Neurodegeneration Promotes Tumorigenesis in Colorectal Cancer: Insights From Single-Cell and Spatial Multiomics.

Purpose: Colorectal cancer (CRC) ranks third in global incidence and second in mortality, with rates increasing among younger populations. The enteric nervous system (ENS) is crucial for gastrointestinal function, and its dysfunction is associated with the progression of CRC. Neurodegeneration may disrupt ENS function and facilitate tumor growth although the mechanisms remain unclear.

Deficient FANCL Predisposes to Endothelial Damage: A New Therapeutic Target for Pulmonary Hypertension.

Clinical observations have suggested an association between alkylating agent-based chemotherapy and pulmonary arterial hypertension (PAH). The Fanconi anemia (FA) pathway, the principal mechanism for resolving alkylating agent-induced DNA damage, has been implicated in this process. To establish the interplay among the FA pathway, DNA damage, and PAH.

Foxp3 confers long-term efficacy of chimeric antigen receptor-T cells via metabolic reprogramming.

The tumor microenvironment, characterized by low oxygen tension and scarce nutrients, impairs chimeric antigen receptor (CAR)-T cell metabolism, leading to T cell exhaustion and dysfunction. Notably, Foxp3 confers a metabolic advantage to regulatory T cells under such restrictive conditions. Exploiting this property, we generated CAR-T cells by co-expressing Foxp3 with a third-generation CAR construct.

Targeting tumor monocyte-intrinsic PD-L1 by rewiring STING signaling and enhancing STING agonist therapy.

STING is an important DNA sensing machinery in initiating immune response, yet therapies targeting STING have shown poor outcomes in clinical trials. Here, we reveal that STING signaling induces PD-L1 tumor monocytes (Tu.Mons) that dominate the resistance against STING agonist therapy.

Integrating genome-wide association studies and transcriptomics prioritizes drug targets for meningioma.

Meningioma, a prevalent central nervous system tumour, presents a significant challenge in neuro-oncology. This study harnesses genome-wide association studies (GWAS) and transcriptomic analysis to illuminate the pathological underpinnings of meningioma and spearhead the discovery of novel drug targets. By employing summary-data-based Mendelian randomization (SMR), colocalization analyses and Mendelian randomization, we pinpointed four genes as pivotal therapeutic targets.

Scientometric analysis of research trends in hemorrhagic fever with renal syndrome: A historical review and network visualization.

Background: Hemorrhagic fever with renal syndrome (HFRS) research has undergone significant global transformation over the past decades. A comprehensive scientometric overview of research trends and scholarly cooperation in HFRS is absent. This study employs scientometric analysis to map the evolution of research themes, identify widely and scarcely explored areas, and anticipate future research directions.

Deficiency of Endothelial Impairs Pulmonary Vascular Angiogenesis and Predisposes Pulmonary Hypertension.

Background: Mechanosensitive Piezo1 (Piezo Type Mechanosensitive Ion Channel Component 1) channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.

Methods: Endothelial cell (EC)-specific Piezo2 knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.

Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats.

The oral administrated thiazolidinediones (TZDs) have been widely reported to alleviate experimental pulmonary hypertension (PH). However, previous studies mainly focused on their beneficial effects on the cardiopulmonary vascular system but failed to determine their potential roles on gut microenvironment. This study aims to investigate the effects of pioglitazone, an oral TZD drug, on gut microbiome in classic PH rat models induced by hypoxia (HPH) or SU5416/hypoxia (SuHx-PH) and evaluate the therapeutic potential of supplementation of selective probiotics for experimental PH.

Rg3-lipo biomimetic delivery of paclitaxel enhances targeting of tumors and myeloid-derived suppressor cells.

Liposomal drug delivery systems have revolutionized traditional cytotoxic drugs. However, the relative instability and toxicity of the existing liposomal drug delivery systems compromised their efficacy. Herein, we present Rg3-lipo, an innovative drug delivery system using a glycosyl moiety-enriched ginsenoside (Rg3).

Crosstalk among proximal tubular cells, macrophages, and fibroblasts in acute kidney injury: single-cell profiling from the perspective of ferroptosis.

The link between ferroptosis, a form of cell death mediated by iron and acute kidney injury (AKI) is recently gaining widespread attention. However, the mechanism of the crosstalk between cells in the pathogenesis and progression of acute kidney injury remains unexplored. In our research, we performed a non-negative matrix decomposition (NMF) algorithm on acute kidney injury single-cell RNA sequencing data based specifically focusing in ferroptosis-associated genes.

Prognostic implication of UBE2C + CD8 + T cell in neoadjuvant immune checkpoint blockade plus chemotherapy for locally advanced esophageal cancer.

Background: Immune checkpoint blockers (ICBs) plus chemotherapy as neoadjuvant therapy for patients with esophageal cancer (EC) has gained substantial attention. This study aimed to investigate the early and mid-term outcome of neoadjuvant ICBs plus chemotherapy and discover immune-associated predictors of major pathological response (MPR) for locally advanced EC.

Method: Patients with locally advanced EC who received neoadjuvant ICBs plus chemotherapy were retrospectively included between June 2019 to December 2021.

Construction of a New Ferroptosis-related Prognosis Model for Survival Prediction in Colorectal Cancer.

