Antidepressants account for the causal effect of major depressive disorder on type 2 diabetes.

Background: Patients with major depressive disorder (MDD) face an elevated risk of type 2 diabetes (T2D). However, the contribution of the disease itself versus the side effects of antidepressants to this increased risk remains unclear.

Objective: This study aimed to investigate the overall and independent effects of MDD and exposure to antidepressants on T2D risk.

Burden of biliary tract carcinoma in China (1990-2021): Findings from the 2021 Global Burden of Disease Study.

Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study.

Nuclear translocation of plasma membrane protein ADCY7 potentiates T cell-mediated antitumour immunity in HCC.

Background: The potency of T cell-mediated responses is a determinant of immunotherapy effectiveness in treating malignancies; however, the clinical efficacy of T-cell therapies has been limited in hepatocellular carcinoma (HCC) owing to the extensive immunosuppressive microenvironment.

Objective: Here, we aimed to investigate the key genes contributing to immune escape in HCC and raise a new therapeutic strategy for remoulding the HCC microenvironment.

Design: The genome-wide in vivo clustered regularly interspaced short palindromic repeats (CRISPR) screen library was conducted to identify the key genes associated with immune tolerance.

Identification of New Potential Targets for Pancreatic Ductal Adenocarcinoma by Integrated Bioinformatic Analysis.

Background/aim: Pancreatic cancer is the fourth leading cause of cancer-related death in both men and women worldwide. The 5-year relative survival rate for pancreatic ductal adenocarcinoma (PDAC) is 10%, which is the lowest among all cancers. This study aimed to find more effective targets to improve the diagnosis, prognostic prediction, and treatment of PDAC.

The natural flavonoid pinocembrin shows antithrombotic activity and suppresses septic thrombosis.

Sepsis, an extreme host response to systemic infection, remains one of the leading causes of mortality worldwide. Platelets, which are integral to both thrombosis and inflammation, play a crucial role in the pathophysiology of sepsis. Excessive platelet activation and aggregation significantly increase the risk of thrombosis, thereby elevating mortality in septic patients.

SIN3B Loss Heats up Cold Tumor Microenvironment to Boost Immunotherapy in Pancreatic Cancer.

Despite progress significant advances in immunotherapy for some solid tumors, pancreatic ductal adenocarcinoma (PDAC) remains unresponsive poorly responsive to such interventions, largely due to its highly immunosuppressive tumor microenvironment (TME) with limited CD8 T cell infiltration. This study explores the role of the epigenetic factor Sin3B in the PDAC TME. Using murine PDAC models, we found that tumor cell-intrinsic Sin3B loss reshapes the TME, increasing CD8 T cell infiltration and cytotoxicity, thus impeding tumor progression and enhancing sensitivity to anti-PD1 treatment.

Circadian system disorder induced by aberrantly activated EFNB2-EPHB2 axis leads to facilitated liver metastasis in gastric cancer.

Background: Liver is one of the most preferred destinations for distant metastasis of gastric cancer (GC) and liver metastasis usually predicts poor prognosis. The achievement of liver metastasis requires continued cross-talk of complex members in tumor microenvironment (TME) including tumor associated macrophages (TAMs).

Methods: Results from 35 cases of ex vivo cultured living tissues of GC liver metastasis have elucidated that circadian rhythm disorder (CRD) of key molecules involved in circadian timing system (CTS) facilitates niche outgrowth.

Coating Dormant Collagenase-Producing Bacteria with Metal-Anesthetic Networks for Precision Tumor Therapy.

Tumor malignancy highly depends on the stiffness of tumor matrix, which mainly consists of collagen. Despite the destruction of tumor matrix is conducive to tumor therapy, it causes the risk of tumor metastasis. Here, metal-anesthetic network-coated dormant collagenase-producing Clostridium is constructed to simultaneously destruct tumor matrix and inhibit tumor metastasis.

In situ formation of biomolecular condensates as intracellular drug reservoirs for augmenting chemotherapy.

