Voriconazole Steady-State Trough Concentrations and Clinical Outcomes in Patients with Talaromycosis.

Background: Voriconazole (VRC) has been used as an alternative treatment for talaromycosis. However, there are few studies reporting the VRC plasma concentration in patients with talaromycosis. The purpose of this study was to analyze the correlations between VRC initial steady-state trough concentration and clinical outcomes.

Identification of a novel Eps 15 homology domain-containing protein 1 (EHD1) and EHD4-binding motif in phostensin.

Phostensin (PTS) encoded by KIAA1949 binds to protein phosphatase 1, F-actin, Eps 15 homology domain-containing protein 1 (EHD1) and EHD4. Most EHD-binding proteins contain a consensus motif, Asn-Pro-Phe (NPF), which interacts with the C-terminal EH domain of EHD proteins. Nevertheless, the NPF motif is absent in PTS.

Drug-drug interaction of phenytoin sodium and methylprednisolone on voriconazole: a population pharmacokinetic model in children with thalassemia undergoing allogeneic hematopoietic stem cell transplantation.

Purpose: Voriconazole (VRC) is recommended for the prevention and treatment of invasive fungal infections in children undergoing hematopoietic stem cell transplantation (HSCT). It demonstrates nonlinear pharmacokinetics (PK) and exhibits substantial inter- and intraindividual variability. Phenytoin sodium (PHT) and methylprednisolone (MP) are commonly used in the early stages of HSCT to prevent epilepsy and graft-versus-host disease.

Total, dietary, and supplemental calcium intake and risk of all-cause, cardiovascular, and cancer mortality among U.S. adults: a prospective cohort study from the National Health and Nutrition Examination Survey.

Unlabelled: Calcium intake is widely recommended, but its association with mortality remains unclear. This study indicated higher levels of calcium intake were associated with lower mortality in American adults. However, a nonlinear association between calcium intake and mortality suggested that excessive calcium intake beyond a certain threshold may increase mortality risk.

Mesenchymal stem cell-derived extracellular vesicles in joint diseases: Therapeutic effects and underlying mechanisms.

Joint diseases greatly impact the daily lives and occupational functioning of patients globally. However, conventional treatments for joint diseases have several limitations, such as unsatisfatory efficacy and side effects, necessitating the exploration of more efficacious therapeutic strategies. Mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have demonstrated high therapeutic efficacyin tissue repair and regeneration, with low immunogenicity and tumorigenicity.

Association of dietary carbohydrate intake with bone mineral density, osteoporosis and fractures among adults without diabetes: Evidence from National Health and Nutrition Examination Survey.

Background: The impact of dietary carbohydrate intake on bone health remains a subject of controversy, potentially influenced by individuals with diabetic osteoporosis who exhibit normal or elevated bone mineral density (BMD). The cross-sectional study was conducted to explore the association between carbohydrate intake and BMD, osteoporosis and fractures among adults without diabetes, based on the National health and nutrition examination survey (NHANES).

Methods: Participants were from the NHANES 2005-2010, excluding individuals with diabetes and those with incomplete data.

Total body water percentage and 3rd space water are novel risk factors for training-related lower extremity muscle injuries in young males.

Purpose: To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.

Methods: A total of 282 healthy young male volunteers aged 18 - 20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries.

Lymphatic vessels: roles and potential therapeutic intervention in rheumatoid arthritis and osteoarthritis.

Lymphatic vessel networks are a main part of the vertebrate cardiovascular system, which participate in various physiological and pathological processes via regulation of fluid transport and immunosurveillance. Targeting lymphatic vessels has become a potent strategy for treating various human diseases. The presence of varying degrees of inflammation in joints of rheumatoid arthritis (RA) and osteoarthritis (OA), characterized by heightened infiltration of inflammatory cells, increased levels of inflammatory factors, and activation of inflammatory signaling pathways, significantly contributes to the disruption of cartilage and bone homeostasis in arthritic conditions.

A Novel Cargo Delivery System-AnCar-Exo Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances.

ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex.

53BP1 is primarily known as a key regulator in DNA double-strand break (DSB) repair. However, the mechanism of DSB-triggered cohesin modification-modulated chromatin structure on the recruitment of 53BP1 remains largely elusive. Here, we identified acetyltransferase ESCO2 as a regulator for DSB-induced cohesin-dependent chromatin structure dynamics, which promotes 53BP1 recruitment.

Degradation strategies of pesticide residue: From chemicals to synthetic biology.

