Long-Read Sequencing Reveals Tumor-Specific Splicing Isoforms as Therapeutic Targets In NSCLC.

Despite extensive transcriptomic alterations observed in tumors, the global landscape of isoform-level alternative splicing in cancer remains largely unexplored. Leveraging long-read sequencing, we successfully identified and characterized full-length isoforms, along with tumor-specific splicing events in non-small cell lung cancer (NSCLC). Our analysis identified 38,058 previously unannotated isoforms, which were subsequently validated using orthogonal multi-omics datasets to confirm their transcriptional and translational activities.

Gut microbiome and metabolome characteristics of patients with cholesterol gallstones suggest the preventive potential of prebiotics.

Cholesterol gallstones (CGS) still lack effective noninvasive treatment. The etiology of experimentally proven cholesterol stones remains underexplored. This cross-sectional study aims to comprehensively evaluate potential biomarkers in patients with gallstones and assess the effects of microbiome-targeted interventions in mice.

A machine learning-based prediction of hospital mortality in mechanically ventilated ICU patients.

Background: Mechanical ventilation (MV) is vital for critically ill ICU patients but carries significant mortality risks. This study aims to develop a predictive model to estimate hospital mortality among MV patients, utilizing comprehensive health data to assist ICU physicians with early-stage alerts.

Methods: We developed a Machine Learning (ML) framework to predict hospital mortality in ICU patients receiving MV.

Prediction of 30-day mortality for ICU patients with Sepsis-3.

Background: There is a growing demand for advanced methods to improve the understanding and prediction of illnesses. This study focuses on Sepsis, a critical response to infection, aiming to enhance early detection and mortality prediction for Sepsis-3 patients to improve hospital resource allocation.

Methods: In this study, we developed a Machine Learning (ML) framework to predict the 30-day mortality rate of ICU patients with Sepsis-3 using the MIMIC-III database.

Integrative analyses of multi-omics data constructing tumor microenvironment and immune-related molecular prognosis model in human colorectal cancer.

The increasing prevalence and incidence of colorectal cancer (CRC), particularly in young adults, underscore the imperative to comprehend its fundamental mechanisms, discover novel diagnostic and prognostic markers, and enhance therapeutic strategies. Here, we integrated multi-omics data, including gene expression, somatic mutation data and DNA methylation data, to unravel the intricacies of tumor microenvironment (TME) in CRC and search for novel prognostic markers. By calculating the immune score for each patient from the expression profile, we delineated the differential immune cell fraction, constructed an immune-related multi-omics atlas, and identified molecular characteristics.

Small molecule NMD and MDM2 inhibitors synergistically trigger apoptosis in HeLa cells.

The nonsense-mediated mRNA decay (NMD) pathway and the p53 pathway, linked to tumorgenesis, are also promising targets for cancer treatment. NMD plays an important role in RNA quality control, while the p53 pathway is involved in cancer suppression. However, their individual and combined effects on cervical cancer are poorly understood.

Comprehensive analysis of m A methylome and transcriptome by Nanopore sequencing in clear cell renal carcinoma.

N -methyladenosine (m A) is the most prevalent epigenetic modification on eukaryotic messenger RNAs. Recent studies have focused on elucidating the key role of m A modification patterns in tumor progression. However, the relationship between m A and transcriptional regulation remains elusive.

Small extrachromosomal circular DNAs as biomarkers for multi-cancer diagnosis and monitoring.

Background: Small extrachromosomal circular DNAs (eccDNAs) have the potential to be cancer biomarkers. However, the formation mechanisms and functions of small eccDNAs selected in carcinogenesis are not clear, and whether the small eccDNA profile in the plasma of cancer patients represents that in cancer tissues remains to be elucidated.

Methods: A novel sequencing workflow based on the nanopore sequencing platform was used to sequence naturally existing full-length small eccDNAs in tissues and plasma collected from 25 cancer patients (including prostate cancer, hepatocellular carcinoma and colorectal cancer), and from an independent validation cohort (including 7 cancer plasma and 14 healthy plasma).

C1q/TNF-related protein 4 mediates proliferation and migration of vascular smooth muscle cells during vascular remodelling.