Biomolecular condensates, which arise from liquid-liquid phase separation within cells, may provide a means of enriching and prolonging the retention of small-molecule drugs within cells. Here we report a method for the controlled in situ formation of biomolecular condensates as reservoirs for the enrichment and retention of chemotherapeutics in cancer cells, and show that the approach can be leveraged to enhance antitumour efficacies in mice with drug-resistant tumours. The method involves histones as positively charged proteins and doxorubicin-intercalated DNA strands bioorthogonally linked via a click-to-release reaction between trans-cyclooctene and tetrazine groups.

SKAP1 Expression in Cancer Cells Enhances Colon Tumor Growth and Impairs Cytotoxic Immunity by Promoting Neutrophil Extracellular Trap Formation via the NFATc1/CXCL8 Axis.

The mechanisms underlying the development and progression of colon cancer are not fully understood. Herein, Src kinase associated phosphoprotein 1 (SKAP1), an immune cell adaptor, is identified as a novel colon cancer-related gene. SKAP1 expression is significantly increased in colon cancer cells.

c-Myc alone is enough to reprogram fibroblasts into functional macrophages.

Background: Macrophage-based cell therapy is promising in solid tumors, but the efficient acquisition of macrophages remains a challenge. Induced pluripotent stem cell (iPSC)-induced macrophages are a valuable source, but time-consuming and costly. The application of reprogramming technologies allows for the generation of macrophages from somatic cells, thereby facilitating the advancement of cell-based therapies for numerous malignant diseases.

The Epstein-Barr Virus Nuclear Antigen 1 Variant Associated with Nasopharyngeal Carcinoma Defines the Sequence Criteria for Serologic Risk Prediction.

Purpose: Antibodies to select Epstein-Barr virus proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against Epstein-Barr virus nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years before diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay.

Syndecan-1 inhibition promotes antitumor immune response and facilitates the efficacy of anti-PD1 checkpoint immunotherapy.

Tumor cell-originated events prevent efficient antitumor immune response and limit the application of anti-PD1 checkpoint immunotherapy. We show that syndecan-1 (SDC1) has a critical role in the regulation of T cell-mediated control of tumor growth. SDC1 inhibition increases the permeation of CD8 T cells into tumors and triggers CD8 T cell-mediated control of tumor growth, accompanied by increased proportions of progenitor-exhausted and effector-like CD8 T cells.

Decreased Serum CTRP3 level was associated with connective tissue diseases.

Objective: Complement C1q tumor necrosis factor-related protein 3 (CTRP3) and 9 (CTRP9) are two of the most extensively studied adipokines, known for their diverse biological functions. However, it remains unclear whether serum levels of CTRP3 or CTRP9 are associated with connective tissue diseases (CTD).

Methods: Serum CTRP3 and CTRP9 levels were measured by enzyme-linked immune sorbent assay (ELISA) and analyzed in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS), ankylosing spondylitis (AS), undifferentiated connective tissue disease (UCTD), as well as in healthy controls (HCs).

Cascade-responsive size/charge bidirectional-tunable nanodelivery penetrates pancreatic tumor barriers.

The pancreatic tumor microenvironment presents multiple obstacles for polymer-based drug delivery systems, limiting tumor penetration and treatment efficacy. Here, we engineer a hyaluronidase/reactive oxygen species cascade-responsive size/charge bidirectional-tunable nanodelivery (btND, G/R@TKP/HA) for co-delivery of gemcitabine and KRAS siRNA, capable of navigating through tumor barriers and augmenting anticancer efficiency. When penetrating the tumor stroma barrier, the hyaluronic acid shell of the nanodelivery undergoes degradation by hyaluronidase in an extracellular matrix, triggering size tuning from large to small and charge tuning from negative to positive, thereby facilitating deeper penetration and cellular internalization.

Fluorescence and photoacoustic (FL/PA) dual-modal probe: Responsive to reactive oxygen species (ROS) for atherosclerotic plaque imaging.

Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O-OH) and ROS-specific group phenylboronic acid ester.

Evaluation of a new scoring system for assessing nerve invasion in resected pancreatic cancer: A single-center retrospective analysis.

Nerve invasion (NI) is a characteristic feature of pancreatic cancer. Traditional dichotomous statements on the presence of NI are unreasonable because almost all cases exhibit NI when sufficient pathological sections are examined. The critical implications of NI in pancreatic cancer highlight the need for a more effective criterion.