Characterizing Pharmacokinetic Variability of Topiroxostat in Chinese Population: Insights from a Phase I Randomized Clinical Trial.

Objective: This Phase I clinical trial aimed to address the knowledge gap regarding topiroxostat's use outside Japan by characterizing its pharmacokinetic profile, safety, and efficacy in healthy Chinese subjects.

Methods: The trial followed a randomized, open-label, three-dose group design, enrolling 12 healthy participants and administering topiroxostat at three different dose levels. The study utilized NONMEM software for pharmacokinetic analysis, evaluating the impact of demographic and biochemical covariates on drug disposition.

-Heterocyclic carbene catalytic 1,2-boron migrative acylation accelerated by photocatalysis.

The transformation of organoboron compounds plays an important role in synthetic chemistry, and recent advancements in boron-migration reactions have garnered considerable attention. Here, we report an unprecedented 1,2-boron migrative acylation upon photocatalysis-facilitated -heterocyclic carbene catalysis. The design of a redox-active boronic ester substrate, serving as an excellent β-boron radical precursor, is the linchpin to the success of this chemistry.

Ursodeoxycholic acid and COVID-19 outcomes: a cohort study and data synthesis of state-of-art evidence.

Background: The potential of ursodeoxycholic acid (UDCA) in inhibiting angiotensin-converting enzyme 2 was demonstrated. However, conflicting evidence emerged regarding the association between UDCA and COVID-19 outcomes, prompting the need for a comprehensive investigation.

Research Design And Methods: Patients diagnosed with COVID-19 infection were retrospectively analyzed and divided into two groups: the UDCA-treated group and the control group.

Palladium-catalyzed ()-selective allylation of phosphine oxides with vinylethylene carbonates to construct phosphorus allyl alcohols.

Allylphosphine oxide compounds are important building blocks with broad applications in organic synthesis and pharmaceutical science. Herein, we report an unprecedented palladium-catalyzed allylation of phosphine oxides with vinylethylene carbonates, producing various phosphorus allyl alcohols in excellent yields with high -selectivity. In addition, gram-scale synthesis and further functional group transformations demonstrate the practical utility of this synthetic method.

Supramolecular chitin-based hydrogels with self-adapting and fast-degradation properties for enhancing wound healing.

Due to the features of high porosity, high water content, and tunable viscoelasticity, hydrogels have attracted numerous attentions in the promotion of wound closure. However, the lack of abilities to adapt the wounds of complex shapes and prevent postoperative adhesion limits their therapeutic outcomes in wound healing. To address the above challenges, the supramolecular chitin-based (SMCT) hydrogels are created via the host-guest pre-assembly strategy of β-cyclodextrin (βCD) and adamantane (Ad).

Clinical efficacy of transcrestal sinus floor augmentation, in comparison with lateral approach, in sites with residual bone height ≤6 mm: A systematic review and meta-analysis.

Objective: This paper addressed two focused questions: Focused question 1 (Q1) "what is the clinical efficacy of transcrestal sinus floor augmentation (TSFA), as compared to lateral sinus floor augmentation (LSFA) in sites with residual bone height (RBH) ≤6 mm, in randomized clinical trials (RCTs) and controlled clinical trials (CCTs)?"; Focused question 2 (Q2) "what is the estimated effectiveness of TSFA for outcomes in Q1, in RCTs, CCTs or cohort studies?"

Materials And Methods: An electronic search (PubMed, EMBASE, The Cochrane Central Register of Controlled Trials) and hand search were conducted from January 1986 until December 2022. All eligible clinical studies expressly reporting TSFA in sites with RBH ≤6 mm were included. The data were extracted, and the risk of bias in individual studies was evaluated.

ATP-Binding Cassette Exporter PDR11-Mediated Terpenoid Secretion in Engineered Yeast.

The metabolic burden caused by terpenoid accumulation limits the development of highly efficient microbial cell factories, which can be circumvented using exporter-mediated product secretion. Although our previous study showed that the pleiotropic drug resistance exporter (PDR11) mediates the export of rubusoside in , the underlying mechanism is still unclear. Herein, we used GROMACS software to simulate PDR11-mediated rubusoside recruitment and found six residues (D116, D167, Y168, P521, R663, and L1146) on PDR11 that are critical for this process.

Mechanistic Study of Icaritin-Induced Inactivation of Cytochrome P450 2C9.

Icaritin (ICT) is a prenylflavonoid derivative that has been approved by National Medical Products Administration for the treatment of hepatocellular carcinoma. This study aims to evaluate the potential inhibitory effect of ICT against cytochrome P450 (CYP) enzymes and to elucidate the inactivation mechanisms. Results showed that ICT inactivated CYP2C9 in a time-, concentration-, and NADPH-dependent manner with K = 1.

Phase I Metabolism of Pterostilbene, a Dietary Resveratrol Derivative: Metabolite Identification, Species Differences, Isozyme Contribution, and Further Bioactivation.

Pterostilbene (PTE), a dietary derivative of resveratrol, displayed pleiotropic health-promoting activities. This study aimed to explore the metabolic profiles and species differences of the phase I metabolism of PTE and to investigate subsequent detoxification after PTE bioactivation. PTE was found to be biotransformed to two pharmacologically active metabolites, pinostilbene and 3'-hydroxypterostilbene, and with substantial species differences.

