Early metabolomics revealed the sensitivity of sacubitril/valsartan to person with end-stage renal disease accompanied by heart failure.

Heart failure (HF) is a major complication in patients with end-stage renal disease (ESRD) and is the leading cause of death in this high-risk population. Sacubitril/Valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) that has been shown to improve treatment outcomes in patients with ESRD accompanied by HF. Unfortunately, in clinical practice, some patients who received sacubitril/valsartan treatment not only did not show a good therapeutic effect, but also got worse with the passage of time.

Dietary herbs that interact with gut microbiota: roles as anti-stroke agents.

Unlabelled: Growing evidence suggests that dietary herbs can prevent stroke by regulating the composition and structure of gut microbiota. The components of dietary herbs can also be metabolized or converted into bioactive molecules for treating stroke by gut microbiota, and exert therapeutic effects by inhibiting inflammation, oxidative stress, apoptosis, and other processes caused by stroke. A deep understanding of the mechanism of gut microbiota-mediated dietary herbal intervention in stroke is of great significance for the treatment and drug screening of stroke diseases.

Covalent organic frameworks as superior adsorbents for the removal of toxic substances.

Developing new materials capable of the safe and efficient removal of toxic substances has become a research hotspot in the field of materials science, as these toxic substances pose a serious threat to human health, both directly and indirectly. Covalent organic frameworks (COFs), as an emerging class of crystalline porous materials, have advantages such as large specific surface area, tunable pore size, designable structure, and good biocompatibility, which have been proven to be a superior adsorbent design platform for toxic substances capture. This review will summarize the synthesis methods of COFs and the properties and characteristics of typical toxicants, discuss the design strategies of COF-based adsorbents for the removal of toxic substances, and highlight the recent advancements in COF-based adsorbents as robust candidates for the efficient removal of various types of toxicants, such as animal toxins, microbial toxins, phytotoxins, environmental toxins, The adsorption performance and related mechanisms of COF-based adsorbents for different types of toxic substances will be discussed.

CLK2 Condensates Reorganize Nuclear Speckles and Induce Intron Retention.

Intron retention (IR) constitutes a less explored form of alternative splicing, wherein introns are retained within mature mRNA transcripts. This investigation demonstrates that the cell division cycle (CDC)-like kinase 2 (CLK2) undergoes liquid-liquid phase separation (LLPS) within nuclear speckles in response to heat shock (HS). The formation of CLK2 condensates depends on the intrinsically disordered region (IDR) located within the N-terminal amino acids 1-148.

Rapid classification and identification of chemical compositions of Pu-zhi-hui-ling decoction by UHPLC-Q-Orbitrap HRMS.

Pu-zhi-hui-ling decoction (PZHLD) is a traditional Chinese medicine (TCM) formula for the treatment of Alzheimer's disease (AD), but its chemical composition has not been reported. In this study, we aimed to establish a mass spectrometry (MS) analysis method for rapid classification and identification of the chemical constituents in PZHLD. The sample was analysed by ultrahigh-performance liquid chromatography coupled to quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS).

Rapid and selective removal of aristolochic acid I in natural products by vinylene-linked iCOF resins.

Rapid, efficient, and selective removal of toxicants such as aristolochic acid I (AAI) from complex natural product systems is of great significance for the safe use of herbal medicines or medicine-food plants. Addressing this challenge, we develop a high-performance separation approach based on ionic covalent organic frameworks (iCOFs) to separate and remove AAI. Two vinylene-linked iCOFs (NKCOF-46-Br and NKCOF-55-Br) with high crystallinity are fabricated in a green and scalable fashion via a melt polymerization synthesis method.

A novel EGFR variant EGFRx maintains glioblastoma stem cells through STAT5.

Background: Glioblastomas are universally lethal brain tumors containing tumor-propagating glioblastoma stem cells (GSCs). EGFR gene amplification or mutation is frequently detected in GBMs and is associated with poor prognosis. However, EGFR variants in GSCs and their role in the maintenance of GSCs and progression of GBM are unclear.

Rapid identification of chemical constituents in Hugan tablets by ultra-performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry.

Hugan tablet is a Chinese medicine preparation. It is composed of Bupleuri Radix, Artemisiae Scopariae Herba, Isatidis Radix, Schisandrae Chinensis Fructus, Suis Fellis Pulvis, and Vigna radiata L. It has the effects of dispersing stagnated liver qi, strengthening the spleen and eliminating food to be used for the treatment of chronic hepatitis and early cirrhosis.

Rapid screening of active ingredients and action mechanisms of Ecliptae Herba for treating Alzheimer's disease by UPLC-Q-TOF/MS and "component-target-pathway" network.

Alzheimer's disease (AD) is a common neurodegenerative disease. The drugs widely used in clinic are mainly single-target drugs for symptomatic treatment, which can only alleviate symptoms to a certain extent. Ecliptae Herba (EH) is considered a potential therapeutic drug for AD due to its neuroprotective effects.

Efficient selective removal of uremic toxin precursor by olefin-linked covalent organic frameworks for nephropathy treatment.