Background: Vascular remodelling is an essential pathophysiological state in many circulatory diseases. Abnormal vascular smooth muscle cell (VSMC) behaviour leads to neointimal formation and may eventually results in major adverse cardiovascular events. The C1q/TNF-related protein (C1QTNF) family is closely associated with cardiovascular disease.

The screening of compounds regulating PD-L1 transcriptional activity in a cell functional high-throughput manner.

Immune checkpoints are protein molecules expressed on the immune cell membrane, which regulate the immune system to kill tumor cells. As an essential immune checkpoint, overexpressed PD-1 on tumor cells could inhibit T-cell activation after being bonded to PD-1. Due to this inhibitory effect, T-cell proliferation and cytokine secretion are suppressed, leading to immune escape of tumor cells.

Artificial intelligence-based recognition for variant pathogenicity of BRCA1 using AlphaFold2-predicted structures.

With the surge of the high-throughput sequencing technologies, many genetic variants have been identified in the past decade. The vast majority of these variants are defined as variants of uncertain significance (VUS), as their significance to the function or health of an organism is not known. It is urgently needed to develop intelligent models for the clinical interpretation of VUS.

Modular Bioinspired Hand with Multijoint Rigid-Soft Finger Possessing Proprioception.

Soft robot hands have the advantage of remarkable adaptability for grasping. Especially for the soft and fragile objects, soft fingers had presented their much excellent potential compared with their rigid counterparts. However, less degree of freedom, lower force output, lack of proprioception, and poor controllability still limit the application.

Nonsense-mediated mRNA decay inhibition synergizes with MDM2 inhibition to suppress TP53 wild-type cancer cells in p53 isoform-dependent manner.

The restoration of the normal function of the tumour suppressors, such as p53, is an important strategy in tumour therapeutics. Nonsense-mediated mRNA decay (NMD) inhibition by NMD inhibitor (NMDi) upregulates functional p53 isoforms, p53β and p53γ, and activates the p53 pathway. XR-2, a novel mouse double minute 2 homolog (MDM2) inhibitor, can disrupt the interaction between p53 and MDM2, thus decreasing the MDM2-mediated degradation of p53 and increasing the p53 protein levels.

Peripheral Blood Microbiome Analysis via Noninvasive Prenatal Testing Reveals the Complexity of Circulating Microbial Cell-Free DNA.

While circulating cell-free DNA (cfDNA) is becoming a powerful marker for noninvasive identification of infectious pathogens in liquid biopsy specimens, a microbial cfDNA baseline in healthy individuals is urgently needed for the proper interpretation of microbial cfDNA sequencing results in clinical metagenomics. Because noninvasive prenatal testing (NIPT) shares many similarities with the sequencing protocol of metagenomics, we utilized the standard low-pass whole-genome-sequencing-based NIPT to establish a microbial cfDNA baseline in healthy people. Sequencing data from a total of 107,763 peripheral blood samples of healthy pregnant women undergoing NIPT screening were retrospectively collected and reanalyzed for microbiome DNA screening.

Mutational Pattern Induced by 5-Fluorouracil and Oxaliplatin in the Gut Microbiome.

Chemotherapeutic agents, such as 5-fluorouracil (5-FU) and oxaliplatin (Oxi), can not only kill the cancer cell but also influence the proliferation of gut microbiota; however, the interaction between these drugs and gut microbiota remains poorly understood. In this study, we developed a powerful framework for taxonomy composition and genomic variation analysis to investigate the mutagenesis effect and proliferation influence of chemotherapeutic agents, such as 5-FU and Oxi, on gut microbiota and the interaction between these drugs and gut microbiota during chemotherapy. Using the gut microbiome data, we detected 1.

Comprehensive Analysis of DNA 5-Methylcytosine and N6-Adenine Methylation by Nanopore Sequencing in Hepatocellular Carcinoma.

DNA methylation is a widespread epigenetic signal in human genome. With Nanopore technology, differential methylation modifications including 5-methylcytosine (5mC) and 6-methyladenine (6mA) can be identified. 5mC is the most important modification in mammals, although 6mA may also function in growth and development as well as in pathogenesis.

