Rationale And Objectives: Isocitrate dehydrogenase (IDH) status, glioma subtypes and tumor proliferation are important for glioma evaluation. We comprehensively compare the diagnostic performance of amide proton transfer-weighted (APTw) MRI and its related metrics in glioma diagnosis, in the context of the latest classification.
Materials And Methods: Totally 110 patients with adult-type diffuse gliomas underwent APTw imaging.
: About half of adults with acute myeloid leukemia with normal cytogenetics (CN-AML) have mutations. There is controversy regarding their prognosis and best therapy. : We studied 150 subjects with these features using targeted regional sequencing.
View Article and Find Full Text PDFBackground: Vascular territory mapping (VTM) software estimates which intracerebral vessel provides predominant arterial flow to a brain voxel. The presence of antegrade flow in the setting of acute middle cerebral artery (MCA) occlusion is associated with improved outcomes. We identify whether VTM software is a determinant of antegrade flow in patients with proximal MCA occlusion.
View Article and Find Full Text PDFRoles of liver-specific genes (LSGs) in tumor initiation and progression are rarely explored in hepatocellular carcinoma (HCC). Here we show that LSGs are generally downregulated in HCC tumor tissues compared to non-HCC liver tissues, and low-LSG HCCs show poor prognosis and the activated c-Myc pathway. Among the c-Myc- and patient prognosis-associated LSGs, PGRMC1 significantly blocks c-Myc-induced orthotopic HCC formation.
View Article and Find Full Text PDFHierarchical self-assembly driven by non-covalent interactions is a prevalent strategy employed by nature to construct sophisticated biomacromolecules, such as proteins. However, the construction of protein-like superstructures that rely on weaker dispersion forces-driven hierarchical assembly remains largely unexplored. Here, we report the first example of dispersion forces driving the high-order assembly of the lanthanide trinuclear circular helicate [HNEt₃]₃[Eu₃(L)₆] (ΔΔΔ-1) into a protein-like lanthanide octamer ((ΔΔΔ-1)₈-2).
View Article and Find Full Text PDFProprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein-cholesterol (LDL-C) by decreasing the expression of the LDL-receptor on hepatic cells. Ongericimab (JS002) is a novel PCSK9 monoclonal antibody that exhibits a long-acting LDL-C lowering effect by exclusively inhibiting PCSK9 in pre-clinical studies. Two randomized, double-blind, placebo-controlled trials were conducted to evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetic, and pharmacodynamic profiles of ongericimab in healthy subjects and patients with hypercholesterolemia.
View Article and Find Full Text PDFUnique metabolites contribute to the performance of meat flavor and potential function. In this study, UHPLC-Q Exactive HF-X-based metabolomics and multivariate analysis were applied to explore the characteristic metabolites in the breast meat of Beijing-You chicken (BYC) aged 150, 300, and 450 days (D150, D300, and D450). Based on the criteria of variable importance in the projection (VIP) > 1 and < 0.
View Article and Find Full Text PDFLancet Reg Health West Pac
August 2024
Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. RNA-binding proteins are identified as regulators of cardiac disease; DDX5 (dead-box helicase 5) is a master regulator of many RNA processes, although its function in heart physiology remains unclear.
Methods: We assessed DDX5 expression in human failing hearts and a mouse HF model.
Background: Macrophage-driven inflammation critically involves in cardiac injury and repair following myocardial infarction (MI). However, the intrinsic mechanisms that halt the immune response of macrophages, which is critical to preserve homeostasis and effective infarct repair, remain to be fully defined. Here, we aimed to determine the ubiquitination-mediated regulatory effects on averting exaggerated inflammatory responses in cardiac macrophages.
View Article and Find Full Text PDFInhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER) breast cancer preclinical models. PF-07248144 is a selective catalytic inhibitor of KAT6A and KAT6B. In the present study, we report the safety, pharmacokinetics (PK), pharmacodynamics, efficacy and biomarker results from the first-in-human, phase 1 dose escalation and dose expansion study (n = 107) of PF-07248144 monotherapy and fulvestrant combination in heavily pretreated ER human epidermal growth factor receptor-negative (HER2) metastatic breast cancer (mBC).
