Innovative Bacterial Therapies and Genetic Engineering Approaches in Colorectal Cancer: A Review of Emerging Strategies and Clinical Implications.

Colorectal cancer (CRC) is considered a widespread cancer, ranking second in mortality and incidence among cancer patients worldwide. CRC develops from adenoma to carcinoma through the dynamic interplay of genetic and environmental factors. The conventional modes of treatment, including operation, chemotherapy, and irradiation, are associated with significant challenges, such as drug resistance and toxicity, necessitating the exploration of new treatment modalities.

Absolute quantitative and base-resolution sequencing reveals comprehensive landscape of pseudouridine across the human transcriptome.

Pseudouridine (Ψ) is one of the most abundant modifications in cellular RNA. However, its function remains elusive, mainly due to the lack of highly sensitive and accurate detection methods. Here, we introduced 2-bromoacrylamide-assisted cyclization sequencing (BACS), which enables Ψ-to-C transitions, for quantitative profiling of Ψ at single-base resolution.

Targeted Drug Nanodelivery and Immunotherapy for Combating Tumor Resistance.

Chemotherapy resistance is a common cause of tumor treatment failure. Various molecular responses, such as increased expression of efflux transporter proteins, including Pglycoprotein (P-gp), changes in the tumor microenvironment (TME), the role of platelets, and the effects of cancer stem cells (CSCs), can lead to drug resistance. Through extensive research on the mechanisms of drug resistance, more effective anti-resistance drugs and therapeutic approaches are being developed.

DMRT1 regulates human germline commitment.

Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo.

Mapping epigenetic modifications by sequencing technologies.

The "epigenetics" concept was first described in 1942. Thus far, chemical modifications on histones, DNA, and RNA have emerged as three important building blocks of epigenetic modifications. Many epigenetic modifications have been intensively studied and found to be involved in most essential biological processes as well as human diseases, including cancer.

Sarcoidosis with the livedo reticularis-like appearance.

Sarcoidosis is a multisystem inflammatory disease manifesting as noncaseating epithelioid cell granulomas. 25 to 30% of individuals with systemic sarcoidosis show variable cutaneous manifestations. A 59-year-old female was seen with reticular purplish-red nodules and plaques on the legs for three months.

Modular Oxidation of Cytosine Modifications and Their Application in Direct and Quantitative Sequencing of 5-Hydroxymethylcytosine.

Selective, efficient, and controllable oxidation of cytosine modifications is valuable for epigenetic analyses, yet only limited progress has been made. Here, we present two modular chemical oxidation reactions: conversion of 5-hydroxymethylcytosine (5hmC) into 5-formylcytosine (5fC) using 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (ACTBF) and further transformation of 5fC into 5-carboxycytosine (5caC) through Pinnick oxidation. Both reactions are mild and efficient on double-stranded DNA.

Whole-genome long-read TAPS deciphers DNA methylation patterns at base resolution using PacBio SMRT sequencing technology.

Long-read sequencing provides valuable information on difficult-to-map genomic regions, which can complement short-read sequencing to improve genome assembly, yet limited methods are available to accurately detect DNA methylation over long distances at a whole-genome scale. By combining our recently developed TET-assisted pyridine borane sequencing (TAPS) method, which enables direct detection of 5-methylcytosine and 5-hydroxymethylcytosine, with PacBio single-molecule real-time sequencing, we present here whole-genome long-read TAPS (wglrTAPS). To evaluate the performance of wglrTAPS, we applied it to mouse embryonic stem cells as a proof of concept, and an N50 read length of 3.

The Economic Impact of Climate Change on Wheat and Maize Yields in the North China Plain.

Climate change has significantly affected agricultural production. As one of China's most important agricultural production regions, the North China Plain (NCP) is subject to climate change. This paper examines the influence of climate change on the wheat and maize yields at household and village levels, using the multilevel model based on a large panel survey dataset in the NCP.

Zero trust in edge computing environment: a blockchain based practical scheme.

Edge computing offloads the data processing capacity to the user side, provides flexible and efficient computing services for the development of smart city, and brings many security challenges. Aiming at the problems of fuzzy boundary security protection and dynamic identity authentication in the edge computing environment in smart city, the zero trust architecture based on blockchain is studied, and a digital identity model and dynamic authentication scheme of edge computing nodes based on distributed ledger are proposed. Firstly, a digital identity model of two-way authentication between edge computing node and sensing terminal is established to realize fine-grained authorization and access control in edge computing.

Cell-free DNA TAPS provides multimodal information for early cancer detection.

Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes.

Endonuclease enrichment TAPS for cost-effective genome-wide base-resolution DNA methylation detection.

Whole genome base-resolution methylome sequencing allows for the most comprehensive analysis of DNA methylation, however, the considerable sequencing cost often limits its applications. While reduced representation sequencing can be an affordable alternative, over 80% of CpGs in the genome are not covered. Building on our recently developed TET-assisted pyridine borane sequencing (TAPS) method, we here described endonuclease enrichment TAPS (eeTAPS), which utilizes dihydrouracil (DHU)-cleaving endonuclease digestion of TAPS-converted DNA to enrich methylated CpG sites (mCpGs).