Indoxyl sulfate is a protein-bound uremic toxin synthesized from indole that cannot be efficiently removed by the hemodialysis method and thus becomes a key risk factor for the progression of chronic kidney disease. Here, we develop a non-dialysis treatment strategy to fabricate an ultramicroporous olefin-linked covalent organic framework with high crystallinity in a green and scalable fashion for selectively removing the indoxyl sulfate precursor (i.e.

Catalytic Asymmetric Diels-Alder Reaction of 2'-Hydroxychalcone as a Dienophile with a VANOL-Borate Ester Complex.

Numerous flavonoid Diels-Alder-type natural products have been isolated and received great attention from the synthetic community. Herein, we reported a catalytic strategy for an asymmetric Diels-Alder reaction of 2'-hydroxychalcone with a range of diene substrates using a chiral ligand-boron Lewis acid complex. This method enables the convenient synthesis of a wide range of cyclohexene skeletons in excellent yields with moderate to good enantioselectivities, which is critical to prepare natural product congeners for further biological studies.

Rapid identification of chemical components in vitro and in vivo of Menispermi Rhizoma by integrating UPLC-Q-TOF-MS with data post-processing strategy.

Introduction: Menispermi Rhizoma (MR), the dried rhizome of Menispermum dauricum DC. (Menispermaceae), has been used to treat sore throat, enteritis, dysentery, and rheumatic arthralgia. Despite extensive research on its pharmacological effects, the chemical components in vitro and in vivo have not been thoroughly studied.

Antitumor effects of new glycoconjugated Pt agents dual-targeting GLUT1 and Pgp proteins.

A novel and highly efficient dual-targeting Pt system was designed to improve the drug delivery capacity and selectivity in cancer treatment. The dual-targeting monofunctional Pt complexes (1-8) having glycosylated pendants as tridentated ligand were achieved by introducing glycosylation modification in the thioaminocarbazone compounds with potential lysosomal targeting ability. The structures and stability of 1-8 were further established by various techniques.

Study on the potential mechanism of the active components in YiYiFuZi powder in homotherapy for hetropathy of coronary heart disease and rheumatoid arthritis.

In recent years, the incidence of coronary heart disease and rheumatoid arthritis has been increasing, which has become a common public health problem worldwide. YiYiFuZi (YYFZ ) powder is a classical traditional Chinese prescription, which is commonly used to treat metabolic diseases such as rheumatoid arthritis, with an ideal curative effect, but the therapeutic mechanism is still unclear. In this study, from the perspective of clinical metabolomics, combined with network pharmacology, we sought the comorbidity mechanism and key targets of coronary heart disease and rheumatoid arthritis and the mechanism by which YYFZ powder exerts therapeutic effects, combined with molecular docking and atomic force microscopy to determine the effective components, and found that the higenamine and steroid components in YYFZ powder can bind acid sphingomyelinase enzymes to affect the sphingolipid pathway to produce therapeutic effects, which can bind to sugars existing as a glycoside.

Integrated Serum Pharmacochemistry and Network Pharmacology Approach to Explore the Effective Components and Potential Mechanisms of Menispermi Rhizoma Against Myocardial Ischemia.

Myocardial ischemia (MI) is a leading cause of death worldwide. Menispermi Rhizoma is a traditional Chinese medicine that exerts a variety of beneficial pharmacological activities in many diseases, including MI. Serum pharmacochemistry and network pharmacology were used to explore the material basis and mechanism of action of Menispermi Rhizoma against MI.

A serum lipidomics study for the identification of specific biomarkers for endometrial polyps to distinguish them from endometrial cancer or hyperplasia.

Endometrial diseases, including endometrial polyps (EP), endometrial cancer (EC) and endometrial hyperplasia (EH), are common gynecological diseases that affect women of childbearing and perimenopausal age. Clinically, biopsy or imaging methods are usually used to screen and diagnose these diseases; however, due to the invasiveness and heterogeneity of these tests, a noninvasive, convenient, objective and accurate biomarker is needed for the differential diagnosis of EP, EC or EH. In the present study, serum samples from 326 patients with endometrial diseases and 225 healthy volunteers were analyzed using nontargeted lipidomics.

A New Strategy for the Rapid Identification and Validation of the Direct Targets of Aconitine-Induced Cardiotoxicity.

Background: The interaction of small molecules with direct targets constitutes the molecular initiation events of drug efficacy and toxicity. Aconitine, an active compound of the species, has various pharmacological effects but is strongly toxic to the heart. The direct targets of aconitine-induced cardiotoxicity remain unclear.

Synthesis, crystal structures, anticancer activities and molecular docking studies of novel thiazolidinone Cu(II) and Fe(III) complexes targeting lysosomes: special emphasis on their binding to DNA/BSA.