Aim: This study was designed to develop a ferroptosis-related gene signature for guiding the prognostic prediction in colorectal cancer (CRC) and to explore the potential in the molecular functions of the gene signature.

Background: Ferroptosis is mainly characterized by lipid peroxide accumulation on the cell membranes in an iron-dependent manner, resulting in cellular oxidative stress, metabolic disorders, and, ultimately, cell death. This study aimed to develop a prognostic ferroptosis signature in CRC and explore its potential molecular function.

Development and validation of CT-based radiomics deep learning signatures to predict lymph node metastasis in non-functional pancreatic neuroendocrine tumors: a multicohort study.

Background: Lymph node status is an important factor for the patients with non-functional pancreatic neuroendocrine tumors (NF-PanNETs) with respect to the surgical methods, prognosis, recurrence. Our aim is to develop and validate a combination model based on contrast-enhanced CT images to predict the lymph node metastasis (LNM) in NF-PanNETs.

Methods: Retrospective data were gathered for 320 patients with NF-PanNETs who underwent curative pancreatic resection and CT imaging at two institutions (Center 1, n = 236 and Center 2, n = 84) between January 2010 and March 2022.

Single-cell dissection, hdWGCNA and deep learning reveal the role of oxidatively stressed plasma cells in ulcerative colitis.

Ulcerative colitis (UC) develops as a result of complex interactions between various cell types in the mucosal microenvironment. In this study, we aim to elucidate the pathogenesis of ulcerative colitis at the single-cell level and unveil its clinical significance. Using single-cell RNA sequencing and high-dimensional weighted gene co-expression network analysis, we identify a subpopulation of plasma cells (PCs) with significantly increased infiltration in UC colonic mucosa, characterized by pronounced oxidative stress.

Identification of antigen-presentation related B cells as a key player in Crohn's disease using single-cell dissecting, hdWGCNA, and deep learning.

Crohn's disease (CD) arises from intricate intercellular interactions within the intestinal lamina propria. Our objective was to use single-cell RNA sequencing to investigate CD pathogenesis and explore its clinical significance. We identified a distinct subset of B cells, highly infiltrated in the CD lamina propria, that expressed genes related to antigen presentation.

A precise molecular subtyping of ulcerative colitis reveals the immune heterogeneity and predicts clinical drug responses.

Background And Aims: We sought to identify novel molecular subtypes of ulcerative colitis (UC) based on large-scale cohorts and establish a clinically applicable subtyping system for the precision treatment of the disease.

Methods: Eight microarray profiles containing colon samples from 357 patients were utilized. Expression heterogeneity was screened out and stable subtypes were identified among UC patients.

Single-cell dissection reveals the role of DNA damage response patterns in tumor microenvironment components contributing to colorectal cancer progression and immunotherapy.

Colorectal cancer (CRC) is one of the leading malignant cancers. DNA damage response (DDR), referring to the molecular process of DNA damage, is emerging as a promising field in targeted cancer therapy. However, the engagement of DDR in the remodeling of the tumor microenvironment is rarely studied.

Minimally invasive versus open McKeown esophagectomy for patients with esophageal squamous cell carcinoma after neoadjuvant PD-1 inhibitor plus chemotherapy.

Introduction: The purpose of this study was to compare short and mid-term outcomes in esophageal squamous cell carcinoma (ESCC) patients undergoing open or minimally invasive McKeown esophagectomy (MIE) after neoadjuvant PD-1 inhibitor plus chemotherapy.

Methods: Patients with locally advanced ESCC underwent open or minimally invasive McKeown esophagectomy after neoadjuvant PD-1 inhibitor plus chemotherapy were retrospectively included from June 2019 to June 2021. The baseline characteristics, pathological data, short-and mid-term outcomes were collected and compared based on the surgical approach.

A High-Throughput Sequencing Data-Based Classifier Reveals the Metabolic Heterogeneity of Hepatocellular Carcinoma.

Metabolic heterogeneity plays a key role in poor outcomes in malignant tumors, but its role in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we aim to disentangle the metabolic heterogeneity features of HCC by developing a classification system based on metabolism pathway activities in high-throughput sequencing datasets. As a result, HCC samples were classified into two distinct clusters: cluster 1 showed high levels of glycolysis and pentose phosphate pathway activity, while cluster 2 exhibited high fatty acid oxidation and glutaminolysis status.

Systematic single-cell dissecting reveals heterogeneous oncofetal reprogramming in the tumor microenvironment of gastric cancer.

Oncofetal reprogramming of the tumor microenvironment is clinically relevant. This study used the non-negative matrix factorial (NMF) algorithm for single-cell RNA sequencing data of gastric cancer (GC) based on embryonic stem genes. Pseudotime analysis, cell-cell interaction analysis, and SCENIC analysis revealed that cancer-associated fibroblasts (CAFs), tumor-associated endothelial cells (TECs), and tumor-associated macrophages (TAMs) have different oncofetal reprogramming that affects cell function, enhances intercellular communication, and activates multiple transcription factors in these cells.

Machine Learning Model in Predicting Sarcopenia in Crohn's Disease Based on Simple Clinical and Anthropometric Measures.

Sarcopenia is associated with increased morbidity and mortality in Crohn's disease. The present study is aimed at investigating the different diagnostic performance of different machine learning models in identifying sarcopenia in Crohn's disease. Patients diagnosed with Crohn's disease at our center provided clinical, anthropometric, and radiological data.