Ultraperformance Liquid Chromatography Tandem Mass Spectrometry Assay of DNA Cytosine Methylation Excretion from Biological Systems.

Measuring DNA cytosine methylation excretion presents challenges because methylated cytosine species are released in various forms including free molecules and those bound in DNA fragments. Herein, we report a novel UPLC-MS/MS method that allows the quantification of both free and DNA fragment-bound forms of methylated cytosine species excreted, providing total amounts for each. Cell culture medium and genomic DNA isolated from cells are analyzed to quantify methylated cytosine species.

Metabolomic and lipidomic profiling of traditional Chinese medicine and its substitutes.

Introduction: (Gray) species-sourced (TCP) is an animal-based traditional Chinese medical material, and its decoction or extract possesses multiple pharmacological effects. However, other species-sourced substitutes are sometimes used in the market, potentially impairing the quality and effectiveness of TCP medications. To address this issue, it is very necessary to develop applicable approaches that can accurately differentiate genuine TCP from its counterfeit counterparts.

Hypoxia-induced phase separation of ZHX2 alters chromatin looping to drive cancer metastasis.

Hypoxia and dysregulated phase separation can both activate oncogenic transcriptomic profiles. However, whether hypoxia regulates transcription-associated phase separation remains unknown. Here, we find that zinc fingers and homeoboxes 2 (ZHX2) undergoes phase separation in response to hypoxia, promoting their occupancy on chromatin and activating a cluster of oncogene transcription that is enriched by metastatic genes distinct from the targets of hypoxia-inducible factor (HIF) and pathologically relevant to breast cancer.

Clinical, Epidemiological, Virological Characteristics and Outcomes of 286 Patients Infected With Monkeypox Virus in China.

Background: Monkeypox virus (mpox) outbreak since 2022 has already constituted a public health emergency of international concern. A comprehensive study on epidemiological features, symptoms and signs, complications, sequelae, and clinical outcomes has been lacking. Accordingly, we performed a large-scale multicenter study to comprehensively summarize the clinical, epidemiological, behavioral, laboratory, virological characteristics, and treatment-related outcomes of mpox in China.

Self-assembled hyaluronic acid nanoparticles delivered by polymeric microneedles for targeted and long-acting therapy of psoriasis.

Psoriasis is an autoimmune-driven inflammatory skin disease, clinically characterized by skin thickening, erythema, and scaling, significantly impacting patients' life quality and mental health. Clinically, oral pill or injection of methotrexate (MTX) formulation is a common route for psoriasis therapy, while both methods often cause undesired toxicity due to systemic administration, and limit patient compliance because of the frequent-dosing requirement. Here, we introduce a dissolvable microneedle (MN) patch made of polyvinyl alcohol (PVA) that incorporates self-assembled hyaluronic acid (HA) nanoparticles (NPs) conjugating MTX, which is designed for treating skin diseases, offering reduced adverse effects and improved patient adherence through its targeted and long-acting properties.

β-Catenin disruption decreases macrophage exosomal α-SNAP and impedes Treg differentiation in acute liver injury.

Hepatic macrophages and regulatory T cells (Tregs) play an important role in the maintenance of liver immune homeostasis, but the mechanism by which hepatic macrophages regulate Tregs in acute liver injury remains largely unknown. Here, we found that the hepatic Treg proportion and β-catenin expression in hepatic macrophages were associated with acetaminophen- and d-galactosamine/LPS-induced acute liver injury. Interestingly, β-catenin was markedly upregulated only in infiltrating macrophages but not in resident Kupffer cells.

Double-Layered Microneedle Patch Integrated with Multifunctional Nanoparticles and Live Bacteria for Long-Term Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a complex and prevalent chronic inflammatory skin disease that impacts a significant portion of the global population. Conventional treatments often focus on a singular pathogenic factor or suffer from limited skin penetration, resulting in unsatisfactory outcomes. Here, a multifunctional double-layered microneedle (MN) patch is proposed for long-term and effective treatment of AD by integrating therapeutic nanoparticles (NPs) and live bacteria.

Molecular beacon-peptide probe based double recycling amplification for multiplexed detection of serum exosomal microRNAs.

