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.

[Clinical characteristics and survival analysis of pediatric Hodgkin lymphoma: a multicenter study].

Objectives: To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL).

Methods: A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors.

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.

mRNA m5C Alteration in Azacitidine Demethylation Treatment of Acute Myeloid Leukemia.

The DNA demethylating therapy with azacitidine (AZA) is a promising therapeutic strategy for elderly patients with acute myeloid leukemia (AML). AZA primarily inhibits DNA methylation, promotes cell differentiation and apoptosis in AML. However, as a cytosine nucleoside analog, AZA also has the potential to be incorporated into RNA molecules.

Philadelphia chromosome-positive or Philadelphia chromosome-like B-cell precursor acute lymphoblastic leukemia with multilineage involvement in pediatric patients: a report of two cases and literature review.

Based on driver mutations and gene expression profiles, the International Consensus Classification currently divided the entity 'Philadelphia chromosome-positive (Ph + ) B-cell precursor acute lymphoblastic leukemia (ALL)' into two subtypes: lymphoid-only and multilineage involvement (Ph + ALL-L and -M, respectively). The similar biological characteristics of Ph-like ALL and Ph + ALL drove us to assume that Ph-like ALL-M subtypes exist. This report presents two pediatric ALL cases (one Ph + and one Ph-like) with minimal residual disease negativity established by multicolor flow cytometry but persistent transcript detection by quantitative PCR (qPCR) even after second-line treatment with tyrosine kinase inhibitors combined with blinatumomab immunotherapy.

An ultrasensitive DNA-enhanced amplification method for detecting cfDNA drug-resistant mutations in non-small cell lung cancer with selective FEN-assisted degradation of dominant somatic fragments.

Objectives: Blood cell-free DNA (cfDNA) can be a new reliable tool for detecting epidermal growth factor receptor () mutations in non-small cell lung cancer (NSCLC) patients. However, the currently reported cfDNA assays have a limited role in detecting drug-resistant mutations due to their deficiencies in sensitivity, stability, or mutation detection rate.

Methods: We developed an -derived flap endonuclease ( FEN)-based DNA-enhanced amplification system of mutated cfDNA by designing a pair of hairpin probes to anneal with wild-type cfDNA to form two 5'-flaps, allowing for the specific cleavage of wild-type cfDNA by FEN.

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 mA methylome alterations after azacytidine plus venetoclax treatment for acute myeloid leukemia by nanopore sequencing.

N6 adenosine methylation (mA), one of the most prevalent internal modifications on mammalian RNAs, regulates RNA transcription, stabilization, and splicing. Growing evidence has focused on the functional role of mA regulators on acute myeloid leukemia (AML). However, the global mA levels after azacytidine (AZA) plus venetoclax (VEN) treatment in AML patients remain unclear.

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).

Metastasis pattern and prognosis in children with neuroblastoma.

Background: We aimed to investigate the different metastases and prognoses of neuroblastoma (NB) and determine the risk factors of metastasis.

Method: Data of 1224 patients with NB were obtained from the Surveillance, Epidemiology and End Results database (2010-2018). Pearson's chi-square test, Kaplan-Meier analysis, multivariable logistic regression and Cox regression analysis were used to determine the factors associated with prognosis.

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.

Modifying a bacterial tyrosinase zymogen for use in protease activity assays.

Current clinical laboratory assays are not sufficient for determining the activity of many specific human proteases yet. In this study, we developed a general approach that enables the determination of activities of caspase-3 based on the proteolytic activation of the engineered zymogen of the recombinant tyrosinase from Verrucomicrobium spinosum (Vs-tyrosinase) by detecting the diphenolase activity in an increase in absorbance at 475 nm. Here, we designed three different zymogen constructs of Vs-tyrosinase, including RSL-pre-pro-TYR, Pre-pro-TYR, and Pro-TYR.

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.

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.

