Integrative Analysis of Multi-Omic Data for the Characteristics of Endometrial Cancer.

Endometrial cancer (EC) is a frequently diagnosed gynecologic cancer. Identifying reliable prognostic genes for predicting EC onset is crucial for reducing patient morbidity and mortality. Here, a comprehensive strategy with transcriptomic and proteomic data was performed to measure EC's characteristics. Based on the publicly available RNA-seq data, death-associated protein kinase 3, recombination signal-binding protein for the immunoglobulin kappa J region, and myosin light chain 9 were screened out as potential biomarkers that affect the EC patients' prognosis. A linear model was further constructed by multivariate Cox regression for the prediction of the risk of being malignant. From further integrative analysis, exosomes were found to have a highly enriched role that might participate in EC occurrence. The findings were validated by qRT-polymerase chain reaction (PCR) and western blotting. Collectively, we constructed a prognostic-gene-based model for EC prediction and found that exosomes participate in EC incidents, revealing significantly promising support for the diagnosis of EC.

Practice guideline on ovarian tissue cryopreservation and transplantation in the prevention and treatment of iatrogenic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.

Multi-Body Biomarker Entrapment System: An All-Encompassing Tool for Ultrasensitive Disease Diagnosis and Epidemic Screening.

Ultrasensitive identification of biomarkers in biofluids is essential for the precise diagnosis of diseases. For the gold standard approaches, polymerase chain reaction and enzyme-linked immunosorbent assay, cumbersome operational steps hinder their point-of-care applications. Here, a bionic biomarker entrapment system (BioES) is implemented, which employs a multi-body Y-shaped tetrahedral DNA probe immobilized on carbon nanotube transistors. Clinical identification of endometriosis is successfully realized by detecting an estrogen receptor, ERß, from the lesion tissue of endometriosis patients and establishing a standard diagnosis procedure. The multi-body Y-shaped BioES achieves a theoretical limit of detection (LoD) of 6.74 aM and a limit of quantification of 141 aM in a complex protein milieu. Furthermore, the BioES is optimized into a multi-site recognition module for enhanced binding efficiency, realizing the first identification of monkeypox virus antigen A35R and unamplified detection of circulating tumor DNA of breast cancer in serum. The rigid and compact probe framework with synergy effect enables the BioES to target A35R and DNA with a LoD down to 991 and 0.21 aM, respectively. Owing to its versatility for proteins and nucleic acids as well as ease of manipulation and ultra-sensitivity, the BioES can be leveraged as an all-encompassing tool for population-wide screening of epidemics and clinical disease diagnosis.

Structural Basis of Inhibition of ERα-Coactivator Interaction by High-Affinity N-Terminus Isoaspartic Acid Tethered Helical Peptides.

Direct inhibition of the protein-protein interaction of ERα and its endogenous coactivators with a cell permeable stabilized peptide may offer a novel, promising strategy for combating ERα positive breast cancers. Here, we report the co-crystal structure of a helical peptide stabilized by a N-terminal unnatural cross-linked aspartic acid (TD) in complex with the ERα ligand binding domain (LBD). We designed a series of peptides and peptide 6 that showed direct and high-affinity binding to ERα with selective antiproliferative activity in ERα positive breast cancer cells. The co-crystal structure of the TD-stabilized peptide 6 in complex with ERα LBD further demonstrates that it forms an α helical conformation and directly binds at the coactivator binding site of ERα. Further studies showed that peptide 6W could potently inhibit cellular ERα's transcriptional activity. This approach demonstrates the potential of TD stabilized peptides to modulate various intracellular protein-protein interactions involved in a range of disorders.

Thioether-derived Macrocycle for Peptide Secondary Structure Fixation.

Recently, we developed methods to stabilize peptides into various secondary structures, including α-helix, type III turn and ß-hairpin via proper thioether based macrocyclization. These conformationally constrained peptidomimetics confer enhanced biophysical properties and provide a valuable avenue towards clinically-relevant therapeutic molecules. In this personal account, thioether-derived macrocyclization methods developed by our group for stabilization of α-helix, type-III ß turn and ß-hairpin conformations are discussed.

An in-tether sulfoxide chiral center influences the biophysical properties of the N-capped peptides.

Thanks to their large binding interfaces, peptides are attractive ligands targeting protein-protein interactions compared with small molecules. Various strategies to improve peptides' pharmaceutical properties have been developed to constrain peptides into their functional three-dimensional structures. In our previous work, we reported that an in-tether chiral center could modulate peptides' biophysical properties. Herein, we applied this concept to construct a chiral sulfoxide center into the N-terminal end-cap system. We proved that this in-tether sulfoxide chiral center influences the structure of this N-capped template. In addition, longer peptides targeting estrogen receptor were also synthesized and we revealed that this chiral center could also modulate binding affinity to estrogen receptor alpha with enhanced protease resistance.

Switching substitution groups on the in-tether chiral centre influences backbone peptides' permeability and target binding affinity.

Different substitution groups on the in-tether chiral centre of chirality-induced helical peptides (CIH peptides) showed distinguishable effects on the peptides' cellular uptakes and binding affinities with the estrogen receptor α(ER-α). This study proves that in-tether chiral centres are a valuable modification site for constructing peptide ligands with preferable biophysical properties.

Disulfide Bridges in Defensins.

Defensins are small cationic cysteine rich peptides, which usually contain 18-45 amino acids and possess amphiphilic properties. The term "defensin" was coined as the sequences of rabbit and human leukin/phagocytin molecules were first reported in 1985. Since then, various defensins were isolated and characterized from insects, plants and vertebrates. Using vertebrate defensins as examples, defensins are categorized into three sub-families based on their different patterns of intramolecular disulfide linkages: α defensins, ß defensins, and θ defensins. During the past decades, continuous attentions were casted on various defensins for their broad activity against bacteria, fungi and viruses. In this review, we focus on the effect of characteristic intramolecular disulfide bonds on the antimicrobial activity of defensins. The disulfide bonds are important for holding the defensins in their three dimensional structures, while also contribute to their antimicrobial activity and chemotactic activity. This review summarizes the effects of disulfide bonds, their synthetic formation pathways and potential pharmaceutical applications.