A hybrid breast cancer classification algorithm based on meta-learning and artificial neural networks.

The incidence of breast cancer in women has surpassed that of lung cancer as the world's leading new cancer case. Regular screening and measures become an effective way to prevent breast cancer and also provide a good foundation for later treatment. Women should receive regular checkups in the hospital after reaching a certain age.

Research on red tide short-time prediction using GRU network model based on multi-feature Factors--A case in Xiamen sea area.

Red tide caused severe impacts on marine fisheries, ecology, economy and human life safety. The formation mechanism of the red tide is rather complicated; thus, red tide prediction and forecasting have long been a research hotspot around the globe. This study collected ocean monitoring data before and after the occurrence of red tides in Xiamen sea area from 2009 to 2017.

Analyzed and Simulated Prediction of Emission Characteristics of Construction Dust Particles under Multiple Pollution Sources.

Dust pollution in construction sites is an invisible hazard that is often ignored as a nuisance. Regulatory and engineering control methods are predominantly used for its mitigation. To control dust, dust-generating activities and their magnitudes need to be established.

De novo biosynthesis of rubusoside and rebaudiosides in engineered yeasts.

High-sugar diet causes health problems, many of which can be addressed with the use of sugar substitutes. Rubusoside and rebaudiosides are interesting molecules, considered the next generation of sugar substitutes due to their low-calorie, superior sweetness and organoleptic properties. However, their low abundance in nature makes the traditional plant extraction process neither economical nor environmental-friendly.

The Overexpression of SLC25A13 Predicts Poor Prognosis and Is Correlated with Immune Cell Infiltration in Patients with Skin Cutaneous Melanoma.

Purpose: Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers with poor prognosis due to its rapid progression towards metastasis. Thus, finding clinically relevant biomarkers for early diagnosis, prognosis, and therapy prediction is essential. This study focused on the identification of SLC25A13 as a novel biomarker for SKCM and is aimed at investigating the biological functions of solute carrier family 25 member 13 (SLC25A13) in the development of SKCM.

Subacute oral toxicology and toxicokinetics of pterostilbene, a novel Top1/Tdp1 inhibiting anti-tumor reagent.

This study evaluated the subacute toxicity and toxicokinetics of a potential anti-cancer drug candidate, pterostilbene, in rats. Animals were orally administered at two repeated doses of 200 and 500 mg/kg for 28 days. No mortality was observed during the 28 days of continuous administration of pterostilbene.

Effect of Pterostilbene, a Natural Derivative of Resveratrol, in the Treatment of Colorectal Cancer through Top1/Tdp1-Mediated DNA Repair Pathway.

Topoisomerase 1 (Top1) inhibitor is an effective anticancer drug, but several factors limit its clinical application such as drug inactivation, tyrosyl-DNA phosphodiesterase 1 (Tdp1)-mediated tumor drug resistance, and its toxicity. Our previous study identified pterostilbene (PTE) and resveratrol (RE) to suppress these two proteins by binding to their active center. PTE and RE could inhibit the proliferation of various colorectal cancer cells, induce cell apoptosis, and make cell cycle stay in G2/M phase in vitro.

Adipose mesenchymal stem cell-derived antioxidative extracellular vesicles exhibit anti-oxidative stress and immunomodulatory effects under PM exposure.

PM exposure elevates the level of reactive oxygen species (ROS) in the lungs and leads to lung injury or other pulmonary conditions. Nrf2 is a key antioxidative regulator that suppresses ROS production. Extracellular vesicles (EVs) secreted by adipose mesenchymal stem cells (ADSCs) have been identified as therapeutic as well as potential drug/gene/protein carriers.

Evaluation of bronchoalveolar lavage fluid combined with the loop-mediated isothermal amplification assay in lower respiratory tract infections.

The clinical application of the loop-mediated isothermal amplification (LAMP) assay has been problematic because of conflicting results obtained from the LAMP assay and bacterial culture. In order to eliminate the interference of oral microorganisms and more accurately evaluate the diagnostic performance of the LAMP assay, we utilized bronchoalveolar lavage fluid (BALF) as a sample to test whether the LAMP assay and bacteria culture yielded similar results. A total of 1092 BALF samples from patients with suspected lower respiratory tract infections were collected.

Distal airway stem cells ameliorate bleomycin-induced pulmonary fibrosis in mice.

Background: Idiopathic pulmonary fibrosis is characterized by loss of lung epithelial cells and inexorable progression of fibrosis with no effective and approved treatments. The distal airway stem/progenitor cells (DASCs) have been shown to have potent regenerative capacity after lung injury. In this work, we aimed to define the role of mouse DASCs (mDASCs) in response to bleomycin-induced lung fibrosis in mice.

Mask-Free Laser Lithography for Rapid and Low-Cost Microfluidic Device Fabrication.

Microfluidics has become recognized as a powerful platform technology associated with a constantly increasing array of applications across the life sciences. This surge of interest over recent years has led to an increased demand for microfluidic chips, resulting in more time being spent in the cleanroom fabricating devices using soft lithography-a slow and expensive process that requires extensive materials, training and significant engineering resources. This bottleneck limits platform complexity as a byproduct of lengthy delays between device iterations and affects the time spent developing the final application.