancer patients reveals that spermine levels are significantly elevated and correlate with poor prognosis. Using a multi-omics approach, we identify Serpinb9 as a vulnerability in spermine metabolism in pancreatic cancer.

Specific Pathogen Free Ten Gene-Edited Donor Pigs for Xenotransplantation.

Xenotransplantation has entered the clinical phase in an effort to address the global organ shortage. However, recent clinical studies have revealed that current xenografts from gene-edited (GE) pigs still pose risk of immune rejection and biosafety concerns. In this study, we successfully produced a large batch of 582 GE cloned donor (GEC) pigs with 10-(GTKO/CMAHKO/β4GalNT2KO/hCD46/hCD55/ hCD59/hTBM/ hEPCR/hCD39/hCD47) gene edits via gene editing and somatic cell cloning technologies, and successfully obtained the F1 generation.

WZ4003 sensitizes hepatocellular carcinoma to OSI-027 by inhibiting ARK5-mediated autophagy.

Mammalian target of rapamycin kinase inhibitors (mTOR-KIs) represent a novel promising treatment option for cancer therapy. OSI-027, a typical mTOR-KI, has been confirmed to suppress the proliferation of hepatocellular carcinoma (HCC) in preclinical models. However, mTOR-KIs confer limited therapeutic response against HCC, and the underlying mechanism remains enigmatic.

Endovascular Intervention of Portal Vein Stenosis in Pediatric Patients After Liver Transplantation: A Single-Center Experience.

BACKGROUND Portal vein stenosis (PVS) is a prevalent complication following pediatric liver transplantation (pLT) and significantly impacts long-term graft outcomes. This study assessed the efficacy and safety of balloon angioplasty and stent placement, calculated rates of restenosis or reintervention, and determined optimal interventional strategies for managing PVS following pLT. MATERIAL AND METHODS We retrospectively analyzed 884 pLT recipients at our institution.

Utilization of Whole Slide Pathological Images and Tumor Clinical Data: A Hybrid Graph Convolutional Network Model for Hepatocellular Carcinoma Prognosis Prediction.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, ranking fourth in cancer-related mortality. Prognostic risk prediction for HCC patients can optimize treatment strategies, assess therapeutic efficacy, and ultimately improve post-operative survival rates. Pathological slides are considered the gold standard for cancer diagnosis and prognosis, playing a crucial role in prognostic risk stratification.

RNA target-independent non-canonical activation (RINCA) of Cas13 trans-nuclease activity.

A thorough understanding of unintended Cas13 activity is critical for ensuring the safe in vivo application of CRISPR-Cas13. In this study, we uncover the RNA target-independent, non-canonical activation (RINCA) of Cas13 by crRNA alone and elucidate its structural basis. RINCA poses both challenges and opportunities for Cas13-based technologies.

Bacteria and tumor debris induced pancreatic cancer progression via the NF-κB signaling pathway.

The tumor microenvironment (TME) of metastatic pancreatic ductal adenocarcinoma (PDAC) is characterized by significant cellular and spatial heterogeneity, and long-term hypoxia, leading to micronecrotic regions. PDAC clinical specimens were employed to investigate micronecrosis and we identified that bacteria and lipopolysaccharide (LPS) co-existed in PDAC tissue. Tumor-associated macrophages (TAMs) polarized by these complex components exhibit a distinct pro-inflammatory effect and correlate with drug resistance in pancreatic cancer.

Nanoliposomal PD-1 antagonist target tumor-draining lymph nodes to revitalize T cells and improve anti-tumor effect in hepatocellular carcinoma.

Background: Tumor-draining lymph nodes (TdLNs) are pivotal in tumor immunotherapy, including the action of immune checkpoint inhibitors such as PD-1/PD-L1 blockade. However, fully harnessing the therapeutic potential of TdLNs to improve clinical outcomes remains a significant challenge.

Methods: A PD-1 antagonist peptide-conjugated nanoliposome (LPs) was developed to improve lymph node targeting and therapeutic efficacy.

Robotic pancreatoduodenectomy reduces grade B pancreatic fistula in patients with a small main pancreatic duct: a propensity score-matched study compared to laparoscopic pancreatoduodenectomy.

Background: The benefits of robotic pancreaticoduodenectomy (RPD) over laparoscopic pancreaticoduodenectomy (LPD) remain less reported, this study aimed to evaluate the superiority of RPD over LPD.

Methods: A retrospective 1:1 propensity score-matched (PSM) analysis of the characteristics and perioperative variables of patients who underwent RPD and LPD between January 2021 and June 2023 in a high-volume centre was performed.

Results: The analysis included 193 patients who underwent RPD and 355 who underwent LPD.

Integrating Body Composition and Nutritional Indices: A Novel Prognostic Tool for Survival in Pancreatic Cancer.

Background: Sarcopenia and malnutrition have been independently associated with a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), but their combined association with patient outcomes is not fully understood. This study aimed to systematically evaluate the synergistic effects of body composition parameters and nutritional index as prognostic indicators in patients with PDAC.

Methods: A total of 596 patients with PDAC who underwent surgical resection from two centres were initially enrolled in this retrospective study.

Comparison of Omicron and respiratory virus infections in pediatric liver transplantation: Impact of perioperative identification status.

Peri-operative respiratory virus (RV) infection is critical in paediatric liver transplantation. However, it has been inadequately studied, especially in terms of the clinical latency of infection (incubation period) and Omicron variant infection. Herein, we compared the infection profile of common RVs and Omicron variants in paediatric liver transplantation, aiming to identify the association of virus infection with outcomes.

Management of hepatic artery thrombosis and stenosis after pediatric liver transplantation: Variability and agreement in management practices.