Exosomal microRNAs (exomiRs) have been shown to play crucial roles as biomarkers for early detection and prognosis of cancer. However, simultaneous quantification of multiplex exomiRs is hindered by methods that require additional steps, such as labeling with fluorophores or gel visualization, which are susceptible to various factors. Herein, we developed a mass spectrometry-detectable and target-triggered method for multiplexed exomiR detection using three enzyme-based double recycling amplification in combination with well-designed molecular beacon-peptide (MBP) probes, called molecular beacon-peptide probe-based double recycling amplification (MBPDRA).

Simultaneous quantification of co-administered trastuzumab and pertuzumab in serum based on nano-surface and molecular-orientation limited (nSMOL) proteolysis.

Monoclonal antibodies (mAbs) are pivotal therapeutic agents for various diseases, and effective treatment hinges on attaining a specific threshold concentration of mAbs in patients. With the rising adoption of combination therapy involving multiple mAbs, there arises a clinical demand for multiplexing assays capable of measuring the concentrations of these mAbs. However, minimizing the complexity of serum samples while achieving rapid and accurate quantification is difficult.

Discovery of Novel ERα and Aromatase Dual-Targeting PROTAC Degraders to Overcome Endocrine-Resistant Breast Cancer.

Estrogen receptor α (ERα) plays a pivotal role in the proliferation, differentiation, and migration of breast cancer (BC) cells, and aromatase (ARO) is a crucial enzyme in estrogen synthesis. Hence, it is necessary to inhibit estrogen production or the activity of ERα for the treatment of estrogen receptor-positive (ER) BC. Herein, we present a new category of dual-targeting PROTAC degraders designed to specifically target ERα and ARO.

Simultaneous Quantification of Seven Antifungal Agents in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry.

Systemic antifungal agents are essential for high-risk patients undergoing immunosuppressive therapy or cancer chemotherapy because of the rapid increase in opportunistic fungal infections. Therapeutic drug monitoring is crucial to ensuring the efficacy and safety of antifungal agents owing to their pharmacokinetic variability. In the present study, we developed and validated a quantitative method for the simultaneous detection of seven commonly used antifungal drugs (amphotericin B, isavuconazole, voriconazole, fluconazole, posaconazole, caspofungin, and micafungin) using liquid chromatography-tandem mass spectrometry.

Targeting METTL3 reprograms the tumor microenvironment to improve cancer immunotherapy.

The tumor microenvironment (TME) is a heterogeneous ecosystem containing cancer cells, immune cells, stromal cells, cytokines, and chemokines which together govern tumor progression and response to immunotherapies. Methyltransferase-like 3 (METTL3), a core catalytic subunit for RNA N-methyladenosine (mA) modification, plays a crucial role in regulating various physiological and pathological processes. Whether and how METTL3 regulates the TME and anti-tumor immunity in non-small-cell lung cancer (NSCLC) remain poorly understood.

A mitochondrial EglN1-AMPKα axis drives breast cancer progression by enhancing metabolic adaptation to hypoxic stress.

Mitochondria play essential roles in cancer cell adaptation to hypoxia, but the underlying mechanisms remain elusive. Through mitochondrial proteomic profiling, we here find that the prolyl hydroxylase EglN1 (PHD2) accumulates on mitochondria under hypoxia. EglN1 substrate-binding region in the β2β3 loop is responsible for its mitochondrial translocation and contributes to breast tumor growth.

Glucose-responsive, antioxidative HA-PBA-FA/EN106 hydrogel enhanced diabetic wound healing through modulation of FEM1b-FNIP1 axis and promoting angiogenesis.

The diabetic wounds remain to be unsettled clinically, with chronic wounds characterized by drug-resistant bacterial infections, compromised angiogenesis and oxidative damage to the microenvironment. To ameliorate oxidative stress and applying antioxidant treatment in the wound site, we explore the function of folliculin-interacting protein 1 (FNIP1), a mitochondrial gatekeeper protein works to alter mitochondrial morphology, reduce oxidative phosphorylation and protect cells from unwarranted ROS accumulation. And our experiments showed the effects of FNIP1 in ameliorating oxidative stress and rescued impaired angiogenesis of HUVECs in high glucose environment.

Aptamer-based sample purification for mass spectrometric quantification of trastuzumab in human serum.