Calmette-Guérin Treatment Changes the Tumor Microenvironment of Non-Muscle-Invasive Bladder Cancer.

Background: Calmette-Guérin (BCG) is currently the most effective intravesical therapy for non-muscle-invasive bladder cancer (NMIBC) as it can prevent disease recurrence and progression and lower mortality. However, the response rates to BCG vary widely and are dependent on a multitude of factors.

Methods: We performed a systematic discovery by analyzing the whole exome sequence, expression profile, and immune repertoire sequence of treatment-naive and 5-year time-serial relapsed tumors from 24 NMIBC patients.

Lactylated Histone H3K18 as a Potential Biomarker for the Diagnosis and Predicting the Severity of Septic Shock.

Objective: To date, there are no studies regarding the lactylation profile and its role in critically ill patients. Thus, we aimed to examine expression of histone H3 lysine 18 (H3K18) lactylation and its role in patients with septic shock.

Methods: Thirteen healthy volunteers and 35 critically ill patients from the Department of Surgical Intensive Care Medicine, Beijing Hospital were enrolled in our study.

Copper-catalyzed [3 + 1] cyclization of cyclopropenes/diazo compounds and bromodifluoroacetamides: facile synthesis of α,α-difluoro-β-lactam derivatives.

We have developed a novel copper-catalyzed cyclization of cyclopropenes/diazo compounds and bromodifluoroacetamides, efficiently synthesizing a series of α,α-difluoro-β-lactams in moderate to excellent yields under mild reaction conditions. This reaction represents the first example of [3 + 1] cyclization for the synthesis of β-lactams utilizing a metal carbene intermediate as the C1 synthon.

Long-read sequencing reveals the structural complexity of genomic integration of HBV DNA in hepatocellular carcinoma.

The integration of HBV DNA into the human genome can disrupt its structure in hepatocellular carcinoma (HCC), but the complexity of HBV genomic integration remains elusive. Here we applied long-read sequencing to precisely elucidate the HBV integration pattern in the human hepatocellular genome. The DNA library was sequenced using the long-read sequencing on GridION and PacBio Sequel II, respectively.

Research progress on biomarkers of pulmonary embolism.

Objectives: To present a review on the traditional and new biomarkers of pulmonary embolism (PE).

Data Source: A systematic search has been carried out using keywords as PE, biomarker, diagnosis and risk stratification.

Results: The results of this work have been structured into three parts: first, conventional biomarkers for vascular, cardiac and inflammation, including static markers and dynamic markers for measuring the time course; next, a review of new biomarkers in recent years, such as RNAs and markers obtained through proteomics and mass spectrometry; finally, use of new detection methods to directly detect the activity of existing markers, such as the determination of coagulation factor II and plasmin activities based on the proteolytic activation of an engineered zymogen.

Discovery of plasma biomarkers with data-independent acquisition mass spectrometry and antibody microarray for diagnosis and risk stratification of pulmonary embolism.

Background: Pulmonary embolism (PE) is a leading cause of cardiovascular mortality worldwide. Rapid and accurate diagnosis and risk stratification are crucial for timely treatment options, especially in high-risk PE.

Objectives: The study aims to profile the comprehensive changes of plasma proteomes in PE patients and identify the potential biomarkers for both diagnosis and risk stratification.

Identification of differentially expressed circular RNAs associated with thymoma.

Background: Thymomas and thymic carcinomas are the most common tumor types among anterior mediastinal lesions. However, the relationship between molecular aberrations and thymoma patients are poorly understood, especially abnormal changes in the expression profiles of circRNAs. The purpose of the present study was to investigate the expression profiles of circRNAs in thymoma patients and their possible roles in the pathogenesis of thymoma.

Five Circular RNAs in Metabolism Pathways Related to Prostate Cancer.

Prostate cancer (PCa) is the most common malignant tumor in men, and its incidence increases with age. Serum prostate-specific antigen and tissue biopsy remain the standard for diagnosis of suspected PCa. However, these clinical indicators may lead to aggressive overtreatment in patients who have been treated sufficiently with active surveillance.