Guidelines for managing hepatic artery thrombosis (HAT) and stenosis (HAS) after pediatric liver transplantation (pLT) are lacking, with heterogeneous local practices. This study aims to evaluate management practices for HAT and HAS after pLT. An online and paper-based survey was sent to 36 international pLT centers.

Lipid metabolism reprograming by SREBP1-PCSK9 targeting sensitizes pancreatic cancer to immunochemotherapy.

Background: Pancreatic cancer's aberrant lipid metabolism fuels cell growth, invasion, and metastasis, yet its impact on immune surveillance and immunotherapy is unclear. This study investigated how sterol regulatory element-binding transcription factor 1 (SREBP1)-driven lipid metabolism affects the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC).

Methods: Clinical significance of SREBP1 was assessed in a PDAC cohort from China and The Cancer Genome Atlas (TCGA) cohorts.

Sphingolipid synthesis in tumor-associated macrophages confers immunotherapy resistance in hepatocellular carcinoma.

Dysregulated metabolism of immune cells in the tumor microenvironment leads to immune evasion and tumor progression. As a major cell component in the tumor, the metabolic reprogramming of tumor-associated macrophages (TAMs) creates an immunosuppressive microenvironment in hepatocellular carcinoma (HCC). Our study found that sphingolipid (particularly, sphingosine-1-phosphate or S1P) levels are a clinical indicator for prognosis and immunotherapy response in patients with HCC.

Exploring the mechanism of intestinal bacterial translocation after severe acute pancreatitis: the role of Toll-like receptor 5.

Severe acute pancreatitis (SAP)-induced intestinal bacterial translocation and enterogenic infection are among the leading causes of mortality in patients. However, the mechanisms by which SAP disrupted the intestinal barrier and led to bacterial translocation remained unclear. Therefore, we employed multi-omics analysis including microbiome, metabolome, epigenome, transcriptome, and mass cytometry (CyTOF) to identify potential targets, followed by functional validation using transgenic mice.

[F]FAPI- 04 PET/CT for pathologic response assessment in pancreatic cancer patients with systemic treatment.

Purpose: To study the association between [F]FAPI- 04 uptake on positron emission tomography/computed tomography (PET/CT) and pathologic treatment response (PTR) in patients with pancreatic cancer (PC).

Methods: We enrolled 59 patients from August 2021, of whom 28 underwent surgical treatment after systemic therapy. The patients were investigated for a correlation between baseline fibroblast activation protein inhibitor (FAPI) uptake and PTR using College of American Pathologists (CAP) scores.

The Regulation of Trace Metal Elements in Cancer Ferroptosis.

Ferroptosis, as novel type of regulated cell death that has garnered widespread attention over the past decade, has witnessed the continuous discovery of an increasing number of regulatory mechanisms. Trace metal elements play a multifaceted and crucial role in oncology. Interestingly, it has been increasingly evident that these elements, such as copper, are involved in the regulation of iron accumulation, lipid peroxidation and antiferroptotic systems, suggesting the existence of "nonferrous" mechanisms in ferroptosis.

Efficacy of Neoadjuvant Therapy and the Prognostic Significance of Serum Carcinoembryonic Antigen Level in Patients with Localized Pancreatic Adenocarcinoma with Non-elevated Carbohydrate Antigen 19-9 Levels.

Objective: This study evaluated the effect of neoadjuvant therapy (NAT) and the prognostic significance of carcinoembryonic antigen (CEA) levels in patients with non-elevated serum carbohydrate antigen (CA) 19-9 levels.

Summary Background Data: The impact of NAT followed by surgical resection on oncologic outcomes in patients with localized pancreatic ductal adenocarcinoma (PDAC) remains unclear.

Methods: This retrospective and propensity-score matched (PSM) study included primary and validation cohorts from four centers.

5-Year survival rate over 20 % in pancreatic ductal adenocarcinoma: A retrospective study from a Chinese high-volume center.

Standardized clinical management of pancreatic adenocarcinoma (PDAC) remains challenging and high-volume centers provide essential insights for establishing effective multimodal treatment approaches. This retrospective observational study evaluated the impact of standardized, multimodal clinical management on survival outcomes in patients with PDAC across all stages, based on NCCN guidelines resectability criteria, at a high-volume center. From 2019, 4143 patients were diagnosed with PDAC, with 3268 patients receiving further treatment, including surgical resection and/or systemic therapy.

Oncolytic virus VG161 in refractory hepatocellular carcinoma.

Hepatocellular carcinoma remains a life-threatening malignancy with limited therapeutic options following the failure of second-line treatments. Oncolytic viruses selectively replicate in and lyse cancer cells, releasing neoantigens and stimulating systemic antitumour immunity, offering a potential therapeutic option. Here we present the results of a multicentre phase 1 clinical trial evaluating VG161, an engineered oncolytic herpes simplex virus that expresses IL-12, IL-15, IL-15Rα and a PD-1-PD-L1-blocking fusion protein, for safety and efficacy in patients with advanced liver cancer.

Coupling CRISPR-Cas and a personal glucose meter with an enzymatic reporter for portable detection of human papillomavirus in biological samples.

Significant efforts and resources have been dedicated to developing CRISPR-Cas based point-of-care testing (POCT) and self-diagnosis methods for nucleic acid pathogens, aiming to complement the gold standard quantitative PCR tests, particularly in settings where centralized facilities, trained personnel, or resource-intensive equipment are unavailable. However, the reliance on stationary, high-cost readout machinery hinders their full deployment at the point of care. We aimed to develop a solid-phase invertase-labeled reporter (ILR) system that enables convenient readout of CRISPR-Cas reactions, facilitate HPV detection in a POCT-compatible manner.