Development of PBPK Population Model for End-Stage Renal Disease Patients to Inform OATP1B-, BCRP-, P-gp-, and CYP3A4-Mediated Drug Disposition with Individual Influencing Factors.

Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool for predicting pharmacokinetics (PK) to support drug development and precision medicine. However, it has not been established for non-renal clearance pathways in patients with end-stage renal disease (ESRD), a population that bears heavy medication burden and is thereby at high risk for drug-drug-disease interactions (DDDIs). Furthermore, the pronounced inter-individual variability in PK observed in ESRD patients highlights the urgent need for individualized PBPK models.

Insula Deep Brain Stimulation for Neuropathic Pain: A Cross-Over, Randomized, Sham-Controlled Trial.

Objective: Despite neuropathic pain affecting a significant portion of the population, many people still experience refractory conditions. Here, we evaluated the efficacy and safety of posterior-superior insula deep brain stimulation for pharmaco-resistant neuropathic pain.

Materials And Methods: This was a phase 2 randomized, double-blind, sham-controlled, cross-over trial.

Cu/Zn superoxide dismutase homologs participate in antiviral responses.

Superoxide dismutases (SODs) serve as the first line of defense against reactive oxygen species. Copper-zinc superoxide dismutase () is an enzyme whose activity depends on copper availability. induction is shown to be involved in the antioxidative and antiviral activity of acetylsalicylic acid in hepatitis C virus (HCV)-expressing cells.

The Effects of Dietary Supplementation of Chestnut Tannic Acid on the Growth Performance, Gut Morphology and Microbiota of Weaned Piglets.

: This study investigated the effects of chestnut tannic acid (TA) on the growth performance, the expression of tight junction proteins and the composition of the gut microbiota of weaned piglets, which could provide novel insights into the application of TA in swine production. : In a 42-day trial, 180 healthy, 21-day-old Duroc × Landrace × Yorkshire piglets were randomly assigned to a Control group and four treatment groups (TA1-4), fed commercial diets supplemented with 0, 0.06%, 0.

Timing optimization of teriparatide dosing for postmenopausal osteoporosis: a randomized controlled trial.

Background: Accumulating evidence highlights the critical role of circadian rhythms in regulating bone turnover. Bone turnover markers, including parathyroid hormone, C-terminal telopeptide of type I collagen, and N-terminal propeptide of type I procollagen, all exhibit distinct diurnal variations. Teriparatide, a recombinant parathyroid hormone analog, demonstrates time-dependent efficacy influenced by these endogenous rhythms.

[Retracted] Isorhamnetin inhibits IL‑1β‑induced expression of inflammatory mediators in human chondrocytes.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blot data shown in Fig. 3B on p. 4256 were strikingly similar to data that had already appeared in a paper written by different authors at different research institutes that had already been published in the journal .

Direct generation of high peak power noise-like pulse from an all-fiber Mamyshev oscillator at 1550 nm.

We report on the direct generation of 0.565 µJ, 80.7 kW noise-like pulse (NLP) from an all-fiber Mamyshev oscillator (MO) at 1550 nm wavelength experimentally.

ADSC exosomes improve high glucose induced fibroblast oxidative stress injury and accelerate DFU wound healing via regulating Keap1/Nrf2 axis.

Background: Diabetic foot ulcer (DFU) is a common and challenging chronic disease that can lead to non-traumatic amputation. Studies have indicated that complex cellular environments in DFU often lead to the dysfunction of several cells at the wound site; however, the mechanism of this injury is still difficult to elucidate.

Methods: DFU and normal skin tissue from patients were analyzed by pathological examination using hematoxylin and eosin (H&E), Masson, myeloperoxidase (MPO) and 8-Oxo-2'-deoxyguanosine (8OHdG) immunohistochemical staining.

Multi-omics analysis of Stenotrophomonas maltophilia S-11 reveals its potential for Pb bioremediation in contaminated soil.

Lead (Pb²⁺) contamination in soil poses a significant environmental threat, but bioremediation using plant growth-promoting bacteria offers a sustainable solution. We evaluated the Pb²⁺ detoxification potential of Stenotrophomonas maltophilia strain S-11, isolated from the buckwheat rhizosphere. The strain exhibited high Pb²⁺ tolerance, with a minimum inhibitory concentration of 18 mM, along with a Pb²⁺ removal efficiency of 78.

