Drug interaction evaluation of the novel phosphodiesterase type 5 inhibitor tunodafil (youkenafil): effects of tunodafil on omeprazole pharmacokinetics based on CYP2C19 gene polymorphism, and effects of ritonavir on tunodafil pharmacokinetics.

Purpose: To evaluate the drug-drug interactions (DDI) of tunodafil (youkenafil), a novel phosphodiesterase type 5 inhibitor, its inhibitory effects on CYP450 enzymes in vitro and its clinical trials in combination with ritonavir or omeprazole were conducted.

Methods: The inhibitory effect of tunodafil on seven major CYP450 enzymes in human liver microsomes was investigated by probe substrate method. The effect of tunodafil on the pharmacokinetics of omeprazole (CYP2C19 substrate) in 40 healthy subjects, who received a single dose of 40 mg omeprazole in combination with tunodafil on the day 8 after taking 100 mg tunodafil daily for 7 days, was assessed based on CYP2C19 genotypes.

Study on the Flexural Performance of Ultrahigh-Performance Concrete-Normal Concrete Composite Slabs.

In recent years, there have been an increasing number of examples of using ultrahigh-performance concrete (UHPC) as a pavement layer to form an ultrahigh-performance concrete-normal concrete (UHPC-NC) composite structure to improve the bearing capacity of bridges. In order to study the flexural performance of this kind of structure, this research studied the flexural performance of UHPC-NC composite slabs, with UHPC in the compression zone, using experiments, numerical simulation, and theoretical analysis. The results showed the following.

Comprehensive comparative analysis and development of molecular markers for Lasianthus species based on complete chloroplast genome sequences.

Background: Lasianthus species are widely used in traditional Chinese folk medicine with high medicinal value. However, source materials and herbarium specimens are often misidentified due to morphological characteristics and commonly used DNA barcode fragments are not sufficient for accurately identifying Lasianthus species. To improve the molecular methods for distinguishing among Lasianthus species, we report the complete chloroplast (CP) genomes of Lasianthus attenuatus, Lasianthus henryi, Lasianthus hookeri, Lasianthus sikkimensis, obtained via high-throughput Illumina sequencing.

LC-MS/MS method for dual-ligand peptide-drug CBP-1018 and its deconjugated payload MMAE including sample stabilization strategy for its MC-Val-Cit-PABC linker.

Recently, peptide-drug conjugate (PDC) has become the most promising conjugated drug for tumor therapy after antibody-drug conjugate due to stronger tumor penetration capacity and lower immunogenicity. CBP-1018 was a PDC with dual-ligand conjugated to MMAE via a cleavable linker (MC-Val-Cit-PABC) that can be lysed by cathepsins B. In this study, two specific LC-MS/MS methods were developed and validated for the determination of CBP-1018 and its metabolite MMAE in human plasma.

Blockage of L2HGDH-mediated S-2HG catabolism orchestrates macrophage polarization to elicit antitumor immunity.

The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression.

Relationship between autism and brain cortex surface area: genetic correlation and a two-sample Mendelian randomization study.

Background: Alterations in surface area (SA) in specific regions of the cortex have been reported in many individuals with autism spectrum disorder (ASD), however, the genetic background between ASD and SA is still unclear. This study estimated the genetic correlation and causal effect of ASD and cortical SA.

Methods: Summarized data of genome-wide association studies (GWAS) were separately downloaded from the Psychiatric Genomics Consortium (18,381 cases of ASD, and 27,969 controls) and the Enhancing Neuroimaging Genetics through Meta-Analysis Consortium (33,992 participants of Europeans).

Development and validation of pharmacokinetics assays for a novel HER2-targeting antibody-drug conjugate (SHR-A1201): Application to its dose-escalation pharmacokinetic study.

Approximately 25% of breast cancer patients with HER2 overexpression tend to have a high risk of disease progression and death. Various HER2-targeting therapies have been approved for treatment. Recently, a novel antibody-drug conjugate, SHR-A1201, is being researched and developed.

Integrative analysis of long noncoding RNAs dysregulation and synapse-associated ceRNA regulatory axes in autism.