Novel [CuLCl]Cl·HO (1) and [FeLCl]Cl·MeOH·CHCl·HO (2) complexes of ()-'-(()-3-methyl-4-oxothiazolidin-2-ylidene)picolinohydrazonamide (L) as antitumor agents were designed and synthesized in order to explore DNA and serum albumin interaction. X-ray diffraction revealed that both 1 and 2 were a triclinic crystal system with 1̄ space group, which consisted of a positive electric main unit, a negative chloride ion and some solvent molecules. The complexes with DNA and bovine serum albumin (BSA) were studied by fluorescence and electronic absorption spectrometry.

Pharmacodynamic substances in Salvia miltiorrhiza for prevention and treatment of hyperlipidemia and coronary heart disease based on lipidomics technology and network pharmacology analysis.

In this study, untargeted lipidomics based on UPLC-Q/TOF-MS, network pharmacology and atomic force microscopy were used to explore the common biomarkers of hyperlipidemia and coronary heart disease, the therapeutic mechanism of the main components of Salvia miltiorrhiza as well as the action mechanism of key lipids. Firstly, the serum samples of 30 healthy people, 30 patients with coronary heart disease and 30 patients with hyperlipidemia were analyzed by using lipidomics technology to obtain biomarkers which can be used to link hyperlipidemia and coronary heart disease and to find potential targets; then, the key components and core targets of Salvia miltiorrhiza intervention in hyperlipidemia and coronary heart disease were analyzed by network pharmacology, the results were verified by atomic force microscopy. It showed that SMS2 might be the key target.

Pharmacokinetics, tissue distribution and excretion of 6-O-demethylmenisporphine, a bioactive oxoisoaporphine alkaloid from Menispermi Rhizoma, as determined by a HPLC-MS/MS method.

6-O-demethylmenisporphine, a major active oxoisoaporphine alkaloid isolated from Menispermi Rhizoma, has been confirmed to possess significant bioactivities, including anti-cancer and anti-hypoxia effects. However, few researches on quantifying 6-O-demethylmenisporphine in biosamples have been performed. In this research, a sensitive HPLC-MS/MS approach for determining 6-O-demethylmenisporphine in various biological matrices (plasma, tissue, urine, bile and feces) of rat has been constructed.

Rosamultin Attenuates Acute Hypobaric Hypoxia-Induced Bone Injuries by Regulation of Sclerostin and Its Downstream Signals.

Wang, Xing-Min, Hui Liu, Jian-Yu Li, Jin-Xia Wei, Xia Li, Yong-Liang Zhang, Ling-Zhi Li, and Xi-Zheng Zhang. Rosamultin attenuates acute hypobaric hypoxia-induced bone injuries by regulation of sclerostin and its downstream signals. 21:273-286, 2020.

Kaji-Ichigoside F1 and Rosamultin Protect Vascular Endothelial Cells against Hypoxia-Induced Apoptosis via the PI3K/AKT or ERK1/2 Signaling Pathway.

As a pair of differential isomers, Kaji-ichigoside F1 and Rosamultin are both pentacyclic triterpenoids isolated from the subterranean root of L., a plant used in folk medicine in western China as antihypoxia and anti-inflammatory treatments. We demonstrated that Kaji-ichigoside F1 and Rosamultin effectively prevented hypoxia-induced apoptosis in vascular endothelial cells.

Euscaphic acid and Tormentic acid protect vascular endothelial cells against hypoxia-induced apoptosis via PI3K/AKT or ERK 1/2 signaling pathway.

Aims: Euscaphic acid and Tormentic acid are aglycones of Kaji-ichigoside F1 and Rosamultin, respectively. These four compounds are pentacyclic triterpenoid, isolated from the subterranean root of the Potentilla anserina L. Based on the protective roles against hypoxia-induced apoptosis of Euscaphic acid and Tormentic acid in vascular endothelial cells, this study was designed to determine the mechanisms.

Controlled Synthesis of Manganese Oxide Nanoparticles Encaged in Hollow Mesoporous Silica Nanoreactors and Their Enhanced Dye Degradation Activity.

In this study, controlled synthesis of hollow mesoporous silica nanoreactors with small manganese oxide nanoparticles in their cavities (Mn O @HMSNs) is reported, and the dye degradation performance in the presence of hydrogen peroxide over Mn O @HMSNs is investigated. Specifically, triple ligands (a compound with three dipicolinic acid groups) were used to coordinate manganese ions to form negatively charged coordination complex networks, which further combine with positively charged copolymers to obtain metal ion-containing polymer micelles. Following silica deposition onto micellar coronas and calcinations simultaneously result in hollow mesoporous silica nanoreactors and manganese oxide nanoparticles in their cavities.

Impact of Donor and Recipient Genotype on Tacrolimus Population Pharmacokinetics in Chinese Adult Liver Transplant Recipients.

Tacrolimus (TAC) is widely used after liver transplantation, but the therapeutic window is narrow. The purpose was to study both donor and recipient genotypes affecting TAC apparent clearance rate (CL/F) and investigate a TAC population pharmacokinetic (PPK) model in Chinese liver transplant recipients for potential starting-dose individualized medication. A data set of 721 TAC concentrations was obtained from 43 adult liver transplant recipients.