Safety and feasibility of anlotinib in children with high risk, recurrent or refractory sarcomas: an open-label, single-centre, single-arm, phase Ia/Ib trial.

Background: Anlotinib is a novel highly potent multitargeted tyrosine kinase inhibitor. However, the safety, recommended dosage, pharmacokinetics (PK) characteristics, and efficacy of anlotinib in paediatric patients have not been fully studied. We aimed to evaluate the safety, PK, and feasibility of anlotinib in children with high risk, recurrent or refractory sarcomas.

Population pharmacokinetic and exposure-response study of a novel anti-tuberculosis drug to inform its dosage design in phase III clinical trial.

Although bedaquiline (BDQ) received conditional approval for multi-drug resistance tuberculosis (MDR-TB), a black box warning was added due to QT prolongation risk. WX-081, a promising second-in-class drug that finished phase II clinical trial, exhibited comparable anti-TB activity and better cardiac safety. The accumulation of its active metabolite WX-081-M3 leads to QT prolongation, whereas the relationships between dosage, exposure and response have not been established.

Maternal-Fetal Physiologically Based Population Pharmacokinetics Model Development of Lopinavir/Ritonavir in HIV/HBV Co-infected Pregnant Women to Quantitatively Describe the Gestational PK Characteristics and Predict the Potential Disease-Drug-Drug Interaction (DDDI).

Background And Objective: Lopinavir/ritonavir (LPV/r) has been widely used in HIV/HBV co-infected pregnant-women. We aim to characterize the maternal-fetal (m-f) pharmacokinetic (PK) of LPV/r and support the dose optimization and potential drug-drug interaction (DDI) evaluation in this population.

Methods: Lopinavir PK characteristics in human immunodeficiency virus/hepatitis B virus (HIV/HBV) co-infected pregnant women (n = 35) and fetus were calculated using non-compartmental analysis followed by quantification of maternal PK characteristics using population PK (PopPK) analysis.

Prediction of Interspecies Translation for Targeting Delivery Coefficients of GalNAc-siRNA Silencing Apolipoprotein C-III Using a Mechanistic Minimal Physiologically Based Pharmacokinetic/Pharmacodynamic Model.

Background And Objective: The emerging N-acetylgalactosamine-small interfering RNA (GalNAc-siRNA) conjugates lead the way for liver-targeting delivery to exert gene-silencing therapeutic effects. To facilitate the drug development of GalNAc-siRNA, further detailed understanding of the key modality-specific mechanisms underlying the temporal discordance between pharmacokinetics and pharmacodynamics and how these processes can be extrapolated from animals to humans is needed.

Methods: A mechanistic minimal physiologically based pharmacokinetic/pharmacodynamic (mPBPK-PD) model for an investigational new apolipoprotein C-III (APOC3)-silencing GalNAc-siRNA (RBD5044) was developed using available pharmacokinetic/pharmacodynamic (PK/PD) data.

High efficiency and broadly wavelength-tunable mid-infrared nanosecond erbium-doped fiber laser pumped at ∼1.7 μm.

We demonstrate a high efficiency and broadly wavelength-tunable nanosecond mid-infrared (mid-IR) erbium (Er)-doped fluoride fiber laser pumped at ∼1.7 μm experimentally. In the continuous-wave operation regime, the mid-IR fiber laser output with a slope efficiency of approximately 40% has been obtained with a tuning range 143 nm spanning from 2695 nm to 2838 nm and a linewidth of 0.

Predictive Value of Inflammation Markers for Frailty in Older Patients with CVD.

Background: Chronic inflammation plays a pivotal role in the development of frailty in patients with cardiovascular diseases (CVD). Systemic inflammatory response index (SIRI) has been shown to reflect the overall inflammatory status. This study aimed to investigate the relationship between SIRI and frailty in older patients with CVD, and to develop a nomogram for predicting the risk of frailty in this population.

Injection site-retained lipid nanoparticles for targeted intramuscular delivery of mRNA RSV prefusion-F vaccine.

mRNA therapeutics, particularly mRNA vaccines, hold significant promise for a wide range of medical applications. Lipid nanoparticles (LNPs) are the most clinically advanced delivery vehicles for mRNA, but issues such as off-target effects and liver accumulation hinder their broader clinical adoption. In this study, we designed and synthesized a library of 26 novel ionizable lipids to screen for better delivery efficiency and tissue specificity.