Autism spectrum disorder (ASD) is a complex disorder of neurodevelopment, the function of long noncoding RNA (lncRNA) in ASD remains essentially unknown. In the present study, gene networks were used to explore the ASD disease mechanisms integrating multiple data types (for example, RNA expression, whole-exome sequencing signals, weighted gene co-expression network analysis, and protein-protein interaction) and datasets (five human postmortem datasets). A total of 388 lncRNAs and five co-expression modules were found to be altered in ASD.

Simultaneous determination of tipiracil, trifluridine and its metabolite 5-trifluoromethyluracil in human plasma using segmented polarity LC-MS/MS: A fully validated assay with clinical application.

Trifluridine (FTD) and tipiracil (TPI) hydrochloride tablets (TAS-102) were used for the treatment of patients with metastatic rectal cancer that was resistant to conventional chemotherapy drugs. In this study, a rapid and sensitive liquid chromatography-tandem mass spectrometry method was developed and fully validated for the simultaneous determination of TPI, FTD, and the metabolite 5-trifluoromethyluracil (FTY) of FTD in human plasma. The plasma samples were prepared by protein precipitation.

Calcium Homeostasis and Psychiatric Disorders: A Mendelian Randomization Study.

Observational studies have investigated the impact of calcium homeostasis on psychiatric disorders; however, the causality of associations is yet to be established. Bidirectional Mendelian randomization (MR) analysis of calcium homeostasis hormones was conducted on nine psychiatric disorders. Calcium, serum 25-hydroxyvitamin D levels (25OHD), parathyroid hormone, and fibroblast growth factor 23 are the major calcium homeostasis hormones.

Physical, mechanical, and biological properties of collagen membranes for guided bone regeneration: a comparative in vitro study.

Background: To provide a reference for clinical selection of collagen membranes by analyzing the properties of three kinds of collagen membranes widely used in clinics: Bio-Gide membrane from porcine dermis (PD), Heal-All membrane from bovine dermis (BD), and Lyoplant membrane from bovine pericardium (BP).

Methods: The barrier function of three kinds of collagen membranes were evaluated by testing the surface morphology, mechanical properties, hydrophilicity, and degradation rate of collagen membranes in collagenase and artificial saliva. In addition, the bioactivity of each collagen membrane as well as the proliferation and osteogenesis of MC3T3-E1 cells were evaluated.

Autism spectrum disorder research: knowledge mapping of progress and focus between 2011 and 2022.

Background: In recent years, a large number of studies have focused on autism spectrum disorder (ASD). The present study used bibliometric analysis to describe the state of ASD research over the past decade and identify its trends and research fronts.

Methods: Studies on ASD published from 2011 to 2022 were obtained from the Web of Science Core Collection (WoSCC).

Targeting IRG1 reverses the immunosuppressive function of tumor-associated macrophages and enhances cancer immunotherapy.

Immune-responsive gene 1 (IRG1) encodes aconitate decarboxylase (ACOD1) that catalyzes the production of itaconic acids (ITAs). The anti-inflammatory function of IRG1/ITA has been established in multiple pathogen models, but very little is known in cancer. Here, we show that IRG1 is expressed in tumor-associated macrophages (TAMs) in both human and mouse tumors.

Development and validation of a highly sensitive and selective LC-MS/MS method for the determination of 15-hydroxylubiprostone in human plasma: application to a pharmacokinetic study in healthy Chinese volunteers.

Lubiprostone, a derivative of prostaglandin E1, is the first chemical-type constipation treatment approved by FDA. Lubiprostone has low systemic exposure after oral administration. Therefore, it is recommended that 15-hydroxylubiprostone, which is a dominant active metabolite of lubiprostone, be used as the pharmacokinetic evaluation indicator.

Pharmacokinetic and pharmacodynamic similarity evaluation between an insulin glargine biosimilar product and Lantus in healthy subjects: Pharmacokinetic parameters of both parent insulin glargine and M1 were used as endpoints.

Insulin glargine is a long-acting insulin analog, which plays an important role in the treatment of diabetes mellitus. Biosimilar products of insulin glargine can provide patients with additional safe, high-quality, and potentially cost-effective options for treating diabetes. This article presents a randomized, double-blind, single-dose, two-treatment, four-period, replicate crossover, euglycemic clamp study which was designed to evaluate the PK and PD similarity between the recombinant insulin glargine developed by Wanbang (test) and Lantus (reference) in healthy volunteers.

