Development and validation of a novel nomogram for predicting good neoangiogenesis after encephaloduroarteriosynangiosis in patients with moyamoya disease and type 2 diabetes mellitus: a case-control study.

Objective: Diabetes is often linked to poorer outcomes in patients with moyamoya disease (MMD). However, experience has shown that certain individuals with diabetes have favorable outcomes after encephaloduroarteriosynangiosis (EDAS). The authors aimed to develop a nomogram to predict good neoangiogenesis in patients with MMD and type 2 diabetes mellitus (T2DM) to aid neurosurgeons in the identification of suitable candidates for EDAS.

Development and validation of a novel nomogram for predicting long-term rebleeding risk among patients with hemorrhagic moyamoya disease: a 10-year multicenter retrospective cohort study.

Objective: The aim of this study was to develop and validate a predictive nomogram model for long-term rebleeding events in patients with hemorrhagic moyamoya disease (HMMD).

Methods: In total, 554 patients with HMMD from the Fifth Medical Center of the Chinese PLA General Hospital (5-PLAGH cohort) were included and randomly divided into training (390 patients) and internal validation (164 patients) sets. An independent cohort from the First Medical Center and Eighth Medical Center of Chinese PLA General Hospital (the 1-PLAGH and 8-PLAGH cohort) was used for external validation (133 patients).

A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real-world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real-world setting and to explore possible correlates.

Integrative proteomics and metabolomics study reveal enhanced immune responses by COVID-19 vaccine booster shot against Omicron SARS-CoV-2 infection.

Since its outbreak in late 2021, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely reported to be able to evade neutralizing antibodies, becoming more transmissible while causing milder symptoms than previous SARS-CoV-2 strains. Understanding the underlying molecular changes of Omicron SARS-CoV-2 infection and corresponding host responses are important to the control of Omicron COVID-19 pandemic. In this study, we report an integrative proteomics and metabolomics investigation of serum samples from 80 COVID-19 patients infected with Omicron SARS-CoV-2, as well as 160 control serum samples from 80 healthy individuals and 80 patients who had flu-like symptoms but were negative for SARS-CoV-2 infection.

Altered plasma metabolites and inflammatory networks in HIV-1 infected patients with different immunological responses after long-term antiretroviral therapy.

Background: Chronic metabolic changes relevant to human immunodeficiency virus type 1 (HIV-1) infection and in response to antiretroviral therapy (ART) remain undetermined. Moreover, links between metabolic dysfunction caused by HIV and immunological inflammation in long-term treated individuals have been poorly studied.

Methods: Untargeted metabolomics and inflammatory cytokine levels were assessed in 47 HIV-infected individuals including 22 immunological responders (IRs) and 25 non-responders (INRs) before and after ART.

Long-term outcomes after conservative and EDAS treatment for 111 elderly patients with moyamoya disease: longitudinal and cross-sectional study.

Objective: This study aimed to explore the clinical features of moyamoya disease (MMD) and the efficacy of encephaloduroarteriosynangiosis (EDAS) in elderly patients with MMD and to identify the risk factors for long-term stroke events.

Methods: Clinical data were retrospectively collected on elderly patients with MMD (age ≥ 60 years) who had been treated at the authors' center from May 2007 to December 2017. Clinical features, angiographic findings, and long-term outcomes (> 5-year follow-up) were analyzed.

Multi-omics data integration using ratio-based quantitative profiling with Quartet reference materials.

Characterization and integration of the genome, epigenome, transcriptome, proteome and metabolome of different datasets is difficult owing to a lack of ground truth. Here we develop and characterize suites of publicly available multi-omics reference materials of matched DNA, RNA, protein and metabolites derived from immortalized cell lines from a family quartet of parents and monozygotic twin daughters. These references provide built-in truth defined by relationships among the family members and the information flow from DNA to RNA to protein.

Quantitative Analysis of Nucleoside Triphosphate Pools in Mouse Muscle Using Hydrophilic Interaction Liquid Chromatography Coupled with Tandem Mass Spectrometry Detection.

Defects in deoxyribonucleoside triphosphate (dNTP) metabolism are associated with a number of mitochondrial DNA (mtDNA) depletion syndromes (MDS). These disorders affect the muscles, liver, and brain, and the concentrations of dNTPs in these tissues are already normally low and are, therefore, difficult to measure. Thus, information about the concentrations of dNTPs in tissues of healthy animals and animals with MDS are important for mechanistic studies of mtDNA replication, analysis of disease progression, and the development of therapeutic interventions.

Using an untargeted metabolomics approach to analyze serum metabolites in COVID-19 patients with nucleic acid turning negative.

The coronavirus disease of 2019 (COVID-19) is a severe public health issue that has infected millions of people. The effective prevention and control of COVID-19 has resulted in a considerable increase in the number of cured cases. However, little research has been done on a complete metabonomic examination of metabolic alterations in COVID-19 patients following treatment.

