Structural insights into the LGR4-RSPO2-ZNRF3 complexes regulating WNT/β-catenin signaling.

WNT/β-catenin signaling plays key roles in development and cancer. ZNRF3/RNF43 modulates Frizzleds through ubiquitination, dampening WNT/β-catenin signaling. Conversely, RSPO1-4 binding to LGR4-6 and ZNRF3/RNF43 enhances WNT/β-catenin signaling.

Indocyanine green highlights the lymphatic drainage pathways, enhancing the effectiveness of radical surgery for mid-low rectal cancer: A non-randomized controlled prospective study.

Background: Fluorescence-guided lymphadenectomy (FLND) using indocyanine green (ICG) has emerged as a promising technique to enhance the accuracy of lymphadenectomy in rectal cancer surgery. Effective lymphadenectomy is crucial for improving prognosis in patients with advanced rectal cancer, but it remains technically challenging and controversial.

Methods: This prospective nonrandomized controlled study was conducted involving 129 patients underwent laparoscopic surgery, and 64 patients assisted by FLND.

A self-assembled fluorescent nanoprobe recognized by FA1 site for specifically selecting HSA: Its applications in hemin detection, cell imaging and fluorescent tracing drug delivery.

As naturally essential biomacromolecule, HSA has become diagnostic indicators for various diseases and universal carriers for anticancer drug delivery, therefore, fluorescence detection and labeling for HSA possess significant application value in the biomedical field. In this paper, hydrazide Schiff base fluorescent probe NDQC was designed and synthesized, which self-assembled into nanoparticles in aqueous solution system and demonstrated excellent selectivity and sensitivity towards HSA. Through displacement assay and molecular docking simulation, the binding of NDQC with HSA in FA1 site was demonstrated, thereby no obvious fluorescence signal presented for homologous protein BSA due to their structural differences in binding site.

Habitat radiomics based on CT images to predict survival and immune status in hepatocellular carcinoma, a multi-cohort validation study.

Background And Objective: Though several clinicopathological features are identified as prognostic indicators, potentially prognostic radiomic models are expected to preoperatively and noninvasively predict survival for HCC. Traditional radiomic models are lacking in a consideration for intratumoral regional heterogeneity. The study aimed to establish and validate the predictive power of multiple habitat radiomic models in predicting prognosis of hepatocellular carcinoma (HCC).

Safety and efficacy of intraoperative radiation therapy using a low-energy X-ray source for resectable pancreatic cancer: an interim evaluation of an ongoing prospective phase II study.

Objective: The role of intraoperative radiation therapy (IORT) in the management of resectable pancreatic cancer (RPC) remains unclear. To date, the application of IORT using a low-energy X-ray source has not been extensively investigated. Therefore, this study was conducted to evaluate the safety and efficacy of IORT using a 50 kV X-ray source in treating RPC.

Advancing precision medicine: the transformative role of artificial intelligence in immunogenomics, radiomics, and pathomics for biomarker discovery and immunotherapy optimization.

Artificial intelligence (AI) is significantly advancing precision medicine, particularly in the fields of immunogenomics, radiomics, and pathomics. In immunogenomics, AI can process vast amounts of genomic and multi-omic data to identify biomarkers associated with immunotherapy responses and disease prognosis, thus providing strong support for personalized treatments. In radiomics, AI can analyze high-dimensional features from computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) images to discover imaging biomarkers associated with tumor heterogeneity, treatment response, and disease progression, thereby enabling non-invasive, real-time assessments for personalized therapy.

Elucidating the expression and role of cGAS in pan-cancer using integrated bioinformatics and experimental approaches.

cGAS plays an important role in regulating both tumor immune responses and DNA damage repair. Nevertheless, there was little research that comprehensively analyzed the correlation between cGAS and the tumor microenvironment, immune cell infiltration, and DNA damage repair in different cancers. In this study, The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) data were used to analyze the mRNA expression and genomic alterations of cGAS in pan-cancer.

Predictive markers of rapid disease progression and chemotherapy resistance in triple-negative breast cancer patients following postoperative adjuvant therapy.

Triple-negative breast cancer (TNBC) is a diverse category with a subset that displays particularly aggressive characteristics, referred to in this study as "rapid relapse" TNBC (rrTNBC). This term is defined as the occurrence of distant metastasis or death within 24 months post-diagnosis. The paper mainly studies the clinicopathologic traits of TNBC patients experiencing rapid disease progression and chemotherapy resistance and identify predictive markers for this outcome.

AMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress.

Glucose metabolism has been studied extensively, but the role of glucose-derived excretory glycerol remains unclear. Here we show that hypoxia induces NADH accumulation to promote glycerol excretion and this pathway consumes NADH continuously, thus attenuating its accumulation and reductive stress. Aldolase B accounts for glycerol biosynthesis by forming a complex with glycerol 3-phosphate dehydrogenases GPD1 and GPD1L.

Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study.

This study (NCT04728035) aimed to explore the safety and efficacy of liposomal irinotecan (HE072) in patients with metastatic triple-negative breast cancer (mTNBC). This study consisted of two parts. In part 1, the 3 + 3 design was used to investigate three dose levels of HE072 (50, 70 and 90 mg/m).