Novel MDM2 Inhibitor XR-2 Exerts Potent Anti-Tumor Efficacy and Overcomes Enzalutamide Resistance in Prostate Cancer.

The inactivation of tumor-suppressor p53 plays an important role in second generation anti-androgens (SGAs) drug resistance and neuroendocrine differentiation in castration-resistant prostate cancer (CRPC). The reactivation of p53 by blocking the MDM2-p53 interaction represents an attractive therapeutic remedy in cancers with wild-type or functional p53. Whether MDM2-p53 inhibitor could overcome SGAs drug resistance in CRPC is still needed further research.

Effects of , and Genetic Variants on 6-Mercaptopurine Toxicity for Pediatric Patients With Acute Lymphoblastic Leukemia in Yunnan of China.

6-Mercaptopurine (6-MP) is the cornerstone of current antileukemia regimen and contributes greatly to improve the survival of pediatric acute lymphoblastic leukemia (ALL) patients. However, 6-MP dose-related toxicities limit its application. , and are pharmacogenetic markers predicting 6-MP-related toxicities, but their genetic polymorphisms differ from those of ethnic populations.

Comparative Genome Analysis Reveals the Molecular Basis of Niche Adaptation of Strains.

is one of the most commonly isolated species from human skin and the second leading cause of bloodstream infections. Here, we performed a large-scale comparative study without any pre-assigned reference to identify genomic determinants associated with the diversity and adaptation of strains to various environments. Pan-genome of was open with 435 core proteins and had a pan-genome size of 8,034 proteins.

Continuation of Aspirin Therapy before Cataract Surgery with Different Incisions: Safe or Not?

Purpose: To assess whether to continue aspirin therapy while having uncomplicated phacoemulsification cataract surgery with different incisions.

Methods: Consecutive patients having cataract surgery under topical anesthesia with different incisions between May 2016 and August 2017 were followed. 236 eyes of 166 patients on routine aspirin therapy were randomized into 2 groups: continuation group, 112 eyes; discontinuation group, 124 eyes.

RNA-Seq Based De Novo Transcriptome Assembly and Gene Discovery of Cistanche deserticola Fleshy Stem.

Backgrounds: Cistanche deserticola is a completely non-photosynthetic parasitic plant with great medicinal value and mainly distributed in desert of Northwest China. Its dried fleshy stem is a crucial tonic in traditional Chinese medicine with roles of mainly improving male sexual function and strengthening immunity, but few mechanistic studies have been conducted partly due to the lack of genomic and transcriptomic resources.

Results: In this study, we performed deep transcriptome sequencing in fleshy stem of C.

Transcriptomic study of the red palm weevil Rhynchophorus ferrugineus embryogenesis.

The red palm weevil (RPW), Rhynchophorus ferrugineus (Coleoptera: Curculionidae), is an invasive, concealed and destructive tissue borer, and it becomes a lethal pest of the palm family of plants and has been reported to attack 20 palm species around the globe. Here we report a systematic transcriptomic study on embryogenesis of RPW, where we analyze the transcriptomes across five developmental stages of RPW embryogenesis, involving four embryonic stages (E1, E2, E3 and E4) and one larval stage (L1). Using the RNA-seq and next-generation platforms, we generated 80 to 91 million reads for each library and assemble 22 532 genes that are expressed at different embryonic stages.

Seasonally variable intestinal metagenomes of the red palm weevil (Rhynchophorus ferrugineus).

The intestinal microbes residing in the red palm weevil (RPW, Rhynchophorus ferrugineus) larva consume tender interior fibrous tissues of date palm trunks. The understanding of such microbiota at molecular level provides vital clues for the biological control of this devastating pest. Using pyrosequencing and shotgun strategy, we first study taxonomic profiles of the microbiota sampled at different months (March, July and November), and then confirm the impact of high-temperature stress on the microbial populations based on data from 16S rRNA amplicons using both field and laboratory samples.