Different Doses of Oxycodone for Endoscopic Injection Sclerotherapy of Esophageal Varices.

BACKGROUND The aim of the present study was to evaluate the effects of different doses of oxycodone during endoscopic injection sclerotherapy (EIS) for esophageal varices with painless sclerosing agents. MATERIAL AND METHODS A total of 119 patients were randomly divided into 3 groups: Group A, midazolam and 0.075 mg/kg oxycodone (n=40); Group B, midazolam and 0.

Subtraction-free and bisulfite-free specific sequencing of 5-methylcytosine and its oxidized derivatives at base resolution.

Although various methods have been developed for sequencing cytosine modifications, it is still challenging for specific and quantitative sequencing of individual modification at base-resolution. For example, to obtain both true 5-methylcytosine (5mC) and true 5-hydroxymethylcytosine (5hmC) information, the two major epigenetic modifications, it usually requires subtraction of two methods, which increases noise and requires high sequencing depth. Recently, we developed TET-assisted pyridine borane sequencing (TAPS) for bisulfite-free direct sequencing of 5mC and 5hmC.

Mapping the epigenetic modifications of DNA and RNA.

Over 17 and 160 types of chemical modifications have been identified in DNA and RNA, respectively. The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics. Developing chemical and biological tools to detect specific modifications in the genome or transcriptome has greatly facilitated their study.

Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS.

We present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compatible with both Oxford Nanopore and PacBio Single-Molecule Real-Time (SMRT) sequencing, lrTAPS detects methylation with accuracy comparable to short-read Illumina sequencing but with long-range epigenetic phasing. We applied lrTAPS to sequence difficult-to-map regions in mouse embryonic stem cells and to identify distinct methylation events in the integrated hepatitis B virus genome.

5-Carboxylcytosine is resistant towards phosphodiesterase I digestion: implications for epigenetic modification quantification by mass spectrometry.

DNA cytosine modifications are important epigenetic modifications in gene regulation and pathogenesis. DNA hydrolysis followed by HPLC-MS/MS is the gold standard in DNA modification quantification. In particular, it is the only sensitive and accurate method for low abundance modifications, such as 5-carboxylcytosine (5caC).

Systematic allelic analysis defines the interplay of key pathways in X chromosome inactivation.

Xist RNA, the master regulator of X chromosome inactivation, acts in cis to induce chromosome-wide silencing. Whilst recent studies have defined candidate silencing factors, their relative contribution to repressing different genes, and their relationship with one another is poorly understood. Here we describe a systematic analysis of Xist-mediated allelic silencing in mouse embryonic stem cell-based models.

Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1/TET1/5hmC.

Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression , and substantially prolongs survival of mice bearing murine or human AML. Strikingly, homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and depletion mimics homoharringtonine's therapeutic effects in AML.

Bisulfite-free direct detection of 5-methylcytosine and 5-hydroxymethylcytosine at base resolution.

Bisulfite sequencing has been the gold standard for mapping DNA modifications including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) for decades. However, this harsh chemical treatment degrades the majority of the DNA and generates sequencing libraries with low complexity. Here, we present a bisulfite-free and base-level-resolution sequencing method, TET-assisted pyridine borane sequencing (TAPS), for detection of 5mC and 5hmC.

Bisulfite-free and base-resolution analysis of 5-methylcytidine and 5-hydroxymethylcytidine in RNA with peroxotungstate.

5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), two of the best-studied DNA modifications, play crucial roles in normal development and disease in mammals. Although 5-methylcytidine (m5C) and 5-hydroxymethylcytidine (hm5C) have also been identified in RNA, their distribution and biological function in RNA remain largely unexplored, due to the lack of suitable sequencing methods. Here, we report a base-resolution sequencing method for hm5C in RNA.

Glucose and glutamine availability regulate HepG2 transcriptional responses to low oxygen.

Little is known about the impact of nutrients on cellular transcriptional responses, especially in face of environmental stressors such as oxygen deprivation. Hypoxia-inducible factors (HIF) coordinate the expression of genes essential for adaptation to oxygen-deprived environments. A second family of oxygen-sensing genes known as the alpha-ketoglutarate-dependent dioxygenases are also implicated in oxygen homeostasis and epigenetic regulation.

Simultaneously Monitoring Immune Response and Microbial Infections during Pregnancy through Plasma cfRNA Sequencing.

Background: Plasma cell-free RNA (cfRNA) encompasses a broad spectrum of RNA species that can be derived from both human cells and microbes. Because cfRNA is fragmented and of low concentration, it has been challenging to profile its transcriptome using standard RNA-seq methods.

Methods: We assessed several recently developed RNA-seq methods on cfRNA samples.