A Rigorous Nuclear DNA-Excluding Mass Spectrometry Assay for Accurate Identification of 5-Methylcytosine in Mitochondrial DNA.

5-Methylcytosine (5mC) functions as a well-characterized epigenetic DNA mark in nuclear DNA, but its presence in mitochondrial DNA (mtDNA) remains elusive. Here, we report a new and rigorous nuclear DNA (nDNA)-excluding mass spectrometry assay enabling the reliable and accurate identification of 5mC in mtDNA for the first time. First, circular mtDNA is enriched over 809-946-fold by combining alkaline lysis and linear DNA-specific RecBCD cutting; nDNA accounts for ∼12-19% of the DNA remaining after this step.

Circulating short-chain and branched short-chain fatty acids and the risk of incident type 2 diabetes: findings from the 4C study.

Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study.

The rational design, biofunctionalization and biological properties of orthopedic porous titanium implants: a review.

Porous titanium implants are becoming an important tool in orthopedic clinical applications. This review provides a comprehensive survey of recent advances in porous titanium implants for orthopedic use. First, the review briefly describes the characteristics of bone and the design requirements of orthopedic implants.

Integrated analysis of single-cell and bulk transcriptomes uncovers clinically relevant molecular subtypes in human prostate cancer.

Objective: Prostate cancer (PCa) is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment (TME) and high tumor heterogeneity, which challenges clinically stratified management and reinforces the need for novel strategies to fight against castration-resistant PCa (CRPC).

Methods: We performed single-cell RNA sequencing (scRNA-seq) on 10 untreated primary PCa tissues and integrated public scRNA-seq resources from three normal prostate tissues, two untreated primary PCa tissues, and six CRPC tumors to portray a comprehensive cellular and molecular interaction atlas of PCa. We further integrated the single-cell and bulk transcriptomes of PCa to establish a molecular classification system.

Framework nucleic acid-programmed aptamer-paclitaxel conjugates as targeted therapeutics for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is highly invasive with a poor prognosis, and chemotherapy remains the clinical treatment of choice. Paclitaxel is a commonly used first-line chemotherapy drug, but its untargeted distribution poses clinical challenges. Inspired by antibody-drug conjugates, we develop a precisely structured framework nucleic acid-programmed aptamer-paclitaxel conjugate (FAPC) with chemically well-defined paclitaxel loading dosing, enabling the regulation of receptor-aptamer affinity to facilitate tumor-targeted chemotherapy.