The KRAS-G12D mutation induces metabolic vulnerability in B-cell acute lymphoblastic leukemia.

Mutations in RAS pathway genes are highly prevalent in acute lymphoblastic leukemia (ALL). However, the effects of RAS mutations on ALL cell growth have not been experimentally characterized, and effective RAS-targeting therapies are being sought after. Here, we found that Reh ALL cells bearing the KRAS-G12D mutation showed increased proliferation rates but displayed severely compromised growth in mice.

Monitoring Antihypertensive Medication Adherence by Liquid Chromatography-Tandem Mass Spectrometry: Method Establishment and Clinical Application.

Proper medication compliance is critical for the integrity of clinical practice, directly related to the success of clinical trials to evaluate both pharmacological-based and device-based therapies. Here, we established a liquid chromatography-tandem mass spectrometry method to accurately detect 55 chemical entities in the human urine sample, which accounting for the most commonly used 172 antihypertensive drugs in China. The established method had good accuracy and intraday and interday precision for all analyses in both bench tests and validated in 21 hospitalized patients.

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients.

ITGB3/CD61: a hub modulator and target in the tumor microenvironment.

β3 integrin (ITGB3), also known as CD61 or GP3A, is one of the most widely studied components in the integrin family. As an adhesion receptor on the cell surface, ITGB3 participates in reprogramming tumor metabolism, shaping the stromal and immune microenvironment, facilitating epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (End-MT) and maintaining tumor stemness, etc. Recent studies proposed various intervention strategies against ITGB3 and have achieved promising outcomes in several types of tumor.

Differential Activities of DNA Polymerases in Processing Ribonucleotides during DNA Synthesis in Archaea.

Consistent with the fact that ribonucleotides (rNTPs) are in excess over deoxyribonucleotides (dNTPs) in vivo, recent findings indicate that replicative DNA polymerases (DNA Pols) are able to insert ribonucleotides (rNMPs) during DNA synthesis, raising crucial questions about the fidelity of DNA replication in both Bacteria and Eukarya. Here, we report that the level of rNTPs is 20-fold higher than that of dNTPs in Pyrococcus abyssi cells. Using dNTP and rNTP concentrations present in vivo, we recorded rNMP incorporation in a template-specific manner during in vitro synthesis, with the family-D DNA Pol (PolD) having the highest propensity compared with the family-B DNA Pol and the p41/p46 complex.

Simultaneous determination of ribonucleoside and deoxyribonucleoside triphosphates in biological samples by hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry.

Information about the intracellular concentration of dNTPs and NTPs is important for studies of the mechanisms of DNA replication and repair, but the low concentration of dNTPs and their chemical similarity to NTPs present a challenge for their measurement. Here, we describe a new rapid and sensitive method utilizing hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry for the simultaneous determination of dNTPs and NTPs in biological samples. The developed method showed linearity (R2 > 0.

The in vitro, in vivo antifungal activity and the action mode of Jelleine-I against Candida species.

Recently, the mortality of life-threatening fungal infections increased dramatically. However, there are few antifungals existed. Antimicrobial peptides (AMPs) as promising antifungal candidates have attracted much attention.

D-amino acid substitution enhances the stability of antimicrobial peptide polybia-CP.

With the increasing emergence of resistant microbes toward conventional antimicrobial agents, there is an urgent need for the development of antimicrobial agents with novel action mode. Antimicrobial peptides (AMPs) are believed to be one kind of ideal alternatives. However, AMPs can be easily degraded by protease, which limited their therapeutic use.

Hydroxyurea-Mediated Cytotoxicity Without Inhibition of Ribonucleotide Reductase.

In many organisms, hydroxyurea (HU) inhibits class I ribonucleotide reductase, leading to lowered cellular pools of deoxyribonucleoside triphosphates. The reduced levels for DNA precursors is believed to cause replication fork stalling. Upon treatment of the hyperthermophilic archaeon Sulfolobus solfataricus with HU, we observe dose-dependent cell cycle arrest, accumulation of DNA double-strand breaks, stalled replication forks, and elevated levels of recombination structures.

Antifungal effect and action mechanism of antimicrobial peptide polybia-CP.

The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents.

The N-terminal domain of human hemokinin-1 influences functional selectivity property for tachykinin receptor neurokinin-1.

Human hemokinin-1 (hHK-1) is a substance P-like tachykinin peptide preferentially expressed in non-neuronal tissues. It is involved in multiple physiological functions such as inflammation, hematopoietic cells development and vasodilatation via the interaction with tachykinin receptor neurokinin-1 (NK1). To further understand the intracellular signal transduction mechanism under such functional multiplicity, current study was focused on the differential activation of Gs and Gq pathways by hHK-1 and its C-terminal fragments, which is termed as functional selectivity.