The characterization of tumor immune microenvironment after neoadjuvant immunotherapy in head and neck squamous cell cancer using multiplex immunohistochemistry.

Objective: Optimizing clinical decision-making in head and neck squamous cell carcinoma (HNSCC) is challenging due to the ambiguous understanding of the immune cell dynamics and immune checkpoints regulation in the disease after the administration of neoadjuvant immunotherapy (NIT).

Methods: HNSCC biopsy samples collected before and after the neoadjuvant treatment are classified into the pathologic response (PR) and the non-pathologic response (NPR) groups according to treatment responses and the expression of immune cells and checkpoints was labeled using multiplex immunohistochemistry (m-IHC).

Results: The populations of CD4 T cells, CD8 T cells, regulatory T cells (Treg), PD-1, and PD-L1 were particularly higher in the PR group than the NPR group in pre-treatment tissues, with the p-values of log-transformed positive cell density <0.

Notch2 Inhibition and Kidney Cyst Growth in Autosomal Dominant Polycystic Kidney Disease.

Background: Notch signaling, a conserved mechanism of cell-to-cell communication, plays a crucial role in regulating cellular processes such as proliferation and differentiation in a context-dependent manner. However, the specific contribution of Notch signaling to the progression of polycystic kidney disease (PKD) remains unclear.

Methods: We investigated the changes in Notch signaling activity (Notch1-4) in the kidneys of autosomal dominant PKD (ADPKD) patients and two ADPKD mouse models (early and late onset).

The effect of intraoperative radiotherapy in musculoskeletal malignancy: A population study from US SEER database.

The aim of our study was to explore the effect of IORT on survival outcome of patients with musculoskeletal malignancy. The prognostic factors of patients with IORT treatment were also identified in this study. The retrospective analysis was conducted based on the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2000 to 2020.

Quantitative Histopathology Analysis Based on Label-free Multiphoton Imaging for Breast Cancer Diagnosis and Neoadjuvant Immunotherapy Response Assessment.

Accurate diagnosis and assessment of breast cancer treatment responses are critical challenges in clinical practice, influencing patient treatment strategies and ultimately long-term prognosis. Currently, diagnosing breast cancer and evaluating the efficacy of neoadjuvant immunotherapy (NAIT) primarily rely on pathological identification of tumor cell morphology, count, and arrangement. However, when tumors are small, the tumors and tumor beds are difficult to detect; relying solely on tumor cell identification may lead to false negatives.

High-throughput screening of dual-target inhibitors for SARS-CoV-2 main protease and papain-like protease from Chebulae Fructus: prediction and experimental verification.

Background: The unavoidable propagation of the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has underscored the urgent requirement for efficacious therapeutic agents. The dried fruit of Retz., namely Chebulae Fructus, is widely used for treating bacterial and viral infectious diseases, which was witnessed to perform anti-SARS-CoV-2 activity in recommended Chinese patent medicine.

Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases.

Esophageal squamous cell carcinoma (ESCC) patients often face a grim prognosis due to lymph node metastasis. However, a comprehensive understanding of the cellular and molecular characteristics of metastatic lymph nodes in ESCC remains elusive. In this study involving 12 metastatic ESCC patients, we employed single-cell sequencing, spatial transcriptomics (ST), and multiplex immunohistochemistry (mIHC) to explore the spatial and molecular attributes of primary tumor samples, adjacent tissues, metastatic and non-metastatic lymph nodes.

Intratumoural CD8 CXCR5 follicular cytotoxic T cells have prognostic value and are associated with CD19 CD38 B cells and tertiary lymphoid structures in colorectal cancer.

Background: Colorectal cancer (CRC) is the most common digestive cancer in the world. Microsatellite stability (MSS) and microsatellite instability (MSI-high) are important molecular subtypes of CRC closely related to tumor occurrence and progression and immunotherapy efficacy. The presence of CD8 CXCR5 follicular cytotoxic T (T) cells is strongly associated with autoimmune disease and CD8 effector function.

Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma.

Background: Research has consistently highlighted the key role of hepatocyte nuclear factor 1β (HNF1B) in organ development and cancer, including its involvement in colon cancer via shifted-code mutations. However, the specific effects of HNF1B on cancer immunotherapy and the immune microenvironment are not fully understood. This study investigated the impact of HNF1B on colon cancer immunotherapy in depth.

A real-world pharmacovigilance analysis of potential ototoxicity associated with sacubitril/valsartan based on FDA Adverse Event Reporting System (FAERS).

Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, is widely used to treat heart failure. Despite its efficacy, sacubitril/valsartan inevitably causes adverse events such as hypotension, renal dysfunction, hyperkalemia, and angioedema. Sacubitril/valsartan-associated ototoxicity is often underreported in clinical studies and real-world settings.

Immunochemotherapy plus radiotherapy versus immunochemotherapy alone as first-line treatment for treatment-naïve, advanced esophageal squamous cell carcinoma (AEC-ICR-1st): A multi-center cohort study.

Immunochemotherapy is Currently the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). However, its prognosis remains unsatisfactory. We aimed to evaluate the efficacy and safety of immunochemotherapy plus radiotherapy (ICR) compared with immunochemotherapy (IC) alone as a first-line treatment for advanced ESCC.