Applications of pharmacometrics in drug development.

The last two decades have witnessed profound changes in how advanced computational tools can help leverage tons of data to improve our knowledge, and ultimately reduce cost and increase productivity in drug development. Pharmacometrics has demonstrated its impact through model-informed drug development (MIDD) approaches. It is now an indispensable component throughout the whole continuum of drug discovery, development, regulatory review, and approval.

Novel cocktail therapy based on multifunctional supramolecular hydrogel targeting immune-angiogenesis-nerve network for enhanced diabetic wound healing.

Diabetes-associated chronic skin wounds present a formidable challenge due to inadequate angiogenesis and nerve regeneration during the healing process. In the present study, we introduce a groundbreaking approach in the form of a novel cocktail therapy utilizing a multifunctional supramolecular hydrogel. Formulated through the photo-crosslinking of gelatinized aromatic residues and β-cyclodextrin (β-CD), this injectable hydrogel fosters weak host-guest interactions, offering a promising solution.

Strain-Induced Tunable Enhancement of Piezoelectricity in a Novel Molecular Multiferroic Material.

Multiferroics are appealing because of application potentials in data storage devices, sensors, transducers, and energy harvesters. Molecular multiferroics emerge as a promising alternative to inorganic multiferroics due to flexibility, light weight, low toxicity, solution processing, structural diversity, and chemical tunability. While researches have predominantly focused on perovskite structures, studies on molecular ionic multiferroics remain relatively limited.

Research trends in nutritional interventions for stroke: a bibliometric analysis and literature review.

Background: Over the past 23 years, there has been a thorough analysis of literature concerning nutritional interventions, nutrients, and feeding approaches related to stroke. Furthermore, a scientific knowledge map was established, elucidating the current state of research, examining its development and trends, and offering new research viewpoints for the future. This study aimed to investigate global and emerging research trends in nutritional interventions for stroke from 2000 to 2023 through bibliometric analysis.

Microenvironment-responsive nanomedicines: a promising direction for tissue regeneration.

Severe tissue defects present formidable challenges to human health, persisting as major contributors to mortality rates. The complex pathological microenvironment, particularly the disrupted immune landscape within these defects, poses substantial hurdles to existing tissue regeneration strategies. However, the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine, providing encouraging prospects for tissue regeneration and restoration.

Research progress of gene therapy combined with tissue engineering to promote bone regeneration.

Gene therapy has emerged as a highly promising strategy for the clinical treatment of large segmental bone defects and non-union fractures, which is a common clinical need. Meanwhile, many preclinical data have demonstrated that gene and cell therapies combined with optimal scaffold biomaterials could be used to solve these tough issues. Bone tissue engineering, an interdisciplinary field combining cells, biomaterials, and molecules with stimulatory capability, provides promising alternatives to enhance bone regeneration.

Nanoarchitecture-Integrated Hydrogel Boosts Angiogenesis-Osteogenesis-Neurogenesis Tripling for Infected Bone Fracture Healing.

Infected fracture healing is a complicated process that includes intricate interactions at the cellular and molecular levels. In addition to angiogenesis and osteogenesis, the significance of neurogenesis in fracture healing has also been recognized in recent years. Here, a nanocomposite hydrogel containing pH-responsive zinc-gallium-humic acids (HAs) nanoparticles is developed.

Modulating d-Orbital electronic configuration via metal-metal oxide interactions for boosting electrocatalytic methanol oxidation.

Coordinating the interfacial interaction between Pt-based nanoparticles (NPs) and supports is a significant strategy for the modulation of d-orbital electronic configuration and the adsorption behaviors of intermediates, which is of critical importance for boosting electrocatalytic performance. Herein, we demonstrated a specific synergy effect between the ordered PtFe intermetallic and neighboring oxygen vacancies (Ov), which provides an "ensemble reaction pool" to balance the barriers of both the activity, stability, and CO poisoning issues for the methanol oxidation reaction (MOR). In our proposed "ensemble reaction pool", the deprotonation of methanol occurs on the Pt site to form the intermediate *CO, where the strain derived from the PtFe intermetallic could alter the d-orbital electronic configuration of Pt, intrinsically weakening the *CO adsorption energy, and Ov in CeO promote hydroxyl species (*OH) adsorption, which will react with *CO, facilitating the dissociative adsorption of *CO, thus cooperatively enhancing the performance of MOR.

Orbital electron delocalization of axial-coordinated modified FeN and structurally ordered PtFe intermetallic synergistically for efficient oxygen reduction reaction catalysis.

Regulating the chemical environment of materials to optimize their electronic structure, leading to the optimal adsorption energies of intermediates, is of paramount importance to improving the performance of electrocatalysts, yet remains an immense challenge. Herein, we design a harmonious axial-coordination Pt Fe/FeNCCl catalyst that integrates a structurally ordered PtFe intermetallic with an orbital electron-delocalization FeNCCl support for synergistically efficient oxygen reduction catalysis. The obtained PtFe/FeNCCl with a favorable atomic arrangement and surface composition exhibits enhanced oxygen reduction reaction (ORR) intrinsic activity and durability, achieving a mass activity (MA) and specific activity (SA) of 1.

Ageing-related bone and immunity changes: insights into the complex interplay between the skeleton and the immune system.

Ageing as a natural irreversible process inherently results in the functional deterioration of numerous organ systems and tissues, including the skeletal and immune systems. Recent studies have elucidated the intricate bidirectional interactions between these two systems. In this review, we provide a comprehensive synthesis of molecular mechanisms of cell ageing.