In this study, we developed a simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to quantify trastuzumab in human serum using aptamers for sample purification. Trastuzumab was extracted from serum samples using the capture probe based on its aptamer CH1S-3, followed by reduction, alkylation, trypsin digestion, and quantification using LC-MS/MS. Additionally, a unique peptide, FTISADTSK, was employed as a surrogate peptide and quantified, and *FTISADTSK (CN-labeled phenylalanine) was used as an internal standard to minimize variability in detection among the samples.

Identification of molecular subtypes based on liquid-liquid phase separation and cross-talk with immunological phenotype in bladder cancer.

Background: Mounting evidence has demonstrated that an imbalance in liquid-liquid phase separation (LLPS) can induce alteration in the spatiotemporal coordination of biomolecular condensates, which plays a role in carcinogenesis and cachexia. However, the role of LLPS in the occurrence and progression of bladder cancer (BLCA) remains to be elucidated. Identifying the role of LLPS in carcinogenesis may aid in cancer therapeutics.

Comparative metabolic profiling of wild species and their substituents by liquid chromatography-tandem mass spectrometry.

is a genus of ascomycete fungi and used widely in fungal drugs. However, in-depth studies of the metabolites of wild species and their substituents are lacking. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics analysis was carried out to comprehensively profile the metabolites in wild Chinese species ( (Berk.

Efficacy and safety of adjunctive antiseizure medications for dravet syndrome: A systematic review and network meta-analysis.

Recently, the U.S. Food and Drug Administration (FDA) approved stiripentol, cannabidiol, and fenfluramine to treat patients with Dravet syndrome (DS).

Using Haemocoagulase Agkistrodon in Patients Undergoing Transurethral Plasmakinetic Resection of the Prostate: A Pilot, Real-World, and Propensity Score-Matched Study.

Objectives: To compare the clinical outcomes of using different hemostatic agents after transurethral plasmakinetic resection of the prostate (TUPKP) in benign prostatic hyperplasia (BPH) patients.

Methods: The patients were divided into 5 groups according to the hemostatic agents used after TUPKP, including the haemocoagulase agkistrodon for injection (HCA), hemocoagulase for injection (HC), hemocoagulase bothrops atrox for injection (HCB), ethylenediamine diaceturate injection (EDD), and tranexamic acid (TXA). Propensity score matching was performed based on age, body mass index, prostate volume, hypertension status, fasting blood glucose, smoking, and drinking history.

(±)-Walskiiglucinol A, a pair of rearranged acylphloroglucinol derivative enantiomers from .

(±)-Walskiiglucinol A (1a/1b), a pair of rearranged acylphloroglucinol derivatives with a new carbon skeleton, was obtained from . Compounds 1a/1b were the first examples of naturally occurring acylphloroglucinol derivatives possessing a unique 1-oxaspiro[4.4]nonane core bearing a new 5/5 ring system.

Global and Regional Burden of Bacterial Antimicrobial Resistance in Urinary Tract Infections in 2019.

Background: There are still no detailed data about the burden of bacterial antimicrobial resistance (AMR) in urinary tract infections (UTI). Concrete knowledge of global and regional bacterial AMR data is crucial for developing informed programs and policies to control bacterial AMR and for prudent use of antibiotics to optimize antibiotic therapy in patients with UTI. This study aimed to provide comprehensive global and regional estimates for the AMR burden of UTI in 2019.

A density-tunable liquid-phase microextraction system based on deep eutectic solvents for the determination of polycyclic aromatic hydrocarbons in tea, medicinal herbs and liquid foods.

A novel density-tunable liquid-phase microextraction (DT-LPME) system was developed with high-density deep eutectic solvents (DESs) as extractant and low-density organic solvents as emulsifier and density regulator. DES-rich phase was induced to form in the bottom or in the top by adjusting the emulsifier amount. This system was used to directly extract polycyclic aromatic hydrocarbons (PAHs) from liquid and solid foods, and the obtained DES-rich phase was easy to be collected for quantification.

A green liquid chromatography method for rapid determination of ergosterol in edible fungi based on matrix solid-phase dispersion extraction and a core-shell column.

Developing a green analytical method for the analysis of components in food samples is an important research aspect of liquid chromatography (LC). The traditional LC method usually consumes a lot of toxic solvent for sample extraction and LC separation. In the current study, a green analytical method for the rapid determination of ergosterol in edible fungi was established.