View Article and Find Full Text PDFBackground: Myocardial mitochondrial dysfunction underpins the pathogenesis of heart failure (HF), yet therapeutic options to restore myocardial mitochondrial function are scarce. Epigenetic modifications of mitochondrial DNA (mtDNA), such as methylation, play a pivotal role in modulating mitochondrial homeostasis. However, their involvement in HF remains unclear.
View Article and Find Full Text PDFBackground: Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression; however, its role in vascular calcification is poorly understood.
Methods: We generated NR4A3 mice and 2 different types of medial arterial calcification models to investigate the biological roles of NR4A3 in vascular calcification.
The transcription and replication processes of non-segmented, negative-strand RNA viruses (nsNSVs) are catalyzed by a multi-functional polymerase complex composed of the large protein (L) and a cofactor protein, such as phosphoprotein (P). Previous studies have shown that the nsNSV polymerase can adopt a dimeric form, however, the structure of the dimer and its function are poorly understood. Here we determine a 2.
View Article and Find Full Text PDFSynth Syst Biotechnol
June 2024
Due to the complicated metabolic and regulatory networks of l-serine biosynthesis and degradation, microbial cell factories for l-serine production using non-model microorganisms have not been reported. In this study, a combination of synthetic biology and process optimization were applied in an ethanologenic bacterium for l-serine production. By blocking the degradation pathway while introducing an exporter EceamA from , l-serine titer in recombinant was increased from 15.
View Article and Find Full Text PDFBackground: The SSaSS (Salt Substitute and Stroke Study) has shown that use of a potassium-enriched salt lowers the risk of stroke, total cardiovascular events, and premature death. The effects on cause-specific cardiac outcomes are reported here.
Methods: SSaSS was an unblinded, cluster-randomised trial assessing the effects of potassium-enriched salt compared with regular salt among 20 995 Chinese adults with established stroke and older age and uncontrolled hypertension.
CPT Pharmacometrics Syst Pharmacol
May 2024
Ciprofol (HSK3486) is a newly developed, highly selective γ-aminobutyric acid-A (GABA) receptor potentiator that is recently approved for a new indication of sedation for patients in the intensive care unit (ICU) in China. This analysis aimed to characterize the population pharmacokinetics (PopPKs) of ciprofol and evaluate the relationship of exposure with hypotension in mechanically ventilated patients in the ICU. A total of 462 subjects with 3918 concentration measurements from two clinical trials of mechanically ventilated patients in the ICU, four clinical trials of elective surgical patients, and six clinical trials of healthy subjects were used in the PopPK analysis.
View Article and Find Full Text PDFCrimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus, prevalent in more than 30 countries worldwide. Human infection by this virus leads to severe illness, with an average case fatality of 40%. There is currently no approved vaccine or drug to treat the disease.
View Article and Find Full Text PDFPurpose: We aimed to analyze the trends and patterns in outpatient health service treatment of dry eye disease (DED) using real-world data from Yinzhou District in China.
Methods: The Yinzhou Health Information System is a comprehensive database including electronic medical records from 277 medical institutions representing over 1.64 million residents.
Introduction: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment.
View Article and Find Full Text PDFBackground: 3', 5'-cyclic AMP (cAMP) regulates numerous cardiac functions. Various hormones and neurotransmitters elevate intracellular cAMP (i[cAMP]) in cardiomyocytes through activating GsPCRs (stimulatory-G-protein-coupled-receptors) and membrane-bound ACs (adenylyl cyclases). Increasing evidence has indicated that stimulating different GsPCRs and ACs exhibits distinct, even opposite effects, on cardiomyocyte viability.
View Article and Find Full Text PDFBackground: Exposure to radon has been linked to lung cancer and other lung diseases. Although biologically plausible, research of residential radon exposure in relation to stroke risk is scarce.
Methods: Study participants were from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort (n=30 239), which consisted of male and female non-Hispanic Black and White adults aged 45 and older.