Standard: human liver-on-a-chip.

Organs-on-chips are microphysiological systems designed to replicate key functions of human organs, thereby accelerating innovation in life sciences, such as disease modeling, drug development, and precision medicine. However, the lack of standardized definitions, structural designs, cell sources, model constructions, and functional validations has posed challenges to their widespread translational applications. On April 29, 2024, the Chinese Society of Biotechnology introduced "Organs-on-chips: Liver", China's first group standard for human liver-on-a-chip technology.

Neutrophil serine proteases NE and PR3 controlled by the miR-223/STAT3 axis potentiate MASH and liver fibrosis.

Background And Aims: Metabolic dysfunction-associated steatohepatitis (MASH) and its related liver fibrosis represent a substantial public health burden with limited treatment options. Although MASH is associated with enhanced neutrophil infiltration in the liver, the mediators and mechanisms underlying neutrophil-driven progression of MASH and fibrosis remain largely unknown. This study aimed to investigate the role of neutrophil serine proteases neutrophil elastase (NE) and proteinase 3 (PR3) in the development of MASH and fibrosis.

Evaluation of the Effects of Acorns on the Meat Quality and Transcriptome Profile of Finishing Yuxi Pigs.

In this study, we explored the effects of dietary acorn on the meat quality and transcriptome profile of finishing Yuxi pigs. A total of 90 pigs (99.60 ± 1.

Pharmacokinetics, Pharmacodynamics, and Safety Evaluation of the Novel HIF-PH Inhibitor Enarodustat: An Open-Label Phase I Study in Healthy Chinese Participants.

Background And Objectives: Enarodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor. We evaluated the pharmacokinetics, pharmacodynamics, and safety profile of domestic enarodustat (SAL-0951) and analyzed the influence of ethnic factors.

Methods: In this phase I study, healthy Chinese participants received single and multiple oral doses (1, 5, and 15 mg) of SAL-0951 while in a fasted state.

Factors associated with patient-physician relationships: perspectives of medical personnel in Guangxi Zhuang Autonomous Region, China.

Background: Disputes between physicians and patients is a global problem. In this study, we aimed to explore the factors associated with patient-physician relationships from the perspective of medical personnel in the Guangxi Zhuang Autonomous Region, China.

Methods: This is a cross-sectional study in Guangxi, which was conducted from April 1, 2023, to April 30, 2023.

Effects of Acorns on Subcutaneous Fat Deposition in Yuxi Black Pigs by Transcriptomic Analysis.

The backfat thickness of pigs is closely related to dorsal subcutaneous fat deposition and meat quality, and appropriate reduction in backfat thickness is important for improving pork quality. The present study investigated the effect of acorn diet on the backfat thickness and lipase activity of Yuxi black pigs and to gain further insight into the molecular mechanism of the acorn diet on the dorsal subcutaneous fat deposition of Yuxi black pigs by transcriptome sequencing (RNA-seq). Thirty-six Yuxi black pigs with an initial body weight of 99.

Turning antagonists into allies: Bacterial-fungal interactions enhance the efficacy of controlling wilt disease.

Intense microbial competition in soil has driven the evolution of resistance mechanisms, yet the implications of such evolution on plant health remain unclear. Our study explored the conversion from antagonism to coexistence between () and () and its effects on wilt disease (FWD) control. We found a bacilysin transmembrane transporter (MFS4) in , critical during cross-kingdom dialogue with v.

Public satisfaction with Healthy China Action Plan implementation: a web-based cross-sectional survey in southwest China.

Objective: The Healthy China (Guangxi) Action Plan has been in effect for approximately 4 years, with its primary goals being to improve public health and prevent diseases. However, there is limited information available on the community-level public satisfaction with the outcomes of its implementation. Therefore, we intend to conduct an assessment based in southwest China.

Construction of a microalgal-fungal spore co-culture system for the treatment of wastewater containing Zn(II) and estrone: Pollutant removal and microbial biochemical reactions.

The co-culture system of Chlorella sorokiniana and Aspergillus oryzae has demonstrated exceptional tolerance and efficiency in the removal of pollutants from swine manure. This study evaluates the ability of the co-culture system to remove Zn(II) and estrone, while assessing the impact of these pollutants on the system's overall functionality. Results indicated that co-cultivation achieved higher biomass accumulation, peaking at 0.