The past 50 years have witnessed a massive expansion in the demand and application of pesticides. However, pesticides are difficult to be completely degraded without intervention hence the pesticide residue could pose a persistent threat to non-target organisms in many aspects. To aim at the problem of the abuse of pesticide products and excessive pesticide residues in the environment, chemical and biological degradation methods are widely developed but are scaled and insufficient to solve such a pollution.

Dosage optimization of voriconazole in children with haematological malignancies based on population pharmacokinetics.

What Is Known And Objectives: Voriconazole has a complex pharmacokinetic profile and exhibits different pharmacokinetic characteristics in adults and children. Nevertheless, few studies have been conducted on the population pharmacokinetics (PPK) of voriconazole in children with haematological malignancies. This study aims to build a PPK model and propose a suitable voriconazole treatment scheme for children with haematological malignancies.

Exogenous Indian hedgehog antagonist damages intervertebral discs homeostasis in adult mice.

Background: Vismodegib, as an exogenous Indian hedgehog (Ihh) antagonist, has been approved by the Food and Drug Administration (FDA) for the clinical treatment of patients with basal cell carcinoma, and previous observations implicate the potential therapeutic of vismodegib in osteoarthritis treatment. However, there is no direct evidence for the role of Ihh signaling in intervertebral discs (IVDs) homeostasis of adult mice. The aim of the present study is to assess the effect of systemic administration of Smoothened inhibitor (SMOi) - vismodegib on IVDs homeostasis during the adult stage.

Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis.

The high variability and unpredictability of the plasma concentration of voriconazole (VRC) pose a major challenge for clinical administration. The aim of this study was to develop a population pharmacokinetics (PPK) model of VRC and identify the factors influencing VRC PPK in patients with talaromycosis. Medical records and VRC medication history of patients with talaromycosis who were treated with VRC as initial therapy were collected.

Inhibition of aberrant Hif1α activation delays intervertebral disc degeneration in adult mice.

The intervertebral disc (IVD) is the largest avascular tissue. Hypoxia-inducible factors (HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease (DDD) is one of the leading causes of disability, and current therapies are ineffective.

Analysis of SI-Related Family Genes and Response of to SI Signal in L.

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is not only involved in carbohydrate metabolism, but also plays an important role in stress resistance. However, it has not been reported in . In this study, we performed a genome-wide identification of in and performed cloning and expression analysis of one of the differentially expressed genes, .

STAT3 is critical for skeletal development and bone homeostasis by regulating osteogenesis.

Skeletal deformities are typical AD-HIES manifestations, which are mainly caused by heterozygous and loss-of-function mutations in Signal transducer and activator of transcription 3 (STAT3). However, the mechanism is still unclear and the treatment strategy is limited. Herein, we reported that the mice with Stat3 deletion in osteoblasts, but not in osteoclasts, induced AD-HIES-like skeletal defects, including craniofacial malformation, osteoporosis, and spontaneous bone fracture.

Long term usage of dexamethasone accelerating accelerates the initiation of osteoarthritis via enhancing chondrocyte apoptosis and the extracellular matrix calcification and apoptosis of chondrocytes.

Systemic application of glucocorticoids is an essential anti-inflammatory and immune-modulating therapy for severe inflammatory or autoimmunity conditions. However, its long-term effects on articular cartilage of patients' health need to be further investigated. In this study, we studied the effects of dexamethasone (Dex) on the homeostasis of articular cartilage and the progress of destabilization of medial meniscus (DMM)-induced osteoarthritis (OA) in adult mice.

Influential Factors and Efficacy Analysis of Tacrolimus Concentration After Allogeneic Hematopoietic Stem Cell Transplantation in Children with β-Thalassemia Major.

Purpose: To analyze factors influencing tacrolimus (TAC) trough concentration (C) in β-thalassemia major (β-TM) pediatric patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and to investigate the effects of genotype polymorphism and drug-drug interactions on TAC trough concentration in children with β-TM. Furthermore, to analyze the correlation between TAC C and efficacy and adverse reactions.

Patients And Methods: Prospectively collection of demographic information and details of combined treatment of patients with β-TM receiving HSCT, and genotypes of CYP3A4, CYP3A5, and ABCB1 (rs1045642, rs1128503, rs2032582) were obtained for each patient.

Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway.

Acquired heterotopic ossification (HO) is the extraskeletal bone formation after trauma. Various mesenchymal progenitors are reported to participate in ectopic bone formation. Here we induce acquired HO in mice by Achilles tenotomy and observe that conditional knockout (cKO) of fibroblast growth factor receptor 3 (FGFR3) in Col2 cells promote acquired HO development.