Pharmacokinetics and Bioequivalence of 2 Safinamide Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

To assess the bioequivalence of a generic safinamide tablet (test) vs a brand-name safinamide tablet (reference) and effects of food on the pharmacokinetics of safinamide in healthy Chinese subjects, a single-center, single-dose, randomized, open-label, 2-preparation, 2-period study with a 15-day washout period was undertaken. A total of 56 healthy subjects were recruited in this study (fasting, n = 28; fed, n = 28). A single dose of a 100-mg test or reference safinamide tablet was administered to each subject in a randomized sequence.

Carbon dots enhance extracellular matrix secretion for dentin-pulp complex regeneration through PI3K/Akt/mTOR pathway-mediated activation of autophagy.

Pulp injury is one of the most common clinical diseases, and severe cases are usually associated with the functional loss of the tooth, while the current clinical treatment modality is only a cavity filling procedure without the regeneration of the dentin-pulp complex, thus leading to a devitalized and brittle tooth. In this study, carbon dots (CDots) with excellent biocompatibility are prepared from ascorbic acid and polyethyleneimine a hydrothermal method. The as-prepared CDots can enhance extracellular matrix (ECM) secretion of human dental pulp stem cells (DPSCs), giving rise to increased cell adhesion on ECM and a stronger osteogenic/odontogenic differentiation capacity of DPSCs.

Effects of itraconazole and rifampicin on the pharmacokinetics and safety of youkenafil, a novel phosphodiesterase type 5 inhibitor, in healthy Chinese subjects.

Youkenafil is a novel selective phosphodiesterase type 5 inhibitor to treat erectile dysfunction. In order to study the drug-drug interactions of youkenafil, in vitro experiments were conducted with human liver microsomes and recombinant isoenzymes to identify the effect of cytochrome P450 (CYP) enzymes on the metabolism of youkenafil. Then two clinical studies were performed to investigate the effects of itraconazole and rifampicin (potent CYP3A4/5 inhibitor and inducer, respectively) on the pharmacokinetics of youkenafil and its main metabolite, N-desethyl youkenafil (M1).

Altered Expression of Brain-specific Autism-Associated miRNAs in the Han Chinese Population.

Autism is a complex neurodevelopmental disorder. However, its etiology is still unknown. MicroRNAs (miRNAs) are key post-transcriptional regulators.

Synthesis of carbon dots with strong luminescence in both dispersed and aggregated states by tailoring sulfur doping.

Carbon dots (CDots), a class of environmentally friendly carbon-based luminescent nanomaterial, have been applied in a wide variety of fields, including bioimaging and light-emitting diodes (LEDs). Prior to these applications, however, CDots usually require modifications because some of its limitations (e.g.

Neutrophil Cyto-Pharmaceuticals Suppressing Tumor Metastasis via Inhibiting Hypoxia-Inducible Factor-1α in Circulating Breast Cancer Cells.

Circulating tumor cells (CTCs) are reported as the precursor of tumor metastases, implying that stifling CTCs would be beneficial for metastasis prevention. However, challenges remain for the application of therapies that aim at CTCs due to lack of effective CTC-targeting strategy and sensitive therapeutic agents. Herein, a general CTC-intervention strategy based on neutrophil cyto-pharmaceuticals is proposed for suppressing CTC colonization and metastasis formation.

IL-6 deficiency promotes colitis by recruiting Ly6C monocytes into inflamed colon tissues in a CCL2-CCR2-dependent manner.

Interleukin 6 (IL-6) is a pleiotropic cytokine that is elevated in inflammatory bowel disease. However, the role of IL-6 deficiency in colitis is not well-defined. Some IL-6 and IL-6 receptor antagonists are associated with severe gastrointestinal immune adverse effects, but the mechanisms of the effects are not clear.

Quercetin alleviates acute kidney injury by inhibiting ferroptosis.

Introduction: Ferroptosis is an iron-dependent regulated necrosis and has been proven to contribute to the progress of acute kidney injury (AKI). Quercetin (QCT), a natural flavonoid which is commonly found in numerous fruits and vegetables, has extensive pharmacological effects, such as anti-oxidant, anti-inflammatory and anti-senescence effects.

Objectives: This study aims to explain whether ferroptosis is a therapeutic strategy to AKI, and to explore the effect of QCT on AKI ferroptosis.