Cooperation of selenium, iron and phosphorus for simultaneously minimizing cadmium and arsenic concentrations in rice grains.

Cadmium (Cd) and arsenic (As), two toxic elements to humans, are ubiquitously coexisting contaminant found in paddy fields. The accumulation of Cd and As in rice, a major food source for many people around the world, can pose a serious threat to food safety and human health. Therefore, it is crucial to be aware of these contaminants and take adequate measures to reduce the accumulation of these two elements in rice.

Bioactive nanocomposite hydrogel enhances postoperative immunotherapy and bone reconstruction for osteosarcoma treatment.

Osteosarcoma, a malignant bone tumor often characterized by high hedgehog signaling activity, residual tumor cells, and substantial bone defects, poses significant challenges to both treatment response and postsurgical recovery. Here, we developed a nanocomposite hydrogel for the sustained co-delivery of bioactive magnesium ions, anti-PD-L1 antibody (αPD-L1), and hedgehog pathway antagonist vismodegib, to eradicate residual tumor cells while promoting bone regeneration post-surgery. In a mouse model of tibia osteosarcoma, this hydrogel-mediated combination therapy led to remarkable tumor growth inhibition and hence increased animal survival by enhancing the activity of tumor-suppressed CD8 T cells.

Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study.

Objectives: To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.

Methods: In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12.

[Temporal and Spatial Evolution and Prediction of Ecosystem Carbon Storage in Jiangxi Province Based on PLUS-InVEST Model].

Land-use changes are an important factor affecting the change in carbon storage in terrestrial ecosystems. Exploring the relationship between land-use changes and carbon storage provides reliable data support for optimizing regional land-use structure and maintaining regional carbon balance. Taking Jiangxi Province as an example, we first analyzed the land-use changes; then simulated the land-use pattern under three scenarios (i.

Factors Associated with Erectile Dysfunction Among Older Gay Men.

Erectile dysfunction (ED) is a common issue that aging men encounter, but whether internalized gay ageism (i.e., the internalization of ageist messages within the context of aging as a gay man) is related to ED among older gay men is unknown.

The crucial role of HFM1 in regulating FUS ubiquitination and localization for oocyte meiosis prophase I progression in mice.

Background: Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes.

SHG Assisted Mixed-Phases Anatomizing in a Molecular Ferroelectric.

Anatomizing mixed-phases, referring to analyzing the mixing profiles and quantifying the phases' proportions in a material, which is of great significance in the genuine applications. Here, by using second-harmonic generation (SHG) polarimetry and piezoresponse force microscopy (PFM) techniques, this work elucidates the contributions and distributions of two different symmetric phases mixed in an archetype monoaxial molecular ferroelectric, diisopropylammonium chloride (DIPACl). The two competing phases are preferred in thermodynamics or kinetic process respectively, and this work evidences the switching behavior between the two competing phases facilitated by an external electrical field as opposed to a heating process.

[Authenticity and adulteration identification of Bubali Cornu based on DNA fingerprints].

Whether adulteration exists is a difficult problem in the identification of traditional Chinese medicine(TCM). Bubali Cornu is mainly available in the medicinal material market in the form of buffalo horn silk or buffalo horn powder but lacks obvious identification characteristics, so there is a risk of adulteration. However, the method of identification of adulteration in Bubali Cornu is lacking at present.

Enhancement of phase transition temperature through hydrogen bond modification in molecular ferroelectrics.

Molecular ferroelectrics are attracting great interest due to their light weight, mechanical flexibility, low cost, ease of processing and environmental friendliness. These advantages make molecular ferroelectrics viable alternatives or supplements to inorganic ceramics and polymer ferroelectrics. It is expected that molecular ferroelectrics with good performance can be fabricated, which in turns calls for effective chemical design strategies in crystal engineering.

Organic-Inorganic Hybrid Perovskite Ferroelectric Nanosheets Synthesized by a Room-Temperature Antisolvent Method.

Over the past years, the application potential of ferroelectric nanomaterials with unique physical properties for modern electronics is highlighted to a large extent. However, it is relatively challenging to fabricate inorganic ferroelectric nanomaterials, which is a process depending on a vacuum atmosphere at high temperatures. As significant complements to inorganic ferroelectric nanomaterials, the nanomaterials of molecular ferroelectrics are rarely reported.

Social and Mental Health Factors Associated with Sexual Satisfaction Among Older Gay Men.

The internalization of ageist stereotypes or messages based on the framework of an aging gay man is known as internalized gay ageism. Internalized gay ageism may influence an older gay man's sexual satisfaction. The aim of this study was to examine the relationship between internalized gay ageism and sexual satisfaction and determine if body image was a potential mediator.

Design, synthesis and structure-activity relationship of 1,8-naphthalimide derivatives as highly potent hCYP1B1 inhibitors.

Human cytochrome P450 1B1 enzyme (hCYP1B1), a member of hCYP1 subfamily, plays a crucial role in multiple diseases by participating in many metabolic pathways. Although a suite of potent hCYP1B1 inhibitors have been previously reported, most of them also act as aryl hydrocarbon receptor (AhR) agonists that can up-regulate the expression of hCYP1B1 and then counteract their inhibitory potential in living systems. This study aimed to develop novel efficacious hCYP1B1 inhibitors that worked well in living cells but without AhR agonist effects.